Attention-Deficit Hyperactivity Disorder: Diagnosis, Prevalence and Treatment 1536194433, 9781536194432

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NEUROLOGY - LABORATORY AND CLINICAL RESEARCH DEVELOPMENTS

ATTENTION-DEFICIT HYPERACTIVITY DISORDER DIAGNOSIS, PREVALENCE AND TREATMENT

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NEUROLOGY - LABORATORY AND CLINICAL RESEARCH DEVELOPMENTS

ATTENTION-DEFICIT HYPERACTIVITY DISORDER DIAGNOSIS, PREVALENCE AND TREATMENT

BRIAN M. KYSER EDITOR

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Library of Congress Cataloging-in-Publication Data Names: Kyser, Brian M., editor. Title: Attention-deficit hyperactivity disorder : diagnosis, prevalence and treatment / Brian M. Kyser, editor. Description: New York : Nova Science Publishers, [2021] | Series: Neurology - laboratory and clinical research developments | Includes bibliographical references and index. | Identifiers: LCCN 2021012330 (print) | LCCN 2021012331 (ebook) | ISBN 9781536194432 (paperback) | ISBN 9781536194692 (adobe pdf) Subjects: LCSH: Attention-deficit hyperactivity disorder. | Attention-deficit hyperactivity disorder--Treatment. Classification: LCC RJ506.H9 A92 2021 (print) | LCC RJ506.H9 (ebook) | DDC 618.92/8589--dc23 LC record available at https://lccn.loc.gov/2021012330 LC ebook record available at https://lccn.loc.gov/2021012331

Published by Nova Science Publishers, Inc. † New York

CONTENTS Preface Chapter 1

Chapter 2

Chapter 3

Index

vii Pharmacological Approaches for the Treatment of Attention-Deficit/ Hyperactivity Disorder Juan Carlos Corona

1

A Study on Supports for Postsecondary Students with Attention-Deficit/ Hyperactivity Disorder Yuko Furuhashi

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Multimedia Learning in ADHD Students Alessandro Antonietti, Alice Cancer, Rosa Angela Fabio, Paola Iannello and Elisa Zugno

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PREFACE This monograph comprises three chapters, each focusing on a different aspect of Attention-Deficit/Hyperactivity Disorder (ADHD). Chapter One presents an overview of diverse pharmacological therapies and differences in the mechanisms of action of psychostimulants, non-psychostimulants, and other treatments for ADHD. Chapter Two evaluates the effects of practical interventions for students with ADHD pursuing higher education. Chapter Three describes how multimedia formats, which simultaneously provide visual and verbal information, can help students learn by taking advantage of “dual processing,” wherein information is processed through two channels instead of through a single channel. This approach to teaching is speculated to be particularly beneficial for students with ADHD. Chapter 1 - Attention-deficit/hyperactivity disorder (ADHD), a neurobehavioural disorder in children and adolescents, impacts several areas of life, including academic performance and social and family interactions which can continue into adulthood. Currently, the management of ADHD includes pharmacological approaches such as psychostimulants, non-psychostimulants and other treatments. This chapter presents an overview of diverse pharmacological therapies and differences in the mechanisms of action of psychostimulants (methylphenidate and amphetamines), non-psychostimulants (atomoxetine and -2 adrenergic

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receptor agonists) and other treatments (glutamatergic agents). Additionally, the authors will highlight differences in effectiveness, tolerability and use in clinical trials as well as some of the adverse side effects of these diverse medications, with the aim to enhance their understanding of their therapeutic use and to open up new intervention routes for alternative therapies to improve ADHD in patients of all ages. Chapter 2 - Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by core symptoms of inattention, hyperactivity and/or impulsivity with the stipulation that at least some symptoms emerge in childhood or adolescence (American Psychiatric Association, 2013). Individuals with ADHD are vulnerable to several psychiatric and neurological disorders such as depression, sleep disorder, anxiety disorder, and substance abuse disorder. These psychiatric and neurological difficulties often impair the quality of life of adults with ADHD. In addition, postsecondary students with ADHD may also struggle in multiple areas compared with typically developed peers. Furthermore, students pursuing higher education require high-level time management and organization skills, which are areas that students with ADHD tend to struggle with. Thus, students with ADHD need academic or psychological support while pursuing college or university programs. This study aimed to evaluate the effects of practical interventions for students with ADHD pursuing higher education. Chapter 3 - Current advances in technology allowed teachers to make use of the potential advantages of multimedia learning in their education practices. Literature suggests that learning is improved by multimodal presentation of information (e.g., audio-visual modality) through a reinforcing processing effect. As a result, students understand and remember information better when notions are presented via associated text and images. Such enhanced information processing was suggested to be particularly useful for supporting learning in students with attentional problems. More precisely, students with a diagnosis of Attention Deficit and Hyperactivity Disorder (ADHD) may benefit from the use of multimedia tools supporting their learning process, thanks to the salient property of the visual presentation of learning contents, which are effective

Preface

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in enhancing both selective and sustained attention. However, a line of research argued that multimedia could hinder a functional learning process in children with attention deficit, due to an overload effect. To date, the effects of multimedia learning in ADHD students have been poorly investigated. The present chapter reports and discusses results from original studies assessing multimedia and hypertext learning in children with and without attentional and self-regulation problems. Understanding the specific effect of multimedia/hypertext learning on cognitive processing is fundamental to device teaching practices aimed at supporting a successful learning in ADHD students.

In: Attention-Deficit Hyperactivity Disorder ISBN: 978-1-53619-443-2 Editor: Brian M. Kyser © 2021 Nova Science Publishers, Inc.

Chapter 1

PHARMACOLOGICAL APPROACHES FOR THE TREATMENT OF ATTENTION-DEFICIT/ HYPERACTIVITY DISORDER Juan Carlos Corona, PhD Laboratory of Neurosciences, Hospital Infantil de México Federico Gómez, Mexico City, Mexico

ABSTRACT Attention-deficit/hyperactivity disorder (ADHD), a neurobehavioural disorder in children and adolescents, impacts several areas of life, including academic performance and social and family interactions which can continue into adulthood. Currently, the management of ADHD includes pharmacological approaches such as psychostimulants, nonpsychostimulants and other treatments. This chapter presents an overview of diverse pharmacological therapies and differences in the mechanisms of action of psychostimulants (methylphenidate and amphetamines), nonpsychostimulants (atomoxetine and -2 adrenergic receptor agonists) and 

Corresponding Author’s E-mail: [email protected].

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Juan Carlos Corona other treatments (glutamatergic agents). Additionally, we will highlight differences in effectiveness, tolerability and use in clinical trials as well as some of the adverse side effects of these diverse medications, with the aim to enhance our understanding of their therapeutic use and to open up new intervention routes for alternative therapies to improve ADHD in patients of all ages.

Keywords: psychostimulants, non-psychostimulants, glutamatergic agents, medication

INTRODUCTION Overactivity, excessive lack of attention and impulsivity are the main features of attention-deficit/hyperactivity disorder (ADHD), which is the most common neurobehavioural disorder in children and adolescents (Corona 2018; Cortese 2020; Posner et al. 2020). ADHD has a significant impact on not only school performance but also social interactions as it can cause impairment in personal, occupational, academic or social functioning, leading to isolation and worse grades, with increased risk of depression, drug abuse and delinquent and antisocial behaviour in adolescents (Faraone et al. 2015; Fredriksen et al. 2014; Wolraich et al. 2019). The worldwide prevalence of ADHD is around 5% in children and adolescents and 2.5% in adults (Polanczyk et al. 2007; Posner et al. 2020; Simon et al. 2009), and ADHD predominantly impacts boys, with a male/female ratio of 2 to 1 (Polanczyk et al. 2007; Sayal et al. 2018; Faraone et al. 2015).

AETIOLOGY OF ADHD ADHD is a disorder with high inheritability (Posner et al. 2020; Faraone et al. 2005). Moreover, genome-wide association studies have identified 12 genome-wide significant risk loci accounting for 22% of the inheritability. Data have also shown enrichment of copy number variants

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(Martin et al. 2015; Thapar 2018; Posner et al. 2020). However, genetic factors are not the only causes of ADHD which has a diverse aetiology, with contributions from genetic and environmental factors as well as from interactions among them. Diverse environmental risk factors associated with ADHD and exposure to environmental pesticides, toxins and food substances have been suggested as causal factors in ADHD (Braun et al. 2006; Nigg et al. 2016). On the other hand, perinatal and prenatal factors also play a role in the development of ADHD. For example, alcohol consumption, smoking, stress and obesity during gestation as well as low birth weight and prematurity have been also associated with ADHD (Nigg and Breslau 2007; Button et al. 2007; Banerjee et al. 2007; Senol et al. 2001; Knopik et al. 2005). Therefore, children of teenage mothers are more likely to be diagnosed with ADHD and the relationship between early maternal age and ADHD is explained by maternal genetic factors inherited by the child and mother’s age at childbirth (Chang et al. 2014).

PATHOPHYSIOLOGY OF ADHD Numerous lines of evidence from clinical, genetic, brain imaging and pharmacological studies implicate abnormalities in the catecholaminergic activity, mainly in dopaminergic neurotransmission in ADHD (Genro et al. 2010; Swanson, J. M. et al. 2007). Therefore, deregulation of catecholaminergic neurotransmission is suggested to be associated with the pathophysiology of ADHD (Prince 2008; Del Campo et al. 2011; Corona 2018). Given its role in executive function, attention, motor activity and sensitivity to rewards, the catecholaminergic system plays a role in behaviours that are important to the ADHD symptomatology. Moreover, several studies have found an association between animal models of ADHD and impairment of the dopaminergic system (Sontag et al. 2010; Russell et al. 2005). Furthermore, evidence suggests oxidative stress as a contributory pathophysiological factor in ADHD (Alvarez-Arellano et al. 2020; Joseph et al. 2015; Corona 2020). Altogether, catecholaminergic dysregulation, imbalance between oxidants and antioxidants, certain

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medications used for treatment and environmental and/or genetic factors might lead to the exacerbation of oxidative stress, resulting in a vicious cycle in ADHD. Table 1. Criteria for the diagnosis of ADHD Inattention symptoms  Making careless mistakes in schoolwork, work or other tasks and not playing attention to details  There is difficulty in participating in play activities or sustaining attention in tasks  Failure to finish schoolwork, chores or duties in the workplace and not following instructions  Difficulty in organising activities and tasks  Not listening when spoken to directly  Disliking, avoiding or being unwilling to engage in tasks that require sustained mental effort such as schoolwork  Losing things necessary for activities and tasks such as school materials, keys, toys and mobile telephones  Easy distractibility and forgetfulness in daily duties

Hyperactivity and impulsivity symptoms  Frequent squirming in seat and fidgeting with or tapping feet or hands  Not remaining seated when is expected to do so  Climbing and running excessively in inappropriate situations  Difficulty in quietly engaging in leisurely activities  There is excessive activity  Difficulty awaiting turns, interrupting or intruding on others and talking excessively  Answering before a question is completed

DIAGNOSIS The diagnosis ADHD in children and adolescents is based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (Unsel Bolat et al. 2016; Vande Voort et al. 2014), which separates children younger than 17 years of age presenting with six or more symptoms. Fewer than six symptoms are required to meet the adult criteria and the age of symptom onset is under 12 years old (Posner et al. 2020). Inattention presents as the incapacity to sustain attention to relevant tasks such as

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school-related task and verbal communication. Impulsivity refers to acting without thinking of the consequences, inability to remain seated in situations where it would be expected and failure to complete answers in class. Finally, hyperactivity presents as excessive motor activity or constant movement throughout the day. The criteria for ADHD diagnosis are shown in Table 1.

PHARMACOLOGICAL TREATMENT Routine treatment of ADHD is pharmacological, although nonpharmacological approaches including behavioural training, psychotherapy and psychoeducational treatment are also employed; treatment combinations are the most efficient. Pharmacological therapies are useful in controlling the symptoms of ADHD, such as lack of attention, distraction and impulsive behaviour (Briars and Todd 2016; Brown et al. 2018; Posner et al. 2020; Cortese 2020). Among the currently used pharmacological approaches for the treatment of ADHD, psychostimulants, non-psychostimulant and several emerging drugs such as glutamatergic agents are increasingly used. Medications used for the treatment of ADHD are summarised in Table 2.

PSYCHOSTIMULANTS Psychostimulants have been prescribed for the treatment of ADHD for more than 60 years. The currently available psychostimulants, methylphenidate (MPH) and amphetamines, have comparable clinical effects; however, their pharmacodynamical and pharmacokinetic actions are considerably different.

Increases extracellular levels of dopamine and norepinephrine in prefrontal cortex, striatum and hippocampus through the inhibition of presynaptic dopamine and norepinephrine transporters; has agonist activity at serotonin 1A receptor; redistribution of VMAT-2; increases the release of cortical acetylcholine Increases extracellular levels of dopamine and norepinephrine through the inhibition of dopamine and norepinephrine transporters; releases cytosolic dopamine by reversing the dopamine transporter; increases vesicular dopamine release by inhibiting VMAT-2; inhibits monoamine oxidases A and B Mechanism of action Selectively inhibits norepinephrine and dopamine transporters; increases extracellular levels of norepinephrine and dopamine in prefrontal cortex, cerebellum and hippocampus Stimulates postsynaptic α2A-adrenergic receptors

Ritalin, Ritalin LA, Concerta, Adhansia XR, Aptensio XR, Cotempla XR-ODT, Jornay PM, Metadate CD, Metadate ER, Methylin, QuilliChew ER, Quillivant XR, Relexxii (methylphenidate) Adderall, Adzenys XR-ODT, Adzenys ER, Dyanavel XR, Evekeo, Midayis, ProCentra, Zenzedi (amphetamine)

Estulic, Intuniv, Tenex (guanfacine)

Brand and generic name Strattera (atomoxetine)

Mechanism of action

Brand and generic name

Side effects Diarrhoea, nausea, vomiting, decreased appetite, fatigue, dizziness, mood swings and insomnia Nausea, dizziness, dry mouth, fatigue and changes in blood pressure

Headache, stomach pain, sleep disturbance, decreased appetite, insomnia, fever, emotional lability and nervousness

Anxiety, headache, insomnia, weight loss, agitation and stomach pain

Side effects

Tablets: 1, 2, 3 and 4 mg 1 mg daily

Dosage forms and strengths Capsules: 10, 18, 25, 40, 60 and 80 mg 40 mg daily

Tablets: 5, 7.5, 10, 12.5, 15, 20 and30 mg 12.5 mg once a day in the morning

Dosage forms and strengths Tablets: 5, 10 and 20 mg 10-20 mg orally in two or three divided doses, preferably 30-45 minutes before meals

Table 2. Pharmacological approaches used for the treatment of ADHD

Is a glutamate NMDA receptor antagonist

Stimulates the release of glutamate in the thalamus, striatum and hippocampus; elevates extracellular dopamine by disrupting the activity of the dopamine transporter; stimulation of adrenergic receptors Mechanism of action Is a non-competitive antagonist of NMDA receptors; modulation of the dopamine system and release of dopamine from extravesicular stores

Namenda, Namenda XR (memantine)

Provigil (modafinil)

Side effects Dry mouth, blurred vision, decreased appetite, restlessness confusion, visual hallucinations, insomnia, livedo reticularis and pedal oedema

Drowsiness, sedation, hypotension, dry mouth, constipation, drowsiness, lightheadedness and depression Headache, dizziness, digestive issues, constipation and body aches Nervousness, headache, decreased appetite, dizziness, insomnia, nausea and weight loss

Stimulates postsynaptic α2-adrenergic receptors

Catapres, Kapvay, Nexiclon (clonidine)

Brand and generic name Gocovri, Symadine, Symmetrel (amantadine)

Side effects

Mechanism of action

Brand and generic name

Dosage forms and strengths Tablet or capsule: 100 mg 50 mg daily

Tablets: 100 and 200 mg 200 mg daily

Tablets: 5 and 10 mg 5 mg daily

Dosage forms and strengths Tablets: 0.1, 0.2 and 0.3 mg 0.1 mg daily at bedtime

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METHYLPHENIDATE MPH, first synthesised in 1944, was initially indicated for conditions such as depression, chronic fatigue, narcolepsy, lethargy, psychosis associated with depression and disturbed senile behaviour (Lange et al. 2010). MPH is widely used as first-line therapy for ADHD and exerts its effect by inhibiting presynaptic dopamine and norepinephrine transporters; MPH also acts as a serotonin 1A receptor agonist and aids in the redistribution of vesicular monoamine transporter-2 (VMAT-2) (Markowitz et al. 2009; Gatley et al. 1996; Federici et al. 2005; Riddle et al. 2007; Sandoval et al. 2002; Faraone 2018; Shellenberg et al. 2020). Therefore, MPH increases extracellular dopamine and norepinephrine levels in prefrontal cortex, striatum and hippocampus (Koda et al. 2010; Kuczenski and Segal 1997; Schiffer et al. 2006; Berridge et al. 2006). Evidence also suggests that treatment with MPH increases acetylcholine release in cortex (Acquas and Fibiger 1996). Moreover, MPH impacts regional brain glucose metabolism, with significant increases and decreases observed in cerebellum and basal ganglia, respectively; thus, MPH-associated metabolic changes are regional and significantly correlate with dopamine D2 receptor density (Volkow et al. 1997). MPH has been demonstrated to improve cognitive function driven by prefrontal cortex in monkeys; this effect appears to involve indirect stimulation of -2 adrenergic receptors and dopamine D1 receptors (Gamo et al. 2010). A comprehensive meta-analysis of several double-blind randomised controlled trials in children, adolescents and adults with ADHD revealed that MPH was superior to placebo in the core ADHD symptoms and that MPH was less well tolerated than placebo in adults (Cortese et al. 2018). The therapeutic use of MPH for ADHD is associated with increased recreational use as well as increased risk of intentional overdose related to misuse (Clemow 2017; Morton and Stockton 2000); therefore, MPH dependence, use and abuse continue generating medical and ethical controversy and concerns (Leonard et al. 2004). Importantly, substance use disorder as a comorbidity is more frequent in children and adolescents with ADHD (Tejeda-Romero et al. 2018; Wilens and Morrison 2012). MPH is

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abused through the oral route or by injection or inhalation of tablets crushed into powder. The clinical manifestations of MPH overdose include exhilaration, hallucinations, nervousness, psychosis, seizures, dysrhythmias, hypertension, stroke and heart attack (Clemow 2017). Some of the side effects of MPH during therapy are headache, anxiety, insomnia, weight loss, agitation and stomach pain, which are dose-dependent (Corona 2018; Shellenberg et al. 2020).

AMPHETAMINES Amphetamine, first synthesised in 1887, was initially used for artificial replacement of adrenaline and prescribed primarily as a bronchodilator (Connolly et al. 2015; Reith and Gnegy 2020). Later, amphetamines were used for conditions such as seasickness, low blood pressure, schizophrenia, addiction and cerebral palsy (Connolly et al. 2015). Currently, used for the treatment of ADHD, obesity and narcolepsy, the mechanism of action of amphetamines includes a direct increase in extracellular synaptic levels of dopamine and norepinephrine through the inhibition of transporters (Madras et al. 2005; Avelar et al. 2013; Easton et al. 2007; Berman et al. 2009). Additionally, amphetamines increase vesicular dopamine release via the inhibition of the VMAT-2 in a region-specific and dose-dependent manner and reverse dopamine uptake via the dopamine transporter (DAT) (Easton et al. 2007; Riddle et al. 2007; Sulzer et al. 1995; Faraone 2018; Berman et al. 2009; Reith and Gnegy 2020). Furthermore, amphetamines inhibit the degradative activity of the enzymes monoamine oxidase A and B, thereby reducing the cytoplasmic breakdown and promoting the cytoplasmic accumulation of dopamine, which is then transported to the synapse (Miller, H. H. et al. 1980; Berman et al. 2009). A meta-analysis of several double-blind randomised controlled trials in children, adolescents and adults revealed that amphetamines, albeit less well tolerated than the placebo, were superior to the placebo regarding their effect on core ADHD symptoms evaluated by clinicians (Cortese et al. 2018). In addition to amphetamine, the other clinically used

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amphetamines are methamphetamine, lisdexamfetamine and the two enantiomers of amphetamine, levoamphetamine and dextroamphetamine. Levoamphetamine is associated with more overt peripheral and cardiovascular effects compared with dextroamphetamine (Kuczenski et al. 1995; Berman et al. 2009). At high doses, dextroamphetamine has a potent stimulant effect similar to that observed with levoamphetamine and acts mainly on dopamine. At low doses, levoamphetamine produces stimulation primarily through its action on norepinephrine; this effect is more potent than observed with dextroamphetamine. Conversely, dextroamphetamine exerts a more central and less peripheral effect compared with levoamphetamine and amphetamine, whose potency as a behavioural stimulant is equal to that of dextroamphetamine (Berman et al. 2009; Kuczenski et al. 1995). Acute amphetamine administration produces a wide range of dosedependent behavioural changes including increased arousal or wakefulness, hyperactivity, anorexia, a state of pleasurable effect, euphoria and elation, all of which can lead to the amphetamine abuse. Typical, side effects of amphetamines are headache, stomach pain, sleep disturbances, decreased appetite, insomnia, fever, emotional lability and nervousness (Briars and Todd 2016; Berman et al. 2009).

NON-PSYCHOSTIMULANTS The non-psychostimulants atomoxetine (ATX) and -2 adrenergic receptor agonists, including guanfacine and clonidine, are used as secondline therapy for ADHD.

ATOMOXETINE ATX has been on the market since 2002 and is currently authorised in 97 countries, is a selective norepinephrine reuptake inhibitor that causes an

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increase in norepinephrine and dopamine concentrations in prefrontal cortex, cerebellum and hippocampus (Reed et al. 2016; Koda et al. 2010; Swanson, C. J. et al. 2006a; Bymaster et al. 2002). Importantly, ATX does not cause an increase in norepinephrine or dopamine levels in nucleus accumbens; therefore, it is less likely to be abused compared with the psychostimulants (Briars and Todd 2016; Reed et al. 2016; Banaschewski et al. 2004). Children and adolescents treated with ATX have a slower initial response compared to those treated with psychostimulants and improvement in ADHD symptoms may occur over the course of several weeks and may continuing for up to more than two months (Briars and Todd 2016; Reed et al. 2016). In a meta-analysis of several randomised controlled trials comparing ATX to placebo in adults with ADHD, ATX was more effective than placebo, although its efficacy on inattention was significantly superior than on hyperactivity/impulsivity (Ravishankar et al. 2016). Additionally, a comprehensive meta-analysis of several doubleblind randomised controlled studies, revealed that ATX was better than placebo regarding improvement in core ADHD symptoms in children, adolescents and adults based on evaluation by clinicians; however, ATX was less well tolerated than placebo in adults (Cortese et al. 2018). Side effects of ATX include nausea, diarrhoea, vomiting, decreased appetite, fatigue, dizziness, mood swings and insomnia, which may develop over time (Reed et al. 2016; Corona 2018).

ALPHA-2 ADRENERGIC RECEPTOR AGONISTS The mechanism of action of -2 adrenergic receptor agonists in ADHD has not been completely elucidated. The predominant theory states that -2 adrenergic receptor agonists directly mimic the effects of norepinephrine on -2A adrenergic receptors in prefrontal cortex (Giovannitti et al. 2015).

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GUANFACINE Guanfacine selectively stimulates postsynaptic -2A adrenergic receptors, inhibiting cAMP production and closing HCN channels; therefore, guanfacine enhances the signalling efficacy of pyramidal neurons in prefrontal cortex and consequently improves attention and working memory (Cinnamon Bidwell et al. 2010; Alamo et al. 2016). Due to these effects, guanfacine is currently used as second-line therapy for ADHD (Rizzo and Martino 2015). Numerous studies show that guanfacine improves working memory and regulates attention and cognitive performance (Arnsten et al. 1988; Franowicz et al. 2002; Franowicz and Arnsten 2002; Sagvolden 2006). Guanfacine has been evaluated in children and adolescents with ADHD in several double-blind, randomised controlled trials, which demonstrate improvement in patient outcome (Sallee et al. 2009; Biederman et al. 2008; Connor and Rubin 2010; Newcorn et al. 2013; Scahill et al. 2001; Kollins et al. 2011b). A recent, a comprehensive meta-analysis of double-blind randomised controlled trials in children and adolescents, reported that guanfacine was less well tolerated than placebo (Cortese et al. 2018). However, several adverse side effects have been observed during therapy including dizziness, dry mouth, nausea, fatigue, cardiovascular events and changes in blood pressure (Connor and Rubin 2010; Rizzo and Martino 2015; Corona 2018).

CLONIDINE Initially prescribed as a nasal decongestant, clonidine was later used for the treatment of hypertension as it reduces systemic blood pressure through adrenergic stimulation in the brainstem (Giovannitti et al. 2015). Clonidine also reduces firing of presynaptic neurons that release norepinephrine to prefrontal cortex and improves impulsive and hyperactive behaviour in ADHD (Naguy 2016); therefore, clonidine is also

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used as second-line therapy for ADHD (Jain et al. 2011; Cinnamon Bidwell et al. 2010). Clonidine mimics the effects of norepinephrine in prefrontal cortex by stimulating -2 adrenergic receptors. Thus, the presynaptic action of clonidine is through the reduction of norepinephrine release and reduced firing of norepinephrine in locus coeruleus neurons (Arnsten 2010). Clonidine has also been used in hyperactive and impulsive children with autism spectrum disorder, improving their symptoms to a lesser extent (Jaselskis et al. 1992; Ming et al. 2008). Moreover, in hyperactive children with mental retardation clonidine was reported to be safe and effective (Agarwal et al. 2001). In a double-blind controlled trial in children and adolescents with ADHD and hyperactive children with mental retardation, clonidine was well tolerated by patients and significantly improved ADHD symptoms in children (Jain et al. 2011). Psychostimulants in combination with clonidine were effective in improving ADHD symptoms, in a phase III, double-blind, placebo-controlled trial of children and adolescents with hyperactive or combined subtype of ADHD (Kollins et al. 2011a). Some of the side effects of clonidine are drowsiness, sedation, hypotension, dry mouth, constipation, drowsiness, light-headedness and depression (Naguy 2016; Corona 2018).

THE ROLE OF GLUTAMATERGIC SYSTEM IN ADHD Glutamate is the major excitatory neurotransmitter in the central nervous system; approximately 80%–90% of neurons in the brain use glutamate as a neurotransmitter, and 80%–90% all synapses are glutamatergic. Neurons and glial cells contain glutamate in both the mitochondria and cytoplasm in the soma and processes. Glutamate receptors (GluRs) are divided into ionotropic and metabotropic receptors (mGluR) (Huang et al. 2019; Hassel and Dingledine 2012). Ionotropic receptors are cation channels, whereas mGluR can activate intracellular enzymes through G proteins and they do not permit ion fluxes. The three types of ionotropic receptors are N-methyl-D-aspartate (NMDA), α-amino-

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3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate receptors. Conversely, eight mGluRs, GluR1–mGluR8, have been identified and cloned to date; mGluRs are also subdivided into three functional classes (Hassel and Dingledine 2012; Huang et al. 2019). The glutamatergic system has been shown to play a role in ADHD. Several genome-wide and candidate gene association studies implicated or linked ADHD with various GluRs (Kim et al. 2017; Naaijen et al. 2017; Mick et al. 2008). Additionally, an association between ADHD and polymorphisms in NMDA receptor 2A gene was identified (Turic et al. 2004)., whereas the modulation of NMDA receptors was shown to be associated with the regulation of attention and cognition (Kotecha et al. 2002). A neuroimaging study of children with ADHD reported glutamatergic changes in striatum following treatment with MPH or ATX (Carrey et al. 2002). Moreover, ATX was shown to block NMDA receptors in therapeutic concentrations (Ludolph et al. 2010). A genome-wide copy number variation study found an association between mGluRs and ADHD (Elia et al. 2011). Impaired NMDA receptor function in prefrontal cortex was associated with impaired cognition and inability to sustain attention in the spontaneous hypertensive rat (SHR), an accepted model for ADHD (Lehohla et al. 2004). Additionally, glutamate uptake was altered in prefrontal cortex and striatum of the SHR (Miller, E. M. et al. 2014). Furthermore, diverse GluRs knock-out mouse models manifest core ADHD symptoms such as inattention, hyperactivity and impulsivity (Cowen et al. 2003; Furuse et al. 2010; Umemori et al. 2013; Palucha et al. 2007; Gerlai et al. 2002; Yadav et al. 2012; Boerner et al. 2017). Moreover, an imaging study reported changes in frontostriatal glutamatergic circuits in some children with ADHD; in contrast, a decrease was observed in adults with ADHD, suggesting impaired glutamatergic transmission in some patients with ADHD (Naaijen et al. 2015). Recently, reported associations between the variants of NMDA receptor subunitencoding genes GRIN2A and GRIN2B suggest that these genetic variants may confer increased susceptibility to attention impairment in patients with ADHD (Kim et al. 2020). Therefore, glutamatergic agents represent a promising therapeutic alternative in ADHD.

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GLUTAMATERGIC AGENTS Selective positive allosteric modulators (PAMs) such as Org 26576 which targets AMPA receptor, lead to dose-dependent reduction in locomotor hyperactivity in neonatal 6-hydroxydopamine (6-OHDA)lesioned rats, which is a commonly used model of ADHD. Additionally, in a multicentre, double-blind, placebo-controlled, two-period crossover trial, Org 26576 was superior to placebo for the treatment of symptoms in patients with ADHD (Adler et al. 2012). Moreover, VU6004256, a PAM which targets M1 muscarinic acetylcholine receptor, lead to a dosedependent decrease in hyper-locomotor activity in mice with knockdown of the NR1 subunit of the NMDA receptor (Grannan et al. 2016). SAR218645, a PAM of the mGluR2, improved working memory and abnormal attention in translational models of cognitive symptoms (Griebel et al. 2016). The mGluR5 PAM VU0409551 reversed deficit in neuroplasticity and improved contextual fear memory in a genetic model of NMDA receptor (Balu et al. 2016). Furthermore, several studies demonstrated that the non-competitive AMPA receptor antagonist perampanel and the antagonist NBQX, the dopamine D2 receptor antagonist haloperidol, group II mGluR agonist LY354740 and the mGluR7 agonist AMN082, reduced novelty-induced hyperlocomotion and locomotor hyperactivity in several GluR knock-out mice lines (Boerner et al. 2017; Maksimovic et al. 2014; Palucha et al. 2007; Procaccini et al. 2011; Procaccini et al. 2013). DAT which reuptakes dopamine into presynaptic terminals, regulates the intensity and duration of the dopaminergic signalling. Knock-out mice lacking DAT exhibit changes in dopamine homeostasis and pronounced locomotor hyperactivity, whereas positive modulators of AMPA receptors were shown to facilitate glutamatergic transmission to counteract dopaminergic hyperactivity. Additionally, MK-801-mediated blockade of NMDA receptors prevented the inhibitory effects of amphetamine on hyperactivity (Gainetdinov et al. 2001). Moreover, point mutation in the DAT gene in rats led to impairments in cognition, social behaviour and hyperactivity and led to an increase in subcortical extracellular dopamine

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levels and alteration of monoaminergic transmission. Hyperactivity in mutant rats was reduced with ATX and amphetamine, whereas treatment with the mGluR2/3 antagonist LY341495 reduced hyperactivity with no effect on extracellular dopamine levels (Vengeliene et al. 2017). Finally, fasoracetam (NFC-1), a small synthetic molecule that activates mGluRs (Hirouchi et al. 2000), was demonstrated to improve clinical severity and symptom scales in adolescents with ADHD who were carriers of mGluR risk variants in a 5-week, open-label, single-blind, placebo-controlled trial (Elia et al. 2018).

MEMANTINE Memantine (3,5-dimethyladamantan-1-amine) is an NMDA glutamate receptor antagonist that exerts its effect by specific binding to the cation channels controlled by the NMDA receptor (Johnson and Kotermanski 2006; Parsons et al. 2007). Memantine has been approved for the treatment of moderate/severe Alzheimer’s disease (Kishi et al. 2017). Importantly, memantine was reported to improve ADHD symptoms in an open-label trial of children with combined-type ADHD (Findling et al. 2007). Furthermore, significant improvement of symptoms was observed in an open-label study of adults with ADHD who were treated with memantine for 12 weeks (Surman et al. 2013). Moreover, a randomised clinical trial comparing the efficacy of memantine with MPH in children with ADHD, demonstrated that memantine was less effective than MPH (Mohammadi et al. 2015). Further, a 12-week, double-blind, placebo-controlled, randomised clinical trial of memantine with MPH reported that memantine was associated with improvements in selective areas of executive functioning in adults with ADHD (Biederman et al. 2017). In a recent double‐blind clinical trial memantine was effective in reducing inattention, memory issues and hyperactivity/impulsivity in adults with ADHD (Mohammadzadeh et al. 2019). Some of the side effects of memantine are dizziness, headache, digestive problems, constipation and body ache (Mohammadzadeh et al. 2019).

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MODAFINIL Modafinil ((±)-2-(benzhydrylsulfinyl)acetamide), which increases vigilance, has been approved for the treatment of obstructive sleep apnoea, shift work disorder and narcolepsy (Czeisler et al. 2005; Barateau et al. 2016). While its mechanism of action remains elusive, data suggest that modafinil exerts consistent effects on glutamatergic neurotransmitter systems since it can stimulate the release of glutamate in thalamus, striatum and hippocampus (Minzenberg and Carter 2008; Ferraro et al. 1997). Modafinil also elevates extracellular dopamine concentrations by binding to and disrupting the activity of DAT and increasing the levels of extracellular dopamine through increased stimulation of dopaminergic and adrenergic receptors (Wisor 2013). Improvements in ADHD symptoms were observed in adults with ADHD treated with modafinil in a randomised, double-blind, placebo-controlled, three-phase crossover study (Taylor and Russo 2000). Additionally, in a double-blind, randomised, placebo-controlled crossover study, modafinil improved cognition and response inhibition in adults with ADHD (Turner, D.C. et al. 2004). Moreover, in several randomised, double-blind and placebo-controlled trials, modafinil was well tolerated and significantly improved symptoms in children and adolescents with ADHD (Biederman and Pliszka 2008; Greenhill et al. 2006; Swanson, J. M. et al. 2006b; Kahbazi et al. 2009). However, a randomised double-blind study reported that, although well tolerated, modafinil failed to show benefit in alleviating ADHD symptoms in adults (Arnold et al. 2014). A recent, meta-analysis of several doubleblind randomised controlled trials in children found that modafinil was superior to placebo in improving core ADHD symptoms (Cortese et al. 2018). Some of the side effects of modafinil are headache, decreased appetite, nervousness, dizziness, insomnia, nausea and weight loss (Turner, D. 2006).

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AMANTADINE Amantadine (1-adamantanamine), a tricyclic amine that is a noncompetitive antagonist of NMDA receptors (Bailey and Stone 1975; Blanpied et al. 2005), has been used as an antiviral agent and is approved for Parkinson’s disease-related dyskinesia. The mechanism of action of amantadine includes modulation of the dopaminergic system and release of dopamine from extravesicular stores (Muller et al. 2019). In a 6-week open-label treatment of children with ADHD with amantadine, amantadine was well tolerated and effective in reducing ADHD symptoms, although its activity appeared to be more moderate compared to psychostimulants (Donfrancesco et al. 2007). Moreover, in a double-blind, randomised controlled trial of children treated with amantadine or MPH, the efficacy was comparable between the two treatments (Mohammadi et al. 2010). The common side effects of amantadine are dry mouth, blurred vision, reduced appetite, restlessness, confusion, visual hallucinations, insomnia, livedo reticularis and pedal oedema.

CONCLUSION ADHD can affect several aspects of daily life, and effective treatment is necessary to achieve full performance in family, academic and social functioning. In this chapter, were reviewed pharmacological approaches currently used for the treatment of ADHD and summarised differences in the mechanism of action among psychostimulants, non-psychostimulants and various glutamatergic agents. Were provided an overview of recent literature on available treatment options for ADHD, although, some of the currently prescribe therapeutic are associated with adverse side effects in patients. In most patients, pharmacological treatment usually begin with psychostimulants and adequate dosing and treatment duration as well as alternating with other treatments should be ensured. Behavioural therapy approaches in addition to appropriate pharmacological therapies should be

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considered. Thus, individually customised treatment plans accompanied with psychotherapeutic and psychoeducational therapy can lead to successful outcomes. ADHD is a life-long disorder with high prevalence and comorbidity; therefore, development of more effective long-term treatments for children and adults is warranted. These efforts should take into account the efficacy, adverse side effects, tolerability and potential comorbidities. Research data supporting pharmacological and nonpharmacological approaches are continuing to evolve with new studies in the field with the ultimate goal to establish better therapies to improve ADHD in patients of all ages.

ACKNOWLEDGMENTS I would like to acknowledge support from Fondos Federales (Grant number HIM 2016/013 SSA 1258 and HIM 2017/005 SSA 1301).

REFERENCES Acquas, E., and Fibiger, H. C. 1996. “Chronic lithium attenuates dopamine D1-receptor mediated increases in acetylcholine release in rat frontal cortex.” Psychopharmacology 125 (2): 162-7. Adler, L. A., Kroon, R. A., Stein, M., Shahid, M., Tarazi, F. I., Szegedi, A., Schipper, J., and Cazorla, P. 2012. “A translational approach to evaluate the efficacy and safety of the novel AMPA receptor positive allosteric modulator org 26576 in adult attention-deficit/hyperactivity disorder.” Biological psychiatry 72 (11): 971-7. https://doi.org/ 10.1016/j.biopsych.2012.05.012. Agarwal, V., Sitholey, P., Kumar, S., and Prasad, M. 2001. “Double-blind, placebo-controlled trial of clonidine in hyperactive children with mental retardation.” Mental retardation 39 (4): 259-67.

20

Juan Carlos Corona

https://doi.org/10.1352/0047-6765(2001)039 2.0.CO;2. Alamo, C., Lopez-Munoz, F., and Sanchez-Garcia, J. 2016. “Mechanism of action of guanfacine: a postsynaptic differential approach to the treatment of attention deficit hyperactivity disorder (adhd).” Actas espanolas de psiquiatria 44 (3): 107-12. Alvarez-Arellano, L., Gonzalez-Garcia, N., Salazar-Garcia, M., and Corona, J. C. 2020. “Antioxidants as a Potential Target against Inflammation and Oxidative Stress in Attention-Deficit/Hyperactivity Disorder.” Antioxidants (Basel) 9 (2). https://doi.org/10.3390/ antiox9020176. Arnold, V. K., Feifel, D., Earl, C. Q., Yang, R., and Adler, L. A. 2014. “A 9-week, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study to evaluate the efficacy and safety of modafinil as treatment for adults with ADHD.” Journal of attention disorders 18 (2): 133-44. https://doi.org/10.1177/1087054712441969. Arnsten, A. F. 2010. “The use of alpha-2A adrenergic agonists for the treatment of attention-deficit/hyperactivity disorder.” Expert review of neurotherapeutics 10 (10): 1595-605. https://doi.org/10.1586/ ern.10.133. Arnsten, A. F., Cai, J. X., and Goldman-Rakic, P. S. 1988. “The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes.” The Journal of neuroscience : the official journal of the Society for Neuroscience 8 (11): 4287-98. Avelar, A. J., Juliano, S. A., and Garris, P. A. 2013. “Amphetamine augments vesicular dopamine release in the dorsal and ventral striatum through different mechanisms.” Journal of neurochemistry 125 (3): 373-85. https://doi.org/10.1111/jnc.12197. Bailey, E. V., and Stone, T. W. 1975. “The mechanism of action of amantadine in Parkinsonism: a review.” Archives internationales de pharmacodynamie et de therapie 216 (2): 246-62. Balu, D. T., et al. 2016. “An mGlu5-Positive Allosteric Modulator Rescues the Neuroplasticity Deficits in a Genetic Model of NMDA Receptor

Pharmacological Approaches for the Treatment …

21

Hypofunction in Schizophrenia.” Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 41 (8): 2052-61. https://doi.org/10.1038/npp.2016.2. Banaschewski, T., Roessner, V., Dittmann, R. W., Santosh, P. J., and Rothenberger, A. 2004. “Non-stimulant medications in the treatment of ADHD.” European child & adolescent psychiatry 13 Suppl 1: I102-16. https://doi.org/10.1007/s00787-004-1010-x. Banerjee, T. D., Middleton, F., and Faraone, S. V. 2007. “Environmental risk factors for attention-deficit hyperactivity disorder.” Acta Paediatr 96 (9): 1269-74. https://doi.org/10.1111/j.1651-2227.2007.00430.x. Barateau, L., Lopez, R., and Dauvilliers, Y. 2016. “Treatment Options for Narcolepsy.” CNS drugs 30 (5): 369-79. https://doi.org/10.1007/ s40263-016-0337-4. Berman, S. M., Kuczenski, R., McCracken, J. T., and London, E. D. 2009. “Potential adverse effects of amphetamine treatment on brain and behavior: a review.” Molecular psychiatry 14 (2): 123-42. https://doi.org/10.1038/mp.2008.90. Berridge, C. W., Devilbiss, D. M., Andrzejewski, M. E., Arnsten, A. F., Kelley, A. E., Schmeichel, B., Hamilton, C., and Spencer, R. C. 2006. “Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function.” Biological psychiatry 60 (10): 1111-20. https://doi.org/10.1016/j.biopsych.2006.04.022. Biederman, J., et al. 2017. “Memantine in the Treatment of Executive Function Deficits in Adults With ADHD.” Journal of attention disorders 21 (4): 343-352. https://doi.org/10.1177/1087054714538656. Biederman, J., Melmed, R. D., Patel, A., McBurnett, K., Konow, J., Lyne, A., and Scherer, N. 2008. “A randomized, double-blind, placebocontrolled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder.” Pediatrics 121 (1): e73-84. https://doi.org/10.1542/peds.2006-3695. Biederman, J., and Pliszka, S. R. 2008. “Modafinil improves symptoms of attention-deficit/hyperactivity disorder across subtypes in children and

22

Juan Carlos Corona

adolescents.” The Journal of pediatrics 152 (3): 394-9. https://doi.org/10.1016/j.jpeds.2007.07.052. Blanpied, T. A., Clarke, R. J., and Johnson, J. W. 2005. “Amantadine inhibits NMDA receptors by accelerating channel closure during channel block.” The Journal of neuroscience : the official journal of the Society for Neuroscience 25 (13): 3312-22. https://doi.org/ 10.1523/JNEUROSCI.4262-04.2005. Boerner, T., et al. 2017. “The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice.” The European journal of neuroscience 45 (7): 912-921. https://doi.org/10.1111/ejn.13539. Braun, J. M., Kahn, R. S., Froehlich, T., Auinger, P., and Lanphear, B. P. 2006. “Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children.” Environmental health perspectives 114 (12): 1904-9. https://doi.org/10.1289/ehp.9478. Briars, L., and Todd, T. 2016. “A Review of Pharmacological Management of Attention-Deficit/Hyperactivity Disorder.” The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG 21 (3): 192-206. https://doi.org/10.5863/1551-6776-21.3.192. Brown, K. A., Samuel, S., and Patel, D. R. 2018. “Pharmacologic management of attention deficit hyperactivity disorder in children and adolescents: a review for practitioners.” Translational pediatrics 7 (1): 36-47. https://doi.org/10.21037/tp.2017.08.02. Button, T. M., Maughan, B., and McGuffin, P. 2007. “The relationship of maternal smoking to psychological problems in the offspring.” Early human development 83 (11): 727-32. https://doi.org/10.1016/ j.earlhumdev.2007.07.006. Bymaster, F. P., Katner, J. S., Nelson, D. L., Hemrick-Luecke, S. K., Threlkeld, P. G., Heiligenstein, J. H., Morin, S. M., Gehlert, D. R., and Perry, K. W. 2002. “Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder.” Neuropsychopharmacology: official publication of the American

Pharmacological Approaches for the Treatment …

23

College of Neuropsychopharmacology 27 (5): 699-711. https://doi.org/ 10.1016/S0893-133X(02)00346-9. Carrey, N., MacMaster, F. P., Sparkes, S. J., Khan, S. C., and Kusumakar, V. 2002. “Glutamatergic changes with treatment in attention deficit hyperactivity disorder: a preliminary case series.” Journal of child and adolescent psychopharmacology 12 (4): 331-6. https://doi.org/ 10.1089/104454602762599871. Chang, Z., Lichtenstein, P., D'Onofrio, B. M., Almqvist, C., Kuja-Halkola, R., Sjolander, A., and Larsson, H. 2014. “Maternal age at childbirth and risk for ADHD in offspring: a population-based cohort study.” International journal of epidemiology 43 (6): 1815-24. https://doi.org/10.1093/ije/dyu204. Cinnamon Bidwell, L., Dew, R. E., and Kollins, S. H. 2010. “Alpha-2 adrenergic receptors and attention-deficit/hyperactivity disorder.” Current psychiatry reports 12 (5): 366-73. https://doi.org/ 10.1007/s11920-010-0136-4. Clemow, D. B. 2017. “Misuse of Methylphenidate.” Current topics in behavioral neurosciences 34: 99-124. https://doi.org/10.1007/ 7854_2015_426. Connolly, J. J., Glessner, J. T., Elia, J., and Hakonarson, H. 2015. “ADHD & Pharmacotherapy: Past, Present and Future: A Review of the Changing Landscape of Drug Therapy for Attention Deficit Hyperactivity Disorder.” Therapeutic innovation & regulatory science 49 (5): 632-642. https://doi.org/10.1177/2168479015599811. Connor, D. F., and Rubin, J. 2010. “Guanfacine extended release in the treatment of attention deficit hyperactivity disorder in children and adolescents.” Drugs Today (Barc) 46 (5): 299-314. https://doi.org/10. 1358/dot.2010.46.5.1450095. Corona, J. C. 2018. “Natural Compounds for the Management of Parkinson’s Disease and Attention-Deficit/Hyperactivity Disorder.” BioMed research international 2018: 4067597. https://doi.org/ 10.1155/2018/4067597.

24

Juan Carlos Corona

Corona, J. C. 2020. “Role of Oxidative Stress and Neuroinflammation in Attention-Deficit/Hyperactivity Disorder.” Antioxidants (Basel) 9 (11). https://doi.org/10.3390/antiox9111039. Cortese, S. 2020. “Pharmacologic Treatment of Attention DeficitHyperactivity Disorder.” The New England journal of medicine 383 (11): 1050-1056. https://doi.org/10.1056/NEJMra1917069. Cortese, S., et al. 2018. “Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network metaanalysis.” The lancet. Psychiatry 5 (9): 727-738. https://doi.org/ 10.1016/S2215-0366(18)30269-4. Cowen, M. S., Schroff, K. C., Gass, P., Sprengel, R., and Spanagel, R. 2003. “Neurobehavioral effects of alcohol in AMPA receptor subunit (GluR1) deficient mice.” Neuropharmacology 45 (3): 325-33. https://doi.org/10.1016/s0028-3908(03)00174-6. Czeisler, C. A., et al. 2005. “Modafinil for excessive sleepiness associated with shift-work sleep disorder.” The New England journal of medicine 353 (5): 476-86. https://doi.org/10.1056/NEJMoa041292. Del Campo, N., Chamberlain, S. R., Sahakian, B. J., and Robbins, T. W. 2011. “The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder.” Biological psychiatry 69 (12): e145-57. https://doi.org/ 10.1016/j.biopsych.2011.02.036. Donfrancesco, R., Calderoni, D., and Vitiello, B. 2007. “Open-label amantadine in children with attention-deficit/hyperactivity disorder.” Journal of child and adolescent psychopharmacology 17 (5): 657-64. https://doi.org/10.1089/cap.2006.0128. Easton, N., Steward, C., Marshall, F., Fone, K., and Marsden, C. 2007. “Effects of amphetamine isomers, methylphenidate and atomoxetine on synaptosomal and synaptic vesicle accumulation and release of dopamine and noradrenaline in vitro in the rat brain.” Neuropharmacology 52 (2): 405-14. https://doi.org/10.1016/ j.neuropharm.2006.07.035.

Pharmacological Approaches for the Treatment …

25

Elia, J., et al. 2011. “Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder.” Nature genetics 44 (1): 78-84. https://doi.org/ 10.1038/ng.1013. Elia, J., et al. 2018. “Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling.” Nature communications 9 (1): 4. https://doi.org/10.1038/s41467-017-02244-2. Faraone, S. V. 2018. “The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attentiondeficit/hyperactivity disorder and other psychiatric comorbidities.” Neuroscience and biobehavioral reviews 87: 255-270. https://doi.org/ 10.1016/j.neubiorev.2018.02.001. Faraone, S. V., et al. 2015. “Attention-deficit/hyperactivity disorder.” Nature reviews. Disease primers 1: 15020. https://doi.org/ 10.1038/nrdp.2015.20. Faraone, S. V., Perlis, R. H., Doyle, A. E., Smoller, J. W., Goralnick, J. J., Holmgren, M. A., and Sklar, P. 2005. “Molecular genetics of attentiondeficit/hyperactivity disorder.” Biological psychiatry 57 (11): 1313-23. https://doi.org/10.1016/j.biopsych.2004.11.024. Federici, M., Geracitano, R., Bernardi, G., and Mercuri, N. B. 2005. “Actions of methylphenidate on dopaminergic neurons of the ventral midbrain.” Biological psychiatry 57 (4): 361-5. https://doi.org/ 10.1016/j.biopsych.2004.11.030. Ferraro, L., Antonelli, T., O'Connor, W. T., Tanganelli, S., Rambert, F., and Fuxe, K. 1997. “The antinarcoleptic drug modafinil increases glutamate release in thalamic areas and hippocampus.” Neuroreport 8 (13): 2883-7. https://doi.org/10.1097/00001756-199709080-00016. Findling, R. L., McNamara, N. K., Stansbrey, R. J., Maxhimer, R., Periclou, A., Mann, A., and Graham, S. M. 2007. “A pilot evaluation of the safety, tolerability, pharmacokinetics, and effectiveness of memantine in pediatric patients with attention-deficit/hyperactivity disorder combined type.” Journal of child and adolescent

26

Juan Carlos Corona

psychopharmacology 17 (1): 19-33. https://doi.org/10.1089/cap.2006. 0044. Franowicz, J. S., and Arnsten, A. F. 2002. “Actions of alpha-2 noradrenergic agonists on spatial working memory and blood pressure in rhesus monkeys appear to be mediated by the same receptor subtype.” Psychopharmacology 162 (3): 304-12. https://doi.org/ 10.1007/s00213-002-1110-6. Franowicz, J. S., Kessler, L. E., Borja, C. M., Kobilka, B. K., Limbird, L. E., and Arnsten, A. F. 2002. “Mutation of the alpha2A-adrenoceptor impairs working memory performance and annuls cognitive enhancement by guanfacine.” The Journal of neuroscience : the official journal of the Society for Neuroscience 22 (19): 8771-7. Fredriksen, M., Dahl, A. A., Martinsen, E. W., Klungsoyr, O., Faraone, S. V., and Peleikis, D. E. 2014. “Childhood and persistent ADHD symptoms associated with educational failure and long-term occupational disability in adult ADHD.” Attention deficit and hyperactivity disorders 6 (2): 87-99. https://doi.org/10.1007/s12402014-0126-1. Furuse, T., et al. 2010. “Phenotypic characterization of a new Grin1 mutant mouse generated by ENU mutagenesis.” The European journal of neuroscience 31 (7): 1281-91. https://doi.org/10.1111/j.14609568.2010.07164.x. Gainetdinov, R. R., Mohn, A. R., Bohn, L. M., and Caron, M. G. 2001. “Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter.” Proceedings of the National Academy of Sciences of the United States of America 98 (20): 11047-54. https://doi.org/10.1073/pnas.191353298. Gamo, N. J., Wang, M., and Arnsten, A. F. 2010. “Methylphenidate and atomoxetine enhance prefrontal function through alpha2-adrenergic and dopamine D1 receptors.” Journal of the American Academy of Child and Adolescent Psychiatry 49 (10): 1011-23. https://doi.org/10.1016/j.jaac.2010.06.015. Gatley, S. J., Pan, D., Chen, R., Chaturvedi, G., and Ding, Y. S. 1996. “Affinities of methylphenidate derivatives for dopamine,

Pharmacological Approaches for the Treatment …

27

norepinephrine and serotonin transporters.” Life sciences 58 (12): 2319. https://doi.org/10.1016/0024-3205(96)00052-5. Genro, J. P., Kieling, C., Rohde, L. A., and Hutz, M. H. 2010. “Attentiondeficit/hyperactivity disorder and the dopaminergic hypotheses.” Expert review of neurotherapeutics 10 (4): 587-601. https://doi.org/ 10.1586/ern.10.17. Gerlai, R., Adams, B., Fitch, T., Chaney, S., and Baez, M. 2002. “Performance deficits of mGluR8 knockout mice in learning tasks: the effects of null mutation and the background genotype.” Neuropharmacology 43 (2): 235-49. https://doi.org/10.1016/s00283908(02)00078-3. Giovannitti, J. A., Jr., Thoms, S. M., and Crawford, J. J. 2015. “Alpha-2 adrenergic receptor agonists: a review of current clinical applications.” Anesthesia progress 62 (1): 31-9. https://doi.org/10.2344/0003-300662.1.31. Grannan, M. D., et al. 2016. “Prefrontal Cortex-Mediated Impairments in a Genetic Model of NMDA Receptor Hypofunction Are Reversed by the Novel M1 PAM VU6004256.” ACS chemical neuroscience 7 (12): 1706-1716. https://doi.org/10.1021/acschemneuro.6b00230. Greenhill, L. L., Biederman, J., Boellner, S. W., Rugino, T. A., Sangal, R. B., Earl, C. Q., Jiang, J. G., and Swanson, J. M. 2006. “A randomized, double-blind, placebo-controlled study of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder.” Journal of the American Academy of Child and Adolescent Psychiatry 45 (5): 503-511. https://doi.org/10.1097/01.chi.00002057 09.63571.c9. Griebel, G., et al. 2016. “The mGluR2 positive allosteric modulator, SAR218645, improves memory and attention deficits in translational models of cognitive symptoms associated with schizophrenia.” Scientific reports 6: 35320. https://doi.org/10.1038/srep35320. Hassel, B., and Dingledine, R. 2012. Glutamate and Glutamate Receptors. In Basic Neurochemistry: Academic Press, Elsevier Inc. Oxford, UK. Hirouchi, M., Oka, M., Itoh, Y., Ukai, Y., and Kimura, K. 2000. “Role of metabotropic glutamate receptor subclasses in modulation of adenylyl

28

Juan Carlos Corona

cyclase activity by a nootropic NS-105.” European journal of pharmacology 387 (1): 9-17. https://doi.org/10.1016/s00142999(99)00785-2. Huang, X., Wang, M., Zhang, Q., Chen, X., and Wu, J. 2019. “The role of glutamate receptors in attention-deficit/hyperactivity disorder: From physiology to disease.” American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 180 (4): 272-286. https://doi.org/ 10.1002/ajmg.b.32726. Jain, R., Segal, S., Kollins, S. H., and Khayrallah, M. 2011. “Clonidine extended-release tablets for pediatric patients with attentiondeficit/hyperactivity disorder.” Journal of the American Academy of Child and Adolescent Psychiatry 50 (2): 171-9. https://doi.org/ 10.1016/j.jaac.2010.11.005. Jaselskis, C. A., Cook, E. H., Jr., Fletcher, K. E., and Leventhal, B. L. 1992. “Clonidine treatment of hyperactive and impulsive children with autistic disorder.” Journal of clinical psychopharmacology 12 (5): 322-7. Johnson, J. W., and Kotermanski, S. E. 2006. “Mechanism of action of memantine.” Current opinion in pharmacology 6 (1): 61-7. https://doi.org/10.1016/j.coph.2005.09.007. Joseph, N., Zhang-James, Y., Perl, A., and Faraone, S. V. 2015. “Oxidative Stress and ADHD: A Meta-Analysis.” Journal of attention disorders 19 (11): 915-24. https://doi.org/10.1177/1087054713510354. Kahbazi, M., Ghoreishi, A., Rahiminejad, F., Mohammadi, M. R., Kamalipour, A., and Akhondzadeh, S. 2009. “A randomized, doubleblind and placebo-controlled trial of modafinil in children and adolescents with attention deficit and hyperactivity disorder.” Psychiatry research 168 (3): 234-7. https://doi.org/10.1016/ j.psychres.2008.06.024. Kim, J. I., et al. 2017. “Association of the GRIN2B rs2284411 polymorphism with methylphenidate response in attentiondeficit/hyperactivity disorder.” J Psychopharmacol 31 (8): 1070-1077. https://doi.org/10.1177/0269881116667707.

Pharmacological Approaches for the Treatment …

29

Kim, J. I., Kim, J. W., Park, S., Hong, S. B., Lee, D. S., Paek, S. H., Han, D. H., Cheong, J. H., and Kim, B. N. 2020. “The GRIN2B and GRIN2A Gene Variants Are Associated With Continuous Performance Test Variables in ADHD.” Journal of attention disorders 24 (11): 1538-1546. https://doi.org/10.1177/1087054716649665. Kishi, T., Matsunaga, S., Oya, K., Nomura, I., Ikuta, T., and Iwata, N. 2017. “Memantine for Alzheimer's Disease: An Updated Systematic Review and Meta-analysis.” Journal of Alzheimer's disease : JAD 60 (2): 401-425. https://doi.org/10.3233/JAD-170424. Knopik, V. S., et al. 2005. “Contributions of parental alcoholism, prenatal substance exposure, and genetic transmission to child ADHD risk: a female twin study.” Psychological medicine 35 (5): 625-35. https://doi.org/10.1017/s0033291704004155. Koda, K., Ago, Y., Cong, Y., Kita, Y., Takuma, K., and Matsuda, T. 2010. “Effects of acute and chronic administration of atomoxetine and methylphenidate on extracellular levels of noradrenaline, dopamine and serotonin in the prefrontal cortex and striatum of mice.” Journal of neurochemistry 114 (1): 259-70. https://doi.org/10.1111/j.14714159.2010.06750.x. Kollins, S. H., Jain, R., Brams, M., Segal, S., Findling, R. L., Wigal, S. B., and Khayrallah, M. 2011a. “Clonidine extended-release tablets as addon therapy to psychostimulants in children and adolescents with ADHD.” Pediatrics 127 (6): e1406-13. https://doi.org/10.1542/ peds.2010-1260. Kollins, S. H., Lopez, F. A., Vince, B. D., Turnbow, J. M., Farrand, K., Lyne, A., Wigal, S. B., and Roth, T. 2011b. “Psychomotor functioning and alertness with guanfacine extended release in subjects with attention-deficit/hyperactivity disorder.” Journal of child and adolescent psychopharmacology 21 (2): 111-20. https://doi.org/ 10.1089/cap.2010.0064. Kotecha, S. A., Oak, J. N., Jackson, M. F., Perez, Y., Orser, B. A., Van Tol, H. H., and MacDonald, J. F. 2002. “A D2 class dopamine receptor transactivates a receptor tyrosine kinase to inhibit NMDA receptor

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transmission.” Neuron 35 (6): 1111-22. https://doi.org/10.1016/s08966273(02)00859-0. Kuczenski, R., and Segal, D. S. 1997. “Effects of methylphenidate on extracellular dopamine, serotonin, and norepinephrine: comparison with amphetamine.” Journal of neurochemistry 68 (5): 2032-7. Kuczenski, R., Segal, D. S., Cho, A. K., and Melega, W. 1995. “Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine.” The Journal of neuroscience : the official journal of the Society for Neuroscience 15 (2): 1308-17. Lange, K. W., Reichl, S., Lange, K. M., Tucha, L., and Tucha, O. 2010. “The history of attention deficit hyperactivity disorder.” Attention deficit and hyperactivity disorders 2 (4): 241-55. https://doi.org/ 10.1007/s12402-010-0045-8. Lehohla, M., Kellaway, L., and Russell, V. A. 2004. “NMDA receptor function in the prefrontal cortex of a rat model for attention-deficit hyperactivity disorder.” Metabolic brain disease 19 (1-2): 35-42. https://doi.org/10.1023/b:mebr.0000027415.75432.ad. Leonard, B. E., McCartan, D., White, J., and King, D. J. 2004. “Methylphenidate: a review of its neuropharmacological, neuropsychological and adverse clinical effects.” Human psychopharmacology 19 (3): 151-80. https://doi.org/10.1002/hup.579. Ludolph, A. G., Udvardi, P. T., Schaz, U., Henes, C., Adolph, O., Weigt, H. U., Fegert, J. M., Boeckers, T. M., and Fohr, K. J. 2010. “Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations.” British journal of pharmacology 160 (2): 283-91. https://doi.org/10.1111/j.1476-5381.2010.00707.x. Madras, B. K., Miller, G. M., and Fischman, A. J. 2005. “The dopamine transporter and attention-deficit/hyperactivity disorder.” Biological psychiatry 57 (11): 1397-409. https://doi.org/10.1016/j.biopsych. 2004.10.011. Maksimovic, M., Aitta-aho, T., and Korpi, E. R. 2014. “Reversal of novelty-induced hippocampal c-Fos expression in GluA1 subunitdeficient mice by chronic treatment targeting glutamatergic

Pharmacological Approaches for the Treatment …

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transmission.” European journal of pharmacology 745: 36-45. https://doi.org/10.1016/j.ejphar.2014.10.005. Markowitz, J. S., DeVane, C. L., Ramamoorthy, S., and Zhu, H. J. 2009. “The psychostimulant d-threo-(R,R)-methylphenidate binds as an agonist to the 5HT(1A) receptor.” Die Pharmazie 64 (2): 123-5. Martin, J., O'Donovan, M. C., Thapar, A., Langley, K., and Williams, N. 2015. “The relative contribution of common and rare genetic variants to ADHD.” Translational psychiatry 5: e506. https://doi.org/ 10.1038/tp.2015.5. Mick, E., Neale, B., Middleton, F. A., McGough, J. J., and Faraone, S. V. 2008. “Genome-wide association study of response to methylphenidate in 187 children with attention-deficit/hyperactivity disorder.” American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 147B (8): 1412-8. https://doi.org/ 10.1002/ajmg.b.30865. Miller, E. M., Pomerleau, F., Huettl, P., Gerhardt, G. A., and Glaser, P. E. 2014. “Aberrant glutamate signaling in the prefrontal cortex and striatum of the spontaneously hypertensive rat model of attentiondeficit/hyperactivity disorder.” Psychopharmacology 231 (15): 301929. https://doi.org/10.1007/s00213-014-3479-4. Miller, H. H., Shore, P. A., and Clarke, D. E. 1980. “In vivo monoamine oxidase inhibition by d-amphetamine.” Biochemical pharmacology 29 (10): 1347-54. Ming, X., Gordon, E., Kang, N., and Wagner, G. C. 2008. “Use of clonidine in children with autism spectrum disorders.” Brain & development 30 (7): 454-60. https://doi.org/10.1016/j.braindev 2007.12.007. Minzenberg, M. J., and Carter, C. S. 2008. “Modafinil: a review of neurochemical actions and effects on cognition.” Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 33 (7): 1477-502. https://doi.org/10.1038/sj.npp.1301534.

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Mohammadi, M. R., Kazemi, M. R., Zia, E., Rezazadeh, S. A., Tabrizi, M., and Akhondzadeh, S. 2010. “Amantadine versus methylphenidate in children and adolescents with attention deficit/hyperactivity disorder: a randomized, double-blind trial.” Human psychopharmacology 25 (78): 560-5. https://doi.org/10.1002/hup.1154. Mohammadi, M. R., Mohammadzadeh, S., and Akhondzadeh, S. 2015. “Memantine versus Methylphenidate in Children and Adolescents with Attention Deficit Hyperactivity Disorder: A Double-Blind, Randomized Clinical Trial.” Iranian journal of psychiatry 10 (2): 106-14. Mohammadzadeh, S., Ahangari, T. K., and Yousefi, F. 2019. “The effect of memantine in adult patients with attention deficit hyperactivity disorder.” Human psychopharmacology 34 (1): e2687. https://doi.org/ 10.1002/hup.2687. Morton, W. A., and Stockton, G. G. 2000. “Methylphenidate Abuse and Psychiatric Side Effects.” Primary care companion to the Journal of clinical psychiatry 2 (5): 159-164. Muller, T., Kuhn, W., and Mohr, J. D. 2019. “Evaluating ADS5102 (amantadine) for the treatment of Parkinson's disease patients with dyskinesia.” Expert opinion on pharmacotherapy 20 (10): 1181-1187. https://doi.org/10.1080/14656566.2019.1612365. Naaijen, J., Bralten, J., Poelmans, G., Glennon, J. C., Franke, B., and Buitelaar, J. K. 2017. “Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder: association to overlapping traits in ADHD and autism.” Translational psychiatry 7 (1): e999. https://doi.org/10.1038/tp.2016.273. Naaijen, J., Lythgoe, D. J., Amiri, H., Buitelaar, J. K., and Glennon, J. C. 2015. “Fronto-striatal glutamatergic compounds in compulsive and impulsive syndromes: a review of magnetic resonance spectroscopy studies.” Neuroscience and biobehavioral reviews 52: 74-88. https://doi.org/10.1016/j.neubiorev.2015.02.009. Naguy, A. 2016. “Clonidine Use in Psychiatry: Panacea or Panache.” Pharmacology 98 (1-2): 87-92. https://doi.org/10.1159/000446441.

Pharmacological Approaches for the Treatment …

33

Newcorn, J. H., Stein, M. A., Childress, A. C., Youcha, S., White, C., Enright, G., and Rubin, J. 2013. “Randomized, double-blind trial of guanfacine extended release in children with attentiondeficit/hyperactivity disorder: morning or evening administration.” Journal of the American Academy of Child and Adolescent Psychiatry 52 (9): 921-30. https://doi.org/10.1016/j.jaac.2013.06.006. Nigg, J. T., and Breslau, N. 2007. “Prenatal smoking exposure, low birth weight, and disruptive behavior disorders.” Journal of the American Academy of Child and Adolescent Psychiatry 46 (3): 362-369. https://doi.org/10.1097/01.chi.0000246054.76167.44. Nigg, J. T., Elmore, A. L., Natarajan, N., Friderici, K. H., and Nikolas, M. A. 2016. “Variation in an Iron Metabolism Gene Moderates the Association Between Blood Lead Levels and AttentionDeficit/Hyperactivity Disorder in Children.” Psychological science 27 (2): 257-69. https://doi.org/10.1177/0956797615618365. Palucha, A., Klak, K., Branski, P., van der Putten, H., Flor, P. J., and Pilc, A. 2007. “Activation of the mGlu7 receptor elicits antidepressant-like effects in mice.” Psychopharmacology 194 (4): 555-62. https://doi.org/ 10.1007/s00213-007-0856-2. Parsons, C. G., Stoffler, A., and Danysz, W. 2007. “Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system--too little activation is bad, too much is even worse.” Neuropharmacology 53 (6): 699-723. https://doi.org/10.1016/j.neuropharm.2007.07.013. Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., and Rohde, L. A. 2007. “The worldwide prevalence of ADHD: a systematic review and metaregression analysis.” The American journal of psychiatry 164 (6): 942-8. https://doi.org/10.1176/ajp.2007.164.6.942. Posner, J., Polanczyk, G. V., and Sonuga-Barke, E. 2020. “Attentiondeficit hyperactivity disorder.” Lancet 395 (10222): 450-462. https://doi.org/10.1016/S0140-6736(19)33004-1. Prince, J. 2008. “Catecholamine dysfunction in attentiondeficit/hyperactivity disorder: an update.” Journal of clinical

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psychopharmacology 28 (3 Suppl 2): S39-45. https://doi.org/ 10.1097/JCP.0b013e318174f92a. Procaccini, C., Aitta-aho, T., Jaako-Movits, K., Zharkovsky, A., Panhelainen, A., Sprengel, R., Linden, A. M., and Korpi, E. R. 2011. “Excessive novelty-induced c-Fos expression and altered neurogenesis in the hippocampus of GluA1 knockout mice.” The European journal of neuroscience 33 (1): 161-74. https://doi.org/10.1111/j.14609568.2010.07485.x. Procaccini, C., Maksimovic, M., Aitta-Aho, T., Korpi, E. R., and Linden, A. M. 2013. “Reversal of novelty-induced hyperlocomotion and hippocampal c-Fos expression in GluA1 knockout male mice by the mGluR2/3 agonist LY354740.” Neuroscience 250: 189-200. https://doi.org/10.1016/j.neuroscience.2013.07.010. Ravishankar, V., Chowdappa, S. V., Benegal, V., and Muralidharan, K. 2016. “The efficacy of atomoxetine in treating adult attention deficit hyperactivity disorder (ADHD): A meta-analysis of controlled trials.” Asian journal of psychiatry 24: 53-58. https://doi.org/ 10.1016/j.ajp.2016.08.017. Reed, V. A., Buitelaar, J. K., Anand, E., Day, K. A., Treuer, T., Upadhyaya, H. P., Coghill, D. R., Kryzhanovskaya, L. A., and Savill, N. C. 2016. “The Safety of Atomoxetine for the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Comprehensive Review of Over a Decade of Research.” CNS drugs 30 (7): 603-28. https://doi.org/10.1007/s40263-016-0349-0. Reith, M. E. A., and Gnegy, M. E. 2020. “Molecular Mechanisms of Amphetamines.” Handbook of experimental pharmacology 258: 265297. https://doi.org/10.1007/164_2019_251. Riddle, E. L., Hanson, G. R., and Fleckenstein, A. E. 2007. “Therapeutic doses of amphetamine and methylphenidate selectively redistribute the vesicular monoamine transporter-2.” European journal of pharmacology 571 (1): 25-8. https://doi.org/10.1016/j.ejphar.2007. 05.044. Rizzo, R., and Martino, D. 2015. “Guanfacine for the treatment of attention deficit hyperactivity disorder in children and adolescents.” Expert

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35

review of neurotherapeutics 15 (4): 347-54. https://doi.org/10.1586/14737175.2015.1028370. Russell, V. A., Sagvolden, T., and Johansen, E. B. 2005. “Animal models of attention-deficit hyperactivity disorder.” Behavioral and brain functions : BBF 1: 9. https://doi.org/10.1186/1744-9081-1-9. Sagvolden, T. 2006. “The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and reduces overactivity and impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD).” Behavioral and brain functions : BBF 2: 41. https://doi.org/10.1186/1744-9081-2-41. Sallee, F. R., McGough, J., Wigal, T., Donahue, J., Lyne, A., and Biederman, J. 2009. “Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebocontrolled trial.” Journal of the American Academy of Child and Adolescent Psychiatry 48 (2): 155-65. https://doi.org/10.1097/ CHI.0b013e318191769e. Sandoval, V., Riddle, E. L., Hanson, G. R., and Fleckenstein, A. E. 2002. “Methylphenidate redistributes vesicular monoamine transporter-2: role of dopamine receptors.” The Journal of neuroscience : the official journal of the Society for Neuroscience 22 (19): 8705-10. Sayal, K., Prasad, V., Daley, D., Ford, T., and Coghill, D. 2018. “ADHD in children and young people: prevalence, care pathways, and service provision.” The lancet. Psychiatry 5 (2): 175-186. https://doi.org/ 10.1016/S2215-0366(17)30167-0. Scahill, L., Chappell, P. B., Kim, Y. S., Schultz, R. T., Katsovich, L., Shepherd, E., Arnsten, A. F., Cohen, D. J., and Leckman, J. F. 2001. “A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder.” The American journal of psychiatry 158 (7): 1067-74. https://doi.org/ 10.1176/appi.ajp.158.7.1067. Schiffer, W. K., Volkow, N. D., Fowler, J. S., Alexoff, D. L., Logan, J., and Dewey, S. L. 2006. “Therapeutic doses of amphetamine or methylphenidate differentially increase synaptic and extracellular dopamine.” Synapse 59 (4): 243-51. https://doi.org/10.1002/syn.20235.

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Senol, S., Sener, S., Ergenekon, E., and Gucuyener, K. 2001. “The impact of pre- and perinatal factors on attention-deficit and disruptive behavior disorders.” The Turkish journal of pediatrics 43 (3): 231-6. Shellenberg, T. P., Stoops, W. W., Lile, J. A., and Rush, C. R. 2020. “An update on the clinical pharmacology of methylphenidate: therapeutic efficacy, abuse potential and future considerations.” Expert review of clinical pharmacology 13 (8): 825-833. https://doi.org/10.1080/ 17512433.2020.1796636. Simon, V., Czobor, P., Balint, S., Meszaros, A., and Bitter, I. 2009. “Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis.” The British journal of psychiatry : the journal of mental science 194 (3): 204-11. https://doi.org/ 10.1192/bjp.bp.107.048827. Sontag, T. A., Tucha, O., Walitza, S., and Lange, K. W. 2010. “Animal models of attention deficit/hyperactivity disorder (ADHD): a critical review.” Attention deficit and hyperactivity disorders 2 (1): 1-20. https://doi.org/10.1007/s12402-010-0019-x. Sulzer, D., Chen, T. K., Lau, Y. Y., Kristensen, H., Rayport, S., and Ewing, A. 1995. “Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport.” The Journal of neuroscience : the official journal of the Society for Neuroscience 15 (5 Pt 2): 4102-8. Surman, C. B., Hammerness, P. G., Petty, C., Spencer, T., Doyle, R., Napolean, S., Chu, N., Yorks, D., and Biederman, J. 2013. “A pilot open label prospective study of memantine monotherapy in adults with ADHD.” The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 14 (4): 291-8. https://doi.org/10.3109/15622975.2011.623716. Swanson, C. J., Perry, K. W., Koch-Krueger, S., Katner, J., Svensson, K. A., and Bymaster, F. P. 2006a. “Effect of the attention deficit/hyperactivity disorder drug atomoxetine on extracellular concentrations of norepinephrine and dopamine in several brain regions of the rat.” Neuropharmacology 50 (6): 755-60. https://doi.org/10.1016/j.neuropharm.2005.11.022.

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Swanson, J. M., Greenhill, L. L., Lopez, F. A., Sedillo, A., Earl, C. Q., Jiang, J. G., and Biederman, J. 2006b. “Modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: results of a randomized, double-blind, placebo-controlled, fixed-dose study followed by abrupt discontinuation.” The Journal of clinical psychiatry 67 (1): 137-47. https://doi.org/10.4088/ jcp.v67n0120. Swanson, J. M., et al. 2007. “Etiologic subtypes of attentiondeficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis.” Neuropsychology review 17 (1): 39-59. https://doi.org/10.1007/s11065-007-9019-9. Taylor, F. B., and Russo, J. 2000. “Efficacy of modafinil compared to dextroamphetamine for the treatment of attention deficit hyperactivity disorder in adults.” Journal of child and adolescent psychopharmacology 10 (4): 311-20. https://doi.org/10.1089/cap. 2000.10.311. Tejeda-Romero, C., Kobashi-Margain, R. A., Alvarez-Arellano, L., Corona, J. C., and Gonzalez-Garcia, N. 2018. “Differences in substance use, psychiatric disorders and social factors between Mexican adolescents and young adults.” The American journal on addictions 27 (8): 625-631. https://doi.org/10.1111/ajad.12808. Thapar, A. 2018. “Discoveries on the Genetics of ADHD in the 21st Century: New Findings and Their Implications.” The American journal of psychiatry 175 (10): 943-950. https://doi.org/10.1176/appi.ajp. 2018.18040383. Turic, D., et al. 2004. “Follow-up of genetic linkage findings on chromosome 16p13: evidence of association of N-methyl-D aspartate glutamate receptor 2A gene polymorphism with ADHD.” Molecular psychiatry 9 (2): 169-73. https://doi.org/10.1038/sj.mp.4001387. Turner, D. 2006. “A review of the use of modafinil for attention-deficit hyperactivity disorder.” Expert review of neurotherapeutics 6 (4): 45568. https://doi.org/10.1586/14737175.6.4.455. Turner, D. C., Clark, L., Dowson, J., Robbins, T. W., and Sahakian, B. J. 2004. “Modafinil improves cognition and response inhibition in adult

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Juan Carlos Corona

attention-deficit/hyperactivity disorder.” Biological psychiatry 55 (10): 1031-40. https://doi.org/10.1016/j.biopsych.2004.02.008. Umemori, J., Takao, K., Koshimizu, H., Hattori, S., Furuse, T., Wakana, S., and Miyakawa, T. 2013. “ENU-mutagenesis mice with a nonsynonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response.” BMC research notes 6: 203. https://doi.org/10.1186/17560500-6-203. Unsel Bolat, G., Ercan, E. S., Salum, G. A., Bilac, O., Massuti, R., Uysal Ozaslan, T., Bolat, H., and Rohde, L. A. 2016. “Validity of proposed DSM-5 ADHD impulsivity symptoms in children.” European child & adolescent psychiatry 25 (10): 1121-32. https://doi.org/10.1007/ s00787-016-0839-0. Vande Voort, J. L., He, J. P., Jameson, N. D., and Merikangas, K. R. 2014. “Impact of the DSM-5 attention-deficit/hyperactivity disorder age-ofonset criterion in the US adolescent population.” Journal of the American Academy of Child and Adolescent Psychiatry 53 (7): 736-44. https://doi.org/10.1016/j.jaac.2014.03.005. Vengeliene, V., et al. 2017. “Towards trans-diagnostic mechanisms in psychiatry: neurobehavioral profile of rats with a loss-of-function point mutation in the dopamine transporter gene.” Disease models & mechanisms 10 (4): 451-461. https://doi.org/10.1242/dmm.027623. Volkow, N. D., Wang, G. J., Fowler, J. S., Logan, J., Angrist, B., Hitzemann, R., Lieberman, J., and Pappas, N. 1997. “Effects of methylphenidate on regional brain glucose metabolism in humans: relationship to dopamine D2 receptors.” The American journal of psychiatry 154 (1): 50-5. https://doi.org/10.1176/ajp.154.1.50. Wilens, T. E., and Morrison, N. R. 2012. “Substance-use disorders in adolescents and adults with ADHD: focus on treatment.” Neuropsychiatry 2 (4): 301-312. https://doi.org/10.2217/npy.12.39. Wisor, J. 2013. “Modafinil as a catecholaminergic agent: empirical evidence and unanswered questions.” Frontiers in neurology 4: 139. https://doi.org/10.3389/fneur.2013.00139.

Pharmacological Approaches for the Treatment …

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Wolraich, M. L., et al. 2019. “Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of AttentionDeficit/Hyperactivity Disorder in Children and Adolescents.” Pediatrics 144 (4). https://doi.org/10.1542/peds.2019-2528. Yadav, R., Gupta, S. C., Hillman, B. G., Bhatt, J. M., Stairs, D. J., and Dravid, S. M. 2012. “Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors.” PloS one 7 (3): e32969. https://doi.org/10.1371/journal.pone.0032969.

BIOGRAPHICAL SKETCH

Dr. Juan Carlos Corona Affiliation: Laboratory of Neurosciences, Hospital Infantil de México Federico Gómez, Mexico City, Mexico. Education:   

BSc (Chemistry) 1993 - 1998 MSc (Experimental Biology) 2001 - 2003 PhD (Biological Sciences) 2003 - 2007

Research and Professional Experience: Effect of treatment with the medications used in ADHD on mitochondrial function and oxidative stress and Study of treatment with diverse natural compounds on mitochondrial function and oxidative stress in vivo and in vitro. 1. Research Associate at Department of Cell and Developmental Biology, University College London (UCL), United Kingdom. 2011 - 2013

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Juan Carlos Corona 2. Postdoctoral Research at Department of Cell and Developmental Biology, UCL. 2009 - 2011 3. Postdoctoral Research at Department of Molecular Neurobiology, Centre of Molecular Biology Severo Ochoa, Autonomous University of Madrid, Spain. 2007 - 2009

Professional Appointments: Researcher in Medical Sciences and Head of Laboratory of Neurosciences at Hospital Infantil de México Federico Gómez, Mexico City. Since December 2013 Honors: Member of the National System of Investigators, level I Publications from the Last 3 Years: 1. Alvarez-Arellano L., Salazar-García M. and Corona J. C. (2020) Neuroprotective effects of quercetin in pediatric neurological diseases. Molecules 2020, 25(23), 5597; doi.org/10.3390/ molecules25235597. 2. Corona J. C. (2020) Role of Oxidative Stress and Neuroinflammation in Attention-Deficit/Hyperactivity Disorder. Antioxidants, 9, 1039; doi:10.3390/antiox9111039. 3. Alvarez-Arellano L., González-García N., Salazar-García M. and Corona J. C. (2020) Antioxidants as a potential target against inflammation and oxidative stress in attention- deficit/ hyperactivity disorder. Antioxidants, 9 (2), 176; doi: 10.3390/antiox9020176. 4. Corona J. C., Carreón-Trujillo S., González-Pérez R., GómezBautista D., Vázquez- González D. and Salazar-García M. (2019) Atomoxetine produces oxidative stress and alters mitochondrial function in human neuron-like cells. Scientific Reports. 10;9(1):13011. doi: 10.1038/s41598-019-49609-9. 5. Corona J. C. (2018) Natural compounds for the management of Parkinson’s disease and Attention-deficit/hyperactivity disorder.

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BioMed Research International. Nov 22;2018:4067597. DOI: 10.1155/2018/4067597. 6. Garrido-Armas, M., Corona J. C., Escobar, M. L., Torres, L., Ordóñez-Romero, F., Hernández-Hernández, A. and ArenasHuertero, F. (2018) Paraptosis in human glioblastoma cell line induced by curcumin. Toxicology in Vitro. 51:63-73. 7. Cardenas-Perez, R. E., Fuentes-Mera, L., de la Garza, A. L., TorreVillalvazo, I., Reyes- Castro, L. A., Rodriguez-Rocha, H., GarciaGarcia, A., Corona J. C., Tovar, L., Zambrano, E., Ortiz-Lopez, R., Saville, J., Fuller, M. and Camacho, A. (2018) Maternal overnutrition by hypercaloric diets programs mitochondrial fusion and metabolic dysfunction in rat male offspring. Nutrition & Metabolism. 15(38): 1-16. 8. Tejeda Romero, C., Kobashi Margáin, R. A., Alvarez-Arellano, L., Corona J. C. and González García, N. (2018) Differences in substance use, psychiatric disorders and social factors between Mexican adolescents and young adults. The American Journal on Addictions. 27(8):625-631. Declaration I hereby declare that all the above stated information is true and correct to the best of my knowledge. December 2020

In: Attention-Deficit Hyperactivity Disorder ISBN: 978-1-53619-443-2 Editor: Brian M. Kyser © 2021 Nova Science Publishers, Inc.

Chapter 2

A STUDY ON SUPPORTS FOR POSTSECONDARY STUDENTS WITH ATTENTION-DEFICIT/ HYPERACTIVITY DISORDER Yuko Furuhashi* Health Care Centre, Shizuoka University

ABSTRACT Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by core symptoms of inattention, hyperactivity and/or impulsivity with the stipulation that at least some symptoms emerge in childhood or adolescence (American Psychiatric Association, 2013). Individuals with ADHD are vulnerable to several psychiatric and neurological disorders such as depression, sleep disorder, anxiety disorder, and substance abuse disorder. These psychiatric and neurological difficulties often impair the quality of life of adults with ADHD. In addition, postsecondary students with ADHD may also struggle in multiple areas compared with typically developed peers. Furthermore, students pursuing higher education require high-level time *

Corresponding Author’s E-mail: [email protected].

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Yuko Furuhashi management and organization skills, which are areas that students with ADHD tend to struggle with. Thus, students with ADHD need academic or psychological support while pursuing college or university programs. This study aimed to evaluate the effects of practical interventions for students with ADHD pursuing higher education.

Keywords: postsecondary students, ADHD, intervention, support

1. INTRODUCTION Attention deficit hyperactivity disorder (ADHD) is a lifelong developmental disorder that causes various cognitive, social, and emotional impairments (Kessler et al. 2009), with symptoms ranging from mild to severe in severity and usually persisting throughout one’s lifespan (Faraone et al., 2006). ADHD initially manifests during childhood, however, approximately two-thirds of patients continue to exhibit residual symptoms and impairments into adolescence and adulthood (Faraone et al., 2006). Although the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) requires adults to have fewer symptoms than children to be diagnosed with the condition (American Psychiatric Association, 2013), these symptoms have been stipulated to be the same for adults and children, even though clinical observations suggest that the frank hyperactivity of childhood ADHD manifests more as a sense of internal restlessness among adults (Adler and Cohen, 2004). The prevalence of ADHD among adults has been found to range from 2.5% to 5% (Simon et al., 2009). Moreover, some reports have shown that ADHD in adults is associated with significant impairments in work, education, parenting, driving, financial management, and social relationships (Biederman et al., 2007, Able et al., 2007). Additionally, individuals with ADHD are vulnerable to several other psychiatric and neurological disorders, such as depression, sleep disorder, anxiety disorder, and substance use disorder, all of which are also highly prevalent in adults with ADHD. Taken together, the aforementioned characteristics of ADHD can promote poor outcomes in adults (Hirvikoski

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et al., 2011). Medications, particularly psychostimulants, have proven effective against the core symptoms of ADHD, regardless of patients’ age (Young et al., 2008). However, despite the effectiveness of available medications in reducing core symptoms, symptom improvement does not actually lead to improved academic, vocational, or relationship functioning for many individuals with ADHD. This, coupled with the high prevalence of psychiatric comorbidities, causes many adults with ADHD to seek additional psychosocial treatment to address the mentioned issues (Weiss et al., 2012; Young et al., 2015). Furthermore, the transition period from adolescence into adulthood can be a particularly challenging for individuals with ADHD. Students in postsecondary education face increased social, emotional, and organizational demands associated with the period of emerging adulthood (Arnett, 2000). Postsecondary education environment and timing can be particularly challenging for students with ADHD considering that this is where dramatic changes in lifestyle, independence, and responsibility occur (Fleming and McMahon, 2012). As students enter university or college, they often cope with the abrupt loss of parental support and structure, combined with a sudden increase in independence in areas such as academic work, social activity, financial self-management, and daily structure (Dvorsky et al., 2016; Gray et al., 2016; Harrison et al. 2010). These changes increased the demand for organizational skills and longterm planning, while providing the opportunity for distraction through the increased availability of immediate, short-term rewards. Considering the much higher challenges presented by the college environment, coping with the increased demands and distractions of college life can be difficult for individuals with ADHD whose executive functioning and motivational systems are compromised (Barkley, 1997; Goudreau and Knight, 2018; Lindstrom et al., 2015). Furthermore, students with ADHD showed significantly higher levels of comorbid internalizing disorders, such as anxiety and depression, relative to those without ADHD (Gray et al., 2016; Nelson and Lovett, 2019; Nugent and Smart, 2014). Therefore, postsecondary students with ADHD struggle in multiple areas relative to their peers. However, the

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identification of ADHD in college students has received insufficient empirical investigations (Green and Rabiner, 2012). College students with ADHD are a fast-growing group, with approximately 6% of college freshman reporting to have been diagnosed with ADHD (Dvorsky et al., 2016). Given the increase in the number of students with ADHD encountered during clinical practice over the last decade, there remains an urgent need to identify suitable treatment options. As such, new forms of institutional support have been recommended, such as campus-based summer transition programs, single-room housing, counseling services, applications of universal design, social communication support, peer mentors, and academic accommodations including additional time for exams, note-taking services, alternative exam formats, and adaptive equipment and technology (Anderson et al., 2018; Weyandt and Dupaul, 2008). The current review aimed to identify and evaluate studies that documented firsthand interventions supporting tertiary education students with ADHD as well as provide an update on the impact of such interventions. Despite not being a systematic review, as still selected published studies via a detailed search on MEDLINE, all of which focused on interventions for postsecondary students with ADHD. Therefore, the current review evaluated the literature using a focused framework.

2. METHODS 2.1. Search Procedure This article included the studies that satisfied the following inclusion criteria: (1) study subjects involving individuals with ADHD attending a degree-granting college or university; (2) firsthand descriptions of training, support, or interventions of more than two individuals; and (3) published in English in a peer-reviewed journal. An electronic search of the PubMed and Google Scholar databases was conducted to identify relevant studies based on key terms present in the

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title and abstract. Three search sets were used. The first search set was related to ADHD and used the terms “ADHD” or “attention deficit/hyperactivity disorder” or “ADD” or “attention deficit disorder.” The second search set was related to higher education and used the terms “postsecondary” or “college” or “university” or “graduate student” or “tertiary education.” The final search set was related to intervention and used the terms “interventions” or “support” or “training” or “service”. All three search sets were linked with the instruction “AND.”

2.2. Selection Criteria Articles wherein ADHD was defined by the American Psychiatric Association (APA) in the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition were determined to have been published after 2013. The search sets included all papers published in English from January 2014 to March 2020 and excluded dissertation abstracts. After the database search, the abstract and titles of identified papers were then screened based on whether: (1) the participants were postsecondary students with ADHD; (2) postsecondary support or interventions were delivered in college or university settings; (3) a specific intervention or program was designed to address the needs of the students with ADHD; and (4) quantitative student outcome data were reported. After the initial screening of titles and abstracts, the abstracts of papers were reviewed to determine whether the studies measured the impact of a specific intervention or support on students with ADHD. The reference lists of the included studies were also searched.

2.3. Outcome Measures This review included several theory-guided outcome measures based on clinical symptoms and functioning. Each study was examined for changes in executive function, behavior inhibition, functional impairment,

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and ADHD symptoms. Each study design and outcome were discussed in detail.

3. RESULTS 3.1. Overview of the Reviewed Studies The database search identified 273 papers, the abstracts of which were then manually reviewed to ensure that they investigated postsecondary students with ADHD. After title and abstracts screening, eight articles were identified to have focused on university or college students with ADHD. Most of the excluded articles focused on interventions for adolescents or children, with one case report also being excluded. After full examination of the articles, eight were determined to have satisfied the inclusion criteria. Table 1 provides an overview of the reviewed articles. The eight articles included herein were published in peer-reviewed journals and described postsecondary support or interventions in college or university settings. The articles were published after 2013, when ADHD was defined by the APA based on the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition. Among the eight studies, seven were performed in the United States, while one was performed in Canada. Sample sizes ranged from 4 (Eddy et al. 2015) to 148 (Prevatt and Yelland, 2015), with the mean sample being 53 participants. A total of 424 students with ADHD were enrolled in all eight studies. All papers included college or university students with ADHD. Interventions were designed to help students develop skills that might enable them to cope with the demands of university life. Studies were divided into two groups according to study design (i.e., pre-post studies and randomized controlled trials).

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Table 1. Characteristics of interventions in postsecondary students with ADHD Study

n

mean age

intervention

sessions

LaCount et al. 2018

41

21.9 ± 60. 20.9 ± 2.0

OTMP skills training

3 sessions

Scheithauer and Kelly 2017 LaCount et al. 2015 Anastopoulos et al. 2015 Eddy et al. 2015

41

20.48 18-32 25.4 ± 5.26 18-38 20.3 17-27 21.75 19-25

Study skill

4 sessions

Individual CBT Group CBT

20 sessions

Individual CBT

8 sessions

Mawjee et al. 2015

97

23.9 ± 3.41

CWMT

3 weeks

Prevatt and Yelland 2015 Fleming et al. 2015

148

24.6 ± 9.4 17-60 18-24

ADHD coaching Group DBT

8 sessions

17 43 4

33

8 sessions

8 sessions

Outcome measure BAARS-Ⅳ, WFIRS, GPA, OTMP ASRS, SSC, GAS, M.I.N.I., CAARS CSS-SR, WFIRS CAARS, BRIEFA, ACT CSS, CGI, CAARS, WFIRS, SCI-Ⅰ, BAI, OQ30 ASRS, WASI, TOWRE, WAIS, BDEFS, CANTAB, WRAML LASSI, OQ-45, RSE BAARS-Ⅳ, BADDS, AAQoL, BAI, GPA, FFMQ, CPT-2

AAQoL: ADHD Quality of Life, ACT: ADHD Cognitions Test, ASRS: Adult ADHD Self-Report Scale, BAARS-Ⅳ: Barkley Adult ADHD Rating Scale-Ⅳ, BADDS: Brown ADD Rating Scales, BAI: Beck Anxiety Inventory, BDEFS: Barkley Deficits in Executive Functioning Scale, BRIEF-A: Behavior Rating Inventory of Executive Function-Adult Version, CAARS: Conners Adult ADHD Rating Scale, CANTAB: Cambridge Neuropsychological Testing Automated Battery, CGI: Clinical Global Impression, CPT-2: Conners’ Continuous Performance Test-2nd edition, CSS: Current Symptoms Scale, CWMT: Cognitive Working Memory Training, DBT: Dialectical Behavior Therapy, FFMQ: Five Fast Mindfulness Questionnaire, GAS: Goal Attainment Scale, GPA: Grade Point Average, LASSI: Learning and study Strategies Inventory, OQ-45: outcome Questionnaire-45, OTMP: Organization Time management and Planning skills utilization, RSE: Rosenberg self-Esteem Inventory, TOWRE: Test of Word Reading Efficiency, WAIS: Wechsler Adult Intelligence Scale, WFIRS: Weiss Functional Impairment rating Scale, WRAML: Wide Range Assessment of Memory and Learning

3.2. Pre- and Post-Treatment Studies LaCount et al. (2015) conducted a cognitive behavioral therapy (CBT) intervention designed for adults with ADHD (Safren et al., 2005), that had

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been adapted into a combined group and individual format for college students with ADHD. The program was designed to be completed in 12 sessions. The 12 sessions were divided into four modules: Psychoeducation, Organization, and Planning; Reducing Distractibility; Adaptive Thinking; and Additional Skills. Participants were invited to attend a total of 20 training sessions, each lasting for an hour, over the course of 10 weeks. Participants attended weekly group sessions in addition to individual sessions weekly. The content of the individual sessions typically mirrored that of the group sessions and involved the therapist reviewing the prior week’s homework with their client. A total of 17 students (6 men and 11 women) aged 18 to 38 (mean =25.41, standard division = 5.26) participated in this intervention. Among the 17 participants, 13 received psychotropic medications at the start of the treatment, 11 were taking stimulants, one was taking a selective reuptake inhibitor, and one was taking a sleep medication. The Barkley Current Symptoms Scale-Self Report Form (CSS-SR; Barkley and Murphy, 2006) and the Weiss Functional Impairment Rating Scale (WFIRS) were conducted at the beginning and end of the intervention. The CSS-SR (Barkley and Murphy, 2006) is a self-report measure consisting of 18 items that reflect the criteria needed to diagnose ADHD. Meanwhile, the WFIRS (Weiss, 2000) is a self-report measure consisting of 70 items that examined the effects of ADHD on functional impairment. Accusingly, a large effect on self-report ratings of inattention had been observed following the completion of the program. However, no significant change in hyperactivity/impulsivity and some functioning (Self-Concept and Life Skills) had been noted in this study. LaCount et al. (2018) evaluated the effects of an organization, time management, and planning (OTMP) intervention for college students reporting increased inattention or hyperactivity/impulsivity ADHD symptom severity and academic impairment. A total of 41 college students participated in the study, among whom 25 were enrolled in the intervention group and 16 in the comparison group. Participants were scheduled to complete pre-, and post ratings over 7 weeks. The OTMP intervention was based on the treatment protocol developed by Solanto et al. (2011),

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wherein 1-hour group sessions were conducted thrice weekly, with each session targeting specific OTMP skills. This study utilized several measures, such as the Barkley Adult ADHD Rating Scale (BAARS) containing 18 items closely similar to the DSM-5 criteria for ADHD (Barkley and Murphy, 2006), the WFIRS, course grades, and the OTMT Skills Utilization Scale containing 12 items asking participants to indicate how many days in the past week they used specific OTMP skills and strategies. Session 1 consisted primarily of introducing the task list and calendar systems, as well as the use of timepieces to improve time management. Session 2 presented the strategies gained at improving tasks manageability and increasing motivation through strategies. Session 3 presented strategies for identifying priorities. Students were instructed to create a to-do list and assign priorities to tasks for a week. The intervention group members exhibited significantly better ratings on inattention, hyperactivity/impulsivity, and academic impairment compared to the control group. Anastopoulos and King (2015) conducted an open clinical trial involving combined group CBT and individual mentoring. The intervention included an eight-week active treatment protocol, followed by a maintenance phase in the subsequent semester. During the active treatment phase, participants met weekly for a 90-minute of group CBT and also received eight individual mentoring sessions each lasting 30minute. During the maintenance phase, participants took part in two booster CBT group sessions scheduled near the start and midpoint of the semester, and receive five to six individual 30-minute mentoring sessions every two to three weeks. The CBT program was influenced by the seminal empirical work of Safren et al. (2005) and Solanto et al. (2010). A total of 43 students with ADHD (27 females and 16 males) aged 17 to 27 years (mean 20.3 years) participated in this open clinical trial. Among the 43 participants, three completely dropped out of the treatment. Measures were the ADHD Cognitions Test, the Conners Adult ADHD Rating Scale Self-Report Long Version (Conners et al., 2006), and the Behavior Rating Inventory of Executive Function-Adult Version (Gioia et al., 2000). The Preliminary findings revealed significant increases in ADHD knowledge,

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and use of organizational skills, as well as reductions in maladaptive thinking. Moreover, participants exhibited reduced ADHD symptoms, improved emotional well-being, and increased use of disability services and other campus resources. Eddy et al. (2015) conducted an open clinical trial involving brief CBT. The abbreviated protocol consisted of eight sessions, representing a 33% reduction from the original protocol, which consisted of 12 sessions (Safren et al. 2005). The authors eliminated three sessions (family member involvement, organizing papers, and rehearsal and review of adaptive thinking skills) and collapsed two sessions (application of skills to procrastination and relapse prevention) into one to shorten the 12-week protocol to 8 weeks. The treatment consisted of eight weekly sessions each lasting an hour, as adapted from Mastering your Adult ADHD (Safren et al. 2005). Participants were given the Mastering your Adult ADHD client workbook (Safren et al. 2005) for their personal use during treatment. Therapy sessions were videotaped and reviewed by the therapist to enhance treatment delivery and for additional qualitative data regarding treatment response. Four students with ADHD (one female and three males) aged 19 to 25 years (mean = 21.75) Participants ranged in age from 19 to 25 (mean = 21.75 years) participated in this trial, all of whom had a documented diagnosis of ADHD-Combined (50%) or ADHD-Inattention (50%). Measures were the Current Symptoms Scale (Barkley and Murphy, 2006), the CAARS (Conners et al., 1999), the WFIRS-S (Weiss et al., 2007), the Beck Depression Inventory (Beck et al., 1996), the Beck Anxiety Inventory (Beck and Steer, 1990), the Clinical Global Impression (Guy, 1976), and the Outcome Questionnaire 30 (Lambert et al., 1996). Participants completed measures addressing ADHD symptoms, anxiety, depression, and general impairment in academic, social, and employment domains. Accordingly, a trend toward positive change with various degrees and exact nature of improvement had been noted. Prevatt and Yelland (2015) conducted ADHD coaching, the theoretical orientation of which had been based on the Swartz et al. (2005) model combining CBT with psychoeducational techniques. Between-session assignments (BSAs), which aim to maximize benefit from treatment by

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asking clients to engage in self-help tasks between sessions, have been commonly used by therapists of various theoretical orientations and for a variety of clinical problems (Kazantzis et al., 2005). A total of 148, participants, 49% of them were female aged 17 to 60 (mean = 24.6 years) were included in this study. Participants were seen individually, once a week, over 8 weeks. At the beginning of the coaching process, students completed the Coaching Topics Survey, based on which the coach and client established two to three long-term goals. These long-term goals were broken down into three to four short-term, weekly goals. BSAs were written down and utilized to help implement weekly goals. During weekly sessions, the coaches monitored progress on these goals and used BSAs to facilitate goal attainment. Measures were the BSA Survey (Prevatt et al., 2011), the Client Symptom Checklist, the Coach’s Rating of Motivation and Progress, the Coaching Topics Survey, the Learning and Study Strategies Inventory (Weinstein and palmer, 2002), the Outcome Questionnaire-45 (Lambert and Finch, 1999), and the Rosenberg SelfEsteem Inventory (Rosenberg, 1965). Their results showed improvement in study and learning strategies, self-esteem, emotional distress, and satisfaction with school. This study could provide some preliminary evidence regarding the ADHD coaching structure, processes, efficacy, and correlation with positive outcomes.

3.3. Randomized Controlled Trials Fleming et al. (2015) conducted a dialectical behavior therapy (DBT) group skills training on 33 undergraduates with ADHD between the ages 18 and 24 who were randomized to receive either DBT group skills training or skills handouts (SH) over an 8-week phase. The experimental intervention was delivered according to the DBT group skills training format (Linehan, 1993), which included a 15-min individual pre-group meeting focused on motivation enhancement, eight weekly group sessions lasting 90 min focused on skills acquisition and strengthening, and seven weekly individual coaching phone calls lasting 10- to 15-min focused on

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skills generalization. Participants in the SH treatment condition received 34 pages of SH, derived from a manual on treating of adults with ADHD (Tuckman, 2007) and designed to reflect publicly available self-help materials for ADHD. Topics included psychoeducation on ADHD and executive function, organization, planning, time management, environment structuring, and stress management. The intent-to-treat sample included 17 and 16 participants in the DBT group skills training and self-guided SH, respectively. Participants were assessed before and after an 8-week treatment phase, as well as 3 months following treatment completion. Measures were the Barkley Adult ADHD Rating Scale-Ⅳ, the Brown ADD Rating Scales, the ADHD Quality of Life Questionnaire, the Beck Anxiety Inventory, the Five Facet Mindfulness Questionnaire, and the Conners’ Continuous Performance Test-2nd edition. Participants receiving the DBT group skills training showed greater treatment response rates and clinical recovery rates on ADHD symptoms and executive functioning, and greater improvements in quality of life compared to those who received self-guided SH. Mawjee et al. (2015) conducted working memory training using the CogMed Working Memory Training (CWMT) program, a computer-based cognitive training program developed by CogMed Cognitive Medical Systems AB (Stockholm, Sweden) that claims to improve working memory. The standard CWMT program uses an adaptive algorithm that continually adjusts task difficulty on a trial-by-trial basis to match the individual’s current working memory capacity and ensure consistent maximal challenge. CWMT involves intensive practice (30-45 min per day), 5 days a week for 5 weeks, during which trainees repeatedly perform working memory tasks, with feedback and rewards based on accuracy for every trial. Participants were 97 postsecondary students with ADHD aged 18-35 years. Eligible participants were randomized into one of three arms: standard-length training with 45 min-sessions (standard-length training; n = 33), shortened-length training with 15 min-sessions (shortened-length training; n = 33) or delayed-training waitlist-control group (waitlist control; n = 32). Measures were The Wechsler Adult Intelligence ScaleFourth Addition, the Cambridge Neuropsychological Testing Automated

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Battery, the Wide Range Assessment of Memory and Learning-Second Edition, the Cognitive Failure Questionnaire, the Barkly Deficits in Executive Functioning Scale Short Form, the Woodcock Johnson-Ⅲ, the Test of Word Reading Efficiency-Ⅱ, and the Adult ADHD Self-report Scale. Results showed that shortened-length training conferred as much benefit on working memory performance as did standard-length training, with both CWMT groups showing greater improvements than the waitlistcontrol group. However, Mawjee et al. (2015) concluded that standard CWMT was not an effective approach for improving working memory in postsecondary students with ADHD, as measured by standardized working memory tests or in everyday life. Scheithauer and Kelley (2017) conducted a randomized trial of study skills training in college students. Participant inclusion criteria were enrolled college students, prior ADHD diagnosis, a current psychotropic prescription to target ADHD symptoms, and regular computer access. Using a random member generator, the experimenter randomly assigned the remaining 52 participants to either the study skills and self-monitoring treatment group (SM+) or to the study skills only group (SM-). Initial random assignment resulted in 27 SM+ participants and 25 SMparticipants, respectively. Among the participants, 11 completed the first session but failed to attend later and discontinued the study. Ultimately, 41 participants (22 in the SM+ group and 19 in the SM- group) aged 18 to 32 years (mean age 20.48 years) completed the study, with the sample being predominately female (75.61%). All participants received a one-on-one interview where the interventionist spent 30 minutes discussing study skills using two handouts: one focused on optimizing reading comprehension and test performance and the other describing general study skills and goal setting. After the initial intervention, the SM+ group received additional 30 to 40 minutes to review self-monitoring principles and become oriented with an electronic SM intervention (daily behavioral checklists on predetermined goals, such as class attendance and medication adherence). Participants who failed the integrity check were sent an email reminder by the experimenter to complete the form. Participants in SM+ group exhibited improved their academic behavior, particularly related to

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inattention, test taking, and reading, ADHD symptoms, grade point averages, and goal attainment. These improvements were not observed in the SM- group who received all active components of the intervention except for self-monitoring. As such, self-monitoring provided an additive benefit when compared to study skills instruction and goal setting alone.

4. DISCUSSION 4.1. Review Summary This review outlines the recent practical studies for postsecondary students with ADHD. In particular, most participants showed improvements in core ADHD symptoms, self-esteem, depression, and anxiety. Thus, the included studies have provided evidence for the feasibility and acceptability of interventions for postsecondary students with ADHD. Three interventions methods for postsecondary students have been highlighted herein: CBT, coaching, and skill trainings, such as working memory training. Moreover, these psychological interventions for ADHD had been based on CBT or modifications therein. Cognitive rehabilitation interventions, such as those based on CBT, seem uniquely suited for this population, and may help remediate social and non-social impairments associated with ADHD. Each study was examined in terms of academic performance (e.g., grade point average), executive function, behavior inhibition, functional impairment, and ADHD symptoms, with most studies, except that by Mawjee et al. showing improvements in them. CBT, a form of psychotherapy originally developed for the treatment of depression in the general population, has been found to be an effective treatment for anxiety and depression in typically developing children, adolescents, and adults (Compton et al., 2004; Klein et al., 2005). The defining feature of CBT is its proposed mechanism for clinical improvement, namely, cultivating a change in cognition to correct for dysfunctional cognitive structures. Furthermore, its reliance on structure and predictability makes CBT an attractive treatment option for patients

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with autism spectrum disorder and ADHD (Weiss et al., 2004; Safren et al., 2010; Solanto et al., 2010). CBT remains the most widely researched and endorsed psychological intervention for the general population (James et al., 2005). Psychoeducation on ADHD and related psychiatric symptoms, as well as social training have also been recommended as part of CBT for not only children but also young adults such as postsecondary students (Compton et al., 2004; Safren et al., 2005; Safren et al., 2010; Solanto et al., 2010). There has been a growing interest in developing CBT for patients with ADHD who continue to experience distress and functional interference due to persistent symptoms. The ADHD symptoms impair behaviors for adaptive functioning across academic, occupational, social, and psychological domains. The presentation of ADHD symptoms depends on environmental demands, coping strategies, support, and the presence or absence of comorbid conditions. Suitable support during postsecondary education may be essential in ensuring positive outcomes. Therefore, understanding how ADHD impacts the adjustment to university life and how to promote positive university outcomes among these populations is imperative.

4.2. Characteristics of ADHD Coaching for Postsecondary Students ADHD coaching for postsecondary students is a specialized area within the broader field of personal and life coaching (Parker et al., 2011). Coaching emerged from corporate mentoring models wherein experienced employees guide newer employees through advice regarding how to achieve success in that workplace environment (Quinn et al., 2000). In contrast to psychotherapy which focuses on healing damaged mental health conditions, coaching is a wellness model predicated on the belief that people who are coached are creative, resourceful, and whole (Hart et al., 2001). In this review, Prevatt and Yelland (2015) conducted ADHD coaching based on the model by Swartz et al. (2005), which employed an eight-session program. These were initial sessions that included symptom

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clarification, education, goal setting, establishing the length and type of meetings and between-session communications, and rewards and consequences. Furthermore, Prevatt and Yelland (2015) utilized newer work for executive functioning, which includes behavior activation, focus, sustained effort, management of emotions, memory, and goal-directed action (Brown, 2005). Moreover, Barkley (1997) had identified impaired executive functioning as the underlying cause of ADHD, while Brown (2008) concluded that ADHD is not a behavioral disorder but rather a cognitive disorder due to developmental impairment of executive function. Given that the ADHD coaching study (Prevatt and Yelland, 2015) included all reference CBT principles, this ADHD coaching study similar to CBT. Moreover, topics addressed during ADHD coaching included changing procrastination to persistence, stress management and relaxation, impulse control and anger and frustration management, and confidence and selfesteem building which were substantially similar to those addressed during CBT for ADHD by Safren et al. (2005).

4.3. Characteristics of CBT for Postsecondary Students This review included seven papers on CBT for ADHD that investigated a cohort of patients at the beginning and end of the intervention program (Eddy et al., 2015; Mawjee et al., 2015; La Count et al. 2015; Anastopoulos and King 2015; Fleming et al. 2015; Scheithaur and Kelly 2017; LaCount et al. 2018). Among these seven studies, three studies (Eddy et al., 2015; Mawjee et al., 2015; Scheithaur and Kelly 2017) involved individual settings, three studies (Fleming et al. 2015; Anastopoulos and King 2015; La Count et al. 2015) involved group and individual settings, and one study (LaCount et al. 2018) involved group setting. The results of the aforementioned studies indicated that CBT interventions were effective for postsecondary students with ADHD. While both individual and group CBT studies differed in various factors, such as duration of intervention, number of sessions, treatment comparison, and post-intervention and follow-up outcomes, a number of common findings

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have been observed. Accordingly. CBT appears to be particularly effective as an adjunct to medication in helping postsecondary students with ADHD. Group settings facilitate social interaction and allow patients to share their experiences with others, both of which help reduce social isolation (Attwood, 2005). A group of treatments collectively referred to as “cognitive rehabilitation” has emerged in the context of other disorders, but also appears to be a potentially effective non-pharmacologic intervention for improving the core information processing deficits associated with ADHD in young adults, such as postsecondary students. Compared to individual therapy, group therapy often involves longer and more frequent sessions to teach social skills and emphasize group practice. Additionally, group therapy seems to have several advantages over individual therapy. For instance, the group settings can provide a forum for participants to test out new beliefs and coping strategies, while facilitating other wellbeing-enhancing opportunities, such as the chance to help others. Furthermore, offering group treatment can often be more cost effective, given that experienced therapists are required to implement CBT for ADHD. Several studies examining the characteristics of children and adolescents with ADHD have also demonstrated that manualized group CBT intervention can promote significant decreases in anxiety symptoms (Vidal et al.,2015; Durlak et al. 1991; Reinecke et al., 1998; Antshel et al., 2014), providing initial support for the feasibility of implementing group CBT for this purpose in adults. Group treatment might not only ease feelings of isolation which are often common in individuals with ADHD, but also provide a natural opportunity for growth through positive social interactions. In particular, individuals with ADHD stated that meeting others was helpful as it enabled them to talk with people in similar situations and determine if these individuals share the same problems. Indeed, despite the diverse symptomatology of ADHD, many individuals participating in group therapies experienced similar problems in their environments. Thus, the group created a forum wherein participants offered advice, strategies, and insight to other group members and learned how others with ADHD solve their problems. The group therapy modality therefore provides individuals

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with ADHD an opportunity to feel accepted and understood by peers who struggle with the same disorder, and a chance to practice problem solving skills in a relatively naturalistic and supportive environment. The group might also help reduce patient anxiety by normalizing ADHD and its problems. This comes in contrast to what an individual with ADHD might feel like in a group consisting of their typically developing peers. The support offered by groups might also help reduce demoralization and improve hopefulness, which, in turn, might motivate participants to address their own difficulties or discover solutions through reading, talking to others, or trial and error. Overall, the results showed that group therapy has clear benefits.

4.4. Implications for Future Research Although the aforementioned studies suggest that interventions in postsecondary settings are effective for students with ADHD, additional research is required to refine the therapy, particularly by identifying the most effective components and the optimal methods of delivery. A more rigorous research design using methodologically stricter randomized clinical trials that include treatment comparisons and independent evaluators will also be required to better evaluate treatment efficacy. An additional consideration for the future should include the range of outcomes. In particular, a robust measure of relapse, which can be applied consistently across studies is needed. The lack of treatment effects on relapse rates can be understood in this context. Further research should also seek to better understand the effects of interventions according to the different stages of presenting symptoms. In students prone to relapse and recovery, support specifically aimed at reducing relapse should be investigated. Addressing such concerns may result in a better understanding of how ADHD responds to treatment. In the future, randomized controlled trials with greater statistical power are needed to fully assess primary efficacy, control for non-specific factors of group psychotherapy, and evaluate mediators and moderators of

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treatment effect. A component analysis of mindfulness training and cognitive-behavioral skills training may improve treatment efficiency. Given the strong empirical support for stimulant medication treatment of ADHD among children and adults and the initial evidence of its efficacy among college students, future studies should evaluate the relative efficacy and acceptability of psychopharmacological and psychosocial interventions, both independently and concomitantly, for the treatment of ADHD among postsecondary students.

CONCLUSION There have been several recent reviews on early empirical research on CBT for patients with ADHD. Although some research has supported the efficacy of CBT for improving emotional regulation of adults with ADHD, the literature on ADHD has predominantly focused on children and adolescents. Furthermore, comprehensive approaches designed to address the core neurocognitive and social-cognitive impairments in adults with ADHD have yet to be developed, despite the undoubted a need for them. There are many intervention strategies, both psychological and pharmacological, available to treat individuals with ADHD. Most international guidelines recommend a multimodal treatment approach comprising both types of interventions, with empirical support showing that such combinations have a larger treatment effect on functional outcomes over the long term. A growing population of postsecondary students with ADHD who are seeking psychotherapy. Preliminary evidence obtained in this review suggests that CBT may be efficacious for students with ADHD. As previously mentioned, future directions for CBT research include more robust and well-designed studies to determine the most effective components of CBT for treating ADHD. In addition, studies should include component analysis to evaluate the mechanisms by which the changes occur, which will ultimately lead to more efficient or effective

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interventions for postsecondary students with ADHD. Future interventions should also consider extending the follow-up period

REFERENCES Able, S. L., Johnston, J. A., Adler, L. A. et al. (2007). Functional and psychosocial impairment in adults with undiagnosed ADHD. Psychol Med, 37, 97-107. Adler, L. & Cohen, J. (2004). Diagnosis and evaluation of adults with attention-deficit/hyperactivity disorder. The psychiatric Clinics of North America, 27 (2), 187-201. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington: American Psychiatric Publishing. American Psychiatric Association. (1994). Diagnostic and Statistical Manual of Mental Disorders (DSM-Ⅵ), Washington DC, APA, 1994. Anastopoulos, A. D. & King, K. A. (2015). A Cognitive-Behavior Therapy and Mentoring Program for College Students with ADHD., 22, 141151. http://dx.doi.org/10.1016/j.cbpra.2014.01.002. Anderson, A., Carter, M. & Stephenson, J. (2018). Perspective of university students with autism spectrum disorder. Journal of Autism and developmental Disorders, 48, 651-665. https:// doi.org/10.1007/ s10803-017-3257-3. Antshel, K. M., Faraone, S. V. & Goedon, M. (2014). Cognitive behavioral treatment outcomes in adolescent ADHD. J Atten Disord, 18 (6), 483495. Arnett, J. J. (2000). Emerging adulthood. A theory of development from the late teens through the twenties. American Psychiatry, 55, 469-480. Attwood, T. (2005). Cognitive behavioral therapy for children and adults with Asperger’s syndrome. Behavior Change, 21, 147-161. Barkley, R. A. (1997). Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD. Psychological Bulletin, 121, 65-94.

A Study on Supports for Postsecondary Students …

63

Barkley, R. A. (1998). Attention deficit/hyperactivity disorder: A handbook for diagnosis and treatment. 2 edition. New York, Guilford Press. Barkley, R. A. & Murphy, K. R. (2006). Attention-deficit hyperactivity disorder: A Clinical Workbook. 3rd ed. New York: the Guilford Press. Beck, A. T., Steer, R. A., Ball, R., et al. (1996). Comparison of Beck Depression InventoriesⅠA and Ⅱ in psychiatric outpatients, Journal of Personality Assessment, 67 (3), 588-597. Beck, A. T. & Steer, R. A. (1993). Beck Anxiety Inventory Manual. Harcourt Brace and Company, San Antonio. Biederman, J., Faraone, S. V., Spencer, T. J., et al. (2007). Functional impairments in adults with self-reports of diagnosed ADHD: a controlled study of 1001 adults in the community. J Clin Psychiatry, 67, 524-540. Brown, T. F. (2008). ADD/ADHD and impaired executive function in clinical practice. Current Psychiatry Reports, 10, 407-411. Compton, S. N., March, J. S., Brent, D., et al. (2004). Cognitive behavioral psychotherapy for anxiety and depressive disorders in children and adolescents: An evidence-based medicine review. Journal of the American Academy of Child and Adolescent Psychiatry, 43 (8), 930959. Conners, C. K., Epstein, J. & Johnson, D. E. (2004). Conners Adult ADHD Diagnostic Interview DSM-Ⅳ Toronto Multi Health Systems. Conners, C. K., Erhadt, D. & Sparrow, E. P. (2006). Conners’ adult ADHD Rating Scales. Multi-Health System New York. Durlak, J., Fuhrman, T. & Lampman, C. (1991). The effectiveness of cognitive behaviors therapy for maladaptive children: A meta-analysis. Psychological Bulletin, 110, 204-214. Dvorsky, M. R., Lanberg, J. M., Molitor, S. J. & Bourchtein, E. (2016). Clinical utility and predicting validity of parent and college student symptom ratings in predicting an ADHD diagnosis. Journal of Clinical Psychology, 72, 401-418. http://dx.doi.org/101002/jclp.22268. Eddy, L. D., Cann, W. H., Broman-Fulks, J. J. & Michael, K. D. (2015). Cognitive and Behavioral Practice, 22, 127-140.http://dx.doi.org/ 10.1016/j.cbpra.2014.05.005.

64

Yuko Furuhashi

Eskin, M. & Parrd. (1996). Introduction a Swedish version of an instrument measuring mental stress. Stockholm: Stockholm University. Faraone, S. V., Biederman, J. & Mick, E. (2006). The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol Med, 36, 159-165. Fleming, A. P. & McMahon, R. J. (2012). Developmental context and treatment principles for ADHD among college students. Clinical Child and Family Psychology Review, 15, 303-320. http://dx.doi.org/ 10.1007/s10567-012-0121-z. Fleming, A. P., McMahon, R. J., Moran, L. R., Peterson, A. P. & Dreessen, A. (2015). Pilot Randomized Controlled Trial of Dialectical Behavior Therapy Group Skills Training for ADHD College Students., 19 (3), 260-271. Doi: 10.1177/1087054714535951. Frisch, M. B., Cornell, J., Villanueva, M., et al. (1992). Clinical validation of the Quality of Life Inventory. A measure of life satisfaction for use in treatment planning and outcome assessment. Psychological Assessment, 4(1), 92-101. Gioia, G. A., Isquith, P. K., Guy, S. & Kenworthy, I. (2000). BRIEF: Behavior Rating Inventory of Executive Function Professional manual. Lutz, FL: Psychological Assessment Resources. Goudreau, S. B. & Knight, M. (2018). Executive Function Coaching: Assisting with Transitioning From Secondary to Postsecondary Education. J Atten Disord., 22(4), 379-387. doi: 10.1177/ 1087054715583355. Gray, S. A., Fettes, P., Woltering, S., Mawjee, K. & Tannock, R. (2016). Symptom Manifestation and Impairments in College Students With ADHD. J Learn Disabil., 49(6), 616-630. doi: 10.1177/ 0022219415576523. Green, A. L. & Rabiner, D. L. (2012). What do we really know about college students with ADHD? Neurotherapeutics, 9, 559-568. Guy, W. (1976). The Clinical Global Impressions Scale. ECDEU Assessment Manual for Psychopharmacology Revised, Rockville. MD: National Institute of Mental Health, 218-222.

A Study on Supports for Postsecondary Students …

65

Harrison, A. G. & Rosenblum, Y. (2010). ADHD documentation for students requesting accommodations at the postsecondary level: Update on standards and diagnostic concerns. Can Fam Physician, 56(8), 761-765. Harrison, A. G., Armstrong, I. T., Harrison, L. E., Lange, R. T. & Iverson, G. L. (2014). Comparing Canadian and American normative scores on the Wechsler Adult Intelligence Scale-Fourth Edition. Arch Clin Neuropsychol., 29(8), 737-746. doi: 10.1093/arclin/acu048. Hart, V., Blattner, J. & Leipsic, S. (2001). Coaching versus therapy: A perspective. Consulting Psychology Journal: Practice and Research, 53, 229-237. Hirvikoski, T., Waaler, E., Alferdsson, J., et al. (2011). Reduced ADHD symptoms in adults with ADHD after structured skills training group: results from a randomized controlled trial. Behav Res Ther, 49, 175185. James, A., Soler, A. & Weatherall, R. (2005). Cognitive behavioral therapy for anxiety disorders in children and adolescents. Cochrane Database of Systematic Reviews, Issue 4 Art. No: CD004690. DOI: 10.1002/14651858.CD004690.pub2. Kazantzis, N., Lampropoulos, G. K. & Deane, F. (2005). A national survey of practicing psychologists” use and attitudes toward homework in psychotherapy. Journal of Consulting and Clinical Psychology, 73, 742-748. Kessler, R. C., Adler, L., Ames, M., et al. (2005). The World Health Organization adult ADHD self-Report Scale (ASRs): a short screening scale for use in the general population. Psychological Medicine, 35 (2), 245-256. Kessler, R., Lane, M., Stang, P., et al. (2009). He prevalence and workplace costs of adults attention deficit hyperactivity in a large manufacturing firm. Psychological Medicine, 39 (2), 137-147. Keegan, N. F., Brigham, F. J., Cardellichio, J. M. & Brigham, M. M. (2005). Advocating for students with learning disabilities and attention deficit hyperactivity disorder in public schools. J Long Term Eff Med

66

Yuko Furuhashi

Implants., 15(4), 389-400. doi: 10.1615/jlongtermeffmedim plants.v15.i4.60. LaCount, P. A., Hartung, C. M., Shelton, C. R., Clapp, J. D. & Clapp, T. K. W. (2015). Preliminary Evaluation of a Combined Group and Individual Treatment College Students with AttentionDeficit/Hyperactivity Disorder. Cognitive and Behavioral Practice., 22, 152-160. http://dx.doi.org/10.1016/j.cbpra.2014.07.004. LaCount, P. A., Hartung, C. M., Shelton, C. R. & Stevens, A. E. (2018). Efficacy of an Organization Skills Intervention for College Students with ADHD Symptomatology and Academic Difficulties. Journal of Attention Disorders, 22(4), 356-367. Doi: 10.1177/ 1087054715594423. Lambert, M. J., Burnlingame, G. M., Umphress, V., et al. (1996). The reliability and validity of the Outcome and Questionnaire. Clinical Psychology & psychotherapy, 3, 249-258. Lindstrom, W., Nelson, J. M. & Foels, P. (2015). Postsecondary ADHD Documentation Requirements: Common Practices in the Context of Clinical Issues, Legal Standards, and Empirical Findings. J Atten Disord., 19(8), 655-665. doi: 10.1177/1087054713506262. Linehan, M. M. (1993). Cognitive-behavioral treatment of borderline personality disorder. New York, NY: Guilford. Mawjee, K., Woltering, S. & Tannock, R. (2015). Working Memory Training in Post-Secondary Students with ADHD: A Randomized Controlled Study. PLoS One., 23, 10(9), e0137173. doi: 10.1371/journal.pone.0137173. Nelson, J. M. & Lovett, B. J. (2019). Assessing ADHD in college students: Integrating multiple evidence sources with symptom and performance validity data. Psychol Assess., 31(6), 793-804. doi: 10.1037/ pas0000702. Nugent, K. & Smart, W. (2014). Attention-deficit/hyperactivity disorder in postsecondary students. Neuropsychiatr Dis Treat, 26, 1781-1791. doi: 10.2147/NDT.S64136. eCollection 2014. Parker, D. R., Hoffman, S. F., Sawilowsky, S. & Rolands, L. (2013). Selfcontrol in postsecondary settings: students’ perceptions of ADHD

A Study on Supports for Postsecondary Students …

67

college coaching. Journal of Attention Disorders, 17(3), 215-32. doi: 10.1177/1087054711427561. Prevatt, F., Lampropoulos, G. K., Bowles, V. & Garrett, L. (2011). The use of between-session assignments in ADHD coaching with college students. Journal of Attention Disorders, 15, 18-27. Prevatt, F. & Yelland, S. (2015). An Empirical Evaluation of ADHD Coaching in College Students. Journal of Attention Disorders, 19(8), 666-677. Doi: 10.1177/1087054713480036. Quinn, P. R. N. & Maitland, T. (2000). Coaching college students with ADHD: Issues and answers. Washington, DC: Advantage Books. Reinecke, M. A., Ryan, N. E. & DuBois, D. L. (1998). Cognitive– behavioral therapy of depression and depressive symptoms during adolescence: A review and meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry, 37, 26-34. Rosenberg, M. (1962). The association between self-esteem and anxiety. Journal of Psychiatric Research, 1, 135-152. Safren, S. A., Perlman, C. A., Sprich, S. E. & Otto, M. W. (2005). Mastering your adult ADHD: A cognitive-behavioral treatment program-Therapist guide. Oxford, UK: Oxford University press. Safren, S. A., Sprich, S. E., Cooper-Vince, C., et al. (2010). Life impairments in adults with medication-treated ADHD. J Atten Disord, 13 (5), 524-531. Scheithauer, M. C. & Kelly, M. L. (2017). Self-Monitoring by College Students with ADHD: The Impact on Academic Performance., 21(12), 1030-1039. http://dx.doi.org/10.1177/1087054714556050. Shmulsky, S. & Gobbo, K. (2007). Explanatory style and college students with ADHD and LD. J Atten Disord. 10(3), 299-305. http://dx.doi.org/10.1177/1087054706292103. Simon, V., Czobor, P., Balint, S., et al. (2009). Prevalence and correlates of adults attention-deficit hyperactivity disorder: meta-analysis. British Journal of Psychiatry, 194, 204-211. Solanto, M. V., Marks, D. J., Mitchell, K. J. & Wasserstein, J. (2011). Cognitive-behavioral therapy for adult ADHD: Targeting Executive Dysfunction. New York, NY: Guilford Press.

68

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Solanto, M. V., Marks, D. J., Wasserstein, J., et al. (2010). Efficacy of meta-cognitive therapy for adult ADHD. American Journal of Psychiatry, 167 (8), 958-968. http://dx.doi.org/10.1176/ appi.ajp.2009.09081123. Swartz, S. J., Prevatt, F. & Proctor, B. F. (2005). A coaching intervention for college students with attention deficit/hyperactivity disorder. Psychology in the School, 42, 647-656. http://dx.doi.org/10.1002/ pits.20101. Tuckman, A. (2007). Integrative treatment for adult ADHD. Oakland, CA: New Harbringer. Vidal, R., Castells, J., Richrte, V., Palomar, G., et al. (2015). Group therapy for adolescents with attention-deficit/hyperactivity disorder: a randomized controlled trial. J Am Acad Child Adolesc Psychiatry, 54 (4), 275-282. Virta, M., Salakari, A., Antila, M., et al. (2010). Short cognitive behavioral therapy and cognitive training for adults with ADHD a randomized controlled pilot study. Neuropsychiatric Disease Treatment, 6, 443453. Weinstein, C. E. & Palmer, D. R. (2002). LASSI: Learning and Study Strategies Inventory: Users manual (second ed.). Clearwater, FL: H&H Publishing. Weiss, M., Murray, C., Wasdell, M., et al. (2012). A randomized controlled trial of CBT therapy for adults with ADHD with and without medication. BMC psychiatry, doi: 10.1186/1471-244X-12-30. Weiss, M. D. (2000). Weiss Functional Impairment Rating Scale (WFIRS) Instructions. Vancouver, Canada: University of British Columbia. Weyandt, L. L. & DuPaul, G. J. (2008). ADHD in college students: Developmental findings. Developmental Disabilities Research review, 14, 311-319. Doi: 101002/ddrr.38. Young, S., Khonodoker, M., Emilsson, B., et al. (2015). Cognitivebehavioral therapy in medication-treated adults with attentiondeficit/hyperactivity disorder and co-morbid psychopathology: a randomized controlled trial using multi-level analysis. Psychological Medicine, 45, 2793-2804.

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Young, S., Bramham, J., Gray, K. & Rose, E. (2008). The experience of receiving a diagnosis and treatment of ADHD in adulthood: A qualitative study of clinically referred patients using Interpretative Phenomenological Analysis. Journal of Attention Disorders, 11 (4), 493-503. Young, S. & Ross, R. R. (2007). R&R2 ADHD for Youths and Adults: A Prosocial Training Program Ottawa. Cognitive Centre of Canada.

In: Attention-Deficit Hyperactivity Disorder ISBN: 978-1-53619-443-2 Editor: Brian M. Kyser © 2021 Nova Science Publishers, Inc.

Chapter 3

MULTIMEDIA LEARNING IN ADHD STUDENTS Alessandro Antonietti1, Alice Cancer1, Rosa Angela Fabio2, Paola Iannello1 and Elisa Zugno1 1

Department of Psychology, Catholic University of the Sacred Heart, Milan, Italy 2 Department of Clinical and Experimental Medicine, University of Messina, Italy

ABSTRACT Current advances in technology allowed teachers to make use of the potential advantages of multimedia learning in their education practices. Literature suggests that learning is improved by multimodal presentation of information (e.g., audio-visual modality) through a reinforcing processing effect. As a result, students understand and remember information better when notions are presented via associated text and images. Such enhanced information processing was suggested to be particularly useful for supporting learning in students with attentional problems. More precisely, students with a diagnosis of Attention Deficit and Hyperactivity Disorder (ADHD) may benefit from the use of multimedia tools supporting their learning process, thanks to the salient

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Alessandro Antonietti, Alice Cancer, Rosa Angela Fabio et al. property of the visual presentation of learning contents, which are effective in enhancing both selective and sustained attention. However, a line of research argued that multimedia could hinder a functional learning process in children with attention deficit, due to an overload effect. To date, the effects of multimedia learning in ADHD students have been poorly investigated. The present chapter reports and discusses results from original studies assessing multimedia and hypertext learning in children with and without attentional and self-regulation problems. Understanding the specific effect of multimedia/hypertext learning on cognitive processing is fundamental to device teaching practices aimed at supporting a successful learning in ADHD students.

Keywords: Multimedia learning, ADHD, education, technology

MULTIMEDIA LEARNING After the emergence of the interest about audiovisual tools, substantially linked to the possibility of supporting didactics with television materials (Anderson & Lorch, 1983; Anderson et al., 1986; Sprafkin, Gadow & Grayson, 1984), the period of multimedia tools was inaugurated, marked by the diffusion in school environments of CDs, DVDs and software for the creation of hypertexts and animations and the connection to Internet sites. Today, new tools (apps of various kinds, social networks, serious games, coding software), supported by easier devices (tablets, smartphones, etc.), are being introduced to educators who want to make use of the potential of technology to enrich, enhance, or restructure their teaching approach. Although the characteristics of the tools vary, the same basic question has always been raised in different periods: To what extent does information presented and processed not only in verbal terms, but also in visual formats, facilitate learning? In fact, all the tools mentioned include the co-presence of texts and images. If one shifts one’s attention from the medium to the mental process that it activates, the question about the supposed added value of the visual code in teaching has to be addressed. Questions about the possible learning benefits of the combination of textual messages (provided in writing or

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orally) and figural stimuli (static or dynamic, realistic or schematic, twodimensional or phenomenologically three-dimensional) still have their relevance. The existence of at least two different channels for the processing of information is still assumed. As suggested by Paivio (1986; 1991), one channel processes information as texts or audio messages; the other channel processes non-verbal information as images. Learning is improved when information is processed interactively through the two channels rather than through a single channel. This process, called “dual processing,” produces a “reinforcing” effect on learning, as it helps the learner to build different cognitive paths that can be followed to retrieve information (Yildirim et al., 2001). On this basis Mayer (2001) elaborated a theory of multimedia learning trying to understand how people integrate verbal and visual information. The first step involves paying attention to relevant aspects of information presented in visual and verbal form. From the verbal information that is presented, the learner selects the relevant words for a verbal representation and does the same for visual information. Then the student organizes the selected verbal and visual information in the shortterm memory. The final step is building connections between the two representations and with the knowledge stored in long-term memory. Several contributions highlighted what Mayer (2001) calls the “multimedia effect”: Students learn better (i.e., understand and remember more) from tools that associate texts and images than from texts alone. In fact, Mayer’s (2001) cognitive theory of multimedia learning argues that materials in multimedia format, allowing the simultaneous processing of the corresponding verbal and figural representations in the working memory, act as a support in the construction of a verbal model, a figural model, and the connections between the two. Since the construction of connections is a fundamental step in the understanding of concepts, students are more likely to reach a deeper understanding and, having a richer integrated model, a greater capacity for re-elaboration. However, it should be borne in mind that the richness and diversification of representational formats, if on the one hand is the strong point of multimedia, on the other hand it can also be its weak point

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insofar, as it causes a cognitive overload in the learner (Schnotz & Lowe, 2003). In conclusion, it is possible to state that multimedia tools favor better learning, but they can also produce difficulties, especially if they are not constructed in a coherent way with the learner’s cognitive functioning (Chandler & Sweller, 1991; Colombo, Lissoni & Antonietti, 2009).

MULTIMEDIA AND ADHD A particular type of learners are those with an attention deficit, which is often associated with hyperactivity, forming the category of Attention Deficit and Hyperactivity Disorder (ADHD). ADHD subjects present a specific picture of difficulty in keeping their attention oriented to the current task, in controlling the impulse to act, and in regulating the level of their activity. The specific nature of the attention deficit shown by these subjects is not clear yet. On the one hand, it is believed that subjects with ADHD have a difficulty in maintaining a sufficient amount of attention over time (Douglas, 1983). On the other hand, there are data suggesting that ADHD is the result of too widespread and unselective attention (Ceci & Tishman, 1984). Can multimedia tools be an aid for students with severe difficulties in attention or do they make learning tasks even more difficult for them? From a theoretical point of view, potential benefits can be identified. If the problems concern the focusing of attention, the presence of visual stimuli, generally with eye-catching properties, should facilitate the orientation of attention towards the relevant elements of the information provided (obviously if the pictures are designed to direct attention towards them). Visual elements could also play a role in sustained attention, insofar as they stimulate curiosity and give the possibility to vary the type of stimulation (Crepaldi et al., 2017; 2020a; 2020b). Moreover, multimedia tools give the possibility that information, if not processed by the auditory-verbal system, is processed by the visual system or vice versa: Information, “lost” on one side, would be recovered and elaborated on the other.

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Finally, the power of motivation, both in the start-up phase and in the maintenance of concentration, should not be overlooked (Fabio, Antonietti, Marchetti & Castelli, 2009). In short, according to the theory of arousal, the addition of multimedia elements would function as a cue to recapture discontinuous and periodic attention, provoking and maintaining not only attention, but also helping the selection of relevant contents, thus contributing to making the learning process more interesting (Weiner, 1990). Conversely, multimedia tools could prove counterproductive for students with attention problems. In fact, they might generate an overload or disorient the student who, being unskilled in the management of their own attentional processes, risks not realizing which stimulation (whether verbal or visual) to focus on. It should not be forgotten that the integration of textual and pictorial representations requires an effort, and therefore reduce the amount of the resources which are available to an individual who is already “in distress” in the ordinary management of attention. According to the theory of coherence, multimedia “additions”, especially if not indispensable, can overload the mental system by reducing the effective capacity of working memory (Moreno & Mayer, 2000). Surprisingly, the effects of multimedia learning in ADHD students have been poorly investigated. The very few contributions in the literature seem to indicate the existence of positive effects of multimedia tools in ADHD subjects. For example, Solomonidou, Garagouni-Areou and Zafiropoulou (2004) pointed out that multimedia instruments help to reduce the symptoms of ADHD in learners using educational software. In other studies (Beale, 2002; Tjius, Heimann & Nelson, 2004) which involved subjects with ADHD, multimedia tools were used, but these also included other aspects (high interactivity, systematic structuring of the contents to be learned, etc.) so that it is not possible to attribute the benefits obtained to the specific co-presence of verbal and visual elements (multimedia) since the advantages could depend on the other characteristics of the interventions. In view of the lack of studies on the subject, a number of studies have been undertaken in the past years to

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understand if and how multimedia tools can help students with attention problems in school learning tasks.

AUDIO-VISUAL STIMULI AND LEARNING IN ADHD STUDENTS In a first study (Fabio, Antonietti & Tiezzi, 2003) students with and without attention difficulties were examined by recording their performance when exposed to auditory and visual+auditory messages. In the experiment there was also the manipulation of a further variable: the presence vs. absence of distractors. Lorch, Anderson and Levin (1979) found that the presence of toys when watching television significantly reduces visual attention, but not the understanding of the television programme in ADHD subjects. Similarly, Pezdek and Hartman (1983) showed that 5-year-old children can divide their attention between television and toys while maintaining their understanding of the television programme. The initial sample used in the pretest phase of the study which was conducted was composed of 400 students from the municipalities of the Milan hinterland attending primary (grades 3 and 4) and secondary (grades 2 and 3) school. The pretest phase included the administration of the SDAI questionnaire, composed of items corresponding to the symptoms reported in the DSM-IV (APA, 2000). The questionnaire contains two subscales, one relating to inattention and the other one to hyperactivityimpulsiveness. With this tool it is possible to obtain indications on the three subtypes of ADHD. For each item it is required to assess the severity of the child’s dysfunctional behaviors according to a score ranging from 0 to 3 (from “absent behavior” to “very frequent behavior”). The average cut-off for each item is 1.5 points, so a child’s behavior is to be considered problematic if, in at least one subscale, he/she obtains an overall score equal to or greater than 14.

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On the basis of the results obtained from the SDAI scale, students with a score higher than 14 were identified: ADHD - predominantly inattentive subtype, ADHD - predominantly hyperactive subtype, and ADHD combined subtype, i.e., both inattentive and hyperactive. Students with a score below 14 were considered free of ADHD-related problems. A pre-structured interview was conducted for all students with a score equal to or higher than 14 in order to discriminate those with presumed ADHD from other diagnoses and to exclude students with social and psychiatric pathological conditions. The final sample included in the study consists of 56 students divided as follows:     

14 children with no attention or hyperactivity problems between the ages of 8 and 10; 14 children with problems associated with ADHD, including 7 with inattention-only problems; 7 with inattention and hyperactivity, aged between 8 and 10 years; 14 problem-free children between the ages of 12 and 14; 14 children with problems, 7 of whom are attentive and 7 combined, aged between 12 and 14 years. All 56 subjects were tested by WISC-R (Wechsler, 1974) for IQ assessment and correct diagnostic formulation.

Four documentaries produced by National Geographic Channel, each lasting 7 minutes, have been chosen, which tell, respectively, about a tiger, a beaver, a moose, and a rhinoceros. Of these documentaries, 2 were presented in the video+audio mode and 2 in the audio-only mode. The order of video+audio and audio-only contents was randomized within the subjects, while the sequence of the 4 documentaries was established through a systematic counterbalancing procedure. Each documentary included requests for free retrieval and guided retrieval (for example, the students were asked to recall the period of the day during which the tiger prefers to hunt). A pilot study allowed a preliminary calibration of the materials in order to detect the indices for free and guided retrieval.

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In one session students watched and/or listened to a video+audio documentary and one audio documentary with the presence of attractive toys (distractor); in another session, which took place the following day, they watched and/or listened to the two remaining documentaries in the absence of the toys. The distracting toys included a balloon, a scooter, a video game, figurines, a comic book magazine, and a fashion, beauty and entertainment magazine for girls. Data have been processed according to a factorial design 2 (type of subjects: controls vs. with attentional problems) x 2 (developmental level: 8-10 years vs. 12-14 years) x 2 (mode: video+audio conditions vs. audio-only condition) x 2 (conditions: with vs. without distractor), assuming IQ as covariate. Students with attention difficulties presented a greater loss of information in the audio-only condition: the difference concerning the forgetting of information from the video+audio condition to the audio-only condition is 24% in students with attention difficulties and only 13% in controls. The same type of analysis was conducted on the guided retrieval scores. Also in this case it was found that the multimedia presentation helps students with attention problems, who showed a larger loss of information in the audio-only condition: The difference concerning the decrease from the video+audio condition to the audio-only condition was 32% for them and only 15% for controls. This study showed that the pupils with attention difficulties performed worse than the controls did in all the retrieval tests. However, in the multimedia condition the gap between the two subsamples was reduced. It is likely that visual and auditory information together supports the encoding and maintenance of the notions presented in the documentaries, whereas if information is only auditory the subject is forced to activate more strategic and attentive resources, which are lacking in students with attention problems. According to the model proposed by Fabio (2001) the explanation could be due to the fact that the over-activated arousal levels of subjects with characteristics similar to those of ADHD generate discontinuous perceptions of information; Therefore, when selective and sustained coding is required (as in the case of sustained attention at

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the auditory level), they lose “pieces” of information and therefore fail to recall them.

EDUCATIONAL CDS AND DVDS FOR ADHD STUDENTS The next step in the line of research presented here was to investigate the possible benefits that students with ADHD can derive from the acquisition of knowledge through a hypertext in which textual and visual information is inserted. In the experiment conducted by Fabio and Antonietti (2012 and 2014) a traditional lesson and a multimedia lesson were compared, presenting them to two groups of 12-14 years old students. The multimedia hypertext which was constructed, as well as the parallel traditional lesson, was about the solar system and included parts of written text, images, animations, sounds, and vocal explanations. Students’ learning outcome were evaluated at three levels. As proposed by Anderson (1995), Fitts and Posner (1979), and Gagnè and Briggs (1979), a distinction was made between declarative, conditional, and procedural knowledge. Declarative knowledge concerns the acquisition of notions. Conditional knowledge implies a set of conditionaction sequences. It consists of “if... then” sentences; these sentences describe the relationship between two or more concepts. Conditional knowledge can concern propositions, principles, laws, axioms, theories, or postulates and allows one to predict what will happen if one of the variables (the condition or the action) changes. Procedural knowledge concerns rules and algorithms. It is about how to perform cognitive activities and is often implicit. According to Schunk (1996) the distinction between the three types of knowledge is important for its implications in teaching and learning because finding out what kind of knowledge is deficient is a necessary first step to plan remedial actions. The three levels of knowledge were detected through the construction of an open question test for each level of knowledge on the topic of the lesson. The declarative knowledge questions required the explanation of

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concepts (e.g., “What is a supernova?”). For the construction of the questions on conditional knowledge contents that imply a sequence if ... then and allow to make a prediction if the antecedent or the consequent is known were chosen. The questions included the antecedent or the consequent of the couple “if... then”, by asking the student to complete the couple with the right inference (e.g., “If gas and dust continuously rotate around the Sun, what will happen in the nebula?”). For the evaluation of the procedural knowledge, problems that implied the learning of the rules and the solution procedures underlying them (e.g., “If the distance between two galaxies is 195,000,000 Km, how many light-years are they away?”) have been presented. The students were examined in groups of 4-7. The subjects in the experimental group initially responded to the pre-test and then received brief instructions on how to use the hypertext. Then they browsed (one subject for each computer) the contents of the multimedia hypertext in a 20-minute session and then the post-test was administered. The subjects of the control group, on the other hand, after responding to the pre-test, attended a traditional 20-minute lesson on the solar system. The traditional lesson was conducted presenting the same contents included in the hypertext. One month later the students of the two groups were given the follow-up test to verify the long-term storage of the notions. The recruitment of the students in this study took place as follows. The SDAI and SCOD scales were compiled for 1223 students attending secondary school (grades 2 and 3; 12-14 years). The SCOD scale is aimed at detecting other possible disorders beside ADHD. Students who scored above the cut-off scores were interviewed by a psychologist who was an expert in ADHD, as well as a parent and a teacher in order to gather useful information for the diagnosis. WISC-R (Wechsler, 1974) was applied to the subjects identified as suitable to be included in the clinical groups. The final sample consisted of 84 students: 29 controls (no deficit or disorder), 27 with attentional problems, 28 with attentional problems and learning difficulties. Since in the pre-test phase the three groups were similar in terms of initial knowledge, the scores obtained in the learning questions were taken

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into account only in the application immediately after the lesson and one month later. For each type of knowledge, it turned out that the multimedia hypertext allowed students with attention problems to fill the gap, which is evident in the traditional lesson condition and which differentiates them from the control ones. The benefits of multimedia tool were even more evident in the follow-up, proving the long-lasting effects.

HYPERTEXTS FOR ADHD STUDENTS Often multimedia presentations do not foresee a pre-established and fixed order of access to the contents to be learned, but, having a hypertext structure, they allow the learner to choose the sections to be examined or, if it is mandatory to examine them all, at least the order in which to take them into consideration (Calcaterra, Antonietti & Underwood, 2005; Fiorina, Antonietti, Colombo & Bartolomeo, 2007). Hypertexts show numerous cognitive advantages. Learning is better and more lasting if the student is able to identify the links that exist between the notions he/she encounters and then integrate them with those already present in memory. In this perspective hypertexts would simulate the paths of our thinking activity (Jonassen, 1991; Jonassen & Grabinger, 1990), facilitating the possibility of non-sequential association of information, thus helping to learn in a more functional way (Granic & Lamey, 2000). Hypertexts, moreover, support learning by acting also on the motivational level. A hypertext presentation, in fact, is more attractive than a non-hypertext presentation because learners have the possibility of becoming the “pilots” of their own learning as they can let themselves be guided by their curiosity and choose the order in which to explore the materials (Landow, 1997). In particular, higher interest encourages greater attention and commitment to understanding the materials. Many studies confirmed the effectiveness of hypertexts in learning (Lohr, Ross & Morrison, 1995; Yildirim, Ozden & Yasar, 2001) although they are not without problems. The absence of a predefined sequence, in fact, can lead the learner to disorientation, i.e., to a difficulty in

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understanding the general organization of the materials. Such a disorientation is connected to a loss of the sense of the position in which one finds oneself and to a difficulty in arriving at some other point that one knows (or thinks) exists in the network of notions (Dias & Sousa, 1997; Hanhwe & Hirtle, 1995; Lee & Tedder, 2003; Muller-Kalthoff & Moller, 2003; Shin, Schallert & Savenye, 1994; Van Nimwegen, Pouw & Van Oostendorp, 1999). In order to separate the effects of multimedia from those of hypertext, which are often combined in teaching tools, a learning unit has been specially designed thanks to the contribution by Enrico Gatti, Elisa Pagnini, and Arianna Guarnieri, who were involved in this study. So that the effect of pre-existing knowledge could be eliminated, it was decided to consider learning theories as the subject of study, a topic that the students who participated had certainly never heard of before. Four versions of the same unit have been created: 1. Multimedia and hypertext (MM IP): The concepts were expressed both verbally, by means of written texts, and pictorially, by means of images; The navigation structure was hypertextual; 2. Non-multimedia and hypertext (nMM IP): The notions were presented only in textual form; The navigation structure was hypertextual; 3. Multimedia and not hypertext (MM nIP): The contents were expressed both verbally, by written texts, and pictorially, by images; Students can examine the materials only in a sequential way, i.e., following a pre-established order; 4. Non-multimedia and non-hypertext (nMM nIP): The concepts were presented only in text form and the navigation structure was sequential and predefined. In order to select the sample, 509 secondary school pupils were examined, for each of whom the SDAI, SDAG (the parallel version of SDAI for parents), and SCOD (Disruptive Behaviour Assessment Scale) scales were filled in and a questionnaire consisting of two subscales was

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administered. The first scale of the questionnaire allows to understand if the subject has a Conduct Disorder or an Oppositional/Provocative Disorder. The second scale detects the presence of learning difficulties, particularly in the linguistic and arithmetic field. SCOD also provides some general information on the presence of signs of intellectual disability, psychosis, anxiety, and depression. From the scores that emerged from the administration of the tools described above, together with a consideration of the assessment achieved by each student in Italian and Mathematics in the first four months, three categories of students were identified:   

58 with attentive difficulties; 49 controls with low school performance; 57 controls with high school performance.

The first phase concerned the vision of the assigned form of the learning unit by each pupil, who was accompanied by an operator, who, if necessary, gave indications on how to go from one section to the next and recorded the time taken by the students to examine the unit, as well as the total time (students had no time restrictions) and any notes. In the second phase, at the end of the learning unit, the Raven Progressive Matrixes (Raven, 1969) were administered to verify the homogeneity of the sample from a cognitive point of view, as significant differences in the intellectual level could be reflected in the scores achieved in the learning test. Finally, in the third phase the student was presented a learning test, which consisted of a series of open-ended questions aimed at assessing the declarative, conditional, and procedural knowledge acquired. A factorial between-subject design 4 X 3 was used. The independent variables were the “condition” (MM IP versus MM nIP versus nMM IP versus nMM nIP) and the group (attentive problems versus high controls versus low controls). The dependent variables, on the other hand, consisted of the total number of correct answers in the learning test, as well as the number of correct answers achieved separately in the questions concerning declarative, conditional, and procedural knowledge.

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Initially an analysis of the variance on the total scores reported by all subjects in the learning test was carried out. Irrespective of the condition, students with high school performance obtained higher scores than students with attentive difficulties, who in turn achieved better results than students with low performance. Hypertexts produced an improvement in the performance of all three groups of students. On the other hand, the total score obtained by the students did not vary significantly in relation to the presence or absence of pictures. In students with low school achievement and in those with attention problems performance in the hypertext and multimedia condition tended to worsen compared to the non-multimedia-hypertext one, while in students with high school performance there is an opposite trend. Distinguishing the three types of knowledge, the declarative one showed a trend similar to that found for the total scores: Students with low school achievement and those with attention problems worsened their performance in the hypertext and multimedia condition compared to those in the non-multimedia-hypertext condition; Students with high school performance, on the other hand, showed the opposite trend. In conditional knowledge, students with attention difficulties showed the same trend as in declarative knowledge. Also, in procedural knowledge, students with attention problems showed a higher performance in the hypertext conditions. A first noteworthy fact is related to the beneficial effect of the hypertext component: All students, especially those with attention difficulties, learned better when browsing a hypertext presentation than when the presentation did not allow them to select the parts to be examined. This is in line with what has been said before about the cognitive potentialities connected to the hypertexts and indicates the effectiveness of the hypertext mode in subjects with attention difficulties. It is legitimate to suppose that these subjects, being characterized by a motivational deficit - as Douglas (1983) and Barkley (1997) claimed – if they have the possibility of piloting their learning process, they are more interested and in this way are more able to focus their cognitive resources on the required task. In this sense, hypertexts, besides allowing a more

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coherent learning modality with respect to cognitive functioning, favoring the creation of associations between concepts, would allow for a compensation of the motivational deficit. On the other hand, multimedia tools do not seem to be so promising. First of all, it is possible to evaluate the role played by the organization of the material. In line with Mayer’s (2001) multimedia learning model, the presentation of information by written texts and images may have produced an overload. Written texts and illustrations, in fact, being both perceived through the eyes, are processed the visual channel where, due to the limited resources available, they compete, while the auditory/verbal channel is practically unused. Subjects with ADHD, who have cognitive self-regulatory deficits (Barkley, 1997), may suffer negatively from this condition, struggling to process texts and images simultaneously. Secondly, students with ADHD, due to the particular sensitivity towards the most perceptively salient elements (Douglas, 1983), may be induced, suffering from a perceptive dominance effect, to favor images over text, with a consequent difficulty in understanding the material. Thirdly, multimedia could provoke a cognitive overload in the learners with attention problems, because, in the face of the scarcity of attentive resources, they could widespread their attention on several fragments of information without being able to integrate them into a coherent mental representation. It should also be borne in mind that most of the research carried out on multimedia and hypertext learning made use of topics related to invented stories, or to the functioning of physical or natural systems (Mayer, 2001; Fabio, Antonietti & Tiezzi, 2003); This study, on the contrary, made use of a rather “abstract” topic (learning theories). Probably the use of illustrations may have proved less useful than presentations in which the subject under study lends itself more to a visual representation. Finally, the fact that the presence of images, unlike what emerges in students with attention problems and those with low school achievement, tends to be beneficial in students with high performance seems to confirm that, in order to benefit from multimedia, it is necessary to have attentive and cognitive resources, which the other students lack. In general, it is possible to see how, while in high-performance students

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hypermedia tools facilitate learning, in students with attention problems and low performance the combination of hypertext and multimedia is not profitable. Considering the performances obtained by the different types of students in the different types of knowledge, no significant data emerged; nevertheless, it is possible to observe that students with attention deficit showed the same trend, mirroring the one described above, with reference to all three types of knowledge. In order to ascertain whether the lack of benefit of multimedia for students with attention problems is due to the abstract nature of the contents to be learned proposed in the previous study, the experimental design of the latter study was replicated by proposing multimedia hypertexts focusing on concrete contents (such as, for example, the methods of wheat processing). Seventy-five secondary school students took part in this second study, conducted together with Alessandra Casillo and Enrico Gatti. Based on the compilation of the SDAI, SDAG, SCOD, and WISC-R scales, an interview held by a psychologist and considering the school grades, 3 sub-samples were constituted:   

11 students with attention problems; 11 problem-free students (controls) with low school performance; 11 problem-free students (controls) with high school performance.

Also in this case what students learned from the hypermedia was evaluated in terms of declarative, conditional, and procedural knowledge. The average learning scores were obtained by composing those relative to the three types of knowledge, separating the conditions in which visual elements were present or absent (multimedia) and those in which the organization of the contents was fixed or chosen by the student (hypertext). It appeared that multimedia facilitated high performance control students and students with attention problems, while was not beneficial for low performance controls. Hypertext did not produce particular advantages for the first two subgroups, while hampered learning in low achievers.

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CONCLUSION From the studies described above it emerged that multimedia tools (both in the form of a combination of oral and visual messages and written text and images) help students with attention difficulties in learning tasks. However, this benefit seems to occur only if the contents to be learned are of a concrete type. Visual representations of a schematic kind, through which attempts are made to render abstract concepts in a pictorial form, appear to be scarcely effective, probably because their interpretation is not immediate and therefore requires additional mental work (which makes the task harder, especially for students with low performance). As far as the effects on cognitive processes are concerned, multimedia is a characteristic of educational technologies which us distinct from hypertext, even if the two are often combined. While multimedia helps students with attention difficulties, hypertexts fail to do so, also in this case probably because an open organization of the contents requires an additional commitment to the student (to evaluate the options, to choose the contents to access, to remember the units already inspected, etc.), and this, in the case of problems in attention management, subtracts resources for the latter process. This stresses the need of separating the two features (multimedia and hypertext) of learning tools when considering the possible benefits coming from the two kinds of educational devices (Antonietti, Colombo, Iannello & Inal, 2011; Antonietti, Colombo & Lozotsev, 2008; Antonietti & Giorgetti, 2006; Colombo & Antonietti, 2013). It is important that designers, teachers, and students recognize the specific characteristics of the multimedia/hypertext instructional tools as well, since the role ofpersonal beliefs concerning these aspects has been acknowledged as an influential variable (Antonietti & Colombo, 2008). In a metacognitive perspective, the beliefs about the way the human mind processes multimedia stimuli and hypertexts is relevant to allow learners to identify the optimal strategies to manage those devices, particularly when directions are not provided by instructors but selfregulation is requested (Antonietti, & Colombo, 2014; Antonietti,

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Colombo & Di Nuzzo, 2015; Colombo & Antonietti, 2011), considering the fact that individual differences can modulate the effects of multimedia and hypertexts on learning outcomes (Colombo, Grati, Di Nuzzo & Antonietti, 2013). It is interesting to note that in some of the studies mentioned here the presence of visual elements in addition to the verbal ones allowed students with attention difficulties to perform close to those of the students without difficulties. The advantages of multimedia affected all types of knowledge that need to be learned and were maintained over time. In conclusion, multimedia is a dimension of the instructional tools that can meet the needs of students with learning disabilities, in particular of those who have difficulties in attention control, a capacity that lies at the basis of almost all the activities in which they are engaged at school. Finally, it is worth mentioning that multimedia tools often include elements which stimulate learners’ creativity, for instance since pictures suggest connections with other topics or the combination itself of texts and images stresses unexpected connections. It has been proposed that creativity is enhanced in many neurodevelopmental disorders (Cancer, Manzoli & Antonietti, 2016) and thus students with ADHD may develop a positive attitude toward them because of the match between their creative potential and the creative aspects of those tools. In addition, synchronization between visual and auditory elements in rehabilitation programmes addressed to neurodevelopmental disorders plays a facilitating role (Bonacina et al. 2015; Cancer et al., 2016; Cancer & Antonietti, 2017; Cancer et al., 2020) and we can suppose that the synchronization between verbal and visual elements which occurs in multimedia instruments can produce similar advantages as well in students with ADHD.

REFERENCES American Psychiatric Association (APA) (2000). Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Washington (DC): American Psychiatric Association.

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Anderson, D. R., & Lorch, E. P. (1983). Looking at television: Action or reaction? In J. Bryant & D. R. Anderson, Children’s understanding of television: Research on attention and comprehension (pp. 1-33). New York: Academic Press. Anderson, D. R., Lorch, E. P., Field, D. E., Collins, P. A., & Nathan, J. G. (1986). Television viewing at home: Age trends in visual attention and time with TV. Child Development, 57, 1024-1033. Anderson, J. R. (1995). Cognitive psychology and its implications (4th ed.). New York: W. H. Freeman. Antonietti, A., & Colombo, B. (2008). Computer-supported learning tools: A bi-circular bi-directional framework. New Ideas in Psychology, 26, 120-142. Antonietti, A., & Colombo, B. (2014). Learning from multimedia artifacts: The role of metacognition. In A. Antonietti, E. Confalonieri & A. Marchetti (Eds.), Reflective thinking in educational settings: A cultural framework (pp. 55-101). New York: Cambridge University Press. Antonietti, A., Colombo, B., & Di Nuzzo, B. (2015). Metacognition in self-regulated multimedia learning: Integrating behavioural, psychophysiological and introspective measures. Learning, Media and Technology, 40, 187-209. Antonietti, A., Colombo, B., Iannello, P., & Inal, Y. (2011). Students’ metacognitive knowledge about distance education in virtual communities and multimedia environments: A cross-cultural study. In C. F. MacTeer (Ed.), Distance education (pp. 199-211). Hauppauge, NY: Nova Science Publishers. Antonietti, A., Colombo, B., & Lozotsev Y. (2008). Undergraduates’ metacognitive knowledge about the psychological effects of different kinds of computer-supported instructional tools. Computers in Human Behavior, 24, 2172-2198. Antonietti, A., & Giorgetti, M. (2006). Teachers’ beliefs about psychological aspects of learning through multimedia. Computers in Human Behavior, 22, 267-282. Barkley R. A. (1997). ADHD and the nature of self-control. New York: Guilford Press.

90

Alessandro Antonietti, Alice Cancer, Rosa Angela Fabio et al.

Beale, I. L. (2002). An evaluation model for psychoeducational interventions using interactive multimedia. Cyber Psychology and Behavior, 5, 565-580. Bonacina, S., Cancer, A., Lanzi, P. L., Lorusso, M. L., & Antonietti, A. (2015). Improving reading skills in students with dyslexia: The efficacy of a sublessical training with rhythmic background. Frontiers in Psychology, 6, article 1510, 1-8 (doi: 10.3389/fpsyg.2015.01510). Calcaterra, A., Antonietti, A., & Underwood, J. (2005). Cognitive style, hypermedia navigation and learning. Computers and Education, 44, 441-457. Cancer, A., & Antonietti, A. (2017). Remedial interventions for developmental dyslexia: How neuropsychological evidence can inspire and support a rehabilitation training. Neuropsychological Trends, 22, 73-95 (doi:10.7358/neur-2017-022-canc). Cancer, A., Bonacina, S., Lorusso, M. L., Lanzi, P. L., & Antonietti, A. (2016). Rhythmic Reading Training (RRT): A computer-assisted intervention program for dyslexia. In S. Serino, A. Matic, D. Giakoumis, G. Lopez & P. Cipresso (Eds.), Pervarsive computing paradigms for mental health (Communications in Computer and Information Science, 604) (pp. 249-258). Cham: Springer (doi: 10.1007/978-3-319-32270-4_25). Cancer, A., Bonacina, S., Salandi, A., Antonietti, A., Molteni, M., & Lorusso, M. L. (2020). The effectiveness of interventions for developmental dyslexia: Rhythmic reading training compared with hemisphere-specific stimulation and action video games. Frontiers in Psychology, 11, article 1158, 1-15 (doi: 10.3389/fpsyg.2020.01158). Cancer, A., Manzoli, S., & Antonietti, A. (2016). The alleged link between creativity and dyslexia: Identifying the specific process in which dyslexic students excel. Cogent Psychology, 3, article 1190309, 1-13 (doi: 10.1080/23311908.2016.1190309). Ceci S. J., & Tishman, J. (1984). Hyperactivity and incidental memory: Evidence for attentional diffusion. Child Development, 55, 2192-2203. Chandler, P., & Sweller, J. (1991). Cognitive load theory and the format of instruction. Cognition and Instruction, 8, 293-332.

Multimedia Learning in ADHD Students

91

Colombo, B., & Antonietti A. (2011). Self-regulated strategies and cognitive styles in multimedia learning. In G. Dettori & D. Persico (Eds.), Fostering self-regulated learning through ICT (pp. 54-70). Hershey, PA: IGI Global. Colombo, B., & Antonietti, A. (2013). Naïve conceptions about multimedia learning: A study on primary school textbooks. Frontiers in Psychology, 4, article 450, 1-19 (doi: 10.3389/fpsyg.2013.00450). Colombo, B., Grati, L., Di Nuzzo, C., & Antonietti, A. (2013). The role of individual creativity levels in the cognitive and emotive evaluation of complex multimedia stimuli. A study on behavioural data and psychophysiological indices. In A. Antonietti, B. Colombo & D. Memmert (Eds.), Psychology of creativity. Advances in theory, research and application (pp. 195-216). Hauppauge, NY: Nova Science Publishers. Colombo, B., Lissoni, M., & Antonietti, A. (2009). Do illustrated instructional books promote multimedia learning? In O. Demir & C. Celik (Eds.), Multimedia in education and special education (pp. 3957). Hauppauge, NY: Nova Science Publishers. Crepaldi, M., Colombo, V., Baldassini, D., Mottura, S., & Antonietti, A. (2017). Supporting rehabilitation of ADHD children with serious games and enhancement of inhibition mechanisms. In J. Barbic, M. D’Cruz, M. E. Latoshik, M. Slater & P. Bourdot (Eds.), Virtual reality and augmented reality (Lecture Notes in Computer Science, n. 10770) (pp. 167-181). Cham, Switzerland: Springer. Crepaldi, M., Colombo, V., Mottura, S., Baldassini, D., Sacco, M., Cancer, A., & Antonietti, A. (2020a). Antonyms: A computer game to improve inhibitory control of impulsivity in children with Attention Deficit/Hyperactivity Disorder (ADHD). Information, 11, article 230, 1-10 (doi: 10.3390/info11040230). Crepaldi, M., Colombo, V., Mottura, S., Baldassini, D., Sacco, M., Cancer, A., & Antonietti, A. (2020b). The use of a serious game to assess inhibition mechanisms in children. Frontiers in Computer Science, 2, article 34, 1-11 (doi: 10.3389/fcomp.2020.00034).

92

Alessandro Antonietti, Alice Cancer, Rosa Angela Fabio et al.

Dias, P., & Sousa, P. (1997). Understanding navigation and disorientation in hypermedia learning environments. Journal of Educational Multimedia and Hypermedia, 6, 173-185. Douglas, V. I. (1983). Attentional and cognitive problems. In M. Rutter (Ed.), Developmental neuropsychiatry (pp. 280-329). New York: Guilford Press. Fabio, R. A. (2001), L’attenzione. Fisiologia, patologie e interventi. Milan, Italy: Franco Angeli Editore. Fabio, R. A., & Antonietti, A. (2012). Effects of hypermedia instruction on declarative, conditional and procedural learning in ADHD students. Research in Developmental Disabilities, 33, 2028-2039. Fabio, R. A., & Antonietti, A. (2014). Hypermedia tools enhance learning in ADHD students. The ADHD Report, 22 (4), 8-9. Fabio, R. A., Antonietti, A., Marchetti, A., & Castelli, I. (2009). Attention and communication in Rett Syndrome. Research in Autism Spectrum Disorders, 3, 329-335. Fabio, R. A., Antonietti, A., & Tiezzi, P. (2003). Decodifica di messaggi uditivi e visivi in televisione da parte di soggetti con DDAI: attenzione diffusa o deficit nella quantità di attenzione? Psicologia dell’Educazione e della Formazione, 5, 89-107. [Decoding of auditory and visual messages on television by people with ADHD: widespread attention or deficit in the amount of attention? Psychology of Education and Training] Fiorina, L., Antonietti, A., Colombo, B., & Bartolomeo, A. (2007). Thinking style, browsing primes and hypermedia navigation. Computer and Education, 49, 916-941. Fitts, P. M., & Posner, M. I. (1979), Human Performance. Belmont, CA: Brooks Cole. Gagné, R. M., & Briggs, L. J. (1979), Principles of instructional design (2nd ed.). New York: Rinehart and Winston. Granic, I., & Lamey, A. V. (2000). The self-organization of the Internet and changing modes of thought. New Ideas in Psichology, 18, 93-107.

Multimedia Learning in ADHD Students

93

Hanhwe, K., & Hirtle, S. C. (1995). Spatial metaphors and disorientation in hypertext browsing. Behaviour and Information Technology, 14, 239250. Jonassen, D. H. (1991). Hypertext and instructional design. Educational Technology Research & Development, 39, 83-92. Jonassen, D. H., & Grabinger, R. S. (1990). Problems and issues in designing hypertext/hypermedia for learning. In D. H. Jonassen & H. Mandl (Eds.), Designing hypermedia for learning (pp. 3-25). New York-Berlin-Heidelberg: Springer-Verlag. Landow G. P. (1997) Hypertext 2.0 - The convergence of contemporary critical theory and technology. Baltimore-London: Johns Hopkins University Press. Lee, M. J., & Tedder, M. C. (2003). The effects of three different computer texts on readers’ recall based on working memory capacity. Computers in Human Behavior, 19, 767-783. Lohr, L., Ross, S. M., & Morrison, G. R. (1995). Using a hypertext environment for teaching process writing: An evaluation study of three student groups. Educational Technology Research & Development, 43(2), 33-51. Lorch, E. P., Anderson, D. R., Levin, S. R. (1979). The relationship of visual attention to children’s comprehension of television. Child Development, 50, 722-727. Mayer, R. E. (2001). Multimedia learning. Cambridge: Cambridge University Press. Moreno, R., & Mayer, R. E. (2000). A coherence effect in multimedia learning: The case for minimizing irrelevant sounds in the design of multimedia instructional messages. Journal of Educational Psychology, 92, 117-125. Muller-Kalthoff, T., & Moller, J. (2003). The effects of graphical overviews, prior knowledge, and self-concept on hypertext disorientation and learning achievement. Journal of Educational Multimedia and Hypermedia, 12, 117-134. Paivio, A. (1986). Mental representations: A dual-coding approach. New York: Oxford University Press.

94

Alessandro Antonietti, Alice Cancer, Rosa Angela Fabio et al.

Paivio, A. (1991). Dual coding theory: Retrospect and current status. Canadian Journal of Psychology, 45, 255-287. Pezdek, K., & Hartman, E. F. (1983). Children’s television viewing: Attention and comprehension of auditory versus visual information. Child Development, 54, 1015-1023. Raven, J. C. (1969). Progressive Matrices. Clamart (Seine), Estabilissment d’Application Psycotecniques. Schnotz, W., & Lowe, R. (2003). External and internal representations in multimedia learning. Learning and Instruction, 13, 117-123. Schunk, D. H. (1996). Learning theories (2nd ed.). Englewood Cliffs, NJ, Prentice-Hall. Shin, E. C., Schallert, D. L., & Savenye, W. C. (1994) Effects on learner control, advisement and prior knowledge on young student’s learning in a hypertext environment. Educational Technology Research and Development, 42, 33-45. Solomonidou, C., Garagouni-Areou, F., & Zafiropoulou, M. (2004). Information and communication technologies (ICT) and pupils with Attention Deficit Hyperactivity Disorder (ADHD) symptoms: Do the software and the instruction method affect their behavior? Journal of Educational Multimedia and Hypermedia, 13, 109-128. Sprafkin, J. N., Gadow, K. D., & Grayson, P. (1984). Television and the emotionally disturbed, learning disabled, and mentally retarded. In J. Gadow (Ed.), Advances in learning and behavioral disabilities, vol. 3 (pp. 151-213). Greenwich, CT: JAI. Tjius, T., Heinmann, M., & Nelson, K. (2004). Reading acquisition by implementing a multimedia intervention strategy for fifty children with autism and other learning and communication disabilities. Journal of Cognitive and Behavioral Psychotherapies, 4, 203-221. Van Nimwegen, C., Pouw, M., & Van Oostendorp, H. (1999). The influence of structure and reading-manipulation on usability of hypertexts. Interacting with Computers, 12, 7-21. Wechsler, D. (1974). WISC-R Manual for the Wechsler intelligence scale for children. Revised. New York: Psychological Corporation.

Multimedia Learning in ADHD Students

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Weiner, B. (1990). History of motivational research in education. Journal of Educational Psychology, 82, 616-622. Yildirim, Z., Ozden, M., & Yasar, A. M. (2001). Comparison of hypermedia learning and traditional instruction on knowledge acquisition and retention. Journal of Educational Research, 94, 207214.

INDEX A abuse, 8, 10, 36 academic performance, vii, 1, 56 acetylcholine, 6, 8, 15, 19 acquisition of knowledge, 79 adaptive functioning, 57 ADHD, v, vii, viii, 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 21, 23, 25, 26, 28, 29, 31, 32, 33, 34, 35, 36, 37, 38, 39, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 71, 72, 74, 75, 76, 77, 78, 79, 80, 81, 85, 88, 89, 91, 92, 94 adolescents, vii, 1, 2, 4, 8, 9, 11, 12, 13, 16, 17, 21, 22, 23, 24, 25, 27, 28, 29, 32, 34, 35, 37, 38, 41, 48, 56, 59, 61, 63, 65, 68 adulthood, vii, 1, 44, 45, 62, 69 adults, viii, 2, 8, 9, 11, 14, 16, 17, 19, 20, 24, 36, 37, 38, 43, 44, 49, 54, 56, 59, 61, 62, 63, 65, 67, 68 adverse effects, 21 age, 3, 4, 23, 38, 45, 49, 52, 55, 64 agonist, 6, 8, 15, 20, 22, 31, 34, 35

alcohol consumption, 3 alcoholism, 29 amphetamines, vii, 1, 5, 9, 10 anxiety, viii, 9, 38, 43, 44, 45, 52, 56, 59, 60, 63, 65, 67, 83 anxiety disorder, viii, 43, 44, 65 autism, 13, 31, 32, 57, 62, 94

B basal ganglia, 8 behavior therapy, 53 behaviors, 38, 57, 63, 76 beneficial effect, 84 benefits, 60, 72, 75, 79, 81, 87 biological psychiatry, 36 birth weight, 3, 33 blood, 6, 9, 12, 26 blood pressure, 6, 9, 12, 26 brain, 3, 8, 13, 21, 24, 30, 35, 36, 37, 38 brain functions, 35 brainstem, 12 bronchodilator, 9 browsing, 84, 92, 93

98

Index C

central nervous system, 13 cerebellum, 6, 8, 11 cerebral palsy, 9 challenges, 45 chemical, 27 childhood, viii, 43, 44 children, vii, ix, 1, 2, 3, 4, 8, 9, 11, 12, 13, 14, 16, 17, 18, 19, 21, 22, 23, 24, 27, 28, 29, 31, 32, 33, 34, 35, 37, 38, 44, 48, 56, 59, 61, 62, 63, 65, 72, 76, 77, 91, 93, 94 chromosome, 37 chronic fatigue, 8 clinical application, 27 clinical problems, 53 clinical symptoms, 47 clinical trials, viii, 2, 60 coding, 72, 78, 93, 94 cognition, 14, 15, 17, 31, 37, 56 cognitive function, 8, 21, 74, 85 cognitive impairment, 61 cognitive performance, 12 cognitive process, ix, 72, 87 cognitive processing, ix, 72 cognitive style, 91 cognitive theory, 73 cognitive therapy, 68 coherence, 75, 93 college students, 46, 48, 50, 55, 61, 64, 66, 67, 68 communication technologies, 94 comprehension, 89, 93, 94 computer, 54, 55, 80, 89, 90, 91, 93 constipation, 7, 13, 16 construction, 73, 79 control group, 51, 54, 80 controlled studies, 11 controlled trials, 8, 9, 11, 12, 17, 34, 48, 60 convergence, 93 coping strategies, 57, 59

creative potential, 88 creativity, 88, 90, 91

D declarative knowledge, 79, 84 deficit, vii, viii, ix, 1, 2, 15, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 43, 44, 47, 62, 63, 64, 65, 66, 67, 68, 72, 74, 80, 84, 86, 92 dependent variable, 83 depression, viii, 2, 7, 8, 13, 43, 44, 45, 52, 56, 67, 83 depressive symptoms, 67 developmental disorder, 44 developmental dyslexia, 90 disorder, vii, viii, 1, 2, 8, 13, 17, 19, 20, 21, 22, 23, 24, 25, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 43, 44, 47, 57, 58, 60, 62, 63, 64, 65, 66, 67, 68, 80 distance education, 89 dizziness, 6, 7, 11, 12, 16, 17 dopamine, 6, 7, 8, 9, 10, 11, 15, 17, 18, 19, 20, 22, 24, 26, 29, 30, 35, 36, 37, 38 dopaminergic, 3, 15, 17, 18, 25, 27 double-blind trial, 32, 33 drug abuse, 2 drugs, 5, 21, 34

E education, vii, viii, 39, 44, 45, 46, 47, 57, 58, 64, 71, 72, 89, 90, 91, 92, 95 educational settings, 89 educational software, 75 emotional distress, 53 emotional well-being, 52 environment, 45, 54, 57, 60, 93, 94 environmental factors, 3, 37 environments, 59, 72, 89

Index evidence, 3, 20, 37, 38, 53, 56, 61, 63, 66, 90 executive function, 3, 16, 45, 47, 54, 56, 58, 62, 63 executive functioning, 16, 45, 54, 58 executive functions, 62 experimental design, 86 exposure, 3, 29, 33

F family interactions, vii, 1 financial, 44, 45 fragments, 85 frontal cortex, 19

G genetic factors, 3, 4 genetic linkage, 37 genetics, 25, 28, 31 glutamate, 7, 13, 16, 17, 22, 25, 27, 28, 31, 37, 39 glutamatergic agents, viii, 2, 5, 14, 15, 18 goal attainment, 53, 56 goal setting, 55, 58 grades, 2, 51, 76, 80, 86 group therapy, 59 group treatment, 59

H hallucinations, 7, 9, 18 headache, 6, 7, 9, 10, 16, 17 high school, 83, 84, 86 higher education, vii, viii, 43, 47 hippocampus, 6, 7, 8, 11, 17, 25, 34 human development, 22 hyperactivity, vii, viii, 1, 2, 5, 10, 11, 14, 15, 16, 19, 20, 21, 22, 23, 24, 25, 26, 27,

99

28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40, 43, 44, 47, 50, 62, 63, 64, 65, 66, 67, 68, 74, 76, 77 hypermedia, 86, 90, 92, 93, 95 hypertension, 9, 12 hypertext, ix, 72, 79, 80, 81, 82, 84, 85, 86, 87, 93, 94 hypotension, 7, 13 hypotensive, 20 hypothesis, 37

I images, viii, 71, 72, 73, 79, 82, 85, 87, 88 impairments, 15, 44, 63, 67 improvements, 16, 54, 55, 56 impulsive, 5, 12, 13, 28, 32 impulsiveness, 35, 76 impulsivity, viii, 2, 4, 11, 14, 16, 38, 43, 50, 91 inattention, viii, 11, 14, 16, 43, 50, 56, 76, 77 independence, 45 independent variable, 83 individual differences, 88 individuals, 44, 45, 46, 59, 61 information processing, viii, 59, 71 inhibition, 6, 9, 17, 31, 37, 47, 56, 62, 91 inhibitor, 10, 50 insomnia, 6, 7, 9, 10, 11, 17, 18 instructional design, 92, 93 intervention, viii, 2, 44, 47, 49, 50, 51, 53, 55, 57, 58, 59, 61, 66, 68, 90, 94 intervention strategies, 61 issues, 7, 16, 45, 93

K knowledge acquisition, 95

100

Index L

learners, 74, 75, 81, 85, 87, 88 learning, viii, 27, 53, 65, 71, 72, 73, 74, 75, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95 learning difficulties, 80, 83 learning disabilities, 65, 88 learning environment, 92 learning outcomes, 88 learning process, viii, 71, 75, 84 learning task, 27, 74, 87 long-term memory, 73

M magnetic resonance, 32 magnetic resonance spectroscopy, 32 management, vii, viii, 1, 22, 40, 44, 45, 49, 50, 54, 58, 75, 87 manipulation, 76, 94 manufacturing, 65 materials, 4, 54, 72, 73, 77, 81, 82 maternal smoking, 22 medications, viii, 2, 4, 5, 21, 24, 39, 45, 50 medicine, 24, 29, 63 memory, 15, 16, 20, 27, 33, 38, 54, 58, 73, 81, 90 memory capacity, 54 memory performance, 55 mental health, 57, 90 mental representation, 85 mental retardation, 13, 19 messages, 72, 76, 87, 93 meta-analysis, 8, 9, 11, 12, 17, 24, 34, 36, 63, 64, 67 metabolic change, 8 metabolic dysfunction, 41 metabolism, 8, 38 metacognition, 89 metacognitive knowledge, 89

methamphetamine, 10, 30 methylphenidate, vii, 1, 5, 6, 24, 25, 26, 28, 29, 30, 31, 32, 34, 35, 36, 38 mice, 15, 22, 24, 26, 27, 29, 30, 33, 34, 38 models, 3, 14, 15, 27, 35, 36, 38, 57 multimedia, vii, viii, 71, 72, 73, 74, 75, 78, 79, 80, 81, 82, 84, 85, 86, 87, 88, 89, 90, 91, 93, 94 multimedia learning, v, viii, 71, 72, 73, 75, 85, 89, 91, 93, 94 mutagenesis, 26, 38

N natural compound, 39 nausea, 6, 7, 11, 12, 17 nervousness, 6, 9, 10, 17 neurodevelopmental disorders, 88 neurogenesis, 34 neuroimaging, 14 neurological disease, 40 neurons, 12, 13, 25 neuropsychiatry, 92 neuroscience, 20, 22, 26, 27, 30, 34, 35, 36 neurotransmission, 3, 21 neurotransmitter, 13, 17, 25 non-psychostimulants, vii, 1, 2, 10, 18 norepinephrine, 6, 8, 9, 10, 11, 12, 22, 27, 30, 36

O oxidative stress, 3, 39, 40

P pain, 6, 9, 10 participants, 47, 48, 50, 51, 53, 54, 55, 56, 59 pathophysiological, 3

Index pathophysiology, 3, 24 pharmacokinetics, 25 pharmacological treatment, 18 pharmacology, 22, 25, 28, 30, 31, 34, 36 placebo, 8, 9, 11, 12, 13, 15, 16, 17, 19, 20, 21, 27, 28, 35, 37 point mutation, 15, 38 population, 23, 38, 56, 61, 65 postsecondary students, v, viii, 43, 44, 45, 46, 47, 48, 49, 54, 56, 57, 58, 59, 61, 66 prefrontal cortex, 6, 8, 11, 12, 14, 21, 22, 29, 30, 31 principles, 55, 58, 64, 79 prior knowledge, 93, 94 problem solving, 60 procedural knowledge, 79, 80, 83, 84, 86 proteins, 13 psychiatric disorder, 37, 41 psychiatric disorders, 37, 41 psychiatry, 19, 21, 23, 24, 25, 30, 31, 32, 33, 34, 35, 36, 37, 38, 68 psychoeducational intervention, 90 psychological problems, 22 psychologist, 80, 86 psychology, 89 psychopathology, 68 psychopharmacology, 23, 24, 26, 28, 29, 30, 32, 34, 37 psychosis, 8, 9, 83 psychosocial interventions, 61 psychostimulants, vii, 1, 2, 5, 10, 11, 13, 18, 29, 45 psychotherapy, 5, 56, 57, 60, 61, 63, 65, 66 psychotropic medications, 50 public schools, 65

Q quality of life, viii, 43, 54

101 R

reading, 55, 60, 90, 94 receptor, viii, 1, 6, 7, 8, 10, 11, 14, 15, 16, 19, 20, 22, 24, 25, 26, 27, 29, 30, 31, 33, 37, 39 rehabilitation, 56, 59, 88, 90, 91 rehabilitation program, 88 resources, 52, 75, 78, 84, 85, 87 response, 11, 17, 28, 31, 37, 38, 52, 54 risk, 2, 8, 16, 21, 23, 29 risk factors, 3, 21

S schizophrenia, 9, 27 school, 2, 4, 5, 53, 72, 76, 80, 82, 83, 84, 85, 86, 88 school achievement, 84, 85 school learning, 76 school performance, 2, 83, 84, 86 science, 23, 33, 36 secondary school students, 86 self-concept, 93 self-control, 89 self-esteem, 53, 56, 58, 67 self-monitoring, 55 self-organization, 92 self-regulation, ix, 72, 87 self-reports, 63 serotonin, 6, 8, 27, 29, 30 services, iv, 46, 52 showing, 55, 56, 61 side effects, viii, 2, 9, 10, 12, 13, 16, 17, 18, 20 skills training, 49, 53, 55, 61, 65 sleep disturbance, 6, 10 social behavior, 39 social impairment, 56 social interaction, 2, 59 social network, 72

102

Index

social relations, 44 social relationships, 44 social skills, 59 software, 72, 94 solar system, 79, 80 stimulant, 10, 21, 61 stimulation, 7, 8, 10, 12, 17, 74, 75, 90 stress, 3, 4, 39, 54, 58, 64 stress management, 54, 58 striatum, 6, 7, 8, 14, 17, 20, 29, 31 structure, 45, 53, 56, 81, 82, 94 substance abuse, viii, 43 substance use, 8, 37, 41, 44 support, viii, 19, 44, 45, 46, 47, 48, 57, 59, 60, 61, 73, 81, 90 symptoms, viii, 4, 5, 8, 9, 11, 13, 14, 15, 16, 17, 18, 21, 26, 27, 38, 43, 44, 45, 48, 52, 54, 55, 56, 57, 59, 60, 65, 75, 76, 94 synaptic vesicles, 36 synchronization, 88

T technology, viii, 46, 71, 72, 89, 93, 94 tertiary education, 46, 47 therapeutic use, viii, 2, 8 therapeutics, 22 therapist, 50, 52 therapy, 8, 9, 10, 12, 13, 18, 29, 49, 59, 60, 62, 63, 65, 67, 68 training, 5, 46, 47, 50, 53, 54, 56, 61, 68, 90 transition period, 45 transmission, 14, 15, 29, 30, 31 treatment, 4, 5, 6, 8, 9, 12, 14, 15, 16, 17, 18, 20, 21, 23, 24, 28, 30, 32, 34, 35, 37,

38, 39, 45, 46, 50, 51, 52, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 66, 67, 68, 69 trial, 13, 15, 16, 18, 19, 28, 35, 51, 52, 54, 55, 60, 65, 68 tyrosine, 29

V variables, 79 vesicle, 24 video games, 90 virtual communities, 89 vision, 7, 18, 83 visual attention, 76, 89, 93 visual modality, viii, 71 visual stimuli, 74 visual system, 74

W Wechsler Adult Intelligence Scale, 49, 54, 65 weight loss, 6, 7, 9, 17 working memory, 12, 15, 22, 26, 54, 56, 73, 75, 93 workplace, 4, 57, 65 worldwide, 2, 33

Y young adults, 37, 41, 57, 59 young people, 35