Adolescent Psychosis: Clinical and Scientific Perspectives 0323898327, 9780323898324

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Adolescent Psychosis Clinical and Scientific Perspectives

Edited by Ingrid Agartz NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway; Centre of Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

Runar Elle Smelror Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway; NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

Academic Press is an imprint of Elsevier 125 London Wall, London EC2Y 5AS, United Kingdom 525 B Street, Suite 1650, San Diego, CA 92101, United States 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom Copyright Ó 2023 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

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About the contributors Chapter 1 Introduction to psychotic disorders in adolescence Runar Elle Smelror, PhD, is a clinical psychologist and postdoctoral researcher with the main research interest in clinical and cognitive characteristics in youth with psychosis. Lynn Mørch-Johnsen, MD, PhD, is a medical doctor and researcher with the main research focus on psychotic disorders and neuroimaging. Ingrid Agartz, MD, PhD, is a clinical psychiatrist and professor of psychiatry. She is mainly active in psychosis research and neuroimaging with a current emphasis on youth.

Chapter 2 The epidemiology of early-onset psychosis Imke Lemmers-Jansen, PhD, is an assistant professor of clinical developmental and neuropsychology with a main interest in pathways to psychosis and social interactions. Lydia Krabbendam, PhD, is a clinical psychologist and full professor of developmental neuropsychology, with main research, focus on psychosis, social cognition, and educational neuroscience. Els van der Ven, PhD, is a clinical psychologist and assistant professor studying the social determinants of mental health with a particular interest in understanding disparities in psychosis risk and service use.

Chapter 3 Genetics of psychotic disorders with focus on early-onset psychosis Katrine V. Wirgenes, MD, PhD, is a clinical geneticist primarily working with patients with rare, genetic conditions and their families. Her main research interest is within the field of psychiatric genetics and syndromology. Olav B. Smeland, MD, PhD, is a psychiatrist and a researcher with a main interest in psychiatric genetics.

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xiv About the contributors

Ole A. Andreassen, MD, PhD, is a professor in psychiatry and attending psychiatrist. He is focusing his research on disease mechanisms and translation to the clinic to allow precision psychiatry.

Chapter 4 Early risk factors in early-onset psychosis Katherine H. Karlsgodt, PhD, is an associate professor, with an interest in neurodevelopment and cognition in youth on the psychosis spectrum.

Chapter 5 Adolescent psychosis and transdiagnostic delimitations to other clinical syndromes Christopher Gillberg, MD, PhD, is a child and adolescent psychiatrist and professor of child and adolescent psychiatry at the universities of Gothenburg, Glasgow, London, Kochi, and the Pasteur Institute in Paris. His main research, and clinical, contributions have been in the fields of neurodevelopmental disorders.

Chapter 6 Cognitive functioning in early-onset psychosis Runar Elle Smelror, PhD (background information in Chapter 1) Torill Ueland, PhD, is a specialist in clinical neuropsychology and associate professor. Her research focuses on cognition, functional outcome, and cognitive remediation in schizophrenia and bipolar disorder.

Chapter 7 The immunopsychiatry of early-onset psychosis Kirsten Wedervang-Resell, MD, PhD, is a child and adolescent psychiatrist. Her main research focus is on biomarkers, immunopsychiatry, and biological psychiatry. Attila Szabo, PhD, has a professional background in immunology (Ph.D.) and biochemistry (MSc). His main research interest is in psychoneuroimmunology and biological psychiatry.

Chapter 8 Structural brain imaging in early-onset psychosis Claudia Barth, PhD, is a biologist and a postdoctoral researcher with the main research focus on the effects of hormonal transition periods on mental illnesses and the brain. Christian K. Tamnes, PhD, is a clinical psychologist and professor with extensive experience in the field of developmental cognitive neuroscience. Ingrid Agartz, MD, PhD (background information in Chapter 1)

About the contributors xv

Chapter 9 Functional brain imaging in early-onset psychosis Mathilde Antoniades, Shalaila S. Haas, Shirine Moukaled, Faye New, and Samantha D. Pescatore are affiliated with the Icahn School of Medicine at Mount Sinai, New York, USA. Sophia Frangou, MD, PhD, is a Professor of Psychiatry. Drs Antoniades and Haas are post-doctoral Fellows. Ms. Mukaled, Ms. New, and Ms. Pescatore are graduate students. The research focus of the team is on brain-behavior associations in health and in severe mental illness.

Chapter 10 Adolescence as a vulnerable period for psychosis development Toma´s Paus, MD, PhD, is a professor of psychiatry and neuroscience. He is an expert in population neuroscience, brain development, and mental health.

Chapter 11 Current treatment options in early-onset psychosis Anne Katrine Pagsberg, MD, PhD, is a child and adolescent psychiatrist and professor of child and adolescent psychiatry. Her main research interests are in pharmacological and psychosocial interventions in child and adolescent mental health, primarily within psychosis. Marianne Melau, PhD, is a senior researcher with the main interest in early intervention in psychosis, first episode psychosis, and schizophrenia in adolescence and early adulthood.

Chapter 12 Long-term development and outcome of earlyonset psychosis Helene Gjervig Hansen, MD, is a medical doctor and Ph.D. student with a special interest in register-based research and clinical trials among individuals with first-episode psychosis. Naja Kirstine Andersen, M. Psych, is a clinical psychologist and Ph.D. student with an interest in early-onset psychosis interventions and registerbased research in outcomes. Merete Nordentoft, DrMedSc, is a psychiatrist and professor in clinical psychiatry. She is a specialist in epidemiology, suicidal behavior, and early intervention in psychosis.

xvi About the contributors

Nikolai Albert, PhD, is a medical doctor and a post-doctoral researcher. He has extensive research experience in first-episode psychosis, the trajectory of illness, and early intervention.

Chapter 13 Ethical considerations and current research practices in adolescent psychosis Kerstin Jessica Plessen, MD, PhD, is a child and adolescent psychiatrist and professor in child and adolescent psychiatry. Her main research interest is how to facilitate the positive development of children with neuropsychiatric disorders and of those with mentally ill parents. Ralf J. Jox, MD, PhD, is a professor of medical ethics. He has a particular interest in the ethical implications of health care for vulnerable individuals. Marco Armando, MD, PhD, is a psychiatrist and professor of child and adolescent psychiatry, with a main research interest in early detection and intervention in psychosis and other psychiatric disorders.

Chapter 1

Introduction to psychotic disorders in adolescence Runar Elle Smelror1, 2, Lynn Mørch-Johnsen2, 3 and Ingrid Agartz1, 2, 4 1 Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway; 2NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 3Department of Psychiatry & Department of Clinical Research, Østfold Hospital, Gra˚lum, Norway; 4Centre of Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

Introduction Psychotic disorders presenting in childhood or adolescence are often referred to as early-onset psychosis (EOP). EOP does not denote a recognized diagnostic entity but is a research term describing the spectrum of psychotic disorders that develop in children and adolescents before 18 years of age. The term “early-onset” was introduced by Werry et al. (1991) embracing childhood-onset (before 13 years of age) and adolescence-onset (from 13 through 17 years of age) psychotic disorders. Fig. 1.1 gives a hierarchical overview of EOP based on diagnoses from the fifth version of the Diagnostic

FIGURE 1.1 Hierarchical overview of early-onset psychotic disorders (EOP) based on DSM-5 diagnoses.

Adolescent Psychosis. https://doi.org/10.1016/B978-0-323-89832-4.00006-8 Copyright © 2023 Elsevier Inc. All rights reserved.

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2 Adolescent Psychosis

and Statistical Manual of Mental Disorders (DSM-5) (American Psychiatric Association, 2013). In Table 1.1 we present diagnostic descriptions for the psychotic disorders included under EOP based on diagnoses from the DSM-5 and the 11th revision of the International Classification of Diseases (ICD-11) (World Health Organization, 2019). Most studies of EOP have focused on schizophrenia, which is the most prevalent disorder among youth with EOP (75% of cases in a recent French study; Giannitelli et al., 2020). While the incidence of schizophrenia in childhood is very rare (less than 0.04%; Driver et al., 2020), the occurrence increases to about 0.6% during adolescence; Dalsgaard et al., 2020). Despite the relatively low incidence compared to other mental disorders (e.g., anxiety disorders have an incidence of about 6% before 18 years of age) (Dalsgaard et al., 2020), schizophrenia is nevertheless ranked as the second main cause of disease burden in late adolescence (Gore et al., 2011). See Chapter 2 for detailed information about incidence and prevalence, including the importance of sex differences. Under the EOP umbrella, bipolar disorder with psychotic features is sorted under affective psychotic disorders. The clinical picture is dominated by intermittent periods of depressed or elevated mood (episodes of mania (bipolar I disorder) or hypomania (bipolar II disorder)) (see Table 1.1 for diagnostic descriptions). The incidence rate of bipolar disorder in childhood and adolescence is 0.08%, and it is almost twice as high in girls as in boys (Dalsgaard et al., 2020). Similar to schizophrenia the incidence of bipolar disorder also increases with age (Jensen & Steinhausen, 2016). When psychotic symptoms are considered part of a bipolar disorder, they are by definition related to affective episodes (mania or depression). Pavuluri and colleagues reported that the prevalence of psychotic symptoms varied between 16% and 87.5% in youth with bipolar disorder (Pavuluri et al., 2004).

Clinical characteristics The fundamental principle of psychosis involves a mental state of distorted perception and thought, resulting in difficulties differentiating between actual and misperceived events (i.e., reality distortion). Persons who experience psychosis may hear voices or see things that are not there (hallucinations), or present ideas and beliefs divergent with reality or the subculture they belong to (delusions). Their family and friends may notice changes in the affected person’s behavior, such as withdrawal from social activities, poor grooming, unpredicted agitation, or acting in a peculiar and unusual way.

TABLE 1.1 Diagnostic descriptions of psychotic disorders according to DSM-5 and ICD-11. Diagnosis

DSM-5 diagnostic description

ICD-11 diagnostic description

DSM-5 versus ICD-11

For diagnosis, DSM-5 requires a total duration of 6 months and impaired functioning. ICD-11 requires a total duration of one month. The 4th ICD symptom (i.e., bizarre delusions) is excluded as a separate criterion in DSM-5 and included under delusions.

Non-affective Minimum two of the following symptoms, present for minimum one month, in which at least two must be 1e4: (1) delusions; (2) hallucinations; (3) disorganized thinking; (4) experiences of influence, passivity, or control; (5) negative symptoms; (6) grossly disorganized behavior; (7) psychomotor disturbances.

Schizophreniform disorder

Minimum two of the symptoms of schizophrenia, in which one must be aec. Duration of disturbance is at least one month but less than 6 months. No criterion regarding impaired functioning.

Not included in ICD-11.

3

Minimum two of the following symptoms present for at least one month, in which one must be a-c: (a) delusions; (b) hallucinations; (c) disorganized speech; (d) grossly disorganized behavior; (e) negative symptoms. The disturbance causes impaired functioning and persists for minimum 6 months.

Introduction to psychotic disorders in adolescence Chapter | 1

Schizophrenia

Continued

Diagnosis

DSM-5 diagnostic description

ICD-11 diagnostic description

DSM-5 versus ICD-11

Schizoaffective disorder

Meeting the symptom criterion for schizophrenia with concurrent symptoms of a major mood episode during most of the total duration of the disturbance. During the period of illness, delusions or hallucinations must be present for minimum two weeks in the absence of a major mood episode. No formal criterion about impaired functioning.

Meeting the criteria for schizophrenia concurrent with symptoms of a moderate/ severe mood episode. The onset of psychotic and mood symptoms must be simultaneous or occur within a few days apart.

DSM-5 requires concurrent psychosis and mood symptoms most of the total duration of illness, while ICD-11 specifies that the concurrent symptoms must occur simultaneously or within a few days apart.

Delusional disorder

Delusions for at least one month without other symptoms of schizophrenia or impaired functioning.

Delusions for at least three months without other symptoms of schizophrenia.

DSM-5 formally requires duration of one month while ICD-11 requires duration of three months.

Brief psychotic disorder (DSM-5), acute and transient psychotic disorder (ICD-11)

Minimum one symptom of schizophrenia from a

Minimum one symptom of schizophrenia, except for negative symptoms, with rapid

ICD-11 requires rapid symptom changes and a

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TABLE 1.1 Diagnostic descriptions of psychotic disorders according to DSM-5 and ICD-11.dcont’d

changes in the nature and intensity of symptoms. Duration of disturbance is less than three months.

Symptoms of schizophrenia spectrum and other psychotic disorder that cause significant distress or impaired functioning predominate but do not meet the full criteria for any of the disorders in the schizophrenia spectrum and other psychotic disorder diagnostic class, or without adequate information to make a specific diagnosis.

Symptoms of schizophrenia or other primary psychotic disorders that cause significant distress or impaired functioning predominate but do not meet the full criteria for any of the disorders in the schizophrenia or other primary psychotic disorders diagnostic class, or without adequate information to make a specific diagnosis.

Minimum one manic episode that caused impaired functioning and

Minimum one manic or mixed episode that caused impaired functioning and was

duration of less than three months, while DSM-5 does not formally require rapid symptom changes and duration of less than one month.

Affective Bipolar disorder type I with psychotic features

ICD-11 requires either a manic or mixed episode, while only a manic

Introduction to psychotic disorders in adolescence Chapter | 1

Unspecified schizophrenia spectrum and other psychotic disorder (DSM-5), schizophrenia or other primary psychotic disorder, unspecified (ICD-11)

to c, except for negative symptoms. Duration of disturbance is at least one day and less than one month, with full return to premorbid level of functioning. No formal criterion about impaired functioning.

5 Continued

Diagnosis

DSM-5 diagnostic description

ICD-11 diagnostic description

DSM-5 versus ICD-11

was accompanied by delusions and/or hallucinations

accompanied by delusions and/or hallucinations.

episode fulfills the criteria in DSM-5.

Bipolar disorder type II with psychotic features

Minimum one hypomanic episode and one depressive episode that caused impaired functioning and was accompanied by delusions and/or hallucinations.

Minimum one hypomanic episode and one depressive episode that caused impaired functioning accompanied by delusions and/or hallucinations.

Depressive disorder with psychotic features

Minimum one depressive episode that caused impaired functioning and was accompanied by delusions and/or hallucinations.

Minimum one depressive episode that caused impaired functioning and was accompanied by delusions and/or hallucinations.

Note: The diagnostic descriptions presented in this table do not incorporate all the diagnostic criteria for the psychotic disorders. See DSM-5 and ICD-11 for full diagnostic criteria. Data from the American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (DSM-5); World Health Organization. (2019). International classification of diseases, eleventh revision (ICD-11).

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TABLE 1.1 Diagnostic descriptions of psychotic disorders according to DSM-5 and ICD-11.dcont’d

Introduction to psychotic disorders in adolescence Chapter | 1

7

Psychotic experiences Population-based studies suggest that psychotic experiences often appear along a dimensional gradient, ranging from subtle changes in perception and thought in otherwise healthy individuals, to clear-cut hallucinations and delusions with accompanying functional impairments as part of the spectrum of psychotic disorders (Maijer et al., 2018, 2019). Subclinical psychotic experiences appear more frequently at younger age (Healy et al., 2019; Maijer et al., 2018; Schultze-Lutter et al., 2022) and can complicate a diagnosis of a psychotic disorder in children and adolescents (Schultze-Lutter et al., 2022). For instance, among children between 5 and 12 years of age, 28e65% reported seeing an “imaginary companion” or hallucination-like phenomenon (Pearson et al., 2001). These experiences must be considered within the normal range (Sikich, 2013) and are different from psychotic experiences in at least two aspects: they are voluntary and associated with positive emotions (Jardri et al., 2014). Therefore, a failure to consider the normal developmental trajectories of perception and cognition in children and adolescents when interpreting psychotic experiences may lead to overdiagnosis of severe mental disorders. On the other hand, psychotic-like experiences in community samples of children and adolescents have been associated with increased risk of developing a psychotic or other mental disorders (Healy et al., 2019). Even though hallucinatory experiences in children and adolescents are often transient and self-limiting, they can cause severe distress and dysfunction, and are associated with increased risk of suicidality (Maijer et al., 2019). For more information regarding subclinical psychotic symptoms, see Chapters 2 and 4.

Symptom domains As with the diagnostic criteria, the clinical symptom descriptions of children and adolescents with EOP largely follow the adult psychosis nomenclature (see Table 1.2). Traditionally, the clinical symptoms of psychotic disorders have been divided into two broad categories: positive symptoms, reflecting an excess or a distortion of normal brain functions; and negative symptoms, reflecting a reduction of normal brain functions and behavior. However, over the years, factor-analytic studies of commonly used psychometric scales for assessing psychotic and associated symptoms, such as the Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1987), have suggested that the clinical features of psychotic disorders best can be described by at least four or five domains (Wallwork et al., 2012). These domains include positive, negative, disorganized, depressive, and excited symptoms (Wallwork et al., 2012). Both four-factor (McClellan et al., 2002; Petruzzelli et al., 2018; Thakur, Jagadheesan, & Sinha, 2003; Ulloa et al., 2000), and five-factor models (Bunk et al., 1999; Giannitelli et al., 2020; Rapado-Castro et al., 2010) have been

8 Adolescent Psychosis

TABLE 1.2 Description of psychotic and affective symptoms. Positive symptoms Hallucinations

Sensory perceptions that appear in the absence of any corresponding external stimulus.

Delusions

False beliefs that are maintained despite conflicting evidence.

Negative symptoms Avolition/apathy

Reductions in self-initiated, goal-directed activities due to lack of motivation.

Anhedonia

Reduced experience of pleasure, either “in the moment” (consummatory), or for future anticipated activities (anticipatory).

Asociality

Reduced engagement in social activities and interactions.

Blunted affect

Reduced expression of emotions through facial expressions, intonation of speech, or body gestures.

Alogia

Poverty of speech. Communicates with few words, with little elaboration and spontaneous speech.

Disorganized symptoms Disorganized speech

Incoherent speech, loose associations, vague or unrelated answers, idiosyncratic word usage. Formal thought disorder: Disruption in the flow of thought, manifests as disorganized speech.

Disorganized or abnormal motor behavior

Behaving or dressing in a peculiar or childlike manner, unpredictable agitation, or abnormal motor behavior (including catatonic features). Catatonic features: Resistance to instructions (negativism), bizarre rigid postures, lack of verbal responses (mutism), motoric immobility, stupor, excessive and purposeless motor activity, stereotyped movements, echoing of speech or movement.

Affective symptoms Depressed mood

Feeling sad, empty, or hopeless. Loss of interest and pleasure. Can involve changes in appetite and weight, sleep disturbances, psychomotor agitation or retardation, loss of

Introduction to psychotic disorders in adolescence Chapter | 1

9

TABLE 1.2 Description of psychotic and affective symptoms.dcont’d energy, feelings of worthlessness or guilt, difficulties concentrating or making choices, suicidal ideation. Elevated mood (hypomania or mania)

Elevated or irritable mood. Increased energy and activity. Can involve a decreased need for sleep, pressure to keep talking, grandiosity, racing thoughts, distractibility, psychomotor agitation, involvement in activities with highrisk of harmful consequences.

Data from the American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (DSM-5); Galderisi, S., et al. (2021). EPA guidance on assessment of negative symptoms in schizophrenia. European Psychiatry: The Journal of the Association of European Psychiatrists, 64(1), e23.

described when investigating adolescents with EOP. Discrepancies in the different models could be due to the use of different rating scales, the diagnostic distribution in the different studies, or different stages of disease. In a longitudinal study, Rapado-Castro et al. (2010) examined symptom domains, assessed with the PANSS, at baseline, after 4 weeks, and after 6 months, in 99 adolescents with EOP. They found that the symptoms clustered into five domains at the different time points. Moreover, they discovered that the clusters of symptoms within each factor also varied with time, and that the symptoms constituting the negative symptom domain were most consistent across different time points. Another important feature of psychotic disorders is the impaired cognitive functioning, such as reduced processing speed and learning. In both adolescents and adults with psychotic disorders, impaired cognitive functioning is more often reported to be associated with negative and disorganized symptoms, and less with positive symptoms (de Gracia Dominguez et al., 2009; Mørch-Johnsen et al., 2022) See Chapter 6 for cognitive functioning in youth with EOP.

Positive symptoms In a comprehensive review, Stentebjerg-Olesen and colleagues examined clinical characteristics of 1506 patients (mean age 90%) of individuals with EOS being 14 years and older. Furthermore, Scottish data reporting on the prevalence of EOP suggests a 3-year prevalence in the general population of 5.9 per 100,000 (Boeing et al., 2007). A Canadian retrospective cohort study of 193,400 adolescents born between 1990 and 1998 found that 0.76% were diagnosed with a nonaffective psychotic disorder between the ages of 13 and 19 years (Magee et al., 2022). Incidence rates increased with higher age from 12 to 17 per 100,000, especially in males. The risk of having a psychotic disorder was elevated in lowincome families and neighborhoods, if a parent had health service contact for a mental disorder, and in more recent birth cohorts. Unexpectedly, the risk was reduced among children of immigrants compared to children of nonmigrants (Magee et al., 2022). Another Canadian population-based study estimated the incidence of EOS based on data from physician billings, hospitalizations, pharmacies, and public health clinics from 2004 to 2006, and reported a cumulative incidence of first-episode schizophrenia spectrum disorders of 25 cases per 100,000 at age 18 years (Anderson et al., 2012). Large increases in incidence were found between 14 and 18 years. Since these estimates are much higher than what has been found in other studies, the authors reason that many cases may be missed in studies using clinical samples. They argue that administrative databases may be more useful resources for studying the rarer types of mental disorders such as EOS (Anderson et al., 2012). In Italy, an epidemiologically based survey was conducted among the general population, examining risk of psychosis in relation to age, sex, immigration status, urbanicity, and socioeconomic deprivation. The study was conducted between 2005 and 2007 within the framework of the Psychosis Incident Cohort Outcome Study (PICOS) (Lasalvia et al., 2014) and comprised of a total number of 3,077,555 person-years, that is, the total population in the study catchment area multiplied by the number of years of recruitment. The incidence rates for all psychotic disorders for adolescents aged 15e19 years, was 11.9 per 100,000 person-years. For nonaffective psychosis, the incidence was slightly lower, at 10.3, and for schizophrenia it was half, at 5.9 per person-

The epidemiology of early-onset psychosis Chapter | 2

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years. For affective psychosis the incidence rate was 1.6 per 100,000 person years, including 1.2 and 0.4 per 100,000 for bipolar disorder and major depressive disorder with psychotic features, respectively. The incidence rates of psychotic disorders peaked in the age span 20e29 years, with 30.3 per 100,000 person-years (Lasalvia et al., 2014). The English naturalistic cohort study, known as the Social Epidemiology of Psychoses in East Anglia (SEPEA) study (Kirkbride et al., 2017), with a total of 2,021,663 person-years, reported even higher incidence rates of EOP. The incidence was 45.8 per 100,000 in 16- and 17-year-olds, and 57.2 in 18- and 19-year-olds. Highest incidence rates were found for nonaffective psychosis with approximately 35 per 100,000 in 16- and 17-year-olds and approximately 50 per 100,000 in 18- and 19-year-olds. Considerably fewer cases with affective psychosis were reported, with less than 10 per 100,000 for both age groups (Kirkbride et al., 2017). Similarly, in the Jerusalem Perinatal Study, a population-based cohort derived from all births in Israel between 1964 and 1976, the incidence of schizophrenia-spectrum disorders was examined in different age bands (Kleinhaus et al., 2011). Between the ages of 10e14 years the incidence was 6.6 per 100,000. This rapidly increased to 53 per 100,000 between the ages of 15e19 years and reached a peak incidence of 62.5 per 100,000 between the ages of 20e24 (Kleinhaus et al., 2011). In conclusion, population-based studies report substantial heterogeneity in the incidence and prevalence of EOS and EOP which is at least partially explained by the type of study design and sampling strategies. Studies consistently indicate a significant increase of around 10 times more cases during adolescence (age 12e18 years) compared to psychosis with earlier onset (1% and short insertions or deletions (