Childhood Schizophrenia Research Articles

Treatments in context: transcranial direct current brain stimulation as a potential treatment in pediatric psychosis

Childhood-onset schizophrenia is a chronic, severe form of schizophrenia, and is typically treatment resistant. Even after optimized pharmacotherapy, a majority (over 70%) of these pediatric patients present lasting psychotic symptoms and impaired cognition, necessitating the need for novel treatment modalities. Recent work in transcranial magnetic stimulation suggests moderate efficacy in symptom reduction in adult patients with schizophrenia; however, the transcranial magnetic stimulation treatment is cumbersome for this severely ill population. Transcranial direct current stimulation may provide a safe and effective adjuvant treatment for continued residual symptoms of schizophrenia.

Risk Factors for Neutropenia in Clozapine-Treated Children and Adolescents with Childhood-Onset Schizophrenia

The purpose of this study was to retrospectively analyze rates of neutropenia and risk factors for neutropenia in hospitalized children and adolescents treated with clozapine. A retrospective chart review was conducted for all patients who received clozapine at any time during a hospitalization at the National Institute of Mental Health (NIMH) between 1990 and 2011. All patients satisfied screening criteria for the NIMH childhood-onset schizophrenia study, including onset of psychosis before the age of 13 years. Absolute neutrophil count (ANC) values recorded during inpatient hospitalization were extracted for 87 eligible patients with a mean age of 13.35±2.46 years at hospitalization and a mean length of stay of 117±43 days. Mild neutropenia only (lowest ANC<2000/mm3 but>1500/mm3) was observed in 27 (31%) patients and moderate neutropenia (any ANC<1500/mm3) was observed in 17 (20%) patients. There were no cases of agranulocytosis or severe infection. Significant risk factors for mild neutropenia compared with no hematologic adverse effects (HAEs) were male gender (p=0.012) and younger age (p<0.001). Male gender was also a significant risk factor for moderate neutropenia compared with no HAEs (p=0.003). If a child of African American ethnicity developed neutropenia during hospitalization at all that child was significantly more likely to develop moderate neutropenia than mild neutropenia only (p=0.017). African American boys had the highest rate of moderate neutropenia at 47%. Sixteen of the 17 patients exhibiting moderate neutropenia were successfully treated with clozapine by the time of discharge; 8 of these 16 required adjunctive lithium carbonate administration to maintain ANC>2000/mm3. Our study shows that the rates of neutropenia in clozapine-treated children and adolescents are considerably higher than in the adult population. Younger age, African American ethnicity, and male gender were significant risk factors. These are also risk factors for benign neutropenia in healthy children and adolescents. Despite these high rates of neutropenia, all but one of the patients with neutropenia during hospitalization were successfully discharged on clozapine.

Co‐occurrence of autism, childhood psychosis, and intellectual disability associated with a de novo 3q29 microdeletion

Some copy number variants (CNVs) are strongly implicated in both schizophrenia and autism spectrum disorders (ASDs). Childhood-onset schizophrenia (COS) occurs rarely with 0.1-1% of all schizophrenia diagnoses manifesting before age 10. 3q29 deletions are associated with both autism and schizophrenia, and are rare-the frequency of the deletion estimated to be 1 in 1,750 in developmental disorders. Only one patient with a 3q29 deletion was identified out of the first 1,174 families with ASDs included in the Simons Simplex Collection (SSC). We report on detailed clinical findings for this patient with a de novo 3q29 deletion who, as a young child, developed a very rare overlap of symptoms of both autism and early onset psychosis. His ASD was first diagnosed at the age of 4 years and his psychotic symptoms began at 5 years old. This is only the second case reported thus far of this rare event of co-occurring autism and very early onset psychosis in a child with a 3q29 deletion. It is also the earliest case of a child with autism developing comorbid psychosis-manifesting by the age of 5 years.

Violence in childhood-onset schizophrenia.

Violence is elevated in older adolescents and adults with schizophrenia; however, little is known about younger children. This report focuses on rates of violence in younger children with schizophrenic-spectrum illnesses. A retrospective review of structured diagnostic interviews from a case series of 81 children, ages 4-15 years of age, with childhood onset of schizophrenic-spectrum illness is reported. Seventy-two percent of children had a history of violent behavior, including 25 children (31%) with a history of severe violence. Of those with a history of violence, 60% had a least one episode of violence that did not appear to be in response to an external stimulus (internally driven violence). There was no significant impact of age or gender. For many children, these internally driven violent episodes were rare and unpredictable, but severe. Similar to what is found in adolescents and adults, violence is common in children with schizophrenic-spectrum illnesses. General violence prevention strategies combined with early identification and treatment of childhood psychotic illnesses may decrease the morbidity associated with childhood psychotic violence.

Violence in childhood-onset schizophrenia

Violence is elevated in older adolescents and adults with schizophrenia; however, little is known about younger children. This report focuses on rates of violence in younger children with schizophrenic-spectrum illnesses. A retrospective review of structured diagnostic interviews from a case series of 81 children, ages 4-15 years of age, with childhood onset of schizophrenic-spectrum illness is reported. Seventy-two percent of children had a history of violent behavior, including 25 children (31%) with a history of severe violence. Of those with a history of violence, 60% had a least one episode of violence that did not appear to be in response to an external stimulus (internally driven violence). There was no significant impact of age or gender. For many children, these internally driven violent episodes were rare and unpredictable, but severe. Similar to what is found in adolescents and adults, violence is common in children with schizophrenic-spectrum illnesses. General violence prevention strategies combined with early identification and treatment of childhood psychotic illnesses may decrease the morbidity associated with childhood psychotic violence.

When children with autism become adults

Autism and related conditions have been described since the 1940s, but official recognition did not come until 1980, with the publication of the DSM-III. Early confusion centered on the validity of the condition, that is, whether it could be considered distinct from childhood schizophrenia. This confusion was clarified with work on clinical phenomenology and genetics of the two conditions. Specifically, differences in clinical features were identified, with autism being marked by profound social difficulties and very early onset relative to schizophrenia. It also became clear that autism was a strongly genetic disorder, distinct from schizophrenia. Autism was associated, at least initially, with a rather poor outcome, with the earliest studies suggesting that about two-third of individuals, as adults, required institutional care 1,2. Early treatment approaches were centered on psychotherapy (often of parent and child), but gradually shifted as work indicated that structured behavioral and educational approaches were associated with better outcome, as was earlier diagnosis and intervention. It has become increasingly clear that greater public awareness, earlier intervention, and more effective management have had a major impact on the outcome of the condition 1.

Childhood catatonia, autism and psychosis past and present: is there an 'iron triangle'?

To explore the possibility that autism, catatonia and psychoses in children are different manifestations of a single underlying form of brain pathology - a kind of 'Iron Triangle' of symptomatology - rather than three separate illnesses. Systematic evaluation of historical case literature on autism to determine if catatonic and psychotic symptoms accompanied the diagnosis, as is found in some challenging present-day cases. It is clear from the historical literature that by the 1920s all three diagnoses in the Iron Triangle - catatonia, autism and childhood schizophrenia - were being routinely applied to children and adolescents. Furthermore, it is apparent that children diagnosed with one of these conditions often qualified for the other two as well. Although conventional thinking today regards these diagnoses as separate entities, the presence of catatonia in a variety of conditions is being increasingly recognized, and there is also growing evidence of connections between childhood-onset psychoses and autism. Recognition of a mixed form of catatonia, autism and psychosis has important implications for both diagnosis and treatment. None of the separate diagnoses provides an accurate picture in these complex cases, and when given single diagnoses such as 'schizophrenia', the standard treatment options may prove markedly ineffective.

1948 – Chilhood onset schizophrenia: Epidemiological and clinical preliminary findings from a french population-based study

Introduction Childhood-onset schizophrenia (COS) is a rare but severe psychiatric disorder with important individual, family and societal consequences. Its prevalence is approximately 2 per 10.000 in the general population and the incidence of COS increases with age. Objectives The main objective of our study was to evaluate the prevalence of COS in French medical-social institutions or psychiatric day hospitals for children and adolescents in the PACA region. The secondary objectives were: (1) to estimate the prevalence of children with both COS and autism diagnosis, (2) to characterize clinical and neurocognitive presentation of COS using the evaluation of intensity of positive and negative symptoms (PANSS, SANS), of thought disorganization (TLC), of cognitive functioning, and of attention and executive functions (verbal fluency, TMT A, TMT B). Methods Subjects were patients from medical-social and psychiatric care centers for children and adolescents in three PACA sub-regions in the south-east of France. The study included French speaking girls and boys between 7 and 18 years old, registered in a partner structure of the study, and presenting an IQ > 35 (WISC-IV). The study design was constituted by two phases: the first one was the categorical diagnostic phase using the psychosis section of the Kiddie-SADS Present and Lifetime Version. The second phase consisted of the dimensional COS diagnosis and neurocognitive exploration for the subjects fulfilling the DSM-IV diagnostic criteria for schizophrenia. Results The diagnosis of COS was not exceptional in this population. Most subjects diagnosed with COS also presented autism diagnosis and mental retardation.

A Comparison of Neuroimaging Findings in Childhood Onset Schizophrenia and Autism Spectrum Disorder: A Review of the Literature

Background: Autism spectrum disorder (ASD) and childhood onset schizophrenia (COS) are pediatric neurodevelopmental disorders associated with significant morbidity. Both conditions are thought to share an underlying genetic architecture. A comparison of neuroimaging findings across ASD and COS with a focus on altered neurodevelopmental trajectories can shed light on potential clinical biomarkers and may highlight an underlying etiopathogenesis.Methods: A comprehensive review of the medical literature was conducted to summarize neuroimaging data with respect to both conditions in terms of structural imaging (including volumetric analysis, cortical thickness and morphology, and region of interest studies), white matter analysis (include volumetric analysis and diffusion tensor imaging) and functional connectivity.Results: In ASD, a pattern of early brain overgrowth in the first few years of life is followed by dysmaturation in adolescence. Functional analyses have suggested impaired long-range connectivity as well as increased local and/or subcortical connectivity in this condition. In COS, deficits in cerebral volume, cortical thickness, and white matter maturation seem most pronounced in childhood and adolescence, and may level off in adulthood. Deficits in local connectivity, with increased long-range connectivity have been proposed, in keeping with exaggerated cortical thinning.Conclusion: The neuroimaging literature supports a neurodevelopmental origin of both ASD and COS and provides evidence for dynamic changes in both conditions that vary across space and time in the developing brain. Looking forward, imaging studies which capture the early post natal period, which are longitudinal and prospective, and which maximize the signal to noise ratio across heterogeneous conditions will be required to translate research findings into a clinical environment.

Childhood Onset Schizophrenia: High Rate of Visual Hallucinations

Childhood Onset Schizophrenia: High Rate of Visual Hallucinations

1334 – Age of onset and degrees of cognitive deficit in children and adolescents with endogenous mental disorders

Introduction Cognitive deficit in endogenous mental disorders in children and adolescents is studied less than in adults, particularly age of onset influence. There is very few data about the connection between degree of cognitive deficit and age of psychiatric illness onset in children and adolescents. It’s difficult to determine the specificity of cognitive deficits depending on the clinical form of endogenous mental disorders (schizophrenia). Objectives 93 patients (11.8 ± 2.3 years) with childhood schizophrenia (F20.8, 26 patients), schizotypical disorders (F21, 59 patients), unspecified schizophrenia (F2x.x, 8 patients). We used adaptation of ICD-10 for RF. Aims Assessment of degree of cognitive deficit relative to age of onset and diagnosis. Methods Tests assessing cognitive processes: memory, attention, thinking. Z-scales were used for estimation of cognitive deficit. Results Age of onset was divided into three periods: early, preschool and school age. The least degree of all cognitive functions occurs in patients with school age of onset. F20.8 and F2x.x with early and preschool age of onset have severe thinking deficit. F21 demonstrates decreasing of cognitive deficit degrees in all functions with increasing of age of onset. Degree of cognitive deficit is connected with clinical diagnosis. Patients with F20.8 have strong deficit in all cognitive functions (memory, attention, thinking). F21 patients demonstrate a variety of cognitive deficit degrees including age norm outstrip. F2x.x patients keep intermediate position. Conclusions Age of onset might be important in determination of degrees of cognitive deficit. The last depends on diagnosis, age of onset & kind of cognitive process.

Base rates, blindness, and schizophrenia

GENERAL COMMENTARY article Front. Psychol., 03 April 2013Sec. Psychopathology Volume 4 - 2013 | https://doi.org/10.3389/fpsyg.2013.00157

Absence of anatomic corpus callosal abnormalities in childhood-onset schizophrenia patients and healthy siblings

The corpus callosum (CC) has been implicated in the pathogenesis of schizophrenia, and CC deficits have been reported in adults with schizophrenia. We explored the developmental trajectory of the corpus callosum in childhood-onset schizophrenia (COS) patients, their healthy siblings (SIB) and healthy volunteers. We obtained 235 anatomic brain magnetic resonance imaging (MRI) scans from 98 COS patients, 153 scans from 71 of their healthy siblings, and 253 scans from 100 age- and gender-matched healthy volunteers, across ages 9–30 years. The volumes of five sub-regions of the CC were calculated using FreeSurfer, and summed to give the total volume. Longitudinal data were examined using mixed model regression analysis. There were no significant differences for the total or sub-regional CC volumes between the three groups. There were also no significant differences between the groups for developmental trajectory (slope) of the CC. This is the largest longitudinal study of CC development in schizophrenia and the first COS study of the CC to include healthy siblings. Overall, CC volume and growth trajectory did not differ between COS patients, healthy siblings, or healthy volunteers. These results suggest that CC development, at least at a macroscopic level, may not be a salient feature of schizophrenia.

The presentation of early-onset psychotic disorders

This study aims to describe the clinical course of psychotic disorders, including the premorbid history, symptoms and level of functioning in a group of children and adolescents treated by paediatric mental health services, mainly as inpatients. A sample of 45 children and adolescents with a psychotic disorder (mean age 13.2 years) was assessed using questionnaires, semi-structured interviews, parent interviews and file audit. The symptoms of those with a schizophrenia spectrum disorder (SSD) were compared to those with a mood disorder (MD). This population showed a high level of premorbid impairment, including previous treatment for other psychiatric disorders. As well as hallucinations and delusions, high levels of self-harm, aggression, anxiety and depression were reported. The SSD and MD groups differed mainly in their levels of premorbid functioning. While it is well known that childhood-onset schizophrenia is a severe disorder with a poor outcome, this study found that young people diagnosed with other psychotic disorders also have significant impairment and are likely to require high levels of care to maximize their functional recovery.

A systematic review of the long-term outcome of early onset schizophrenia

BackgroundThe current review analyzes the long-term outcome and prognosis of early onset schizophrenia based on previously published studies in 1980.MethodsA systematic search of articles published in the English-language literature after 1980 identified a total of 21 studies, which included 716 patients who were either suffering from early onset schizophrenia (EOS) or both EOS and other psychotic disorders (MIX). The authors of the current review scored the outcome as either “good,” “moderate,” or “poor.” The mean age of onset in these studies was <18 years.ResultsIn general, the outcome in studies with EOS is worse than the outcome in MIX studies. Only 15.4% of the patients in EOS studies versus 19.6% of the patients in MIX studies experienced a “good” outcome. In contrast, 24.5% of the patients in EOS studies versus 33.6% in MIX studies experienced a “moderate” outcome, and 60.1% in EOS studies versus 46.8% in MIX studies experienced a “poor” outcome. The authors identified various significant effects on outcome. In EOS, the findings were significantly affected by sample attrition, indicating that in studies with a high dropout rate, fewer patients experienced a “moderate” outcome, and more patients experienced a “poor” outcome; however, the effect sizes were small. Furthermore, the effects were also small and more favourable for specific functioning measures, as opposed to more global measures, small to moderate in terms of worse outcomes for follow-up periods >10 years, small to moderate for more unfavourable outcomes in males, and small to large for worse outcomes in studies including patients diagnosed before 1970.ConclusionsIn contrast to the adult manifestation, the early manifestation of schizophrenia in childhood and adolescence still carries a particularly poor prognosis. According to these aggregated data analyses, longer follow-up periods, male sex, and patients having been diagnosed before 1970 contribute predominantly to the rather poor course of EOS.

If Relative Has Schizophrenia, Autism Risk Increases

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessIf Relative Has Schizophrenia, Autism Risk IncreasesJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:7 Sep 2012https://doi.org/10.1176/pn.47.17.psychnews_47_17_16-aAbstractMany years ago, autism spectrum disorders were sometimes regarded as childhood schizophrenia. Then, in 1980, with the publication of an updated edition of APA’s Diagnostic and Statistical Manual of Mental Disorders (DSM-III), autism spectrum disorders and schizophrenia came to be defined as separate disorders. That continues to be the case today.In 2005, however, Danish researchers reported that having a parent with schizophrenia was linked with having an autism spectrum disorder, suggesting that schizophrenia and autism spectrum disorders might have some genetic overlap. And now an international team has produced similar findings.The lead researcher was Patrick Sullivan, M.D., a professor of psychiatry and genetics at the University of North Carolina. The results were published online July 2 in the Archives of General Psychiatry.Sullivan and his team looked to see whether they could find a link between having a parent or sibling with schizophrenia and having autism spectrum disorders in three large population samples. One came from Stockholm, Sweden; one from Sweden overall; and one from Israel. The samples included national personal identification numbers, multi-generation registry data, a national pre-conscription mental health assessment, or other attributes that made them ideal for testing such a hypothesis.“The findings were clear,” Sullivan and his group reported. “The presence of schizophrenia…in first-degree relatives was a consistent and significant risk factor for autism spectrum disorders in all three samples.”They found in the Stockholm and Swedenwide cohorts that if an individual had a parent or a sibling with schizophrenia, the chances of having an autism spectrum disorder were three times greater than for individuals without a parent or a sibling with schizophrenia.And they found in the Israeli cohort that if a person had a sibling with schizophrenia, then his or her chances of having an autism spectrum disorder were 12 times greater than those of individuals without a sibling with schizophrenia.Thus this study, as well as the Danish one, suggest that schizophrenia and autism spectrum disorders appear to share certain genes. Other scientists have reported that some rare variations in gene copy number—notably in genes on chromosomes 15, 16, and 22—are strong risk factors for developing schizophrenia and autism spectrum disorders.And given the increasing evidence for a genetic overlap between schizophrenia and bipolar disorder, Sullivan and his colleagues also looked to see in their study populations whether having a parent with bipolar disorder was linked with a child’s heightened risk of having an autism spectrum disorder.And they did find such a link. But the link was weaker than that for schizophrenia and autism. That is, an individual having a parent with bipolar disorder was twice as likely to have an autism spectrum disorder as was an individual having a parent without bipolar disorder, in contrast to findings for schizophrenia, where the odds ratio was 3 to 1.A possible implication of these findings, the researchers indicated, is that schizophrenia and autism spectrum disorders—and perhaps bipolar disorder and autism spectrum disorders—may share certain clinical characteristics that have previously eluded scientists. For instance, some individuals with an autism spectrum disorder might experience psychotic symptoms.The challenge now, the researchers said, is to identify genetic variants common to schizophrenia, bipolar disorder, and autism spectrum disorders. Scientists participating in the Psychiatric Genomics Consortium (PGC) will be attempting to do so, they said.The PGC is an international project to identify genetic variants that underlie schizophrenia, bipolar disorder, autism spectrum disorders, major depressive disorder, and attention-deficit/hyperactivity disorder. It was founded in 2007 and is headed by Sullivan. PGC scientists are from more than 60 institutions in 19 countries. “Family History of Schizophrenia and Bipolar Disorder as Risk Factors for Autism” is posted at http://archpsyc.jamanetwork.com/article.aspx?articleid=1206780. ISSUES NewArchived

Delayed White Matter Growth Trajectory in Young Nonpsychotic Siblings of Patients With Childhood-Onset Schizophrenia

CONTEXT Nonpsychotic siblings of patients with childhood-onset schizophrenia (COS) share cortical gray matter abnormalities with their probands at an early age; these normalize by the time the siblings are aged 18 years, suggesting that the gray matter abnormalities in schizophrenia could be an age-specific endophenotype. Patients with COS also show significant white matter (WM) growth deficits, which have not yet been explored in nonpsychotic siblings. OBJECTIVE To study WM growth differences in nonpsychotic siblings of patients with COS. DESIGN Longitudinal (5-year) anatomic magnetic resonance imaging study mapping WM growth using a novel tensor-based morphometry analysis. SETTING National Institutes of Health Clinical Center, Bethesda, Maryland. PARTICIPANTS Forty-nine healthy siblings of patients with COS (mean [SD] age, 16.1 [5.3] years; 19 male, 30 female) and 57 healthy persons serving as controls (age, 16.9 [5.3] years; 29 male, 28 female). INTERVENTION Magnetic resonance imaging. MAIN OUTCOME MEASURE White matter growth rates. RESULTS We compared the WM growth rates in 3 age ranges. In the youngest age group (7 to <14 years), we found a significant difference in growth rates, with siblings of patients with COS showing slower WM growth rates in the parietal lobes of the brain than age-matched healthy controls (false discovery rate, q = 0.05; critical P = .001 in the bilateral parietal WM; a post hoc analysis identified growth rate differences only on the left side, critical P = .004). A growth rate difference was not detectable at older ages. In 3-dimensional maps, growth rates in the siblings even appeared to surpass those of healthy individuals at later ages, at least locally in the brain, but this effect did not survive a multiple comparisons correction. CONCLUSIONS In this first longitudinal study of nonpsychotic siblings of patients with COS, the siblings showed early WM growth deficits, which normalized with age. As reported before for gray matter, WM growth may also be an age-specific endophenotype that shows compensatory normalization with age.

Autisme, une brève histoire de la nosographie avec une archive de E. Seguin

Kanner (1943) and Asperger (1944) have given the name of autism to the mental disorder formerly called idiotism and later psychoses or sometimes childhood schizophrenia. These authors bring to the disorder a better definition and establish its very early beginning during infancy. Kanner considers it belongs to the field of the psychoses and discusses its relation to schizophrenia. His report introduces two strong and controversal subjects: firstly about the intelligence of autistic people and secondly the typology of their families. Asperger gives more importance to the mental development and does not mention pejorative familial caracteristics. He also noticed the good or exceptional capacities of some cases by citing the observations of four of them. This is the reason his name is associated today with the less severe forms of the syndrome. During the 19th century, psychiatrists had begun to develop an interest in the classification of infantile psychoses and Seguin — formerly a teacher of children with special needs — gave an illustration of it with his study of the Idiots (annex). But, few authors described the mental diseases of the child as distinct from those of the adult. For example, Kraepelin and Bleuler who mention some cases beginning during childhood, do not treat infantile mental troubles as such and it will be a long time before early psychoses become the subjects of specific research. During the years between 1940 and 1960, there was a revival of interest in autism due to the commonality of symptoms linking it to the most severe cases of affective deprivation in studies of the mother-child relationship. A comparison which leads some influential authors to confuse autism with the effects of this severe deficiency, going as far as to attribute it to disturbed mothering, at a subconcious level, as there is no clear maternal inadequacy. The medical approach is completely different. Developmental disorders cannot be explained as the consequence of unfavourable life experiences and more and more facts support a neurobiological etiology. Autism is considered as a group of various disorders having a common phenotype of Pervasive Developmental Desorder (PDD). DSM and more recently CIM are in phase with this new approach. They enlarge the field of the PDD, as the result of which there is a change in the reported prevalence. These approaches are not very welcome in France as our country has developed a “Classification française” for child and adolescent mental disorders where the concept of psychosis is kept including bordeline states. Its purpose is to support different ways of psychopathological organisation and many French psychiatrists reserve the diagnostic of autism to a limited number of clinical cases. New versions in 2002 and 2010 tend to be better aligned with the international classifications but do not resolve the lack of agreeement according to the understanding of the etiologies and disorders due to a position where the nosographic debate is subordinated to more confusing psychopathologic considerations. For the future, a “double-diagnostic” for each case may be used (its etiology, its phenotype PDD) together with an increased attention to the dimensional approach of each individual profile, which has become possible as a result of advances in clinical methods.

Microduplications disrupting the MYT1L gene (2p25.3) are associated with schizophrenia

Childhood-onset schizophrenia (COS) is a rare severe form of schizophrenia that may have greater salient genetic risk. Despite evidence for high heritability, conclusive genetic causes of schizophrenia remain elusive. Recent genomic technologies in concert with large case-control cohorts have led to several associations of highly penetrant rare copy number variants (CNVs) and schizophrenia. We previously reported two patients with COS who carried a microduplication disrupting the PXDN and MYT1L genes at 2p25.3. This rate of duplications within our COS population (N=92) is significantly higher than that in 2026 healthy controls (P=0.002). As a replication, we report a meta-analysis of four recently published studies that together provide strong evidence for an association between variably sized microduplications involving the MYT1L gene and schizophrenia. None have reported this separately. Altogether, among 5325 patients and 9279 controls, 10 microduplications were observed: nine in patients and one in a control (odds ratio=15.7, P=0.001). Further, the 2% rate observed in our COS patients is also significantly higher than the rate in adult-onset cases (0.14%, odds ratio=16.6, P=0.01). This report adds to the growing body of literature implicating rare CNVs as risk factors for schizophrenia and shows that some risk CNVs are more common among extreme early-onset cases.

Prevalence of psychiatric illness in primary caretakers of childhood-onset schizophrenia subjects.

Childhood-onset schizophrenia (COS) refers to schizophrenia with onset of psychotic symptoms prior to a child's 13th birthday. Optimal treatment likely includes family-based services supplementing antipsychotic pharmacotherapy. However, family-based services can require adjustment based on parental psychopathology; there has been little literature exploring the frequency or type of psychopathology seen in parents of COS cases. This report includes the results of a structured psychiatric evaluation on 80 parents of a COS case with comparison to a sample of 304 parents. Having a child with psychosis and being of minority racial/ethnicity status increased risk for psychiatric illness. Psychotic disorders (15% vs. 5%), mood disorders (54% vs. 27%), anxiety disorders (30% vs. 18%), and substance use disorders (49% vs. 31%) were all increased in the parents with a psychotic child. Psychiatric illness is common in parents of a child with COS and will need to be considered as family-based services for COS are developed.