[Neurodevelopmental Disorders, Psychiatric Comorbidities and Associated Pathologies in Patients with Childhood-Onset Schizophrenia and Premorbid Autistic Symptoms.] / Atteintes Neurodéveloppementales, Comorbidités Psychiatriques Et Pathologies Associées Chez Des Patients Atteints de Schizophrénie Très Précoce Avec Symptômes Autistiques Prémorbides.

INTRODUCTION: Childhood-Onset Schizophrenia (COS) is a rare (1/40000), severe and neurodevelopmental form of schizophrenia beginning before 13 years of age. Little is known about comorbidities and specific COS-related disorders. Thus, the objective of our study was to evaluate them from a psychiatric, neurodevelopmental and somatic perspective. METHOD: This is an ancillary study of the GenAuDiss protocol. A standardized psychiatric interview (K-SADS-PL DSM5) and a neuropsychological assessment (WISC-V/WAIS-IV) were carried out in outpatients with COS as well as a medical history collection concerning pregnancy, perinatal period, development, biography and medical and psychiatric, personal, and family history. RESULTS: 20 outpatients were included. The mean age of onset of COS was 8.90 years (+/- 2.30). Psychiatric comorbidities (DSM5) were Attention Deficit Hyperactivity Disorder (15/20 patients), Anxiety Disorders (14/20) and Autism Spectrum Disorder (13/20). The average IQ was 70.26 (+/- 18.09). A language delay and a break in school career were noted in 18/20 patients. Finally, the main associated somatic disorder was asthma (15/20 patients). DISCUSSION: We highlighted in our patients with COS a high frequency of comorbidities including at least one systematic psychiatric disorder. However, although COS is a severe condition impacting the patient, his family and society, its management remains essentially symptomatic. In clinical practice, it is necessary to look for all these comorbidities and to manage them in order to improve the overall quality of care.

INTRODUCTION: La schizophrénie très précoce (STP) est une forme rare (1/40000), grave et neurodéveloppementale de schizophrénie débutant avant 13 ans. Les comorbidités et atteintes associées spécifiques des STP étant peu étudiées, l'objectif de notre étude a été de les évaluer sur le plan psychiatrique, neurodéveloppemental et somatique. MÉTHODE: Il s'agit d'une étude ancillaire du protocole GenAuDiss. Un entretien psychiatrique standardisé (K-SADS-PL DSM5) et un bilan neuropsychologique (WISC-V/WAIS-IV) ont été effectués chez les patients atteints de STP ainsi qu'une anamnèse concernant la grossesse, la périnatalité, le développement, la biographie et les antécédents médicaux et psychiatriques, personnels et familiaux. RÉSULTATS: 20 sujets ont été inclus. L'âge moyen de début du trouble était de 8,90 ans (+/−2,30). Les comorbidités psychiatriques (DSM5) étaient le Trouble Déficitaire de l'Attention avec Hyperactivité (15/20 patients), les troubles anxieux (14/20) et le Trouble du Spectre de l'Autisme (13/20). Le QI moyen était de 70,26 (+/−18,09). Un retard de langage et une rupture de parcours scolaire étaient notés chez 18/20 patients. Enfin, l'affection somatique principale associée était l'asthme (15/20 patients). DISCUSSION: Nous avons mis en évidence chez nos patients atteints de STP une fréquence élevée de comorbidités dont au moins un trouble psychiatrique systématique. Or, bien que la schizophrénie infantile soit une pathologie de pronostic sévère impactant le patient, sa famille et la société, sa prise en charge demeure essentiellement symptomatique. En pratique clinique, il apparaît nécessaire de rechercher systématiquement ces comorbidités et de les prendre en charge pour améliorer la qualité globale des soins.

Comparison of clinical characteristics and treatment efficacy in childhood-onset schizophrenia and adolescent-onset schizophrenia in mainland China: A retrospective study.

AIM: The comparative study of childhood-onset schizophrenia (COS) and adolescent-onset schizophrenia (AOS) is scarce. This study aimed to examine the differences in clinical presentations and treatment efficacy between COS and AOS and further analyse the factors affecting the efficacy of early-onset schizophrenia (EOS). METHODS: A total of 582 electronic medical records of inpatients with EOS (216 COS and 366 AOS inpatients) between 2012 and 2019 were retrospectively analysed. The positive and negative syndrome scale (PANSS) was used to assess psychotic symptoms. Logistic regression analysis was performed to analyse the predictors of efficacy. RESULTS: The mean age of onset of EOS was 12.87 ± 2.19 years. The importance of better diagnosing COS appeared in a longer illness course, more frequently insidious onset, less frequent delusions, more severe negative symptoms and bizarre behaviours than AOS. Besides, COS had more frequent visual hallucinations and impulsive behaviours than AOS. After hospitalization, the improvement rate of psychotic symptoms in COS and AOS were 38.3% and 47.8%, respectively. The difference of efficacy between the two groups was statistically significant. Days of hospitalization, age of onset, presence of flat affect, PANSS total and negative score at admission were predictors of treatment efficacy in EOS individuals. CONCLUSIONS: COS inpatients suffer more obvious negative symptoms, bizarre behaviours, visual hallucinations and impulsive behaviours and worse efficacy than AOS inpatients. The severity of negative symptoms and age of onset seem the most noteworthy predictors of efficacy. These findings highlight the importance of early detection and early intervention.

Association of family history of schizophrenia and history of obstetric complications at birth: relationship with age at onset and psychopathology dimensions in a Nigerian cohort.

BACKGROUND: The nature of the association between obstetric complications (OCs) at birth and the genetic aetiology of schizophrenia remains unclear, as some authors suggest that it is an independent risk factor while others support either interactionism or an epiphenomenon perspective. OBJECTIVE: To examine the association of family history of schizophrenia (FHS) with history of OCs, with a view to assessing whether this relationship moderates clinical phenotypes such as symptom dimensions and age at onset of illness. METHODS: This study examined OCs among schizophrenia probands using the Obstetric Complications Scale. An inquiry into family history was performed using the Family history method. Psychopathological symptom dimensions were assessed using standard scales. Data were analyzed to examine the interaction of FHS and history of OCs with age at onset and symptom dimensions, using ANCOVA. RESULTS: FHS was significantly associated with the disorganized symptoms dimension (p=0.03). History of OCs was significantly associated with earlier age at onset (p=0.007). However, in ANCOVA, the effect of the interaction between FHS and history of OCs was not significant for age at onset and symptom dimensions (P = 0.059). CONCLUSION: FHS was significantly associated with disorganization syndrome, and OCs was significantly associated with age at onset.

Psychotic symptoms and gray matter deficits in clinical pediatric populations.

BACKGROUND: Neuroanatomic studies have not yet addressed how subtle phenotypic distinctions in psychosis alter the underlying brain changes, and whether there is evidence for psychosis as a dimensional construct. We explored the relationship of cortical GM thickness to psychotic phenotypes in children. METHODS: Cross-sectional comparison of anatomic brain imaging between patients referred as childhood-onset schizophrenia (COS) but ruled out after a drug free inpatient observation. Groups included: patients with no evidence of psychosis (n=22) after drug free observation, patients with psychosis not otherwise specified (PNOS; total n=29) further divided into those without other axis I diagnoses (n=13) and those with other axis I comorbidities (n=16), age/sex matched COS patients (n=48), and 51 matched healthy controls. GM cortical thickness was compared between the groups, and regressed on patients' SAPS, SANS and GAS scores. RESULTS: Patients with no evidence of psychosis showed no cortical GM deficits. Presence of psychosis (PNOS with or without co-morbidities) showed some areas of temporal and prefrontal deficits, more subtle compared to the extensive bilateral cortical deficits seen for COS. GAS SAPS and SANS scores showed a relationship with cortical GM thickness although it did not survive adjustment for multiple comparisons. CONCLUSIONS: These results highlight the need for careful phenotypic characterization, as subtle diagnostic distinctions appear to reflect distinct underlying patterns of brain deficits. The incremental nature of cortical deficits from no psychosis to PNOS to COS may further support dimensional model for psychosis.

Childhood onset schizophrenia: high rate of visual hallucinations.

OBJECTIVE: To document high rates and clinical correlates of nonauditory hallucinations in childhood onset schizophrenia (COS). METHOD: Within a sample of 117 pediatric patients (mean age 13.6 years), diagnosed with COS, the presence of auditory, visual, somatic/tactile, and olfactory hallucinations was examined using the Scale for the Assessment of Positive Symptoms (SAPS). We also compared hallucination modality membership (presence/absence) groups on gender, socioeconomic status, ethnicity, age of onset (of psychosis), Full Scale IQ, Verbal IQ, and clinical severity (Children's Global Assessment Scale [CGAS) and Scale for the Assessment of Negative Symptoms [SANS]). RESULTS: A total of 111 COS patients (94.9%) had auditory and 94 patients (80.3%) had visual hallucinations. Somatic/tactile (60.7%) and olfactory (29.9%) hallucinations occurred almost exclusively in patients who also had visual hallucinations. Children who had visual hallucinations had lower IQ, earlier age of onset, and more severe illness relative to children who did not have visual hallucinations. CONCLUSIONS: In this study, we observed that patients with COS have high rates of hallucinations across all modalities. An increased rate of visual hallucinations is associated with greater clinical impairment and greater compromise in overall brain functioning. Somatic and olfactory hallucinations reflect an additive rather than alternative symptom pattern.

Normalization of cortical gray matter deficits in nonpsychotic siblings of patients with childhood-onset schizophrenia.

OBJECTIVE: Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to "normalize" by age 17 years. Here we present a replication with nonoverlapping groups of healthy full siblings and healthy controls. METHOD: Using an automated measure and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in nonpsychotic full siblings (n = 43, 68 scans; ages 5 through 26 years) of patients with COS, contrasting them with age-, gender-, and scan interval-matched healthy controls (n = 86, 136 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons. RESULTS: As in our previous study, young nonpsychotic siblings (<17 years) showed significant GM deficits in bilateral prefrontal and left temporal cortices and, in addition, smaller deficits in the parietal and right inferior temporal cortices. These deficits in nonpsychotic siblings normalized with age with minimal abnormalities remaining by age 17. CONCLUSIONS: Our results support previous findings showing nonpsychotic siblings of COS probands to have early GM deficits that ameliorate with time. At early ages, prefrontal and/or temporal loss may serve as a familial/trait marker for COS. Late adolescence appears to be a critical period for greatest localization of deficits in probands or normalization in nonpsychotic siblings.

Tourette syndrome and comorbid early-onset schizophrenia.

OBJECTIVE: A study of the shared phenomenology between Tourette syndrome (TS) and schizophrenia. METHOD: An illustrative case report is presented. We used a chart review of 399 clinically ascertained patients with TS to identify 10 cases meeting criteria for schizophrenia. From our 10 patients, salient clinical characteristics were then tabulated. We then extracted similar clinical characteristics from a previously published series of patients with comorbid TS and schizophrenia in order to combine cases and allow for a comparison between childhood-onset schizophrenia (COS), adolescent-onset schizophrenia (AdolOS), and adult-onset schizophrenia (AduOS) cases in these groups. RESULTS: We found 10 cases of schizophrenia (all were males) in the 399 TS patients for a prevalence rate of 2.5% (95% CI 0.96-4.04). Mean age of tic onset for TS diagnostic criteria ranged from 2-14 years with a mean of 8.2 years. The mean age of diagnosis for schizophrenia was 14.2 (range 9-23 years). We found six cases of schizophrenia with onset of positive psychotic symptoms by 13 years of age, two cases with onset after 13 years of age and before 18 years of age, and two cases with onset after 18 years of age. Attention deficit hyperactivity disorder was present at a higher rate (70%) than one would expect in a clinically ascertained group of patients with TS. Comparison between COS, AdolOS and AduOS in our pooled cases noted a sex bias skewed toward males. Catatonic symptoms may be more likely in child or adolescent onset cases and negative symptoms more likely in AduOS cases. CONCLUSIONS: The 2.5% prevalence of schizophrenia in our TS sample exceeds the 1% expected rate of schizophrenia in the general population (chi-square=9.14; P=.0025). The six cases of COS (before 13 years of age) exceeds the expected rate of 1-2 per 100,000 (chi-square=4499; P=.0001). The 752-fold increase in observed rates of comorbid TS and COS over expected rates suggests a role for unknown common underlying etiologic factors. Based on clinical features, patients with TS and comorbid COS, AdolOS, or AduOS do not have different conditions. We conclude with suggestions for further research.

[Early development of childhood-onset schizophrenia]. / Frühentwicklung kindlicher Schizophrenien.

Childhood-onset schizophrenia (COS, age of onset between 7 and 14 years) is a rare and severe form of the disorder. The prevalence is about 1 / 50 of the rate of adult-onset schizophrenia. In COS-children emotional, cognitive and behavioural abnormalities are often seen years before illness onset. Premorbid symptoms including social withdrawal, isolation, introversion, peculiar behaviour, unmotivated temper tantrums, auto- and heteroaggressive acts, suicidal thoughts, anxiousness, paranoid ideas, represent early warning symptoms and are associated with an unfavourable outcome. About 60 % of 67 patients with COS examined by us (44 long-term-, 23 short-term-follow-up examinations) demonstrated premorbid abnormalities prior to the onset of their psychosis. We found a significant correlation between high M-PAS-scores, insidious onset, negative PANSS-Items, and early onset of age (< 12 years). High M-PAS-Scores were positively related to long duration of psychotic and residual states, and vice versa there was a negative correlation between M-PAS and a favourable outcome (long duration of recovery states). It is necessary to identify clinical states of elevated risk for psychosis as early as possible. This is difficult especially in young patients, in whom psychical peculiarities are ambiguous, and they may develop in different directions, most of them into normalization. Nevertheless, it is important to recognize risk-groups by time and to study their development carefully. Thus they could benefit from multiprofessional family-oriented early interventions.

Autism spectrum disorders and childhood-onset schizophrenia: clinical and biological contributions to a relation revisited.

OBJECTIVE: To highlight emerging evidence for clinical and biological links between autism/pervasive developmental disorder (PDD) and schizophrenia, with particular attention to childhood-onset schizophrenia (COS). METHOD: Clinical, demographic, and brain developmental data from the National Institute of Mental Health (and other) COS studies and selected family, imaging, and genetic data from studies of autism, PDD, and schizophrenia were reviewed. RESULTS: In the two large studies that have examined this systematically, COS is preceded by and comorbid with PDD in 30% to 50% of cases. Epidemiological and family studies find association between the disorders. Both disorders have evidence of accelerated trajectories of anatomic brain development at ages near disorder onset. A growing number of risk genes and/or rare small chromosomal variants (microdeletions or duplications) are shared by schizophrenia and autism. CONCLUSIONS: Biological risk does not closely follow DSM phenotypes, and core neurobiological processes are likely common for subsets of these two heterogeneous clinical groups. Long-term prospective follow-up of autistic populations and greater diagnostic distinction between schizophrenia spectrum and autism spectrum disorders in adult relatives are needed.

Longitudinal brain changes in early-onset psychosis.

Progressive losses of cortical gray matter volumes and increases in ventricular volumes have been reported in patients with childhood-onset schizophrenia (COS) during adolescence. Longitudinal studies suggest that the rate of cortical loss seen in COS during adolescence plateaus during early adulthood. Patients with first-episode adolescent-onset schizophrenia show less marked progressive changes, although the number of studies in this population is small. Some studies show that, although less exaggerated, progressive changes are also present in nonschizophrenia early-onset psychosis. The greater loss of brain tissue seen in COS, even some years after the first episode, as compared to adolescent- or adult-onset schizophrenia may be due to variables such as sample bias (more severe, treatment refractory sample of childhood-onset patients studied), a process uniquely related to adolescent development in COS, differential brain effects of drug treatment in this population, clinical outcome, or interactions among these variables. Findings from both cross-sectional studies of first-episode patients and longitudinal studies in COS and adolescent onset support the concept of early-onset schizophrenia as a progressive neurodevelopmental disorder with both early and late developmental abnormalities. Future studies should look for correlates at a cellular level and for pathophysiological explanations of volume changes in these populations. The association of risk genes involved in circuitries associated with schizophrenia and their relationship to developmental trajectories is another promising area of future research.

The stability of inhibitory and working memory deficits in children and adolescents who are children of parents with schizophrenia.

Cognitive deficits are a central feature of schizophrenia and occur in first-degree relatives of schizophrenic probands, even in the absence of psychotic symptoms. A number of cognitive domains have been implicated including measures of response inhibition and working memory. While the stability of cognitive deficits has been demonstrated in individuals with schizophrenia, stability of deficits has not been explored in first-degree relatives. This report focuses on 25 children (ages 6-15 years), all with at least one schizophrenic parent. The children were assessed twice, utilizing inhibitory and working memory tasks, with a mean 2.6 years between visits. Stop reaction time (a measure of motor inhibition) and performance on a counting span task (a measure of verbal working memory) were borderline to mildly impaired (compared with a typically developing comparison group) at both visits with similar effect sizes (stopping task time 1, effect size = 0.46, time 2 effect size = 0.50; counting span time 1 effect size = 0.53, time 2 effect size = 0.42). For these 2 tasks, individual age-adjusted scores also correlated across both time points (r = 0.41-0.76) suggesting that individual children maintained deficits across time. As etiologically driven strategies are developed for the cognitive deficits of schizophrenia, expansion of these treatments to relatives who share the cognitive but not the psychotic symptoms may be worth exploring.

Sequencing and analyzing the t(1;7) reciprocal translocation breakpoints associated with a case of childhood-onset schizophrenia/autistic disorder.

We characterized a t(1;7)(p22;q21) reciprocal translocation in a patient with childhood-onset schizophrenia (COS) and autism using genome mapping and sequencing methods. Based on genomic maps of human chromosome 7 and fluorescence in situ hybridization (FISH) studies, we delimited the region of 7q21 harboring the translocation breakpoint to a approximately 16-kb interval. A cosmid containing the translocation-associated 1:7 junction on der(1) was isolated and sequenced, revealing the positions on chromosomes 1 and 7, respectively, where the translocation occurred. PCR-based studies enabled the isolation and sequencing of the reciprocal 7:1 junction on der(7). No currently recognized gene on either chromosome appears to be disrupted by the translocation. We further found no evidence for copy-number differences in the genomic regions flanking the translocation junctions in the patient. Our efforts provide sequence-based information about a schizophrenia/autism-associated translocation, and may facilitate future studies investigating the genetic bases of these disorders.

Diagnostic and sex effects on limbic volumes in early-onset bipolar disorder and schizophrenia.

OBJECTIVE: The limbic structures in early-onset schizophrenia-spectrum illness (SZ) and bipolar disorder (BPD) were studied to discern patterns associated with diagnosis and sex. METHODS: Thirty-five youths with DSM-IV BPD without psychosis, 19 with BPD with psychosis, 20 with SZ, and 29 healthy controls (HC), similar in age (6-17 years) and sex, underwent structured and clinical interviews, neurological examination, and cognitive testing. Structural magnetic resonance images (MRIs) were acquired on a 1.5 Tesla, General Electric Signa Scanner. Differences in subcortical brain volumes, including the amygdala and hippocampus, were evaluated using two-way (diagnosis, sex) univariate analyses covarying for total cerebral volume and age. RESULTS: Youth with SZ and BPD showed no differences in amygdala and hippocampal volumes. However, boys with SZ had smallest left amygdala and girls with BPD had the smallest left hippocampal volumes. In exploratory analyses, SZ showed reduced thalamic volumes bilaterally and both BPD groups had larger right nucleus accumbens (NA) volumes relative to HC. CONCLUSION: There were no limbic volumetric differences between BPD and SZ. However, there were diagnosis-by-sex interactions in the amygdala and hippocampus, structures that are rich in sex hormone receptors. In addition, smaller thalamus was associated with SZ while larger right NA volumes were most related to BPD. This study underscores the importance of assessing diagnostic effects and sex effects on the brain in future studies and provides evidence that boys and girls with SZ and BPD may have differential patterns of neuropathology associated with disease expression.

Clozapine treatment of childhood-onset schizophrenia: evaluation of effectiveness, adverse effects, and long-term outcome.

OBJECTIVE: Clozapine is a unique atypical antipsychotic with superior efficacy in treatment-resistant schizophrenia. Plasma concentration of clozapine and its major metabolite N-desmethylclozapine (NDMC) as well as the ratio of NDMC to clozapine have been reported to be predictors of clozapine response. Here we evaluate these as well as other measures in an effort to find predictors of response to clozapine in our early-onset treatment-refractory population. METHOD: Fifty-four children and adolescents participated in double-blind (n = 22) or open-label (n = 32) clozapine trials. Clinical evaluations took place at baseline, week 6 on clozapine, and at 2- to 6-year follow-up. The data were analyzed in relation to demographics, age at onset, IQ, clozapine dose, and plasma concentrations of prolactin, clozapine, NDMC, and NDMC/clozapine ratio. Stepwise regression and correlation analyses were performed to find predictors of treatment response. RESULTS: Clinical improvement after 6 weeks of clozapine treatment, as measured by the percentage of improvement on the Brief Psychiatric Rating Scale and the Scale for the Assessment of Positive Symptoms, was strongly associated with the NDMC/clozapine ratio at the 6-week time point (Pearson correlation coefficient: r = 0.41; p < .01 for Brief Psychiatric Rating Scale and r = 0.43; p < .01 for Scale for the Assessment of Positive Symptoms). Although the rate of side effects was higher than that typically found in the adult population, it did not appear to be related to clozapine dose, clozapine or NDMC plasma concentrations, or NDMC/clozapine ratio. Outcome at long-term follow-up, as measured by Children's Global Assessment Scale, was associated with lesser illness severity at baseline and with greater improvement during the initial 6 weeks of clozapine treatment. CONCLUSIONS: The NDMC/clozapine ratio may be a valuable predictor of response to clozapine and may suggest new approaches to clozapine treatment.

Childhood onset schizophrenia: cortical brain abnormalities as young adults.

BACKGROUND: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset illness. METHODS: Neuro-anatomic magnetic resonance scans were obtained prospectively from ages 7 through 26 in 70 children diagnosed with COS and age and sex matched healthy controls. Cortical thickness was measured at 40,962 points across the cerebral hemispheres using a novel, fully automated, validated method. Patterns of patient-control differences in cortical development were compared over a 19-year period. RESULTS: Throughout the age range, the COS group had significantly smaller mean cortical thickness compared to controls. However, the COS brain developmental trajectory appeared to normalize in posterior (parietal) regions, and remained divergent in the anterior regions (frontal and temporal) regions, and the pattern of loss became more like that seen in adults. CONCLUSIONS: Cortical thickness loss in COS appears to localize with age to prefrontal and temporal regions that are seen for both medication naïve and medicated adult onset patients.

High rates of comorbidity are found in childhood-onset schizophrenia.

BACKGROUND: For adults with schizophrenia, comorbidity is common and contributes to impairment. Thus, there has been an increasing effort to identify and treat comorbid symptoms. This report extends that work by examining comorbidity in children and young adolescents with childhood-onset schizophrenia. METHODS: Eighty-two children, ages 4-15 years, with schizophrenia or schizoaffective disorder received structured diagnostic instruments for symptoms and pharmacological treatment history. DSM-IV diagnoses were identified using a non-hierarchical approach. RESULTS: Eighty-one (99%) of the children with schizophrenia or schizoaffective disorder had at least one comorbid psychiatric illness: attention deficit hyperactivity disorder (84%), oppositional defiant disorder (43%), depression (30%), and separation anxiety disorder (25%) were the most common comorbid conditions identified. Pharmacological treatment of the comorbid conditions was uncommon. DISCUSSION: Comorbid syndromes are common in children and young adolescents with schizophrenia or schizoaffective disorder. Pharmacological treatment of the comorbid conditions is rare; however it is unclear if this is due to DSM-IVs hierarchical diagnostic system or to a lack of empirically driven guidelines for appropriate treatment. Additional efforts focused on comorbidity in very-early-onset schizophrenia are warranted.

Sleep disturbances in childhood-onset schizophrenia.

Sleep disturbances in psychiatric disease have long been reported. However, research on sleep disturbances in child and adolescent psychiatric disorders is limited. We examined the relationship of sleep disturbance to clinical severity and co-morbid diagnoses (e.g. anxiety), for a population with childhood-onset schizophrenia (COS). Sixty-one COS patients underwent a medication-free inpatient observation period as part of an NIMH study of COS. Sleep quantity during the last 5-7 days of a patient's medication-free period was measured using safety records and daily nursing notes. Subjects were divided into two groups: "good sleepers" (>6 h) and "poor sleepers" (<6 h) based on the average of total hours slept per night. Comparisons between groups were made with respect to clinical ratings at both admission and during washout period, co-morbid diagnosis of generalized anxiety disorder (GAD) and a susceptibility gene (G72) for COS. The median average sleep score for the entire group was 6.1 (S.D.=2.01) h. The good and poor sleep groups differed significantly in terms of severity of positive symptoms (SAPS) and negative symptoms at admission (SANS) both on admission and during the medication-free period. There was no significant relationship between G72 genotypes and a past and/or present diagnosis of GAD. COS patients suffer from significant sleep disturbances and the sleep disturbance is highly related to the symptom severity. As there are numerous health implications of poor sleep, clinicians should have a low threshold for treating sleep disturbances in this population.

Schizophrenia and related disorders in children and adolescents.

This paper reviews the concept and recent studies on childhood and adolescent psychoses with special reference to schizophrenia. After a short historical introduction, the definition, classification, and epidemiology of child- and adolescent-onset psychoses are described, pointing out that some early-onset psychotic states seem to be related to schizophrenia (such as infantile catatonia) and others not (such as desintegrative disorder). The frequency of childhood schizophrenia is less than 1 in 10,000 children, but there is a remarkable increase in frequency between 13 and 18 years of age. Currently, schizophrenia is diagnosed according to ICD-10 and DSM-IV criteria. The differential diagnosis includes autism, desintegrative disorder, multiplex complex developmental disorder (MCDD) respectively multiple developmental impairment (MDI), affective psychoses, Asperger syndrome, drug-induced psychosis and psychotic states caused by organic disorders. With regard to etiology, there is strong evidence for the importance of genetic factors and for neurointegrative deficits preceding the onset of the disorder. Treatment is based upon a multimodal approach including antipsychotic medication (mainly by atypical neuroleptics), psychotherapeutic measures, family-oriented measures, and specific measures of rehabilitation applied in about 30% of the patients after completion of inpatient treatment. The long-term course of childhood- and adolescent-onset schizophrenia is worse than in adulthood schizophrenia, and the patients with manifestation of the disorder below the age of 14 have a very poor prognosis.