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Aim: The aim of this study was to compare the clinical characteristics of childhood-onset schizophrenia (COS) and early-onset schizophrenia (EOS) during the first- episode psychosis and the stable period, to examine psychopharmacological treatment approaches, and to investigate potential predictive factors for prognosis., Methods: Demographic, clinical, and psychopharmacological therapy data for 31 patients diagnosed with COS and 66 with EOS were retrieved from the file records in this multicenter study. Symptom distribution and disease severity and course were evaluated twice, in the acute psychotic stage and in the latest stable phase, during follow-up using the positive and negative syndrome scale (PANSS) and clinical global impression (CGI) scales., Results: A statistically significant difference was observed between the groups' CGI improvement rates and median last stable stage PANSS positive, negative, and general psychopathology symptom scores (p = .005, p = .031, p = .005, and p = .012, respectively). Premorbid neurodevelopmental disorder and obsessive-compulsive disorder and comorbidities were more common in the COS group (p = .025 and p = .030, respectively), and treatment required greater multiple antipsychotic use in that group (p = .013). When the independent variables affecting the difference between pre- and post-treatment PANSS scores were examined using linear regression analysis, the model established was found to be statistically significant (F = 5.393; p = .001), and the group variable (p = .024), initial disease severity (p = .001), and socioeconomic level (p = .022; p = .007) emerged as predictive factors for the disease course., Conclusion: Although early diagnosis and treatment is an important factor in improving prognosis in schizophrenia, more specific predictors for schizophrenia need to be identified. Additionally, preventive programs and pharmacological methods need to be developed in children with neurodevelopmental problems, particularly those from low socioeconomic status families., (© 2024 John Wiley & Sons Australia, Ltd.)

Approximately 8 % of patients with schizophrenia are diagnosed before age 18, and 18 % experience their first symptoms before age 18. This narrative review explores the management of patients with early-onset schizophrenia (EOS) and childhood-onset schizophrenia (COS) from diagnosis to their transition to adult care settings. Early diagnosis of schizophrenia in children and adolescents is essential for improving outcomes, but delays are common due to overlapping of symptoms with developmental phenomena and other psychiatric conditions, including substance use, and lack of clinicians' awareness. Once diagnosed, antipsychotic treatment is key, with specific second-generation agents generally being preferred due to better tolerability and their broader efficacy evidence-base in youth. Dosing should be carefully individualized, considering age-related differences in drug metabolism and side effect liability. Clinicians must be vigilant in detecting early non-response and consider switching or dose escalation when appropriate. Since early age of illness onset is a consistent risk factor for treatment-resistant schizophrenia (TRS), clinicians need to be competent in diagnosing TRS and using clozapine. Since COS and EOS are associated with cognitive deficits and impaired functioning, psychosocial interventions should be considered to improve overall functioning and quality of life. Good long-term outcomes depend on continuous treatment engagement, and successful transitioning from pediatric to adult care requires careful planning, early preparation, and collaboration between pediatric and adult clinicians. Targeting functional outcomes and quality of life in addition to symptom remission can improve overall patient well-being. Comprehensive evaluations, age-specific assessments, and targeted interventions are needed to address the unique challenges of EOS and COS., Competing Interests: Declaration of competing interest CU Correll has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Biogen, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Jamjoom Pharma, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Neurelis, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Sage, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, Tolmar, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Kuleon Biosciences, LB Pharma, Mindpax, and Quantic. C. Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. B Fagerlund declares travel expenses and writing assistance for the submitted work, funded by Angelini. S Galderisi has received personal fees from Angelini Pharma, Boehringer Ingelheim, Gedeon Richter-Recordati, Janssen, Lundbeck, Otsuka, Recordati Pharmaceuticals, Rovi Pharma, Sunovion Pharmaceuticals, outside the submitted work. MJ Kas has received (non-related) research funding from Novartis. In the last 3 years, he has received fees for lectures from Angelini and Boehringer Ingelheim. S Leucht has been an advisor and/or lecturer and/or has developed educational material for Alkermes, Angelini, Apsen, Eisai, Gedeon Richter, Janssen, Karuna, Kynexis, Lundbeck, Medichem, Medscape, Merck Sharpp and Dome, Mitshubishi, Neurotorium, NovoNordisk, Otsuka, Recordati, Roche, Rovi, Sanofi Aventis, TEVA., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The article presents modern approaches to classification, presents debatable diagnostic issues, including the differences between domestic approaches to the diagnosis of schizophrenia in childhood from foreign taxonomies. The modern hypothesis of the etiological continuum of schizophrenic and autistic spectrum disorders is discussed, as well as clinical models of manifest stages of schizophrenia in childhood, with an emphasis on the influence of the age factor on the clinic, dynamics and prognosis of diseases.

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., (© 2021 John Wiley & Sons Australia, Ltd.)

Altered sleep neurophysiology has consistently been reported in adult patients with schizophrenia. Converging evidence suggests that childhood onset schizophrenia (COS), a rare but severe form of schizophrenia, is continuous with adult onset schizophrenia. The aim of the current study was to characterize sleep neurophysiology in COS. An overnight sleep electroencephalogram (EEG) was recorded in 17 children and adolescents with COS (16 years ± 6.6) and 17 age and gender-matched controls. Non-rapid eye movement (NREM) and rapid eye movement (REM) sleep EEG power and coherence for the frequency bands delta (1.6-4.8 Hz), theta (5-8.4 Hz), alpha (8.6-11 Hz), beta 1 (16.4-20.2 Hz) and beta 2 (20.4-24.2 Hz) were compared between COS patients and controls. COS patients exhibited significant and widespread deficits in beta power during NREM and REM sleep. With regard to coherence, we found increases in COS patients across brain regions, frequency bands and sleep states. This study demonstrates the utility of the sleep EEG for studying vulnerable populations and its potential to aid diagnosis., (© 2020 European Sleep Research Society.)

Cases of very early-onset schizophrenia are poorly described in the modern literature due to the ambiguous attribution of these conditions to a number of schizophrenic disorders. The diagnosis is complicated by the atypical presentation of the disease in early childhood. This clinical case reflects the manifestation, dynamics and outcome of the disease, which is important for early diagnosis and initiation of adequate drug intervention and habilitation.

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., (© 2020 Onu JU et al.)

Objectives: To report the finding of psychosis in a patient with Davidoff-Dyke-Masson Syndrome., Method: Case report., Conclusions: Right-sided hemiatrophy may be an addition to the list of neuro-developmental and structural cerebral anomalies associated with psychotic disorders including schizophrenia.

Children's hallucinations pose the dual challenge of diagnosing a possible medical emergency and a possible psychiatric disorder., Purpose: The main objective was to analyze the causes of such hallucinations in children presenting to a pediatric emergency department., Material and Methods: We conducted a single-center, observational, retrospective study including all children aged less than 15 years experiencing hallucinations and admitted to our tertiary level pediatric emergency department between 1 January 2007 and 31 December 2015. The data collected were demographic; medical: previous medical or psychiatric history, current medications, associated clinical or psychiatric symptoms, type and character of hallucinations, length and recurrence of hallucinatory phenomena; and other biological, radiological and neurological explorations., Results: Sixty-eight patients were included (29 boys). The mean age was 9.1±3 years (range, 2-14 years and 10 months; median, 9.2 years). Admissions were seasonal with a bimodal distribution (a peak during springtime and another one during fall). Hallucinations were mainly visual (90%), acute (77%) and complex (63%). Visual hallucinations were associated with other types of hallucinations: auditory (n=17), somatosensory (n=7). Fifteen children had a psychiatric history and had already experienced hallucinatory phenomena (93%). Among 47 patients (69%), these hallucinations were associated with other symptoms: agitation (41%), headaches (28%), hyperthermia (21%) and negative symptoms of the schizophrenia spectrum (15%). On admission, 20 patients (29%) had one or more treatments under way (34 drugs, 41% known for hallucinogenic adverse effects). Neurological explorations were undertaken in half of the cases. Toxicological analysis prescribed in 19 children was positive in five cases (26%). Fifty-three percent of patients were hospitalized and 51 children received a specialized follow-up (by a neurologist and/or a psychiatrist). A nonpsychiatric origin of these hallucinations was diagnosed in 29 patients (43%): neurological causes (n=10), infectious diseases (n=10), intoxications (n=5) and a medication side effect (n=4)., Conclusion: Hallucinations with a suspected underlying psychiatric cause differed on several factors: chronic duration (p=0.02), an onset after 10 years of age (p=0.004), previous identical episodes (p=0.014) and a parental psychiatric history (p=0.036), auditory hallucinations (p=0.0009), absence of fever (p=0.005), headaches (p=0.036) and the presence of negative symptoms of the schizophrenic spectrum (p=0.02)., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: Treatment of early-onset schizophrenia spectrum psychosis (EOS) is hampered by limited data on clinical presentation and illness course. We aimed to systematically review the clinical characteristics, diagnostic trajectories, and predictors of illness severity and outcomes of EOS., Methods: We conducted a systematic PubMed, PsycINFO, and Embase literature review including studies published from January 1, 1990 to August 8, 2014 of EOS patients with 1) ≥50% nonaffective psychosis cases; 2) mean age of subjects <19 years; 3) clinical samples recruited through mental health services; 4) cross-sectional or prospective design; 5) ≥20 participants at baseline; 6) standardized/validated diagnostic instruments; and 7) quantitative psychotic symptom frequency or severity data. Exploratory analyses assessed associations among relevant clinical variables., Results: Across 35 studies covering 28 independent samples (n = 1506, age = 15.6 years, age at illness onset = 14.5 years, males = 62.3%, schizophrenia-spectrum disorders = 89.0%), the most frequent psychotic symptoms were auditory hallucinations (81.9%), delusions (77.5%; mainly persecutory [48.5%], referential [35.1%], and grandiose [25.5%]), thought disorder (65.5%), bizarre/disorganized behavior (52.8%), and flat or blunted affect/negative symptoms (52.3%/50.4%). Mean baseline Positive and Negative Syndrome Scale (PANSS)-total, positive, and negative symptom scores were 84.5 ± 10.9, 19.3 ± 4.4 and 20.8 ± 2.9. Mean baseline Clinical Global Impressions-Severity and Children's Global Assessment Scale/Global Assessment of Functioning (CGAS/GAF) scores were 5.0 ± 0.7 and 35.5 ± 9.1. Comorbidity was frequent, particularly posttraumatic stress disorder (34.3%), attention-deficit/hyperactivity and/or disruptive behavior disorders (33.5%), and substance abuse/dependence (32.0%). Longer duration of untreated psychosis (DUP) predicted less CGAS/GAF improvement (p < 0.0001), and poor premorbid adjustment and a diagnosis of schizophrenia predicted less PANSS negative symptom improvement (p = 0.0048) at follow-up. Five studies directly comparing early-onset with adult-onset psychosis found longer DUP in EOP samples (18.7 ± 6.2 vs. 5.4 ± 3.1 months, p = 0.0027)., Conclusions: EOS patients suffer substantial impairment from significant levels of positive and negative symptoms. Although symptoms and functioning improve significantly over time, pre-/and comorbid conditions are frequent, and longer DUP and poorer premorbid adjustment is associated with poorer illness outcome.

Objective: Childhood-onset schizophrenia (COS) is a rare but severe form of the disorder, which is often treatment refractory. Short-term studies have indicated a greater differential efficacy, evident through effect sizes, favoring clozapine over other agents in alleviating negative symptoms in COS patients compared with adult-onset patients (AOS). There have been no data for COS patients on long-term compliance with clozapine treatment. Therefore, we wanted to know, over a span of up to 24 years, how many of our COS cohort had remained on clozapine for at least 2 years. We review short-term treatment data and present updated long-term data on compliance and functioning for our patients., Methods: We present the results for long-term medication maintenance over a 24 year observation period for our cohort of 131 patients. Of this cohort, 91.6% (120) were available for follow-up information from either in-person or telephone contact with the patient and/or family members. We defined clozapine compliance as ≥2 years receiving this medication and doing well., Results: We were able to contact 120 of the 131 patients. In spite of the additional cost and inconvenience of regular blood monitoring, 87 patients (72.5%, 87/120) adhered to long-term clozapine maintenance therapy with dosages ranging from 50 to 900 mg, and a median dosage of 500 mg. This rate exceeds the long-term clozapine maintenance rates reported for AOS patients., Conclusions: Short-term data on differential efficacy and long-term maintenance data suggest a possibly greater efficacy of clozapine, relative to other antipsychotics, in COS than in AOS. Our overall findings indicate that very early-onset schizophrenic patients may be more responsive to clozapine. This extends other support for clozapine as an option in the treatment of early-onset schizophrenia.

Objective: To compare clinical and immunological parameters in children with schizophrenia and to analyze the possibility of using them in the assessment of the pathological process activity., Material and Methods: We examined 62 patients, 39 boys and 23 girls, aged from 4 to 17 years, with childhood-onset schizophrenia. Mental state of the patients was assessed using a psychopathological method and with PANSS and CGI scales. The activity of leukocyte elastase (LE) and alpha(1)-proteinase inhibitor (α1-PI) was measured by spectrophotometric method. ELISA was used to determine the level of autoantibodies to neuroantigenes to S-100B and basic myelin protein., Results and Conclusion: The activation of innate immunity assessed by the activity of LE and α1-PI and adaptive immunity (levels of autoantibodies to neuroantigenes to S-100B and basic myelin protein) was identified. Significant correlations of the level of immune system activation with the severity of patient's state on СGI-S (r=0.64, p=0.000001) as well as scores on the PANSS negative symptom subscale (r=0.34, p=0.0077) were found. The results suggest the possibility of using these immunological parameters for the objectification of clinical state of children with schizophrenia.

Schizophrenia is increasingly recognized as a neurodevelopmental disorder with altered connectivity among brain networks. In the current study we examined large-scale network interactions in childhood-onset schizophrenia, a severe form of the disease with salient genetic and neurobiological abnormalities. Using a data-driven analysis of resting-state functional magnetic resonance imaging fluctuations, we characterized data from 19 patients with schizophrenia and 26 typically developing controls, group matched for age, sex, handedness, and magnitude of head motion during scanning. This approach identified 26 regions with decreased functional correlations in schizophrenia compared to controls. These regions were found to organize into two function-related networks, the first with regions associated with social and higher-level cognitive processing, and the second with regions involved in somatosensory and motor processing. Analyses of across- and within-network regional interactions revealed pronounced across-network decreases in functional connectivity in the schizophrenia group, as well as a set of across-network relationships with overall negative coupling indicating competitive or opponent network dynamics. Critically, across-network decreases in functional connectivity in schizophrenia predicted the severity of positive symptoms in the disorder, such as hallucinations and delusions. By contrast, decreases in functional connectivity within the social-cognitive network of regions predicted the severity of negative symptoms, such as impoverished speech and flattened affect. These results point toward the role that abnormal integration of sensorimotor and social-cognitive processing may play in the pathophysiology and symptomatology of schizophrenia., (Published by Oxford University Press on behalf of the Guarantors of Brain 2015. This work is written by US Government employees and is in the public domain in the US.)

Objective: Among children <13 years of age with persistent psychosis and contemporaneous decline in functioning, it is often difficult to determine if the diagnosis of childhood onset schizophrenia (COS) is warranted. Despite decades of experience, we have up to a 44% false positive screening diagnosis rate among patients identified as having probable or possible COS; final diagnoses are made following inpatient hospitalization and medication washout. Because our lengthy medication-free observation is not feasible in clinical practice, we constructed diagnostic classifiers using screening data to assist clinicians practicing in the community or academic centers., Methods: We used cross-validation, logistic regression, receiver operating characteristic (ROC) analysis, and random forest to determine the best algorithm for classifying COS (n=85) versus histories of psychosis and impaired functioning in children and adolescents who, at screening, were considered likely to have COS, but who did not meet diagnostic criteria for schizophrenia after medication washout and inpatient observation (n=53). We used demographics, clinical history measures, intelligence quotient (IQ) and screening rating scales, and number of typical and atypical antipsychotic medications as our predictors., Results: Logistic regression models using nine, four, and two predictors performed well with positive predictive values>90%, overall accuracy>77%, and areas under the curve (AUCs)>86%., Conclusions: COS can be distinguished from alternate disorders with psychosis in children and adolescents; greater levels of positive and negative symptoms and lower levels of depression combine to make COS more likely. We include a worksheet so that clinicians in the community and academic centers can predict the probability that a young patient may be schizophrenic, using only two ratings.

Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-naïve, first-episode EOS patients and 25 age- and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS.

Objective: To explore cognitive disorders in children and adolescents with schizophrenia from the perspective of cognitive dysontogenesis concept, assess severity and specificity of cognitive deficits and identify variants of the dynamics and types of cognitive development., Material and Methods: Three diagnostic groups of patients were studied: 1) childhood onset schizophrenia, 2) schizotypal disorder, and 3) other types of schizophrenia. RESULTS AND СONCLUSION: There was a predomination of cognitive development types, named cognitive dysontogenesis, which structure was determined by a combination of the dynamics of cognitive development and severity of cognitive deficits. Severity and type of the dynamics of cognitive deficits were associated with the diagnosis and cognitive process.

Childhood-onset schizophrenia has been clinically studied and is believed to be on a continuum with adult-onset schizophrenia. However, childhood-onset schizophrenia is more difficult to diagnose than it is in adults, since children are in a developmental state. This article reviewed the literature regarding childhood-onset schizophrenia. This article discusses the clinical features, development until manifestation, possibility of early diagnosis, and treatment. Early intervention may improve the prognosis of psychotic disorders such as schizophrenia. However, early intervention of childhood-onset schizophrenia requires case histories with accurate descriptions of the development of the disease until its onset.

Theodor Heller first described a severe regression of adaptive function in normally developing children, something he termed dementia infantilis, over one 100 years ago. Dementia infantilis is most closely related to the modern diagnosis, childhood disintegrative disorder. We translate Heller's paper, Über Dementia Infantilis, and discuss similarities in presentation between Heller's cases, and a group of children with childhood disintegrative disorder. In particular we discuss a prodromal period of affective dysregulation described by Heller, and also evident in our sample, but not previously described in any detail since the publication of Über Dementia Infantilis.

In the last decades there was an increasing interest in early detection of prodromal symptoms in schizophrenia and, more specifically, in detecting subjects at high risk for psychosis. However, especially in case of childhood-onset schizophrenia (COS), sometimes it is possible to don't recognize its early symptoms and to ascribe the observed clinical picture to other diseases, with consequent delay in diagnosis and treatment of these patients. In this case report we want to underline the importance of an early detection of schizophrenia, with a focus on differential diagnosis between Attention Deficit/Hyperactivity Disorder and schizophrenia.

The treatment of refractory schizophrenia has been a clinical challenge for most psychiatrists; the possible reasons include diagnostic errors, medical conditions and brain dysgenesis. Here, we described a patient with childhood-onset schizophrenia who had severe psychiatric symptoms such as auditory hallucinations and persecutory delusions, and etc. We reexamined all his possible medical conditions and found that the patient had an abnormally enlarged cavus septum pellucidum (CSP) combined with cavum vergae (CV) (maximum length >30 mm). Some reports suggested that abnormal CSP (length >6 mm) has a significant association with schizophrenia. However, abnormally large CSP or CSP/CV and related prognosis were reported rarely. This case suggested that abnormally enlarged CSP or CSP/CV may worsen the prognosis.

Childhood disintegrative disorder (CDD), early onset schizophrenia (EOS), and late onset autism (LOA) often follow a similar course: initially, development is normal, then there is a sudden neuropsychiatric deterioration of social interaction and communication skills, which is combined with a decline in intelligence and reduction in daily activities. A 9-year-old boy was admitted to the paediatric ward with acute onset of secondary epileptic seizures. It was not long until the boy's symptoms resembled that of patients with cdd, eos and loa. Intensive tests led to the diagnosis of anti-NMDA-receptor encephalitis. Anti-NMDA-receptor encephalitis should be regarded as a possible organic cause underlying the syndromal presentation of CDD, EOS and LOA.

Background: This study screened children in Beijing, China, in order to establish the validity of a Mandarin Chinese translation of the ASSQ., Methods: We recruited children diagnosed with autism spectrum disorders (ASDs), attention deficit/hyperactivity disorder (ADHD), childhood-onset schizophrenia (COS) (DSM-IV diagnoses made independently by two senior psychiatrists) and unaffected children attending a public school in Beijing. Their parents were asked to complete the CH-ASSQ., Results: Data from the parents of 94 children with ASD (mean age: 81 ± 47 months), 45 with ADHD (106 ± 27 months), 26 with COS (166 ± 36 months), and 120 unaffected control (72 ± 16 months) were collected. The total scores of ASSQ in children with ASD, ADHD, COS, and unaffected controls were 25.3 ± 9.2, 10.4 ± 7.1, 12.2 ± 10.6, and 5.2 ± 6.6 respectively. Total ASSQ scores of children with ASD were significantly higher than in any other group (all p < .0001). ROC analysis of ASD versus unaffected control subjects showed the area under curve was 0.957, with a cutoff of 12 having the maximum sensitivity (0.957) and specificity (0.825)., Conclusions: Our pilot data suggest that CH-ASSQ successfully differentiates clinically diagnosed ASD patients from unaffected controls, as well as from patients with ADHD and COS. The instrument might therefore be useful for screening for ASD in urban Mandarin Chinese-speaking populations.

The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of "schizophrenia" or "other psychosis" showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents.

During the past two decades, the Child Psychiatry Branch at the National Institute of Mental Health has conducted a longitudinal study (including long-term prospective follow-up) of childhood-onset schizophrenia, a rare form of the disorder. Critical to this research has been accurate diagnosis. Outpatient screening has accurately diagnosed 55% of the 121 childhood-onset schizophrenia patients in the study to date. However, inpatient observation including drug-free observation has proven crucial to ruling out 96 children with alternative diagnoses who had been provisionally admitted for inpatient study. Standardized clinical ratings from outpatient screening only predicted 62% of these nonschizophrenia patients. Historically, medication-free observation was standard clinical care for difficult and unusual patients; this should be employed when possible in similar situations.

The concept, diagnosis and clinical picture of childhood-onset schizophrenia were presented. The cases with childhood-onset schizophrenia were classified into 4 groups according to their process of growth and development. Furthermore, it has been suggested that the progression of childhood-onset schizophrenia developed on the basis of neuro-developmenal hypothesis might contribute to the understanding of adult onset schizophrenia and early diagnosis and intervention of 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.

Objective: To assess the psychometrics of the schedule for affective disorders and schizophrenia for school-age children present and lifetime version (K-SADS-PL) in diagnosing DSM-IV psychiatric disorders and subsyndromal symptomatology in preschool children., Method: Parents were interviewed about their children using the K-SADS-PL, and they completed the early childhood inventory-4 (ECI-4) and child behavior checklist for ages 1(1/2)-5 years (CBCL). Discriminant, divergent, and convergent validity of the K-SADS-PL were evaluated in 204 offspring ages 2-5 years old of parents from an ongoing study. Inter-rater reliability as well as predictive validity of intake diagnoses at second assessment approximately two years after intake were evaluated. Fourteen children were also assessed by the preschool age psychiatric assessment (PAPA)., Results: Children who were diagnosed with oppositional defiant disorder, attention deficit hyperactivity disorder, anxiety, mood, or elimination disorders had significantly higher scores on the ECI-4 than children without these disorders. Significant correlations were found for all convergent CBCL scales. Divergent validity was acceptable for emotional disorders. Inter-rater kappa coefficients for all diagnoses were good. Above noted results were similar for children with at least one positive K-SADS-PL key screen symptom. A significantly higher percentage of children with an intake diagnosis had a diagnosis approximately two years after intake compared to those without an intake disorder. Overall, there was consistency between the PAPA and the K-SADS-PL., Conclusions: Pending further testing, the K-SADS-PL may prove useful for the assessment of psychopathology in preschoolers.

An assessment protocol for the longitudinal measurement of developmental psychopathology in a population-based study of children and adolescents is proposed. The protocol is designed for use in a large cohort of up to 100,000 individuals followed from early gestation to 21 years of age. Although the protocol was constrained by specified methodological parameters, the recommendations may apply to other psychiatric epidemiological research designs. The issues and challenges inherent with psychiatric assessments in longitudinal epidemiological studies of children and adolescents are discussed.

Childhood-onset schizophrenia (COS; defined as onset by age 12 years) is rare, difficult to diagnose, and represents a severe and chronic phenotype of the adult-onset illness. A study of childhood-onset psychoses has been ongoing at the National Institute of Mental Health (NIMH) since 1990, where children with COS and severe atypical psychoses (provisionally labeled "multidimensionally impaired" or MDI by the NIMH team) are studied prospectively along with all first-degree relatives. COS subjects have robust cortical gray matter (GM) loss during adolescence, which appears to be an exaggeration of the normal cortical GM developmental pattern and eventually mimics the pattern seen in adult-onset cases as the children become young adults. These cortical GM changes in COS are diagnostically specific and seemingly unrelated to the effects of medications. Furthermore, the cortical GM loss is also shared by healthy full siblings of COS probands suggesting a genetic influence on the abnormal brain development.

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.

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.

Background: Monitoring brain processes in real time requires genuine subsecond resolution to follow the typical timing and frequency of neural events. Non-invasive recordings of electric (EEG/ERP) and magnetic (MEG) fields provide this time resolution. They directly measure neural activations associated with a wide variety of brain states and processes, even during sleep or in infants. Mapping and source estimation can localise these time-varying activation patterns inside the brain., Methods: Recent EEG/ERP research on brain functions in the domains of attention and executive functioning, perception, memory, language, emotion and motor processing in ADHD, autism, childhood-onset schizophrenia, Tourette syndrome, specific language disorder and developmental dyslexia, anxiety, obsessive-compulsive disorder, and depression is reviewed., Results: Over the past two decades, electrophysiology has substantially contributed to the understanding of brain functions during normal development, and psychiatric conditions of children and adolescents. Its time resolution has been important to measure covert processes, and to distinguish cause and effect., Conclusions: In the future, EEG/ERP parameters will increasingly characterise the interplay of neural states and information processing. They are particularly promising tools for multilevel investigations of etiological pathways and potential predictors of clinical treatment response.

This paper describes the long-term course of 76 patients who had been consecutively admitted to the Department of Child and Adolescent Psychiatry, Philipps University, between 1920 and 1961 with a suspected diagnosis of childhood-onset schizophrenia. By means of a consensus analysis of available data in accordance with ICD-10 criteria, the diagnosis of schizophrenia was confirmed in only 50% of the original sample (n = 38, childhood-onset schizophrenia group); whereas the rest of the sample were allotted other diagnoses (n = 38, non-schizophrenia group). A follow-up investigation was conducted, interviewing all available patients, if possible, or their first-degree relatives or doctors. In the childhood-onset schizophrenia group, age at onset (mean +/- S.D.) was 12.7 +/- 2.5 (range 5-14) years and age at follow-up was 55.0 +/- 4.8 (range 42-62) years. The outcome of this group was poor. According to the Global Assessment Scale (GAS), only 16% had a good (GAS score 71-100) and 24% had a moderate (GAS score 41-70) outcome. In the 16 childhood-onset schizophrenia patients who could be personally investigated at follow-up, 10 (62.5%) displayed severe or moderate depressive symptoms according to the BPRS depressive score. The death rate (including suicide) was significantly higher in the schizophrenia group (n = 15; 39.5%) than in the non-schizophrenia group (n = 7; 18.4%). A comparison of the life-time diagnoses of the total sample (n = 76) at follow-up with the ICD-10 diagnoses made retrospectively revealed a diagnostic stability in 69 (91%) and a change of diagnosis in 7 (9%) cases, among them 4 who were originally diagnosed as having 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.

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.

The anterior cingulate is a key component of neural networks subserving attention and emotion regulation, functions often impaired in patients with psychosis. The study aimed to examine anterior cingulate volumes and sulcal morphology in a group of patients with childhood-onset schizophrenia (COS) compared with controls. Brain magnetic resonance imaging (MRI) scans were obtained in 13 COS and 18 matched control children, ages 6-17 years. Volume measures for the anterior cingulate gyrus (ACG) were obtained through manual labeling. A determination of cingulate sulcal pattern (single or double) was made for each hemisphere. The COS group had a reduced leftward skew of the double cingulate sulcal pattern, and absence of the normal left>right ACG volume asymmetry. The right ACG was larger in the COS than in controls. The schizophrenic children showed decreases in all ACG volumes with age, while the controls showed increases or no change. The data suggest that significant cingulate abnormalities may result from deviations in progressive neurodevelopmental processes, beginning before birth and continuing through childhood and adolescence, in persons who develop schizophrenia. These structural differences may relate to the well-described cognitive deficits these children display, and to the cardinal symptoms of schizophrenia.

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.

Background: Childhood-onset schizophrenia (COS) is a severe form of the adult-onset disorder with a high rate of premorbid developmental abnormalities. Early symptoms of pervasive developmental disorder (PDD) have been reported in five independent studies of COS. In this study, we compared evidence for premorbid PDD as a nonspecific manifestation of impaired neurodevelopment seen in schizophrenia, or as an independent risk factor for COS., Methods: Diagnosis of past or current autism or PDD was made according to the DSM-IV criteria. COS patients with and without PDD were compared with respect to neuropsychological, clinical, and neurobiological measures. Several candidate genes for autism were examined in the entire COS sample and the subgroup with PDD using the Transmission Disequilibrium Test (TDT) and Quantitative TDT (QTDT)., Results: Nineteen (25%) of COS probands had a lifetime diagnosis of PDD: one met criteria for autism, two for Asperger's disorder, and 16 for PDD not otherwise specified. Premorbid social impairment was most common feature for COS-PDD subjects. The PDD group did not differ from the rest of the COS sample with respect to age of onset, IQ, response to medications, and rate of familial schizotypy. Unexpectedly, two siblings of COS-PDD probands met criteria for nuclear autism. There was no difference between PDD and non-PDD groups with respect to initial brain magnetic resonance imaging (MRI) measures. However, rate of gray matter loss was greater for PDD (n = 12) than for the non-PDD (n = 27) subgroup (-19.5 +/- 11.3 mL/year vs. -9.6 +/- 15.3 mL/year; p =.05). None of eight candidate genes for autism were associated with COS or COS-PDD., Conclusions: Premorbid PDD in COS is more likely to be a nonspecific marker of severe early abnormal neurodevelopment. However, the occurrence of two siblings of COS-PDD probands (17%) with nuclear autism remains to be understood.

Background: In the past 10 years, there has been increased research on childhood-onset schizophrenia and clear advances have been achieved., Method: This annotation reviews the recent clinical and treatment literature on childhood-onset schizophrenia., Results: There is now strong evidence that the syndrome of childhood-onset schizophrenia exists and there are several similarities between childhood- and later-onset schizophrenia. Schizophrenia in youth can be reliably diagnosed using the same criteria employed with adults, and childhood-onset schizophrenia is predictive of schizophrenia or schizophrenia spectrum disorders in adulthood. Data is accumulating to guide pharmacological treatment strategies, and practice parameters have been developed to guide clinical care., Conclusions: Despite significant advances, there remains an urgent need for additional research on treatment and service delivery strategies. Promising work with adults highlights the importance of attending to psychosocial as well as pharmacologic treatment strategies, and the potential value of preventive interventions.

Childhood antecedents of schizophrenia were explored for 148 boys seen in child guidance clinics prior to the onset of adolescent or adult disorders. Those most disturbed in childhood were more likely to be preschizophrenic, and their disturbed behavior was relatively specific to that grouping. Childhood problems with motor coordination and attention were associated with impulsive, inappropriate behavior which led to peer rejection followed by increasing seclusiveness. Clinical grouping of the most disturbed boys produced composite descriptions for four groups.

Objective: Childhood-onset schizophrenia is a severe and unremitting form of the disorder. Prospective brain magnetic resonance imaging (MRI) studies have found progressive loss of total cerebral volume during adolescence, primarily attributable to accelerated loss of cortical gray matter. Because there is evidence of cerebellar involvement in schizophrenia, the authors examined cerebellar volume and its relation to cortical gray matter development during adolescence in patients with childhood-onset schizophrenia and healthy comparison subjects., Method: Total cerebellar volume was algorithmically calculated for 108 anatomical brain MRI scans from 50 patients (20 of whom were female) and 101 scans from 50 age- and gender-matched healthy volunteers (20 of whom were female). The age range of the patients and comparison subjects was 8 to 24. Midsagittal vermal area and posterior-inferior vermal lobe volume were measured by hand. Prospective rescans were obtained at approximately 2-year intervals. Cross-sectional and longitudinal data were combined in mixed model regressions to compare developmental changes for the groups., Results: In contrast to healthy volunteers, patients with schizophrenia showed a progressive loss of cerebellar volume during adolescence. Cerebellar and cerebral volume decreases were significantly correlated in childhood-onset schizophrenia., Conclusions: Childhood-onset schizophrenia is associated with significant progressive loss of cerebellar volume during adolescence, consistent with previously reported decreases in total cerebral and cortical gray matter. At least in these patients with severe early-onset schizophrenia, the loss appears secondary to a generalized process.

Background: We tested the hypotheses that certain neurocognitive impairments index genetic liability to schizophrenia and that childhood-onset schizophrenia (COS) is a variant of adult-onset schizophrenia (AOS) by determining whether parents of COS probands show the types of neurocognitive impairments found in relatives of AOS probands., Methods: Parents of COS probands (n = 79) were compared with parents of attention-deficit/hyperactivity disorder (ADHD; n = 190) and community control (CC; n = 115) probands on 3 neurocognitive tasks shown in previous research to detect impairments in patients with AOS and ADHD and in the relatives of patients with AOS. Parents with a diagnosis of psychosis were excluded from the study., Results: On the Degraded Stimulus-Continuous Performance Test and the Trail-Making Test B-Adolescent Version, the parents of COS probands performed significantly worse than the parents of CC and ADHD probands, who did not differ significantly from each other. On the Span of Apprehension, we found no significant group differences. Using rigorous cutoffs, a combination of scores on the 3 neurocognitive tests identified 16 (20%) of the mothers and fathers of COS probands compared with 0% of the mothers and fathers of CC probands. There was diagnostic specificity of the neurocognitive impairments. A combination of neurocognitive scores identified 6 (12%) of the mothers of COS probands vs 0% of the mothers of ADHD probands. A cutoff that identified 2 (2%) of the fathers of ADHD probands classified 5 (17%) of the fathers of COS probands. We found no significant differences in neurocognitive functions between the parents of ADHD and CC probands., Conclusions: The aggregation of neurocognitive impairments in the parents of COS probands provides further evidence of etiologic continuity between COS and AOS. A substantial subgroup of parents of COS probands had a worse neurocognitive performance than that of any of the parents of ADHD and CC probands. Receiver operating characteristic curves showed that when rigorous cutoffs define neurocognitive impairments, the combination of scores on certain neurocognitive tasks produced a level of diagnostic accuracy in the parents of COS probands that is sufficient for use in genetic linkage studies.

Objective: There is increasing interest in the possible relationship between the early diagnosis and treatment of schizophrenia during adolescence and improved long-term outcome. This study reviews the premorbid and prodromal diagnostic and treatment histories for childhood-onset schizophrenia, to assess whether early identification and treatment is possible in this school-age group., Method: Parents of 17 children with childhood-onset schizophrenia or schizoaffective disorder were questioned retrospectively regarding symptoms, exposure to mental health professionals, diagnoses, and treatments., Results: Initial presenting symptoms clustered around violent aggression and school problems. Age of first recognized psychotic symptoms ranged from 2 to 11 years, followed 2.0+/-2.0 years later by a diagnosis of schizophrenia. Prior to a schizophrenia diagnosis, these children were exposed to stimulants, antidepressants, lower-dose typical neuroleptics, mood stabilizers, alternative treatments, and individual and family therapy., Conclusion: Early diagnosis of childhood-onset schizophrenia is met with caution in the psychological and medical community. These children received many diagnoses before schizophrenia or schizoaffective disorder was diagnosed. A diagnosis of schizophrenia or schizoaffective disorder and utilization of effective atypical neuroleptic treatment was delayed until evaluation by a child and adolescent psychiatrist. Obstacles to early identification and treatment are discussed.