Differentiating childhood-onset schizophrenia from psychotic mood disorders.

OBJECTIVE: The authors systematically examined a sample of patients who were referred to an ongoing National Institute of Mental Health (NIMH) study of childhood-onset schizophrenia (COS), but who received diagnoses of mood disorders at the NIMH, to analyze the reliability of these research-setting diagnoses and to characterize the patients clinically. Pilot data regarding the clinical course of these patients over a 2- to 7-year follow-up period were also obtained. METHOD: Thirty-three cases were selected from the 215 pediatric patients who had been screened in person from 1991 to 1999 for admission to the COS study. These 33 patients had been excluded from the COS study on the basis of a day-long evaluation, including a structured diagnostic interview, which yielded a diagnosis of a mood disorder rather than schizophrenia. This subgroup, together with six COS subjects (for a total N= 39), were included in a diagnostic reliability study in which they were reevaluated by three psychiatrists who were blind to the initial research diagnosis. In addition, pilot follow-up data regarding current function and treatment status were obtained for 25 of the 33 patients with mood disorders. RESULTS: Overall, the interrater reliability of the three raters was excellent (kappa = 0.90). Global reliability between these raters and the NIMH research diagnoses was good (average kappa across diagnoses = 0.61), and agreement for those patients who had mood disorders was good (86% agreement; kappa = 0.60). Pilot follow-up data indicate that none of the subjects with a diagnosed mood disorder developed a clinical course resembling schizophrenia. CONCLUSIONS: Many of the patients referred to the NIMH COS study with clinical diagnoses of schizophrenia had psychotic mood disorders diagnosed on the basis of a comprehensive research evaluation including structured diagnostic interviews, and these research diagnoses were reliable. The diagnosis of COS is difficult and requires a time-consuming evaluation process.

Children and adolescents with psychotic disorder not otherwise specified: a 2- to 8-year follow-up study.

Although psychotic phenomena in children with disruptive behavior disorders are more common than expected, their prognostic significance is unknown. To examine the outcome of pediatric patients with atypical psychoses, a group of 26 patients with transient psychotic symptoms were evaluated with clinical and structured interviews at the time of initial contact (mean age, 11.6 +/- 2.7 years) and at follow-up 2 to 8 years later. Measures of functioning and psychopathology were also completed at their initial assessment. Risk factors associated with adult psychotic disorders (familial psychopathology, eyetracking dysfunction in patients and their relatives, obstetrical complications, and premorbid developmental course in the proband) had been obtained at study entry. On follow-up examination (mean age, 15.7 +/- 3.4 years), 13 patients (50%) met diagnostic criteria for a major axis I disorder: three for schizoaffective disorder, four for bipolar disorder, and six for major depressive disorder. The remaining 13 patients again received a diagnosis of psychotic disorder not otherwise specified (NOS), with most being in remission from their psychotic symptoms. Among this group who had not developed a mood or psychotic disorder, disruptive behavior disorders were exceedingly common at follow-up and were the focus of their treatment. Higher initial levels of psychopathology, lower cognitive abilities, and more developmental motor abnormalities were found in patients with a poor outcome. Obstetrical, educational, and family histories did not differ significantly between the groups. Through systematic diagnostic evaluation, children and adolescents with atypical psychotic disorders can be distinguished from those with schizophrenia, a difference with important treatment and prognostic implications. Further research is needed to delineate the course and outcome of childhood-onset atypical psychoses, but preliminary data indicate improvement in psychotic symptoms in the majority of patients and the development of chronic mood disorders in a substantial subgroup.

An open trial of plasma exchange in childhood-onset obsessive-compulsive disorder without poststreptococcal exacerbations.

Patients with childhood-onset obsessive-compulsive disorder (OCD) with symptom exacerbations following streptococcal infections benefit from treatment with plasma exchange. In this study, 5 patients with treatment-refractory OCD without a history of streptococcus-related exacerbations underwent an open 2-week course of therapeutic plasma exchange. Behavioral ratings, completed at baseline and 4 weeks after the initial treatment, included the Clinical Global Impressions Scale and the Yale-Brown Obsessive Compulsive Scale. All 5 patients completed the trial with few side effects, but none showed significant improvement. Plasma exchange does not benefit children and adolescents with OCD who do not have streptococcus-related exacerbations.

Premorbid speech and language impairments in childhood-onset schizophrenia: association with risk factors.

OBJECTIVE: As both premorbid neurodevelopmental impairments and familial risk factors for schizophrenia are prominent in childhood-onset cases (with onset of psychosis by age 12), their relationship was examined. METHOD: Premorbid language, motor, and social impairments were assessed in a cohort of 49 patients with childhood-onset schizophrenia. Familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications were assessed without knowledge of premorbid abnormalities and were compared in the patients with and without developmental impairments. RESULTS: Over one-half of the patients in this group had developmental dysfunction in each domain assessed. The patients with premorbid speech and language impairments had higher familial loading scores for schizophrenia spectrum disorders and more obstetrical complications, and their relatives had worse smooth-pursuit eye movements. The boys had more premorbid motor abnormalities, but early language and social impairments did not differ significantly between genders. There were no other significant relationships between premorbid social or motor abnormalities and the risk factors assessed here. CONCLUSIONS: Premorbid developmental impairments are common in childhood-onset schizophrenia. The rates of three risk factors for schizophrenia (familial loading for schizophrenia spectrum disorders, familial eye-tracking dysfunction, and obstetrical complications) were increased for the probands with premorbid speech and language impairments, suggesting that the pathophysiology of schizophrenia involves the abnormal development of language-related brain regions.

Velocardiofacial syndrome in childhood-onset schizophrenia.

OBJECTIVES: Deletion of chromosome 22q11 (velocardiofacial syndrome) is associated with early neurodevelopmental abnormalities and with schizophrenia in adults. The rate of 22q11 deletions was examined in a series of patients with childhood-onset schizophrenia (COS), in whom early premorbid developmental and cognitive impairments are more pronounced than in adult-onset cases. METHOD: Through extensive recruiting and screening, a cohort of 47 patients was enrolled in a comprehensive study of very-early-onset schizophrenia. All were tested with fluorescence in situ hybridization for deletions on chromosome 22q11. RESULTS: Three (6.4%) of 47 patients were found to have a 22q11 deletion. All 3 COS patients with 22q11 deletions had premorbid impairments of language, motor, and social development, although their physical characteristics varied. Brain magnetic resonance imaging revealed increased midbody corpus callosum area and ventricular volume in relation both to healthy controls and to other COS patients. CONCLUSIONS: The rate of 22q11 deletions in COS is higher than in the general population (0.025%, p < .001) and may be higher than reported for adult-onset schizophrenia (2.0%, p = .09). These results suggest that 22q11 deletions may be associated with an earlier age of onset of schizophrenia, possibly mediated by a more salient neurodevelopmental disruption.

Elevated prolactin in pediatric patients on typical and atypical antipsychotics.

As part of systematic treatment trials of haloperidol, clozapine, and olanzapine with a total of 35 children and adolescents with early onset psychosis, prolactin was measured at baseline and week 6 of treatment. The National Institute of Mental Health patients--13 females, 22 males (mean age, 14.1+/-2.3 years; range, 9.1-19 years) with childhood onset schizophrenia (n = 32), or Psychotic Disorder not otherwise specified (NOS) (n = 3) with onset of psychosis before age 13--were recruited for open or double-blind trials of haloperidol, clozapine, or olanzapine. Baseline serum prolactin was measured after a 3-week washout period and after 6 weeks of treatment. Mean prolactin concentration after 6 weeks of treatment was significantly elevated on all three drugs; however, on clozapine, mean prolactin remained within the normal range. Prolactin was increased above the upper limit of normal for 100% of 10 patients on haloperidol, 70% of 10 patients on olanzapine, and 0% of 15 patients on clozapine (chi2 analyses: H > C, p = 0.004; O > C, p = 0.001). Given the potential endocrine and possible cardiac correlates of hyperprolactinemia, these more robust prolactin elevations in pediatric patients after short-term exposure to olanzapine than those reported for adults justify longer observation intervals with bigger samples to establish treatment safety of atypical antipsychotics in adolescents.