Genetics of schizophrenia in the South African Xhosa.

Africa, the ancestral home of all modern humans, is the most informative continent for understanding the human genome and its contribution to complex disease. To better understand the genetics of schizophrenia, we studied the illness in the Xhosa population of South Africa, recruiting 909 cases and 917 age-, gender-, and residence-matched controls. Individuals with schizophrenia were significantly more likely than controls to harbor private, severely damaging mutations in genes that are critical to synaptic function, including neural circuitry mediated by the neurotransmitters glutamine, γ-aminobutyric acid, and dopamine. Schizophrenia is genetically highly heterogeneous, involving severe ultrarare mutations in genes that are critical to synaptic plasticity. The depth of genetic variation in Africa revealed this relationship with a moderate sample size and informed our understanding of the genetics of schizophrenia worldwide.

Clinical features and outcome of child and adolescent schizophrenia.

Subjects admitted 12 months or more previously to two child and adolescent psychiatric units in New Zealand and the United States with a diagnosis of non-organic, nonautistic psychosis, were contacted and those who received a DSM-III-R diagnosis of schizophrenia were studied (n = 33 [New Zealand] and n = 24 [United States]). Premorbid and first-episode data were obtained from the admission record using global clinical measures of moderate reliability, outcome diagnosis and status by interviews, and professional and family reports. Mean ages at onset were 13.9 (New Zealand) and 15.6 (United States). Premorbid and clinical features resembled those in adult schizophrenia, though there were probable quantitative differences. At outcome (mean interval = 4 years) few subjects were symptom-free or independent, and mean global assessment of functioning had fallen from 55 to 40. Outcome was much worse in schizophrenia than bipolar disorder. Despite a 59 percent attrition rate and higher rates of initial misdiagnosis in the United States, and some demographic differences, New Zealand and United States samples resembled each other clinically and in outcome. Initial misdiagnosis of bipolar disorder as schizophrenia was not due to minimizing mood symptoms, which were common in both disorders. Within this age range (mostly 11-17), age at onset had only minor effects. Outcome was best predicted by premorbid personality.

A follow-up study of early onset psychosis: comparison between outcome diagnoses of schizophrenia, mood disorders, and personality disorders.

This study examined the outcome of youth previously diagnosed with psychotic disorders at a public-sector tertiary care hospital. Of 95 children and adolescents retrospectively identified, follow-up information (mean interval 3.9 years) was obtained on 24 subjects with an outcome diagnosis of schizophrenia, 9 with psychotic mood disorders, 5 with personality disorders (antisocial or borderline), and 1 with schizo-affective disorder. The schizophrenic group was more often odd premorbidly and functioned worse at outcome, while the mood-disordered group had a shorter follow-up period and was more often anxious or dysthymic premorbidly. The personality-disordered group resembled the schizophrenics in their degree of impairment and chronicity. All three groups had high rates of family disruption, low SES, substance abuse, and chronicity, and were similar in their degree of premorbid impairment, length of prodrome, age of onset, initial diagnosis, and family psychiatric history. Misdiagnosis at onset was quite common and highlights the need for systematic longitudinal assessment of early onset psychotic disorders.

Schizophrenia.

Schizophrenia occurring in childhood and adolescence has similar diagnostic, prognostic, and treatment ramifications as those noted with adult-onset schizophrenia. In assessing a child or adolescent suspected of having schizophrenia, care must be given to document DSM-III-R diagnostic criteria within the developmental framework of the patient's functioning, while thoroughly evaluating for other potentially confounding disorders or conditions. Antipsychotic therapy is the only specific treatment for schizophrenia, and should be a fundamental component with a multimodal treatment program that also addresses the psychological, social, and educational needs of the patient and his or her family. Strategies for medication management vary depending on several factors, including the stage of the disorder, noted or potential side effects, and the response of the patient to treatment, and need to be coordinated for the long term by a child or adolescent psychiatrist familiar with the diagnosis and treatment of schizophrenia in this age group.

Predicting outcome in child and adolescent (early onset) schizophrenia and bipolar disorder.

Fifty-nine patients with DSM-III-R early onset (mean, 13.9 years) psychoses of schizophrenia (N = 30) or bipolar disorder (N = 23) were seen at follow-up (mean interval, 5 years; mean age, 19 years). About 50% of the variance in outcome was predictable using stepwise multiple correlation, which has the advantage of eliminating redundancy among variables and giving a quantitative estimate for each predictor. Abnormal premorbid adjustment/personality and degree of recovery after initial hospitalization were the substantial predictors in schizophrenia, whereas in bipolar disorder, they were premorbid adjustment and IQ. Other items such as diagnosis (bipolar or schizophrenia), symptoms, and gender predicted at too low a level to be useful clinically. Though psychosis is necessary for diagnosis, premorbid personality abnormality may be an indicator of an early onset, developmental type schizophrenia with poor prognosis.

Childhood and adolescent schizophrenic, bipolar, and schizoaffective disorders: a clinical and outcome study.

Fifty-nine child and adolescent psychotic patients (mean onset age 13.9, range 7-17, 83% 13 + years) had history and outcome studied using diagnoses confirmed at follow-up after 1 to 16 years (mean, 5 years). There were no differences in sex ratio, socioeconomic status, age of onset, and symptoms, but bipolar patients (N = 23) were often misdiagnosed as schizophrenic, had a better outcome, and a 50% homotypic family history. Schizophrenic subjects (N = 30) were more abnormal premorbidly, and only 17% were well at follow-up. Schizoaffective disorder was unreliable, infrequent, and more severe. Premorbid adjustment and IQ were the best predictors of outcome. Differences from the adult disorders were only quantitative. Careful follow-up of psychotic patients is needed to detect diagnostic errors.

Attention deficit disorder in children at risk for anxiety and depression.

The comorbidity between attention deficit disorder (ADD) and anxiety and/or depressive disorders was examined in the children of parents with panic disorder, major depressive disorder, or with no diagnosis. A child received a diagnosis by a self-report, parent report, and by consensus, using a best estimate procedure. The prevalence rates of ADD were significantly greater in offspring of parents with depressive and panic disorder by the parents' report and in children of depressed parents by consensus. A significant relationship between ADD and anxiety and/or depression was found for parent, child, and consensus diagnoses. Higher rates of ADD were reported by children (1% versus 13%), parents (8% versus 31%), and in the consensus diagnoses (13% versus 29%) when anxiety and/or depression was present. These results suggest that in children referred for evaluation of ADD, the possibility of a primary anxiety or depressive disorder should be considered.

What industrial hygienists should know about TSCA.

Direct participation of industrial hygiene personnel in planning and implementing compliance with several pertinent sections of the Toxic Substances Control Act (TSCA) is warranted. TSCA is administered by the Environmental Protection Agency and there is a variety of areas in which industrial hygiene input is and will be required. Major sections of TSCA which require industrial hygiene participation include Testing, Premanufacture Notices (PMNs), Regulation of Hazardous Chemicals, and Reporting and Recordkeeping. The industrial hygiene input requires interaction with other groups such as Toxicology, Environmental, Government Regulations, Legal, Medical, Research and Development, Marketing and Manufacturing in order to provide a comprehensive response to and compliance with current and anticipated TSCA rules.