Intellectual disability and other neuropsychiatric outcomes in high-risk children of mothers with schizophrenia, bipolar disorder and unipolar major depression.

BACKGROUND: Recent evidence points to partially shared genetics of neuropsychiatric disorders. AIMS: We examined risk of intellectual disability and other neuropsychiatric outcomes in 3174 children of mothers with schizophrenia, bipolar disorder or unipolar major depression compared with 3129 children of unaffected mothers. METHOD: We used record linkage across Western Australian population-based registers. The contribution of obstetric factors to risk of intellectual disability was assessed. RESULTS: Children were at significantly increased risk of intellectual disability with odds ratios (ORs) of 3.2 (95% CI 1.8-5.7), 3.1 (95% CI 1.9-4.9) and 2.9 (95% CI 1.8-4.7) in the maternal schizophrenia, bipolar disorder and unipolar depression groups respectively. Multivariate analysis suggests familial and obstetric factors may contribute independently to the risk. Although summated labour/delivery complications (OR = 1.4, 95% CI 1.0-2.0) just failed to reach significance, neonatal encephalopathy (OR = 7.7, 95% CI 3.0-20.2) and fetal distress (OR = 1.8, 95% CI 1.1-2.7) were independent significant predictors. Rates of rare syndromes in children of mothers with mental disorder were well above population rates. Risk of pervasive developmental disorders, including autism, was significantly elevated for children of mothers with bipolar disorder. Risk of epilepsy was doubled for children of mothers with unipolar depression. CONCLUSIONS: Our findings provide epidemiological support for clustering of neuropsychiatric disorders. Further larger epidemiological studies are warranted.

From inventory to benchmark: quality of psychiatric case registers in research.

In recent years, there has been a marked increase in the use of psychiatric case registers for research purposes. Registers are a valuable data asset but there are no standard guidelines for evaluating their use in research. It is becoming increasingly important for researchers who use register data, and journal editors who publish their work, to set benchmarks to assess the quality of a register and its research application. Several criteria that could form the basis of such an evaluative framework are discussed. The discussion is illustrated using a Western Australian e-cohort of half a million children for whom we have assembled comprehensive data cross-linked across a number of administrative registers.

Do women express and experience psychosis differently from men? Epidemiological evidence from the Australian National Study of Low Prevalence (Psychotic) Disorders.

OBJECTIVE: To examine how women differ from men in their expression and experience of psychosis. METHOD: Using an epidemiological sampling frame, 1090 cases of psychosis (schizophrenia, schizoaffective disorder, affective psychoses, and other psychoses) were randomly selected from a catchment of 1.1 million people as part of the Australian Study of Low Prevalence (Psychotic) Disorders. Women and men were compared with respect to their premorbid functioning, onset and course of illness, symptomatology, levels of disability and service utilization. RESULTS: Results within diagnostic groupings confirm differences in how men and women experience and express their illness. Within each diagnostic group, women reported better premorbid functioning, a more benign illness course, lower levels of disability and better integration into the community than men. They were also less likely to have a chronic course of illness. There were no significant differences in age at onset. Differences between women across the diagnostic groups were more pronounced than differences between women and men within a diagnostic group. In particular, women with schizophrenia were severely disabled compared to other women. CONCLUSIONS: These comparisons across diagnostic groupings are among the most systematic and comprehensive in the literature. It is likely that several mechanisms are needed to explain the differences. Greater social integration and functioning in women across diagnostic groups may well reflect culturally and socially determined gender differences. In contrast, variability and attenuated findings with respect to symptom profiles beg the question of biological mechanisms with some degree of specificity.

A multivariate electrophysiological endophenotype, from a unitary cohort, shows greater research utility than any single feature in the Western Australian family study of schizophrenia.

BACKGROUND: Previous studies have found several electrophysiological endophenotypes that each co-varies individually with schizophrenia. This study extends these investigations to compare and contrast four electrophysiological endophenotype, mismatch negativity, P50, P300, and antisaccades, and analyze their covariance on the basis of a single cohort tested with all paradigms. We report a multivariate endophenotype that is maximally associated with diagnosis and evaluate this new endophenotype with respect to its application to genetic analysis. METHODS: Group differences and covariance were analyzed for probands (n = 60), family members (n = 53), and control subjects (n = 44). Associations between individual endophenotypes and diagnostic groups, as well as between the multivariate endophenotype and diagnostic groups, were investigated with logistic regression. RESULTS: Results from all four individual endophenotypes replicated previous findings of deficits in the proband group. The P50 and P300 endophenotypes similarly replicated significant deficits in the family member group, whereas mismatch negativity and antisaccade measures showed a trend. There was minimal correlation between the different endophenotypes. A logistic regression model based on all four features significantly represented the diagnostic grouping (chi(2) = 32.7; p < .001), with 80% accuracy in predicting group membership. CONCLUSIONS: A multivariate endophenotype, based on a weighted combination of electrophysiological features, provides greater diagnostic classification power than any single endophenotype.

The epidemiology of bipolar disorder: sociodemographic, disability and service utilization data from the Australian National Study of Low Prevalence (Psychotic) Disorders.

OBJECTIVES: Data from the Australian National Study of Low Prevalence (Psychotic) Disorders were used to describe the clinical and sociodemographic profile of individuals with bipolar disorder, their levels of impairment and disability, and use of medication and treatment services. METHODS: A 1-month census of contacts with mental health services, private psychiatric and general practices, as well as contact points in marginalized settings, was conducted in a national catchment of 1.1 million adults. The census yielded 3,800 individuals who screened positive for psychosis, of whom a random sample of 980 were administered a comprehensive semi-structured interview schedule. Results are presented on 112 persons with an ICD-10 diagnosis of bipolar disorder. RESULTS: Overall, 69.6% of the 112 persons who met the ICD-10 criteria for bipolar disorder reported a recurrent episodic illness, 25.0% had a chronic course without clear remissions, and 5.4% had a single episode of mania. Assessed on a lifetime basis, suicidal ideation was common (78.6%) and levels of drug and alcohol abuse/dependence were high (32.1%). The majority (84.8%) had had at least one contact with inpatient, outpatient or emergency services in the previous year. Those with serious impairment had levels of service utilization similar to the rest of the sample, but were more likely to report a poorer quality of life and unmet service needs. While the percentage experiencing social and occupational dysfunction was substantial and similar for both sexes, women appeared to be better integrated socially than men. Comparisons with schizophrenia patients within the same survey sample highlighted less chronic impairment but equal or greater utilization of services by bipolar patients. CONCLUSIONS: Despite low levels of chronicity, the burden of social disablement associated with bipolar disorder is high. The data suggest a number of important gaps in the provision of services for this predominantly treated population.

Pregnancy, delivery, and neonatal complications in a population cohort of women with schizophrenia and major affective disorders.

OBJECTIVE: This study ascertained the incidence of complications during pregnancy, labor, and delivery and the neonatal characteristics of infants born to women with schizophrenia, bipolar disorder, or major depression in a population-based cohort. METHOD: Based on records linkage across a psychiatric case register and prospectively recorded obstetric data, the study comprised women with schizophrenia or major affective disorders who had given birth to 3,174 children during 1980-1992 in Western Australia. A comparison sample of 3,129 births to women without a psychiatric diagnosis was randomly selected from women giving birth during 1980-1992. Complications were scored with the McNeil-Sjöström Scale. Odds ratios were calculated for specific reproductive events. RESULTS: Both schizophrenic and affective disorder patients had increased risks of pregnancy, birth, and neonatal complications, including placental abnormalities, antepartum hemorrhages, and fetal distress. Women with schizophrenia were significantly more likely to have placental abruption, to give birth to infants in the lowest weight/growth population decile, and to have children with cardiovascular congenital anomalies. Neonatal complications were significantly more likely to occur in winter; low birth weight peaked in spring. Complications other than low birth weight and congenital anomalies were higher in pregnancies after psychiatric illness than in pregnancies preceding the diagnosis. CONCLUSIONS: While genetic liability and gene-environment interactions may account for some outcomes, maternal risk factors and biological and behavioral concomitants of severe mental illness appear to be major determinants of increases in reproductive pathology in this cohort. Risk reduction in these vulnerable groups may be achievable through antenatal and postnatal interventions.

Linkage analysis in bipolar pedigrees adds support for a susceptibility locus on 21q22.

Several studies provide suggestive evidence of a susceptibility locus for bipolar disorder at chromosome 21q22-23. In an attempt to replicate these findings, we have analyzed linkage to 11 polymorphic markers from this region in 18 Bulgarian pedigrees with affective disorder. Two-point linkage analysis under assumption of homogeneity and a dominant model with reduced penetrance produced modest positive values for some of the markers tested under a 'narrow' phenotype definition, including bipolar I and II, and schizoaffective disorder. The maximum two-point score (lod=1.76, theta=0.00) was at marker D21S1919. Non-parametric linkage analysis under the same phenotype model, yielded positive NPLall values (P<0.05) over the region between markers D21S211 and D21S416, with a peak at D21S1252 (NPL Zall=2.32, P=0.0003). The multipoint lod score (GENEHUNTER) reached a suggestive value for linkage (lod=2.10) also at marker D21S1252. The results under a recessive model were completely negative. These data add to the evidence for the existence of a susceptibility locus for bipolar affective disorder on chromosome 21q22.

Differential impairment of working memory performance in first-degree relatives of individuals with schizophrenia.

BACKGROUND: Numerous studies have reported neuropsychological impairment in schizophrenia and increasing evidence suggests that individuals with schizophrenia or schizophrenia spectrum disorders and their unaffected first-degree family members exhibit similar deficits in some neuropsychological domains. Substantial modifications to the Wechsler Memory Scale (WMS) have resulted in more sensitive and reliable indicators of various aspects of memory functioning in the WMS-III, which enables generation of auditory, visual and working memory indices. OBJECTIVE: The aim of the present study was to examine the memory profile of individuals with schizophrenia or schizophrenia spectrum disorder (n = 19), their unaffected first-degree family members (n = 11), and healthy controls (n = 9). METHODS: The study involved neuropsychological testing, including the immediate and working memory subtests of the WMS-III, utilizing both auditory and visual domains. Symptom assessment was performed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), version 2.0. Two multivariate analyses of covariance (mancova) were conducted: (i) comparing patients, relatives and controls; and (ii) comparing relatives and controls only. RESULTS: The first analysis indicated that the patient group obtained significantly lower index scores than both relatives and controls on all three indices. The second analysis indicated that the performance of relatives was significantly lower than controls on the working memory index, although there were no significant differences on the auditory and visual immediate index scores. CONCLUSIONS: The differential impairment in working memory performance in clinically asymptomatic family members suggests that the WMS-III working memory index score may be a potential phenotypic marker of schizophrenia.

Death rate from ischaemic heart disease in Western Australian psychiatric patients 1980-1998.

BACKGROUND: People with mental illness suffer excess mortality due to physical illnesses. AIMS: To investigate the association between mental illness and ischaemic heart disease (IHD) hospital admissions, revascularisation procedures and deaths. METHOD: A population-based record-linkage study of 210 129 users of mental health services in Western Australia during 1980-1998. IHD mortality rates, hospital admission rates and rates of revascularisation procedures were compared with those of the general population. RESULTS: IHD (not suicide) was the major cause of excess mortality in psychiatric patients. In contrast to the rate in the general population, the IHS mortality rate in psychiatric patients did not diminish over time. There was little difference in hospital admission rates for IHD between psychiatric patients and the general community, but much lower rates of revascularisation procedures with psychiatric patients, particularly in people with psychoses. CONCLUSIONS: People with mental illness do not receive an equitable level of intervention for IHD. More attention to their general medical care is needed.

Duration mismatch negativity in biological relatives of patients with schizophrenia spectrum disorders.

BACKGROUND: One of the most consistent findings in schizophrenia research over the past decade is a reduction in the amplitude of an auditory event-related brain potential known as mismatch negativity (MMN), which is generated whenever a deviant sound occurs in a background of repetitive auditory stimulation. The reduced amplitude of MMN in schizophrenia was first observed for deviant sounds that differ in duration relative to background standard sounds, and similar findings have been observed for sounds that are deviant in frequency. The aim of this study was to determine whether first-degree relatives of schizophrenia patients show a similar reduction in MMN amplitude to duration deviants. METHODS: We measured MMN to duration increments (deviants 100 msec vs. standards 50 msec) in 22 medicated patients with a diagnosis in the schizophrenia spectrum, 17 individuals who were first-degree unaffected relatives of patients, and 21 healthy control subjects. RESULTS: Mismatch negativity amplitude was reduced in patients and relatives compared with control subjects. There were no significant differences between patients and relatives. In contrast, the subsequent positive component, P3a, was larger in relatives compared with patients. CONCLUSIONS: These findings suggest that a reduced MMN amplitude may be an endophenotype marker of the predisposition to schizophrenia.