While it is known that children of schizophrenia parents perform more poorly on tests of cognitive functioning than children of normal parents, less certain is the degree to which such deficits predict schizophrenia outcome, whether cognitive functioning deteriorates during childhood in preschizophrenia individuals, and whether nongenetic etiologic factors (such as obstetric complications) contribute to these deficits. In the present study, 72 patients with schizophrenia or schizoaffective disorder, 63 of their siblings not diagnosed with schizophrenia, and 7,941 controls with no diagnosis were ascertained from a birth cohort whose members had been evaluated with standardized tests of cognitive functioning at 4 and 7 years of age. Adult psychiatric morbidity was ascertained via a longitudinal treatment data base indexing regional public health service utilization, and diagnoses were made by review of all pertinent medical records according to DSAf-TV criteria. Both the patients with schizophrenia and their unaffected siblings performed significantly worse than the nonpsychiatric controls (but did not differ from each other) on verbal and nonverbal cognitive tests at 4 and 7 years of age. Preschizophrenia cases and their siblings were increasingly overrepresented across decreasing quartiles of the performance distributions. There was not significant intra-individual decline, and there were no significant relationships between obstetric complications and test performance among the preschizophrenia subjects. These results suggest that during the period from age 4 to age 7 years, premorbid cognitive dysfunction in schizophrenia represents a relatively stable indicator of vulnerability deriving from primarily genetic (and/or shared environmental) etiologic influences. Findings of cytoarchitectural and morphologic brain changes consistent with a prenatal and perinatal origin have led to the notion that neurodevelopmental disturbances contribute to the etiology of at least some cases of adult schizophrenia (Kovelman and Scheibel 1984;Jakob and Beckmann 1986;Weintraub 1987;Arnold et al. 1991;Akbarian et al. 1993;Cannon et al. 1993). However, the etiologic correlates of these disturbances and the proportion of the population with schizophrenia that they characterize remain to be determined (Lewis and Murray 1987;Cannon and Mednick 1991). Prospective examination of cognitive functioning in individuals who develop schizophrenia as adults provides an indirect means to address these questions. Longitudinal "high-risk" studies have consistently reported that children of patients with schizophrenia perform more poorly on neuropsychological tests than children of other people (Mednick and Schulsinger 1968;Landau et al. 1972;Asarnow et al. 1978;Rutschmann et al. 1980;Harvey et al. 1981;Winters et al. 1981;Worland et al. 1982;Driscoll 1984;Lifshitz et al. 1985;Sohlberg 1985;Hallett et al. 1986;Fish 1987;Goodman 1987;Sameroff et al. 1987;Weintraub 1987;Erlenmeyer-Kimling et al. 1989;Schreiber et al. 1992;Marcus et al. 1993...

2 ) in a sample of 482 nuclear families segregating extreme obesity and normal weight. MEASUREMENTS: Individual BMI, history of depression treatment and covariates (age, sex, race, education, marital status, socioeconomic status, chronic medical conditions and exercise program). RESULTS: Greater odds for depression were found for the obese, European American, women, the unmarried, the more educated, those with chronic physical disorder(s) and the offspring of depressed parents. A trend test found that the odds ratios for depression increased with BMI and number of chronic medical conditions (Po0.0001). Multivariate logistic regression analyses indicated that BMI, race, marital status, chronic medical conditions and family history were the predicators of depression for both the genders. Hierarchical analyses revealed that BMI significantly increased the risk above that predicated by the combined effects of all other variables. CONCLUSIONS: Extreme obesity was associated with the increased risk for depression across gender and racial groups, even after controlling for chronic physical disease, familial depression and demographic risk factors. More detailed research is needed to determine the underlying mechanisms.

A number of lines of evidence converge in implicating neurodevelopmental processes in the etiology and epigenesis of schizophrenia. In this study we used a prospective, longitudinal design to examine whether adverse obstetric experiences predict schizophrenia and whether there is a deviant functional–developmental trajectory during the first 7 years of life among individuals who manifest schizophrenia as adults. The 9,236 members of the Philadelphia cohort of the National Collaborative Perinatal Project were screened for mental health service utilization in adulthood, and chart reviews were performed to establish diagnoses according to DSM-IV criteria. The risk for schizophrenia increased linearly with the number of hypoxia-associated obstetric complications but was unrelated to maternal infection during pregnancy or fetal growth retardation. Preschizophrenic cases (and their unaffected siblings who were also cohort members) manifested cognitive impairment, abnormal involuntary movements and coordination deficits, and poor social adjustment during childhood. There was no evidence of intraindividual decline in any domain, but preschizophrenic cases did show deviance on an increasing number of functional indicators with age. Together, these findings suggest that both genetic and obstetric factors participate in creating a neural diathesis to schizophrenia, the phenotypic expressions of which are age dependent, probably reflecting the maturational status of a number of interconnected brain systems.

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