Familial/sporadic schizophrenia: Differences in neuropsychological function

Abstract

There is now substantial evidence that both genetic and environmental factors play a role in the etiology of schizophrenia; however, little is known about the relationships between these factors and known markers for schizophrenia. In this paper we apply the familial/sporadic subtyping method as a first step towards examining the contribution of familial (approximated to genetic in this study) and environmental factors to relevant neurobiological markers in schizophrenia. Specifically, we compare cerebral ventricular size and neuropsycho[ogical function in schizophrenic patients with and without a first-degree relative with schizophrenia. Family history was ascertained by interview with the patient and a family member and a review of the medical record in 48 schizophrenic inpatients diagnosed by SADS/RDC and DSM-III-R criteria. Seven patients had a first-degree relative with schizophrenia. Neuropsychological functions were measured on the Wechsler Adult Intelligence Scale-Revised (full scale IQ, verbal IQ, and performance IQ); Trail Making Test Part B; Reaction Time (choice); Wisconsin Card Sorting Test (WCST); and the Controlled Oral Word Association Test. IQ, Trails B, and WCST scores were standardized to acoount for differences in age, sex, and education levels. Ventricle-brain ratios (VBRs) were calculated from CT scans. Patients with positive (FHpos) and negative (FHneg) family histories did not differ on the severity of either positive or negative symptomatology. Our results showed that a negative family history was associated with increased VBR (means -FHpos: 0.06; FHneg: 0.09; p = 0.06); these findings are consistent with several other reports. Of the neuropsychological indicators, only scores on Trails B differed significantly in the FHpos and FHneg groups; positive family history was associated with worse functioning (FHpos: 62.7; FHneg: 84.1; Mann-Whitney U: p = 0.01). These data suggest that nonfamilial factors contribute to ventricular enlargement while familial factors contribute to frontal lobe deficits in schizophrenia. This might reflect the presence of ventricular enlargement and frontal lobe neuropsychological dysfunction on separate pathogenetic pathways in schizophrenia. The results support the utility of the familial/sporadic approach in studying the pathogenetic heterogeneity of schizophrenia.