Relationship between prefrontal gray matter volumes and working memory performance in schizophrenia: a family study.

Diffuse structural abnormalities in the prefrontal cortex have been reported in both schizophrenia patients and their nonpsychotic biological relatives. Additionally, working memory difficulties have long been documented in schizophrenia patients and have been associated with the genetic liability for the disorder. The present analysis investigated the relationship between prefrontal regional gray matter volumes and two facets of working memory in schizophrenia using a family study. Structural neuroimaging scans provided measurements of rostral middle, superior, and inferior prefrontal cortical gray matter volumes. Participants also completed a spatial working memory task that measured both short-term maintenance and manipulation of material in memory. Both schizophrenia patients and relatives had reduced superior and inferior frontal gray matter volumes. Schizophrenia patients demonstrated a spatial working memory deficit compared to both controls and relatives, with no greater impairment when required to manipulate material. Smaller prefrontal volumes in schizophrenia patients were associated with worse working memory performance. These relationships were absent in the nonpsychotic relatives and controls. Despite normative behavioral performance, nonpsychotic relatives demonstrated abnormalities in brain structure similar to those found in schizophrenia patients. Manipulation abilities were not more impaired than maintenance in schizophrenia patients. Consistent with other neuroimaging research, our results suggest that direct measures of the underlying biology may be more sensitive to the effects of the genetic liability for schizophrenia than behavioral measures.