Women have consistently demonstrated better verbal memory on tests that evaluate immediate and delayed free recall. In patients with
schizophrenia, these verbal memory processes are relatively more preserved in women than men. However an understanding of the brain anatomy of the female advantage for verbal memory is still unclear. 29 females and 59 males with
schizophrenia made comparable to 21 female and 27 male healthy volunteers were scanned using structural magnetic resonance imaging (sMRI) in order to assess volumes of regions across the entire brain. Sex differences within and between groups in the covariance structure of memory circuitry regions were evaluated using a novel approach to covariance analysis (the Box M Test). Brain areas of interest included the prefrontal cortex (PFC), inferior parietal lobule (iPAR), anterior cingulate gyrus (
ACG), parahippocampus, and hippocampus (HIPP). Results showed significant differences in the covariance matrices of females and males with
schizophrenia compared with their healthy counterparts, in particular the relationships between iPAR-PFC, iPAR-
ACG, and HIPP-PFC. Sex differences in the iPAR-PFC relationship were significantly associated with sex differences in verbal memory performance. In control women, but not in men
ACG volume correlated strongly with memory performance. In
schizophrenia,
ACG volume was reduced in females, but not in men, relative to controls. Findings suggest that the relationship between iPAR and PFC is particularly important for understanding the relative preservation of verbal memory processing in females with
schizophrenia and may compensate for
ACG volume reductions. These results illustrate the utility of a unique covariance structure modeling approach that yields important new knowledge for understanding the nature of
schizophrenia.