Covariance modeling of MRI brain volumes in memory circuitry in schizophrenia: Sex differences are critical

Abstract

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.

Figure 1

Two cortical parcellations, one for a female (A) and male (B) patient with schizophrenia, which illustrate the location of the regions we defined as PFC (blue), ACG (pink), HIPP (yellow), and iPAR (orange). Overlaid on these parcellations are the correlations between the volumes of these brain regions for all females with schizophrenia (A) and all males with schizophrenia (B). Solid lines indicate a positive correlation and dashed lines indicate a negative correlation. Note: Brains are rotated slightly in the x and y plane to display clearly these regions of interest.