Globally and Locally Reduced MRI Gray Matter Volumes in Neuroleptic-Naive Men With Schizotypal Personality Disorder Association With Negative Symptoms

Importance: Some, but not all, previous magnetic resonance imaging studies have indicated smaller cortical and local gray matter volumes (GMVs) in men with schizotypal personality disorder (SPD) compared with healthy control (HC) subjects. Thus, there is need for a whole-brain comparison to resolve inconsistencies and provide hitherto generally absent data on the association between GMV and symptoms. Objective: To use voxel-based morphometry to evaluate a large sample of neuroleptic-naive men with SPD compared with group-matched HC subjects on local and global GMV and to identify associations with symptoms, especially negative symptoms. Also, to determine whether age-related GMV reductions are greater in men with SPD than HC subjects, providing presumptive evidence on possible progression. Design, Setting, and Participants: This naturalistic study involved 54 neuroleptic-naive men with SPD and 54 male HC subjects aged 18 to 55 years recruited from the community and scanned on the same 1.5-T GE magnetic resonance imaging scanner. Participants were group matched on age, socioeconomic status, handedness, and IQ. Main Outcome Measures: Cross-sectional voxel-based morphometry, GMV in subjects with SPD and HC participants, and the relationship to clinical symptoms. Results: A voxelwise analysis showed participants with SPD had significantly smaller GMV in the left superior temporal gyrus and widespread frontal, frontolimbic, and parietal regions compared with HC subjects. Most of these regional volumes were strikingly and significantly correlated with negative symptoms: the more the volume reduction, the more negative symptoms. Global cortical GMV and most regional GMV showed significant negative relationships with age in both those with SPD and HC subjects, without any group by age interactions. Conclusions and Relevance: Men with SPD showed global and widespread smaller regional GMV. The regional structural abnormalities were correlated with the severity of a participant's negative symptoms. While the pattern of GMV loss is similar to that in schizophrenia, the similar patterns of HC-SPD age-related GMV reduction suggest that SPD showed no progressive GMV loss, pointing to an important difference in the biological mechanisms of SPD and schizophrenia.