Abstract

Schizophrenia (SCZ) is characterized by a disconnect from reality that manifests as various clinical and cognitive symptoms, as well as consistent neurobiological abnormalities. However, unique sex-related differences have been observed regarding clinical presentation that imply separate brain substrates. The present study characterized deep-brain morphology using shape features to understand whether the neurobiology of schizophrenia varies as a function of sex. This study analyzed multi-site archival data from 1,579 male (M) and 836 female (F) participants with SCZ, as well as 1,934 male and 1,828 female healthy controls (CON) from twenty-four cross-sectional study samples from the ENIGMA Schizophrenia Workgroup. Harmonized shape analysis protocols were applied to each site's data independently for bilateral caudate, putamen, globus pallidus, accumbens, amygdala, hippocampus, and thalamus obtained from T1-weighted structural MRI scans. Four separate contrasts were conducted: 1) Schizophrenia-Male/Control-Male; 2) Schizophrenia-Female/Control-Female; 3) Schizophrenia-Male/Schizophrenia-Female; 4) Control-Male/Control-Female. For contrasts 1 & 2, mass univariate meta-analyses revealed more-concave-than-convex shape differences for the hippocampus, amygdala, accumbens, and thalamus, with more-convex-than-concave differences in the putamen and pallidum (d = -0.30 to 0.30, SE = 0.03 to 0.10, p<0.05) in SCZ for both male and female group comparisons. More extensive patterns of deformation were noted in right hippocampus and right thalamus for SCZ women. Contrasts 3 & 4 revealed more-concave-than-convex shape differences in the thalamus, pallidum, putamen, and amygdala among females compared to males, with mixed findings in the hippocampus and caudate in both SCZ and CON contrasts (d = -0.30 to 0.20, SE = 0.03 to 0.09, p<0.05). Pattern and extent of deformation was greater in dorsal, ventral, and lateral aspects of putamen, thalamus, amygdala, and pallidum in SCZ. Findings are consistent with prior volume-based analyses in SCZ, as well as earlier studies on sex differences in the brain. Shape patterns reveal more extensive abnormalities in SCZ women relative to SCZ men that could aid in our understanding of clinical expression and treatment response differences between men and women.

Degree

MS

College and Department

Family, Home, and Social Sciences; Psychology

Rights

https://lib.byu.edu/about/copyright/

Date Submitted

2023-06-06

Document Type

Thesis

Handle

http://hdl.lib.byu.edu/1877/etd12796

Keywords

schizophrenia, sex differences, deep brain shape, meta-analysis, neuroimaging

Language

english

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