Abstract

Schizophrenia (SCZ) is a chronic brain disease characterized by patterns of positive, negative, and cognitive symptoms that interfere with daily functioning and persist throughout the lifespan. Clinical and cognitive symptoms differ between males and females with the disease, suggesting neurobiological abnormalities that vary on the basis of biological sex. The present study used high-dimensional brain mapping and network analysis procedures of cortical and limbic regions known to be involved in memory formation to investigate sex differences in brain correlates of episodic memory among patients with schizophrenia. This study analyzed multi-site archival data from 363 male (M) and 108 female (F) participants with SCZ, as well as 304 male and 191 female healthy controls (CON) from six cross-sectional study samples. Episodic memory (EM) performance was collected from both verbal and visual measures to assess the main effects and interaction of diagnosis and biological sex. A total of 360 cortical regions were derived from imaging data using the Human Connectome Project's Multi-Modal Parcellation (HCP-MMP1), and surface features of the hippocampus were derived through application of FreeSurfer-initiated large-deformation diffeomorphic metric mapping (LDDMM). Four separate contrasts were conducted for network analysis measures: 1) Schizophrenia-Male/Control-Male; 2) Schizophrenia-Female/Control-Female; 3) Schizophrenia-Male/Schizophrenia-Female; 4) Control-Male/Control-Female. Structural covariance network analysis was based on the volume of regions of interest, and global efficiency and number of connections were calculated for each group. Finally, the structural covariance was calculated among the top brain regions with the strongest correlations with EM performance. The findings of the present study showed main effects of diagnosis and sex on EM performance, and a nonsignificant interaction. With regard to structural covariance networks, there were significant differences in global efficiency and degree based on biological sex and diagnosis. SCZ participants, especially females, demonstrated stronger efficiency and a greater number of connections compared to CON, especially across default mode and secondary visual networks. Top-n regions associated with EM performance varied between SCZ males and females, with regions in the cingulo-opercular network for SCZ males and regions in the default mode, language, and secondary visual networks for SCZ females. Findings are consistent with prior volume-based analyses and studies investigating differences in cognitive performance between healthy males and females, although research focusing on sex differences in structural covariance networks is limited. Network analysis reveals differences on the basis of diagnosis and biological sex that can offer important insights regarding episodic memory impairment among individuals with schizophrenia, early detection strategies, and personalized interventions that aim to improve quality of life.

Degree

PhD

College and Department

Family, Home, and Social Sciences; Psychology

Rights

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