Sex‐differential associations between cognitive impairments and white matter abnormalities in first episode and drug‐naïve schizophrenia

Abstract

Aim Previous evidence has suggested that schizophrenia patients may display sex differences in cognitive impairments and cognitive impairments are related to disrupted white matter (WM) microstructure. The current research aims to address the intriguing possibility for the sex‐specific association between cognitive deficits and WM abnormalities in first‐episode and drug‐naïve schizophrenia. Methods Cognitive performance on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was measured in 39 FEND patients (females:males = 23:16) and 30 healthy controls (females:males = 17:13), together with whole‐brain WM fractional anisotropy (FA) values determined using voxel‐based diffusion tensor imaging. Correlations between cognitive performance and FA values were assessed. Results Patients performed significantly worse than healthy controls in the total score and most of the subscores of MCCB. Female patients displayed better cognitive performance than male patients on the Trail Making A Test, the Hopkins Verbal Learning Test and the Spatial Span Test in the Wechsler Memory Scale. More importantly, sex‐differential association between cognitive performance and FA values was found in patients, but not in healthy controls. In particular, FA values in the cerebellum were negatively correlated with the continuous performance and digital sequence scores in male patients but positively correlated with the performance on the Spatial Span Test in the Wechsler Memory Scale in female patients. Conclusions These findings suggest sex‐specific neurobiological substrates involved in cognitive deficits in early‐onset schizophrenia and have important implications for differentially targeted interventions between males and females.

The Poly I:C maternal immune stimulation model shows unique patterns of brain metabolism, morphometry, and plasticity in female rats

“…Moreover, PET studies have shown cortical and subcortical reductions in glucose metabolism at global and specific brain regions compared to controls (Townsend et al, 2022 ), but none of them has studied sex-differences. Some functional magnetic resonance imaging (fMRI) studies have also found sex differences in cerebral function in patients with schizophrenia and the first episode in brain areas associated with different cognitive domains (Mazza et al, 2021 ; Yang et al, 2021 ).…”

The relationship between sex and functional outcome in first-episode schizophrenia: the role of premorbid adjustment and insight

“…The literature on cognitive deficits in FES is comparable with that on multi-episode patients showing that cognitive deficits are present (Mesholam-Gately, Giuliano, Goff, Faraone, & Seidman, 2009 ) and that there is a relationship between neurocognitive and social cognitive functioning and outcome in first episode patients (Fu, Czajkowski, Rund, & Torgalsbøen, 2017 ; Horan et al, 2012 ; Milev, 2005 ). Further, FES studies show that males perform better in the domain of visual perception while females perform better in domains such as verbal learning and memory (Fu et al, 2017 ; Hui et al, 2016 ; Pu et al, 2019 ; Torgalsbøen, Mohn, & Rund, 2014 ; Yang, Gao, Xiong, & Zhang, 2021 ). In one of the largest studies of sex differences in FES, late onset male patients were found to be more impaired than females on measures of verbal memory, executive functions, and other areas of cognitive performance (Ayesa-Arriola et al, 2020 ).…”