Sex difference in association of symptoms and white matter deficits in first-episode and drug-naive schizophrenia

Abstract

Accumulating evidence shows that disruption of white matter (WM) may be involved in the pathophysiology of schizophrenia, even at the onset of psychosis. However, very few studies have explored sex difference in its association with psychopathology in schizophrenia. This study aims to compare sex differences in clinical features and WM abnormalities in first-episode and drug-naive (FEDN) schizophrenia among Han Chinese inpatients. The WM fractional anisotropy (FA) values of the whole-brain were determined using voxel-based diffusion tensor imaging (DTI) in 39 (16 males and 23 females) FEDN patients with schizophrenia and 30 healthy controls (13 males and 17 females) matched for gender, age, and education. Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).Our results showed that compared with the controls, the patients showed widespread areas of lower FA, including corpus callosum, brainstem, internal capsule, cingulate, and cerebellum (all adjusted p < 0.01). Further, male patients showed lower FA values in left cingulate (F = 4.92, p = 0.033), but higher scores on the PANSS total, positive, and general psychopathology subscale scores (all p < 0.01) than female patients. Multivariate regression analysis showed that for male patients, FA values in right corpus callosum were positively associated with the PANSS total (beta = 0.785, t = 3.76, p = 0.002) and the negative symptom scores (beta = 0.494, t = 2.20, p = 0.044), while for female patients, FA values in left cingulate were negatively associated with the PANSS positive symptom score (beta = −0.717, t = −2.25, p = 0.041). Our findings indicate sex difference in white matter disconnectivity and its association with psychopathological symptoms in an early course of schizophrenia onset.

Sex-specific Association of Antipsychotic-induced Weight Gain and Treatment Response for Antipsychotic-Naive First Episode Schizophrenia Patients: A Prospective 8-week Longitudinal Study

“…Previous studies that focused on sex differences in chronic SZ patients showed more negative symptoms but fewer positive symptoms in males than females [7,9]. In this study, we found that sex differences in patients with first-episode SZ were significant only in terms of negative symptoms, as found in some other studies [8,37]. However, several studies reported no sex differences in symptoms among ANFE patients with SZ [38,39].…”

“…Cowell et al published one of the earlier studies showing that female patients with SZ receiving clozapine had significantly greater weight gain than male patients [5], and later work has confirmed these sex differences in antipsychotic-induced weight gain [6][7][8].…”

Characteristics of gray matter alterations in never-treated and treated chronic schizophrenia patients

“…Second, we note that the sex ratio is significantly different among the 4 groups. Previous studies [57][58][59] explored the impact of sex differences on the brain features of schizophrenia, but the results are inconsistent, even a study 58 reported no significant differential sex effects in schizophrenia for either GM cortical thickness or subcortical volume development. In this study, we took age and sex as covariates by ANCOVA analysis to control for potential confounding effects and found that sex has no interactive effect on the results.…”

A new sex-specific underlying mechanism for female schizophrenia: accelerated skewed X chromosome inactivation

“…There are many differences in clinical symptoms, the age of disease onset, and antipsychotic treatment response between male and female SCZ patients [3,[40][41][42]. Abnormal X chromosome function may play an essential role in the sex-related phenotype of SCZ [4].…”