Effects on Multimodal Connectivity Patterns in Female Schizophrenia During 8 Weeks of Antipsychotic Treatment

Respective abnormal structural connectivity (SC) and functional connectivity (FC) have been reported in individuals with schizophrenia. However, transmodal associations between SC and FC following antipsychotic treatment, especially in female schizophrenia, remain unclear. We hypothesized that increased SC-FC coupling may be found in female schizophrenia, and could be normalized after antipsychotic treatment.

Sixty-four female drug-naïve patients with first-diagnosed schizophrenia treated with antipsychotic drugs for 8 weeks, and 55 female healthy controls (HCs) were enrolled. Magnetic resonance imaging (MRI) data were collected from HCs at baseline and from patients at baseline and after treatment. SC and FC were analyzed by network-based statistics, calculating nonzero SC-FC coupling of the whole brain and altered connectivity following treatment. Finally, an Elastic-net logistic regression analysis was employed to establish a predictive model for evaluating the clinical efficacy treatment.

At baseline, female schizophrenia patients exhibited abnormal SC in cortico-cortical, frontal-limbic, frontal-striatal, limbic-striatal, and limbic-cerebellar connectivity compared to HCs, while FC showed no abnormalities. Following treatment, cortico-cortical, frontal-limbic, frontal-striatal, limbic-striatal, temporal-cerebellar, and limbic-cerebellar connectivity were altered in both SC and FC. Additionally, SC-FC coupling of altered connectivity was higher in patients at baseline than in HC, trending toward normalization after treatment. Furthermore, identified FC or/and SC predicted changes in psychopathological symptoms and cognitive impairment among female schizophrenia following treatment.

SC-FC coupling may be a potential predictive biomarker of treatment response. Cortico-cortical, frontal-limbic, frontal-striatal, limbic-striatal, temporal-cerebellar, and limbic-cerebellar could represent major targets for antipsychotic drugs in female schizophrenia.