Antipsychotic-related remodeling of regional brain activity in schizophrenia

This study characterized longitudinal changes in regional brain functional activity after second-generation antipsychotic treatment in patients with schizophrenia (SZ) and examined their associations with clinical symptoms and cognition.

Thirty-three patients with SZ received 12 weeks of second-generation antipsychotic treatment, and 37 healthy controls (HCs) were assessed at matched time points. All participants underwent resting-state functional MRI at baseline and at the 12-week follow-up. Regional spontaneous activity was assessed using amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo). Symptoms and cognition were evaluated with the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB). Analyses were adjusted for age, sex, and education.

At baseline, patients showed increased ALFF in the left hippocampus and right caudate, increased fALFF and ReHo in the left precuneus, and decreased fALFF and ReHo in the right postcentral gyrus compared with HCs. At the 12-week follow-up after treatment, between-group comparisons showed increased ALFF in the right middle temporal pole and right medial orbitofrontal cortex, and decreased ReHo in the right insula and bilateral postcentral gyri. Brain-behavior analyses showed that left precuneus fALFF was positively associated with depressive symptoms, right postcentral gyrus fALFF was negatively associated with semantic fluency, and right middle temporal pole ALFF was positively associated with PANSS positive symptoms.

SZ patients exhibited persistent and treatment-associated regional abnormalities in spontaneous brain activity, suggesting compensatory functional alterations and residual pathological processes after antipsychotic treatment.