Impact of second-generation antipsychotics on white matter microstructure in schizophrenia: A DTI study

Second-generation antipsychotics are widely prescribed for schizophrenia and other psychiatric disorders; however, their potential effects on cerebral white matter (WM) microstructure and associated cognitive changes remain poorly characterized.

Diffusion tensor imaging (DTI) was performed in 43 drug-naïve patients with schizophrenia and 44 healthy controls at baseline, and repeated after 8 weeks during which patients received antipsychotic treatment. Tract-based spatial statistics (TBSS) were applied to assess changes in WM microstructural integrity. Cognitive performance was evaluated using selected measures from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), including story recall, line orientation, picture naming, semantic fluency, digit span, coding, and word recall.

At baseline, no significant group differences were observed in fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), or mean diffusivity (MD). Following treatment, compared with healthy controls, patients exhibited decreased FA in the body of the corpus callosum; increased MD across nearly all WM regions; and elevated RD in the genu and body of the corpus callosum, bilateral anterior corona radiata, left superior corona radiata, and left superior longitudinal fasciculus. Spearman correlation analyses revealed that RD values in RD_cluster1 and RD_cluster2 were negatively correlated with digit span scores (r = -0.359, p = 0.018; r = -0.35, p = 0.021). Although clinical symptoms improved during this period, changes in FA, MD, and RD were not associated with symptom improvement or antipsychotic dosage.

These findings suggest that antipsychotic treatment exerts potential effects on WM microstructure and cognitive function in drug-naïve patients with schizophrenia.