Abstract
Background: A number of studies have reported decreased white matter integrity in patients with schizophrenia, but little is known the relationship between white matter alterations and response to antipsychotic treatment. Methods: We enrolled 30 unmedicated patients with schizophrenia in a 6-week longitudinal trial with risperidone, a commonly used antipsychotic medication. Symptom severity was assessed with the Brief Psychiatric Rating Scale (BPRS). We obtained diffusion-weighted images before treatment was started. Thirty diffusion sampling directions spanning the whole sphere were acquired twice and concatenated (in plane resolution 2.2 mm, slice thickness 2.2 mm, b-value 1000 s/mm(2), 5 b0 images). Motion and eddy current correction were performed with the FSL EDDY tool. Diffusion data were then reconstructed in MNI space using q-space diffeomorphic reconstruction to obtain the spin distribution function, with a sampling length ratio of 1.25. Group diffusion connectometry was performed to examine the relationship between connectivity and clinical response after 6 weeks of treatment (defined as [BPRS total baseline − BPRS total week 6]/ BPRS total at baseline × −100) with multiple regression analyses using age and sex as covariates. Local connectomes were tracked using a deterministic fiber-tracking algorithm, with seeding density of 100 seeds/ mm(2), t-threshold of 2.3, and length threshold of 50 mm; all tracks from bootstrap resampling were included. Track trimming was conducted with 5 iterations. A total of 2000 randomized permutations were applied to obtain the null distribution of the track length. Results: Connectometry analysis indicated that greater connectivity in the corpus callosum, external capsule, and cerebellar peduncle at baseline is related to better treatment response after 6 weeks of treatment; no tracks with lower connectivity related to treatment response were found. Conclusion: Our results suggest a relationship between white matter integrity and response to antipsychotic medications. Future studies investigating the pathophysiological mechanisms underlying white matter alterations will be important for targeted drug development and ultimately improvement of outcomes in patients with poor response to conventional antipsychotic medications.