The effect of antipsychotic medications on white matter integrity in first-episode drug-naive patients with psychosis: A review of DTI studies

Background: Psychotic episodes have been associated with damage to both grey matter (GM) and white matter (WM). Although a recent meta-analysis suggest that in long term treatment, first generation antipsychotics (FGA) are associated with progressive reduction in GM, second generation antipsychotics (SGA) seem to have benefits to WM microstructure. Methods: A search was conducted to identify controlled trials published from January 2000 to January 2021, which assessed WM integrity as measured by DTI in drug-naive patients with FEP before and after antipsychotic administration. Results: 3 studies met the criteria for inclusion. All studies demonstrated lower FA in psychotic patients vs HC. A 6-week study reported that antipsychotic medication results in a further decrease in FA within the bilateral ACG and right ACR, regions important in emotional processing. An 8-week study found that antipsychotic treatment increase FA in the SLF, resulting in improved symptoms and increased processing speed. A 3rd study found an increase in FA in several regions along with a negative correlation between FA and PANSS at remission. Conclusions: Drug-naive FEP patients have WM dysfunction at baseline and antipsychotic medications appear to alter or improve WM especially at remission. More controlled trials are warranted to validate these conclusions.