Hippocampal Structural Changes and Antipsychotic Medication in Schizophrenia Spectrum Disorder: A Systematic Review and Meta-Analysis of Longitudinal MRI Studies Highlighting Current Evidence Gaps.
INTRODUCTION The hippocampus is among the most affected brain structures in schizophrenia and plays a central role in the core pathology of psychotic disorders. Despite observations that hippocampal structural deficits emerge from the early stages of schizophrenia, it remains unclear how these changes progress over the disease course and how antipsychotic medication influences them. METHODS We conducted a systematic review of longitudinal, volumetric MRI studies of patients with First-Episode Psychosis (FEP) and those at the Chronic stage (CH), and extracted data on hippocampal volume and antipsychotic medication exposure for meta-analysis. Both the review and the analysis conformed to PRISMA 2020 guidelines. RESULTS Eighteen reports were included. Longitudinal analysis of the FEP group revealed no significant change in hippocampal volume over time (scan interval), likely due to substantial heterogeneity across studies. By contrast, the CH group exhibited a significantly faster, albeit subtle, reduction in hippocampal volume compared with Healthy Controls (HC). The meta-regression analysis revealed no significant associations between hippocampal volume reduction and any examined factors, including antipsychotic medication exposure, likely reflecting the small number of studies and the paucity of medication-related data. DISCUSSION The pace of hippocampal volume change appears to differ between the early and chronic stages. CONCLUSIONS Substantial heterogeneity and insufficient available data in the current literature limit the ability to draw firm conclusions regarding hippocampal volume changes across disease stages or their relationship with antipsychotic medication. The pace of these changes may differ between the FEP and CH stages, but this observation should be interpreted cautiously. Further longitudinal MRI studies with more detailed and consistent reporting of medication-related variables are needed to clarify these relationships.