Hippocampal perfusion abnormalities and treatment effects in acute phase of first-episode schizophrenia

A subset of first-episode schizophrenia (FES) patients responds poorly to initial antipsychotic therapy. The hippocampus is an early-affected region in schizophrenia, yet neurobiological markers predicting treatment response remain unclear. Arterial spin labeling (ASL) magnetic resonance imaging (MRI) allows non-invasive measurement of cerebral blood flow (CBF), but studies on hippocampal perfusion in acute FES, particularly in those receiving electroconvulsive therapy (ECT) with antipsychotics, are limited.

Fifty FES patients and 28 age- and sex-matched healthy controls underwent high-resolution ASL MRI to assess hippocampal CBF. Patients received either antipsychotics alone (n = 20) or in combination with ECT (n = 30). MRI Scans were acquired before and after six weeks of treatment. Analysis of covariance and linear mixed-effects models were used to assess group differences and longitudinal effects, adjusting for relevant covariates.

At baseline, FES patients exhibited significantly lower hippocampal CBF compared to healthy controls, with no significant difference in hippocampal volume. Longitudinal analysis revealed a significant group × time interaction for hippocampal CBF. Post hoc analysis indicated a significant increase in CBF after treatment in the FES group, while hippocampal volume remained unchanged. CBF changes were not significantly correlated with symptom reduction. We further examined the group differences in longitudinal changes between the ECT + Drug group and the Drug group, however no significant results were found.

Our findings suggest that functional, but not structural, hippocampal alterations are present in early schizophrenia and may be responsive to treatment. These preliminary results should be interpreted cautiously and validated in larger samples with extended follow-up and neurochemical assessments.