Medial temporal lobe and basal ganglia volume trajectories in persistent negative symptoms following a first episode of psychosis

Persistent negative symptoms (PNS, e.g., avolition, anhedonia, alogia) are present in up to 30% of individuals diagnosed with a first episode of psychosis and greatly impact functional outcomes. PNS and secondary PNS (sPNS: concomitant with positive, depressive, or extrapyramidal symptoms) may index distinct pathophysiologies reflected by structural brain changes, particularly in the medial temporal lobe (MTL) and basal ganglia. We sought to characterize dynamic brain changes related to PNS over the course of 2 years following a first episode of psychosis. Longitudinal volumetric trajectories within the MTL (hippocampus, parahippocampal gyrus, entorhinal cortex, perirhinal cortex) and basal ganglia (caudate, putamen, pallidum) were investigated in 98 patients with first-episode psychosis and 86 healthy controls using generalized estimating equations. In left hippocampus, PNS (n = 25 at baseline) showed decreased volumes over time, sPNS (n = 26) volumes remained stable, and non-PNS (n = 47) volumes increased over time to control levels. PNS-specific changes were observed in left hippocampus and left perirhinal cortex, with the greatest decline from 12 to 24 months to levels significantly below those of non-PNS and controls. Affective/non-affective diagnosis, antipsychotic medication dosage and adherence at baseline did not significantly impact these findings. Basal ganglia volume trajectories did not distinguish between PNS and sPNS. The current study highlights distinct structural brain trajectories in PNS that are prominent in the left MTL. Basal ganglia alterations may contribute to PNS irrespective of their etiology. Left MTL volume reductions were most evident after 1 year of treatment, highlighting the importance of targeted early interventions. •Distinct 24-month brain volume trajectories for PNS in first-episode psychosis.•Medial temporal lobe volumes decreased in PNS, stable in sPNS, increased in non-PNS.•Basal ganglia trajectories did not distinguish PNS groups.•Peak volume reductions at 12 to 24 months in PNS support early interventions.