Group-Dependent Associations Between Plasma Adiponectin and Hippocampal Subregional Volumes in Schizophrenia

Leptin and adiponectin are adipose-derived hormones that cross the blood-brain barrier and modulate hippocampal plasticity, neurogenesis, and inflammatory signaling. Dysregulated adipokine signaling may provide a biological link between systemic metabolic disturbances and hippocampal vulnerability in schizophrenia. This study investigated whether peripheral adipokines are associated with hippocampal subregional volumes in schizophrenia.

Thirty-five patients with schizophrenia (SCZ) and 29 healthy controls (HCs) were enrolled in this cross-sectional study. Plasma leptin and adiponectin were quantified using ELISA. Longitudinal hippocampal subregions were delineated manually, and transverse subfields were segmented using FreeSurfer. Group differences in adipokines were assessed with Welch's t-tests. Hippocampal volumetric differences were examined using MANCOVAs followed by univariate ANCOVAs, adjusting for age, sex, body mass index (BMI), and estimated total intracranial volume (eTIV). Group-dependent adipokine-volume associations were evaluated using group × adipokine interaction models followed by group-stratified regression analyses.

Plasma leptin was significantly higher in SCZ than in HCs, whereas adiponectin showed a non-significant reduction. Patients with schizophrenia exhibited widespread hippocampal atrophy across both longitudinal and transverse subregions. Within the schizophrenia group, higher plasma adiponectin was associated with smaller hippocampal head volume, whereas no corresponding association was observed in healthy controls.

Adiponectin-hippocampal associations appeared group-dependent within this sample. Higher plasma adiponectin was associated with smaller hippocampal head volume in schizophrenia but not in healthy controls, supporting further investigation of metabolic-neural relationships in larger longitudinal and mechanistic studies.