In Vivo Cerebral Translocator Protein (TSPO) Binding and Its Relationship with Blood Adiponectin Levels in Treatment-Naive Young Adults with Major Depression: A [11C]PK11195 PET Study

Adiponectin is an adipokine that mediates cellular cholesterol efflux and plays important roles in neuroinflammatory processes. In this study, we undertook positron emission tomography (PET) with the translocator protein (TSPO) ligand [C-11]PK11195 and measured serum adiponectin levels in groups of treatment-naive young adult patients with major depressive disorder (MDD) and matched healthy controls. Thirty treatment-naive MDD patients (median age: 24 years) and twenty-three healthy controls underwent [C-11]PK11195 PET. We quantified TSPO availability in brain as the [C-11]PK11195 binding potential (BPND) using a reference tissue model in conjunction with the supervised cluster analysis (SVCA4) algorithm. Age, sex distribution, body mass index, and serum adiponectin levels did not differ between the groups. Between-group analysis using a region-of-interest approach showed significantly higher [C-11]PK11195 BPND in the left anterior and right posterior cingulate cortices in MDD patients than in controls. Serum adiponectin levels had significant negative correlations with [C-11]PK11195 BPND in the bilateral hippocampus in MDD patients, but significant positive correlations in the bilateral hippocampus in the control group. Our results indicate significantly higher TSPO binding in the anterior and posterior cingulate cortices in treatment-naive young MDD patients, suggesting microglial activation in these limbic regions, which are involved in cognitive and emotional processing. The opposite correlations between [C-11]PK11195 BPND in the hippocampus with serum adiponectin levels in MDD and control groups suggest that microglial activation in the hippocampus may respond differentially to adiponectin signaling in MDD and healthy subjects, possibly with respect to microglial phenotype.

Automated summary

This study found higher TSPO binding in the brain of treatment-naive young patients with major depressive disorder (MDD), indicating microglial activation in these limbic regions involved in cognitive and emotional processing. The correlation between serum adiponectin levels and TSPO binding in the hippocampus differed between MDD patients and healthy controls, suggesting differential responsiveness to adiponectin signaling in microglia in MDD and healthy subjects.