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

Yo-Han Joo,Keun-A Chang,Young-Don Son,Paul Cumming,Maqsood Yaqub,Jong-Hoon Kim,Min-Woo Lee,Hang-Keun Kim

doi:10.3390/biomedicines10010034

Abstract

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 [11C]PK11195 and measured serum adiponectin levels in groups of treatment-naïve young adult patients with major depressive disorder (MDD) and matched healthy controls. Thirty treatment-naïve MDD patients (median age: 24 years) and twenty-three healthy controls underwent [11C]PK11195 PET. We quantified TSPO availability in brain as the [11C]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 [11C]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 [11C]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-naïve young MDD patients, suggesting microglial activation in these limbic regions, which are involved in cognitive and emotional processing. The opposite correlations between [11C]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.

Highlights

The high prevalence of major depressive disorder (MDD) in patients with chronic inflammatory illnesses [1,2,3] suggests a causal association between MDD and inflammatory processes
Since we aimed to examine the translocator protein (TSPO) binding in a priori regions of interest (ROIs) in which elevated TSPO binding was reported in MDD patients, we determined the level of statistical significance at a two-tailed p < 0.05
Sex distribution, body mass index (BMI), serum adiponectin levels, and scan parameters did not differ between the groups (Table 1)

Summary

Introduction

The high prevalence of major depressive disorder (MDD) in patients with chronic inflammatory illnesses [1,2,3] suggests a causal association between MDD and inflammatory processes. Several PET studies with first- or second-generation tracers have reported on cerebral TSPO binding in patients with MDD [8,9,10,11,12,13,14,15,16]. Among these studies, most reported elevated TSPO binding in MDD in various cerebral regions, including the anterior cingulate cortex, posterior cingulate cortex, prefrontal cortex, insula, hippocampus, and temporal cortex [9,10,11,13,14,15]. One PET study found no differences in TSPO availability between MDD and healthy control subjects [8]

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