Differences in mGluR5 Availability Depending on the Level of Social Avoidance in Drug-Naive Young Patients with Major Depressive Disorder

Abstract

Background: Previous research has shown that metabotropic glutamate receptor-5 (mGluR5) signaling is significantly involved in social avoidance. We investigated the relationship between levels of social avoidance and mGluR5 availability in drug-naive young patients with major depressive disorder (MDD). Methods: Twenty non-smoking patients and eighteen matched non-smoking healthy controls underwent [C-11]ABP688 positron emission tomography (PET) and magnetic resonance imaging scans. The binding potential (BPND) of [C-11]ABP688 was obtained using the simplified reference tissue model. Patients' level of social avoidance was assessed using the Social Avoidance and Distress Scale (SADS). For [C-11]ABP688 BPND, the region-of-interest (ROI)-based between-group comparisons and correlations with SADS scores were investigated. The frontal cortices were chosen as a priori ROIs based on previous PET investigations in MDD, and on literature underscoring the importance of the frontal cortex in social avoidance. Results: Independent samples t-tests revealed no significant differences in [C-11]ABP688 BPND in the frontal cortices between the MDD patient group as a whole and healthy controls. One-way analysis of variance with post-hoc tests revealed significantly lower BPND in the bilateral superior frontal cortex (SFC) and left middle frontal cortex (MFC) in MDD patients with low levels of social avoidance (L-SADS) than in healthy controls. The L-SADS patients also had significantly lower BPND in the medial part of the right SFC than both MDD patients with high levels of social avoidance (H-SADS) and healthy controls. The L-SADS patients also showed significantly lower BPND in the orbital parts of the SFC, MFC, and inferior frontal cortex than H-SADS patients. No significant group differences were found between H- SADS patients and healthy controls. The ROI-based correlation analysis revealed significant positive correlations between social avoidance levels and frontal [C-11]ABP688 BPND in the entire patients. Conclusion: Our exploratory study shows significant differences in frontal mGluR5 availability depending on the level of social avoidance in drug-naive non-smoking MDD patients, suggesting that social avoidance should be considered as one of the clinical factors involved in mGluR5 signaling changes in depression.