Neuropsychiatric Disease and Treatment (Sep 2022)
Differences in mGluR5 Availability Depending on the Level of Social Avoidance in Drug-Naïve Young Patients with Major Depressive Disorder
Abstract
Jeong-Hee Kim,1,2 Yo-Han Joo,1 Young-Don Son,1– 3 Hang-Keun Kim,1– 3 Jong-Hoon Kim1,3,4 1Neuroscience Research Institute, Gachon University, Incheon, Republic of Korea; 2Department of Biomedical Engineering, College of Health Science, Gachon University, Incheon, Republic of Korea; 3Gachon Advanced Institute for Health Sciences & Technology, Gachon University, Incheon, Republic of Korea; 4Department of Psychiatry, Gachon University College of Medicine, Gil Medical Center, Incheon, Republic of KoreaCorrespondence: Jong-Hoon Kim, Department of Psychiatry, Gachon University College of Medicine, Gil Medical Center, 1198 Guwol-dong, Namdong-gu, Incheon, 21565, Republic of Korea, Tel +82 32 460 2696, Fax +82 32 472 8813, Email [email protected] Young-Don Son, Department of Biomedical Engineering, College of Health Science, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon, 21936, Republic of Korea, Tel +82 32 820 4416, Email [email protected]: 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-naïve young patients with major depressive disorder (MDD).Methods: Twenty non-smoking patients and eighteen matched non-smoking healthy controls underwent [11C]ABP688 positron emission tomography (PET) and magnetic resonance imaging scans. The binding potential (BPND) of [11C]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 [11C]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 [11C]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 [11C]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-naïve non-smoking MDD patients, suggesting that social avoidance should be considered as one of the clinical factors involved in mGluR5 signaling changes in depression.Keywords: social avoidance, metabotropic glutamate receptor-5, positron emission tomography, [11C]ABP688, major depressive disorder
