Differences in MGluR5 Availability Depending on the Level of Social Avoidance in Drug-Naïve Young Patients with Major Depressive Disorder

Overview

Journal Neuropsychiatr Dis Treat

Publisher Dove Medical Press

Specialty Psychiatry

Date 2022 Sep 20

PMID 36124236

Authors

Jeong-Hee Kim

Yo-Han Joo

Young-Don Son

Hang-Keun Kim

Jong-Hoon Kim

Affiliations

Soon will be listed here.

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-naïve young patients with major depressive disorder (MDD).

Methods: Twenty non-smoking patients and eighteen matched non-smoking healthy controls underwent [C]ABP688 positron emission tomography (PET) and magnetic resonance imaging scans. The binding potential (BP) of [C]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]ABP688 BP, 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 -tests revealed no significant differences in [C]ABP688 BP 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 BP 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 BP 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 BP 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]ABP688 BP 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.

Citing Articles

Metabotropic Glutamate Receptor Subtype 5 Positron-Emission-Tomography Radioligands as a Tool for Central Nervous System Drug Development: Between Progress and Setbacks.

Dupont A, Arlicot N, Vercouillie J, Serriere S, Maia S, Bonnet-Brilhault F Pharmaceuticals (Basel). 2023; 16(8).

PMID: 37631042 PMC: 10458693. DOI: 10.3390/ph16081127.

References

Smart K, Cox S, Nagano-Saito A, Rosa-Neto P, Leyton M, Benkelfat C . Test-retest variability of [ C]ABP688 estimates of metabotropic glutamate receptor subtype 5 availability in humans. Synapse. 2018; 72(9):e22041. DOI: 10.1002/syn.22041. View

DeLorenzo C, Dileep Kumar J, Mann J, Parsey R . In vivo variation in metabotropic glutamate receptor subtype 5 binding using positron emission tomography and [11C]ABP688. J Cereb Blood Flow Metab. 2011; 31(11):2169-80. PMC: 3210337. DOI: 10.1038/jcbfm.2011.105. View

Iijima M, Fukumoto K, Chaki S . Acute and sustained effects of a metabotropic glutamate 5 receptor antagonist in the novelty-suppressed feeding test. Behav Brain Res. 2012; 235(2):287-92. DOI: 10.1016/j.bbr.2012.08.016. View

Chen L, Liu J, Ali U, Gui Z, Hou C, Fan L . Chronic, systemic treatment with a metabotropic glutamate receptor 5 antagonist produces anxiolytic-like effects and reverses abnormal firing activity of projection neurons in the basolateral nucleus of the amygdala in rats with bilateral 6-OHDA.... Brain Res Bull. 2011; 84(3):215-23. DOI: 10.1016/j.brainresbull.2011.01.005. View

Liebowitz M, Gorman J, Fyer A, Klein D . Social phobia. Review of a neglected anxiety disorder. Arch Gen Psychiatry. 1985; 42(7):729-36. DOI: 10.1001/archpsyc.1985.01790300097013. View

Belozertseva I, Kos T, Popik P, Danysz W, Bespalov A . Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced swim and the mouse tail suspension tests. Eur Neuropsychopharmacol. 2006; 17(3):172-9. DOI: 10.1016/j.euroneuro.2006.03.002. View

de Aguiar Neto F, Rosa J . Depression biomarkers using non-invasive EEG: A review. Neurosci Biobehav Rev. 2019; 105:83-93. DOI: 10.1016/j.neubiorev.2019.07.021. View

Wang J, Tian Y, Zeng L, Xu H . Prefrontal Disinhibition in Social Fear: A Vital Action of Somatostatin Interneurons. Front Cell Neurosci. 2021; 14:611732. PMC: 7773700. DOI: 10.3389/fncel.2020.611732. View

Bruder G, Stewart J, McGrath P . Right brain, left brain in depressive disorders: Clinical and theoretical implications of behavioral, electrophysiological and neuroimaging findings. Neurosci Biobehav Rev. 2017; 78:178-191. DOI: 10.1016/j.neubiorev.2017.04.021. View

10.

Patel S, Hamill T, Connolly B, Jagoda E, Li W, Gibson R . Species differences in mGluR5 binding sites in mammalian central nervous system determined using in vitro binding with [18F]F-PEB. Nucl Med Biol. 2007; 34(8):1009-17. DOI: 10.1016/j.nucmedbio.2007.07.009. View

11.

Fitzgerald P, Oxley T, Laird A, Kulkarni J, Egan G, Daskalakis Z . An analysis of functional neuroimaging studies of dorsolateral prefrontal cortical activity in depression. Psychiatry Res. 2006; 148(1):33-45. DOI: 10.1016/j.pscychresns.2006.04.006. View

12.

Terbeck S, Akkus F, Chesterman L, Hasler G . The role of metabotropic glutamate receptor 5 in the pathogenesis of mood disorders and addiction: combining preclinical evidence with human Positron Emission Tomography (PET) studies. Front Neurosci. 2015; 9:86. PMC: 4364244. DOI: 10.3389/fnins.2015.00086. View

13.

Johnstone T, van Reekum C, Urry H, Kalin N, Davidson R . Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression. J Neurosci. 2007; 27(33):8877-84. PMC: 6672169. DOI: 10.1523/JNEUROSCI.2063-07.2007. View

14.

Chung W, Choi S, Lee E, Park H, Kang J, Park H . Social deficits in IRSp53 mutant mice improved by NMDAR and mGluR5 suppression. Nat Neurosci. 2015; 18(3):435-43. DOI: 10.1038/nn.3927. View

15.

Wu Y, Carson R . Noise reduction in the simplified reference tissue model for neuroreceptor functional imaging. J Cereb Blood Flow Metab. 2002; 22(12):1440-52. DOI: 10.1097/01.WCB.0000033967.83623.34. View

16.

Rodrigues S, Bauer E, Farb C, Schafe G, LeDoux J . The group I metabotropic glutamate receptor mGluR5 is required for fear memory formation and long-term potentiation in the lateral amygdala. J Neurosci. 2002; 22(12):5219-29. PMC: 6757718. View

17.

Sheline Y, Price J, Yan Z, Mintun M . Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proc Natl Acad Sci U S A. 2010; 107(24):11020-5. PMC: 2890754. DOI: 10.1073/pnas.1000446107. View

18.

Swanson C, Bures M, Johnson M, Linden A, Monn J, Schoepp D . Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nat Rev Drug Discov. 2005; 4(2):131-44. DOI: 10.1038/nrd1630. View

19.

Ohayon M, Schatzberg A . Social phobia and depression: prevalence and comorbidity. J Psychosom Res. 2010; 68(3):235-43. DOI: 10.1016/j.jpsychores.2009.07.018. View

20.

WATSON D, Friend R . Measurement of social-evaluative anxiety. J Consult Clin Psychol. 1969; 33(4):448-57. DOI: 10.1037/h0027806. View