Association of TMEM132D, COMT, and GABRA6 genotypes with cingulate, frontal cortex and hippocampal emotional processing in panic and major depressive disorder

Abstract

Objective. The aim of the study was to evaluate the association of transmembrane protein 132D (TMEM132D), catechol-O-methyltransferase (COMT), and gamma-aminobutyric acid (GABA) receptor alpha 6 subunit (GABRA6) genotypes with cingulate, frontal cortex and hippocampal emotional processing in panic disorder (PD) and major depressive disorder (MDD). Method. The single nucleotide polymorphisms (SNPs) in TMEM132D, COMT, and GABRA6 were examined in patients with MDD, PD, and healthy controls. Functional magnetic resonance imaging (fMRI) was performed in patients with MDD, PD, and healthy controls. Results. rs4680 in COMT and rs3219151 in GABRA6 showed positive associations with PD and MDD. A dynamic fearful face was shown to the participants during fMRI scanning. In PD patients, responses in the bilateral anterior cingulate were stronger in carriers of the AA genotype of SNP rs11060369 in TMEM132D compared with carriers of the AC + CC genotype, and stronger in CT + TT genotype carriers of SNP rs3219151 in GABRA6 compared with carriers of the CC genotype. The response in the medial orbital frontal cortex was stronger in carriers of the CT + TT genotypes of SNP rs3219151 in PD. In MDD patients, the response in the right parahippocampus of carriers of the GG genotype of rs4680 in COMT was stronger than that of carriers of the AA + AG genotype. Conclusion. These results suggest that TMEM132D, GABRA6, and COMT variants may increase vulnerability to panic.

Key words::

• fMRI
• major depressive disorder
• panic disorder
• TMEM132D
• COMT

Acknowledgements

The study was supported by a Grant-in-Aid for Scientific Research (No. 20591371) from the Japanese Society for the Promotion of Science (JSPS). We are grateful to Mr. Shunsuke Kobayashi for excellent technical assistance.

Statement of interest

None of the authors reports conflicts of interest.