COMT Val158Met × SLC6A4 5-HTTLPR interaction impacts on gray matter volume of regions supporting emotion processing

Joaquim Radua; Wissam El-Hage; Gemma C Monté; Benedicte Gohier; Maria Tropeano; Mary L Phillips; Simon A Surguladze

doi:10.1093/scan/nst089

COMT Val158Met × SLC6A4 5-HTTLPR interaction impacts on gray matter volume of regions supporting emotion processing

Soc Cogn Affect Neurosci. 2014 Aug;9(8):1232-8. doi: 10.1093/scan/nst089. Epub 2013 Jun 6.

Authors

Joaquim Radua¹, Wissam El-Hage², Gemma C Monté², Benedicte Gohier², Maria Tropeano², Mary L Phillips³, Simon A Surguladze³

Affiliations

¹ Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK, Department of Neuroimaging Research, FIDMAG Germanes Hospitalàries, CIBERSAM, Barcelona, Spain, INSERM U930 ERL, Université François Rabelais, Tours, France, Département de Psychiatrie, CHU Angers, LPPL EA4638, Université Angers, Angers, France, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK, Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, Department of Psychological Medicine, Cardiff University School of Medicine, Cardiff, UK, and Social and Affective Neuroscience Lab, Ilia State University, Tbilisi, GeorgiaDepartment of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK, Department of Neuroimaging Research, FIDMAG Germanes Hospitalàries, CIBERSAM, Barcelona, Spain, INSERM U930 ERL, Université François Rabelais, Tours, France, Département de Psychiatrie, CHU Angers, LPPL EA4638, Université Angers, Angers, France, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK, Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, Department of Psychological Medicine, Cardiff University School of Medicine, Cardiff, UK, and Social and Affective Neuroscience Lab, Ilia State University, Tbilisi, Georgia Joaquim.Radua@iop.kcl.ac.uk.
² Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK, Department of Neuroimaging Research, FIDMAG Germanes Hospitalàries, CIBERSAM, Barcelona, Spain, INSERM U930 ERL, Université François Rabelais, Tours, France, Département de Psychiatrie, CHU Angers, LPPL EA4638, Université Angers, Angers, France, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK, Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, Department of Psychological Medicine, Cardiff University School of Medicine, Cardiff, UK, and Social and Affective Neuroscience Lab, Ilia State University, Tbilisi, Georgia.
³ Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK, Department of Neuroimaging Research, FIDMAG Germanes Hospitalàries, CIBERSAM, Barcelona, Spain, INSERM U930 ERL, Université François Rabelais, Tours, France, Département de Psychiatrie, CHU Angers, LPPL EA4638, Université Angers, Angers, France, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK, Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, Department of Psychological Medicine, Cardiff University School of Medicine, Cardiff, UK, and Social and Affective Neuroscience Lab, Ilia State University, Tbilisi, GeorgiaDepartment of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK, Department of Neuroimaging Research, FIDMAG Germanes Hospitalàries, CIBERSAM, Barcelona, Spain, INSERM U930 ERL, Université François Rabelais, Tours, France, Département de Psychiatrie, CHU Angers, LPPL EA4638, Université Angers, Angers, France, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK, Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, Department of Psychological Medicine, Cardiff University School of Medicine, Cardiff, UK, and Social and Affective Neuroscience Lab, Ilia State University, Tbilisi, Georgia.

Abstract

There have been several reports on the association between the Val(158)Met genetic polymorphism of the catechol-O-methyltransferase (COMT) gene, as well as the serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4), and frontolimbic region volumes, which have been suggested to underlie individual differences in emotion processing or susceptibility to emotional disorders. However, findings have been somewhat inconsistent. This study used diffeomorphic anatomic registration through exponentiated Lie algebra (DARTEL) whole-brain voxel-based morphometry to study the genetic effects of COMT Val(158)Met and SLC6A4 5-HTTLPR, as well as their interaction, on the regional gray matter volumes of a sample of 91 healthy volunteers. An interaction of COMT Val(158)Met × SLC6A4 5-HTTLPR genotypes with gray matter volume was found in bilateral parahippocampal gyrus, amygdala, hippocampus, vermis of cerebellum and right putamen/insula. In particular, the gray matter volume in these regions was smaller in individuals who were both COMT-Met and 5-HTTLPR-S carriers, or both COMT-Val and 5-HTTLPR-L homozygotes, as compared with individuals with intermediate combinations of alleles. The interaction of COMT Val(158)Met and SLC6A4 5-HTTLPR adds to the understanding of individual differences in emotion processing.

Keywords: catechol-O-methyltransferase; genetic interaction; gray matter; serotonin transporter gene; serotonin transporter-linked polymorphic region; voxel-based morphometry.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Brain / anatomy & histology*
Catechol O-Methyltransferase / genetics*
Emotions
Female
Genotyping Techniques
Gray Matter / anatomy & histology*
Humans
Image Processing, Computer-Assisted
Magnetic Resonance Imaging
Male
Organ Size
Polymorphism, Single Nucleotide*
Serotonin Plasma Membrane Transport Proteins / genetics*

Substances

SLC6A4 protein, human
Serotonin Plasma Membrane Transport Proteins
COMT protein, human
Catechol O-Methyltransferase

Grants and funding

Wellcome Trust/United Kingdom