title: COMT Val158Met × SLC6A4 5-HTTLPR interaction impacts on gray matter volume of regions supporting emotion processing.
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.
authors.affiliation: 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.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Radua
authors.affiliation: 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.
authors.forename: Wissam
authors.initials: W
authors.lastname: El-Hage
authors.affiliation: 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.
authors.forename: Gemma C
authors.initials: GC
authors.lastname: Monté
authors.affiliation: 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.
authors.forename: Benedicte
authors.initials: B
authors.lastname: Gohier
authors.affiliation: 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.
authors.forename: Maria
authors.initials: M
authors.lastname: Tropeano
authors.affiliation: 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.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
authors.affiliation: 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.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Surguladze
mesh_terms: D000328:Adult; D001921:Brain / Q000033:anatomy & histology*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004644:Emotions; D005260:Female; D060005:Genotyping Techniques; D066128:Gray Matter / Q000033:anatomy & histology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: catechol-O-methyltransferase; genetic interaction; gray matter; serotonin transporter gene; serotonin transporter-linked polymorphic region; voxel-based morphometry