title: TOMM40 rs2075650 may represent a new candidate gene for vulnerability to major depressive disorder.
abstract: Evidence suggests that depression is a risk factor for dementia; however, the relationship between the two conditions is not fully understood. A novel gene (TOMM40) has been consistently associated with Alzheimer's disease (AD), but has received no attention in depression. We conducted a three-level cross-sectional study to investigate the association of the TOMM40 rs2075650 SNP with depression. We recruited a community sample of 1220 participants (571 controls, 649 lifetime depression) to complete a psychiatric background questionnaire, the Brief Symptom Inventory, and Big Five Inventory at Level-1, 243 (102 controls, 97 remitted, 44 currently depressed) to complete a face-to-face clinical interview and neuropsychological testing at Level-2 and 58 (33 controls, 25 remitted) to complete an emotional face-processing task during fMRI at Level-3. Our results indicated that the TOMM40 rs2075650 G allele was a significant risk factor for lifetime depression (p = 0.00006) and, in depressed subjects, was a significant predictor of low extraversion (p = 0.009). Currently depressed risk allele carriers showed subtle executive dysfunction (p = 0.004) and decreased positive memory bias (p = 0.021) together with reduced activity in the posterior (p(FWE) = 0.045) and anterior (p(FWE) = 0.041) cingulate during sad face emotion processing. Our results suggest that TOMM40 rs2075650 may be a risk factor for the development of depression characterized by reduced extraversion, impaired executive function, and decreased positive emotional recall, and reduced top-down cortical control during sad emotion processing.
authors.affiliation: Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Martyn
authors.initials: M
authors.lastname: McFarquhar
authors.affiliation: Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Elliott
authors.affiliation: Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Shane
authors.initials: S
authors.lastname: McKie
authors.affiliation: Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Thomas
authors.affiliation: Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Darragh
authors.initials: D
authors.lastname: Downey
authors.affiliation: Cathie Marsh Centre for Census and Survey Research, School of Social Sciences, Faculty of Humanities, University of Manchester, Manchester, UK.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Mekli
authors.affiliation: Kalman Kando Faculty of Electrical Engineering, Obuda University, Budapest, Hungary.
authors.forename: Zoltan G
authors.initials: ZG
authors.lastname: Toth
authors.affiliation: Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Anderson
authors.affiliation: Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: J F William
authors.initials: JF
authors.lastname: Deakin
authors.affiliation: 1] Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK [2] Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, and MTA-SE, Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Juhasz
mesh_terms: D000293:Adolescent; D000328:Adult; D001008:Anxiety Disorders / Q000209:etiology / Q000235:genetics; D002540:Cerebral Cortex / Q000098:blood supply; D003865:Major Depressive Disorder / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D056344:Executive Function / Q000502:physiology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D011939:Mental Recall / Q000502:physiology; D008875:Middle Aged; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009483:Neuropsychological Tests; D000075384:Neuroticism; D010100:Oxygen / Q000097:blood; D010364:Pattern Recognition, Visual / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human; D010100:Oxygen