TOMM40 rs2075650 May Represent a New Candidate Gene for Vulnerability to Major Depressive Disorder

McFarquhar, Martyn and Elliott, Rebecca and McKie, Shane and Thomas, Emma and Downey, Darragh and Mekli, Krisztina and Toth, Zoltan G. and Anderson, I. M. and Deakin, J. F. and Juhász, Gabriella (2014) TOMM40 rs2075650 May Represent a New Candidate Gene for Vulnerability to Major Depressive Disorder. NEUROPSYCHOPHARMACOLOGY, 39 (7). pp. 1743-1753. ISSN 0893-133X

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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-toface 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.

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