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Neuropsychopharmacology. 2014 Jun;39(7):1743-53. doi: 10.1038/npp.2014.22. Epub 2014 Jan 29.

TOMM40 rs2075650 may represent a new candidate gene for vulnerability to major depressive disorder.

Author information

1
Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
2
Cathie Marsh Centre for Census and Survey Research, School of Social Sciences, Faculty of Humanities, University of Manchester, Manchester, UK.
3
Kalman Kando Faculty of Electrical Engineering, Obuda University, Budapest, Hungary.
4
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.

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.

PMID:
24549102
PMCID:
PMC4023148
DOI:
10.1038/npp.2014.22
[Indexed for MEDLINE]
Free PMC Article
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