Journal
NEUROPSYCHOPHARMACOLOGY
Volume 39, Issue 12, Pages 2857-2866Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2014.137
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Funding
- Cambridge Cognition
- P1vital
- Servier
- Alkermes
- AstraZeneca
- National Institute for Health Research [NF-SI-0509-10229] Funding Source: researchfish
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There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOSI modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS I SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS I showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p = 2.3E-05). These results suggest that NOS I SNPs interact with exposure to economic and psychosocial stressors to alter individual's susceptibility to depression.
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