Neuronal nitric oxide synthase (NOS1) polymorphisms interact with financial hardship to affect depression risk

Jane E. Sarginson, J. F William Deakin, Ian M. Anderson, Darragh Downey, Emma Thomas, Rebecca Elliott, G. Juhász

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 NOS1 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 NOS1 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 NOS1 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 NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual's susceptibility to depression.

Original languageEnglish
Pages (from-to)2857-2866
Number of pages10
JournalNeuropsychopharmacology
Volume39
Issue number12
DOIs
Publication statusPublished - 2014

Fingerprint

Nitric Oxide Synthase Type I
Depression
Single Nucleotide Polymorphism
Haplotypes
Nucleic Acid Regulatory Sequences
Life Change Events
Nitric Oxide Synthase
Nitric Oxide
Economics
DNA
Brain
Population
Genes

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Neuronal nitric oxide synthase (NOS1) polymorphisms interact with financial hardship to affect depression risk. / Sarginson, Jane E.; Deakin, J. F William; Anderson, Ian M.; Downey, Darragh; Thomas, Emma; Elliott, Rebecca; Juhász, G.

In: Neuropsychopharmacology, Vol. 39, No. 12, 2014, p. 2857-2866.

Research output: Contribution to journalArticle

Sarginson, Jane E. ; Deakin, J. F William ; Anderson, Ian M. ; Downey, Darragh ; Thomas, Emma ; Elliott, Rebecca ; Juhász, G. / Neuronal nitric oxide synthase (NOS1) polymorphisms interact with financial hardship to affect depression risk. In: Neuropsychopharmacology. 2014 ; Vol. 39, No. 12. pp. 2857-2866.
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