title: Neuronal nitric oxide synthase (NOS1) polymorphisms interact with financial hardship to affect depression risk.
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.
authors.affiliation: Neuroscience and Psychiatry Unit, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Sarginson
authors.affiliation: Neuroscience and Psychiatry Unit, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: J F William
authors.initials: JF
authors.lastname: Deakin
authors.affiliation: Neuroscience and Psychiatry Unit, 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, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Darragh
authors.initials: D
authors.lastname: Downey
authors.affiliation: Neuroscience and Psychiatry Unit, 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, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Elliott
authors.affiliation: 1] Neuroscience and Psychiatry Unit, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK [2] Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary [3] 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; D015331:Cohort Studies; D003866:Depressive Disorder / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012959:Socioeconomic Factors; D013315:Stress, Psychological / Q000235:genetics*; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I