Gene environment interaction studies in depression and suicidal behavior: An update

Neurosci Biobehav Rev. 2013 Dec;37(10 Pt 1):2375-97. doi: 10.1016/j.neubiorev.2013.07.011. Epub 2013 Jul 22.


Increasing evidence supports the involvement of both heritable and environmental risk factors in major depression (MD) and suicidal behavior (SB). Studies investigating gene-environment interaction (G × E) may be useful for elucidating the role of biological mechanisms in the risk for mental disorders. In the present paper, we review the literature regarding the interaction between genes modulating brain functions and stressful life events in the etiology of MD and SB and discuss their potential added benefit compared to genetic studies only. Within the context of G × E investigation, thus far, only a few reliable results have been obtained, although some genes have consistently shown interactive effects with environmental risk in MD and, to a lesser extent, in SB. Further investigation is required to disentangle the direct and mediated effects that are common or specific to MD and SB. Since traditional G × E studies overall suffer from important methodological limitations, further effort is required to develop novel methodological strategies with an interdisciplinary approach.

Keywords: ABCG1; ACE; APOE; ATP-binding cassette subfamily G member 1; AVPR1B; BDNF; CNR1; COMT; CRH; CRHBP; CRHR1; CRHR2; DBH; DRD1; DRD2; DRD3; DRD4; DRD5; Environment; FK506-binding protein 5; FKBP5; FMR1; GABRA1; GABRA2; GABRA5; GABRG1; GABRG2; GAD1g; GLULg; GPX1; GRIA1g; GRIN2Ag; GRIN2Bg; GRIN2C; GRIN2D; GRIN3A; GRIN3B; GRM7; GSK3B; Genetics; Gene×environment interaction; G×E; HTR1A; HTR1B; HTR2A; HTR2C; HTR3A; IL10; IL18; MAOA; MD; Major depression; NPY; NR3C1; NTRK2; ODC1; OXTR; RGS2; SB; SLC6A2; SLC6A3; SLC6A4; SLEs; Stressful life events; Suicide; TNF; TPH1; TPH2; angiotensin-converting enzyme; apoliprotein E; argivanine vasopressin receptor 1B; brain-derived neurotrophic factor; cannabinoid receptor 1; catechol-O-methyltransferase A; corticotrophin-releasing hormone; corticotrophin-releasing hormone binding protein; corticotrophin-releasing hormone receptor 1; corticotrophin-releasing hormone receptor 2; dopamine beta-hydroxylase; dopamine receptor D1; dopamine receptor D2; dopamine receptor D3; dopamine receptor D4; fragile-X mental retardation protein; gamma-aminobutyric acid receptor alpha1; gamma-aminobutyric acid receptor alpha2; gamma-aminobutyric acid receptor alpha5; gamma-aminobutyric acid receptor gamma1; gamma-aminobutyric acid receptor gamma2; gene–environment interaction; glutamate receptor ionotropic 2C (glutamate receptor 2C); glutamate receptor ionotropic 2D (glutamate receptor 2D); glutamate receptor ionotropic 3A (glutamate receptor 3A); glutamate receptor ionotropic 3B (glutamate receptor 3B); glutamate receptor metabotropic 7; glutathione peroxidase; glycogen-synthase 3beta; interleukin 10; interleukin 18; lutamate decarboxylase 1; lutamate receptor ionotropic 2A (glutamate receptor 2A); lutamate receptor ionotropic 2B (glutamate receptor 2B); lutamate receptor ionotropic AMPA 1 (glutamate receptor 1); lutamate-ammonia ligase (glutamine synthase); major depression; monoamine-oxidase A; neuronal tryptophan hydroxylase; neuropeptide Y; neurotrophic tyrosine kinase receptor 2; nuclear receptor sub family 3 group c member 1 (glucocorticoid receptor); ornithine decarboxylase 1; oxytocin receptor; regulator of G-protein signaling 2; serotonin receptor 1A; serotonin receptor 2A; serotonin receptor 2B; serotonin receptor 2C; serotonin receptor 3A; solute carrier 6 A2 (noradrenalin transporter; solute carrier 6 A3 (dopamine transporter); solute carriers 6A (serotonin transporter); stressful life events; suicidal behavior; tryptophan hydroxylase; tumor necrosis factor.

Publication types

  • Review

MeSH terms

  • Depressive Disorder, Major / genetics*
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Life Change Events
  • Suicide / psychology*