G×E interactive effects are likely for stress- and anxiety-related genes. These include HPA axis genes such as those encoding corticotropin-releasing hormone (CRH), its receptor (CRHR1) and binding protein (CRHBP), the glucocorticoid receptor (NR3C1), and its co-chaperone (FKBP5). GABAergic pathway genes, such as GABRA2, are likely candidates, as are those genes with a glucocorticoid response element located within their promoters (regulatory region). Examples of the latter are the monoamine oxidase A (MAOA) gene that encodes an enzyme involved in the degradation of central nervous system serotonin and norepinephrine; the catechol-O-methyltransferase (COMT) gene that encodes the enzyme that is implicated in central nervous system dopamine and norepinephrine metabolism; and SLC6A4, the gene encoding the serotonin transporter that regulates synaptic serotonin availability. To date, many papers have been published showing interactive effects between stress genes and childhood stressors on depression phenotypes, post-traumatic stress disorder, and suicidal behavior, but there have been relatively few studies demonstrating G×E effects on AUDs and DD. There are, however, studies showing G×E effects on alcohol consumption phenotypes, on behaviors such as childhood conduct/hyperactivity disorders that often predate adult AUDs and DD, and on antisocial behavior that is often comorbid with AUDs and DD.
