Anti-HTR1A (aa 322-334) polyclonal antibody

Behavioral genetic research supports polygenic models of depression in which many genetic variations each contribute a small amount of risk, and prevailing diathesis-stress models suggest gene-environment interactions (G x E). Multilocus profile scores of additive risk offer an approach that is consistent with polygenic models of depression risk. In a first demonstration of this approach in a G x E predicting depression, we created an additive multilocus profile score from 5 serotonin system polymorphisms (1 each in the genes HTR1A, HTR2A, HTR2C, and 2 in TPH2). Analyses focused on 2 forms of interpersonal stress as environmental risk factors. Using 5 years of longitudinal diagnostic and life stress interviews from 387 emerging young adults in the Youth Emotion Project, survival analyses show that this multilocus profile score interacts with major interpersonal stressful life events to predict major depressive episode onsets (hazard ratio [HR] = 1.815, p = .007). Simultaneously, there was a significant protective effect of the profile score without a recent event (HR = 0.83, p = .030). The G x E effect with interpersonal chronic stress was not significant (HR = 1.15, p = .165). Finally, effect sizes for genetic factors examined ignoring stress suggested such an approach could lead to overlooking or misinterpreting genetic effects. Both the G x E effect and the protective simple main effect were replicated in a sample of early adolescent girls (N = 105). We discuss potential benefits of the multilocus genetic profile score approach and caveats for future research.

Background: Depression is thought to involve, in part, dysregulation of serotonergic neurotransmission. In depressed individuals, the number of serotonin receptors, including the 5-hydroxytryptamine (serotonin)-1A (5-HT1A) autoreceptors, are increased. Clinical improvement with selective serotonin reuptake inhibitors (SSRls) is not usually observed until several weeks after treatment initiation. This delay may be due to the time it takes for the autoreceptors to downregulate. Roughly one-third of patients with depression do not respond to an initial trial of antidepressant medication treatment, possibly as a result of structural variations in the 5-HT1A receptor. Aims: This study was designed to determine the allelic frequency of seven 5-HT1A receptor polymorphisms in a depressed versus a nondepressed population, and in SSRI responders versus nonresponders. All the polymorphisms studied are single nucleotide polymorphisms (SNPs) in the HTR1A gene, which encodes 5-HT1A. Seven prevalent SNPs were included in the analysis. Results: The study showed no relationship between any of the HTR1A polymorphisms and SSRI responders versus nonresponders. Conclusion: While the study has several limitations, the results are consistent with a growing body of literature that suggests that the pharmacogenetics of depression (an inherently complex disorder) may turn out to be multifactorial, and may include the HTR1A gene in concert with other serotonin-related genes.