In self-identified white patients with major depressive disorder (N=126) treated with open-label duloxetine (60-120 mg/d), a significant association of (P=0.020) of a composite risk score (based on SLC6A2 rs5569 [G1287A] AA, HTR1A rs6295 [C(-1019)G] GG, and COMT rs174697 AA/AG) with 17-item Hamilton Depression Rating Scale total score change from baseline to 12 weeks was observed.
In order to further delineate the impact of 5-HT1A gene variation on pharmacoresponse in depression over 6 weeks of antidepressant treatment, the influence of the 5-HT1A-1019C/G (rs6295) polymorphism was investigated in 340 Caucasian patients with a Major Depressive Episode (DSM-IV) with particular attention to the subtype of depression (major depression and melancholic depression).
In humans, the G variant of the C(-1019)G 5-HT1A receptor promoter gene polymorphism (rs6295) has been associated with higher expression of 5-HT1A receptors, increased depression, and lower stress preceding completed suicide.
Association studies with the functional HTR1A promoter polymorphism rs6295 suggest a new model for the role of the 5-HT1A receptor in susceptibility to depression involving early deficits in cognitive, fear and stress reactivity as stressors that may ultimately lead to depression.
The G/C single-nucleotide polymorphism in the serotonin 1a receptor promoter, rs6295, has previously been linked with depression, suicide and antidepressant responsiveness.
The combination of disadvantageous allelic expression of rs6295 and rs6265 may result in a 5-HT<sub>1A</sub> receptor profile comparable to affective disorders as increased 5-HT<sub>1A</sub> receptor binding is a well published phenotype of depression.
No association between the serotonin-1A receptor gene single nucleotide polymorphism rs6295C/G and symptoms of anxiety or depression, and no interaction between the polymorphism and environmental stressors of childhood anxiety or recent stressful life events on anxiety or depression.