Association of the C(- 1019)G 5-HT1A promoter polymorphism with exposure to stressors preceding hospitalization for bipolar depression

Rationale: In animals, a higher density of 5-HT1A receptors has been associated with increased behavioral despair after stress. 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. Objectives: We studied the association of rs6295 with the amount of stress in early life and preceding hospitalization for a major depressive episode in course of bipolar disorder. Materials and methods: In 74 consecutively admitted inpatients, early life and recent stressors were rated on the Social Readjustment Rating Scale and on the Risky Family Questionnaire. Results: Homozygote carriers of the rs6295 G variant reported less stressful events before current hospitalization for bipolar depression, but not in early life. The G variant was also associated with a higher overall medication load in naturalistic settings before hospitalization. Conclusions: This is the first study that associated 5-HT1A receptor promoter gene variants with stressors preceding the need of hospitalization for bipolar depression. Our findings support the hypothesis that genetic factors affecting serotonergic neurotransmission might contribute to shape the individual resilience to the depressogenic effects of stress in clinical settings.