In patients with bipolar disorder, the serotonin transporter gene polymorphism (5-HTTLPR) is associated with effectiveness of lithium prophylaxis and with affective instability in response to environmental stress. This cross-sectional study investigated whether bipolar symptomatology at the baseline for a lithium treatment study is consistent with the diathesis-stress model.

Forty-two participants with bipolar disorder completed a battery of measures assessing demographic information, life stress, and symptoms of bipolar disorder. Participants underwent phlebotomy procedures for genotyping.

MANOVA tests showed a significant main effect for event severity (Wilk's λ = .714, F [4,31] = 2.20, p =.029). Participants with presence of a severe event scored significantly higher in depressive symptoms and were deemed more ill by the clinicians. There was a significant omnibus 3-way interaction between severe events, 5- HTTLPR, and lithium status (Wilk's λ = .367, F [4, 33] = 3.020, p =.031). A trend toward significance for 5-HTTLPR was found; i.e., lower depression scores were present in s/s and s/l and participants taking lithium, as opposed to l/l participants, when severe events were present but not when severe events were absent. There was a main effect for loss events predicting manic symptoms (F[1,38] = 4.15, p = .04). Participants with a loss event reported higher manic symptoms than those without. There was an interaction between loss events and lithium status at baseline: in participants with a loss event taking lithium, manic scores were significantly lower (&mgr; = 1.70) than in patients not taking lithium (&mgr; = 9). There was a main effect for goal-attainment events predicting symptoms of depression (F[1,38] = 5.95, p = .01). Participants with at least one goal-attainment event reported lower depressive symptoms than those without.

Findings were partially consistent with the diathesis-stress model. No interaction was found between 5-HTTLPR genotype and event severity predicting bipolar symptomatology. The results suggest lithium prophylaxis is effective in buffering against depressive symptoms when bipolar patients with at least an s 5-HTTLPR allele experience severe environmental events. Results increase understanding of gene by environment mechanisms, imply improvement of identification of patients at risk for poor prognosis and help direct therapeutic techniques.