Polyunsaturated fatty acids as predictors of future suicide attempt

•This is a longitudinal study of plasma glycerophospholipid PUFAs as predictors of SA.•Low AA levels, but not n-3 PUFA, predicted future suicide attempts.•The protective effects of AA against suicide events were most significant in patients with MDD who were prior attempters.•Total LDL- and HDL-cholesterol did not predict subsequent SA. Polyunsaturated fatty acids (PUFAs) and cholesterol are lipids implicated in suicide risk. We prospectively studied plasma glycerophospholipid PUFAs and cholesterol as putative predictors of suicide attempts. In a multicenter cohort study, we enrolled 123 patients admitted to the emergency department (ED) for suicidal ideation or suicide attempt. Clinical assessments were performed, with follow-up telephone evaluations 6, 12, 18, and 24 months later. Blood samples were obtained in the ED and assayed for PUFAs. Using survival analysis, suicide events were not predicted by eicosapentaenoic acid (EPA, HR: -0.83, 95%CI: 0.39–1.76, p = 0.621) or docosahexaenoic acid (DHA, HR: -0.60, 95%CI: 0.19–1.86, p = 0.371). However, higher arachidonic acid (AA) was a trend for a protective factor (HR=0.30, 95%CI: 0.08–1.08, p = 0.065) in the entire trans-diagnostic sample. This protective effect was significant in all participants with a prior suicide attempt history (n = 85; HR=0.16, 95%CI: 0.04–0.67, p = 0.012), and in the subgroup of attempters with major depressive disorder (MDD; n = 55, HR=0.15, 95%CI:0.03–0.76, p = 0.002). Total LDL- and HDL-cholesterol did not predict subsequent suicide events. AA, but not DHA or EPA, positively correlated with baseline depression severity in MDD patients (r = 0.3, p = 0.006). Contrary to our hypothesis that low n-3 PUFA levels would create risk, we found that while higher AA was associated with greater depression severity at baseline, low AA unexpectedly predicted subsequent suicide attempts, the more so in higher-risk patients. Although surprising, this result agrees with a minority of reports concerning n-6 PUFAs and may represent complex interactions with sample characteristics.