Lipids and Suicide Risk

In the search for biomarkers and modifiable risk factors for suicide, lipid status has garnered considerable interest, although the lipid-suicide connection is not without controversy. Major categories of lipids that have been reported as germane to suicide include sterols and polyunsaturated fatty acids (PUFAs). Research concerning lipid effects on mood and suicide risk includes epidemiologic approaches, cohort studies, and clinical trials. In general, current evidence suggests that higher n-3 relative to n-6 PUFA intake may have beneficial effects on depression and suicide risk, particularly in women, while low cholesterol may be detrimental in both sexes. Additionally, low estrogen in women has been associated with suicide attempts, whereas high androgen loads may contribute to the higher suicide completion rate in men. Basic and translational research provides strong evidence for several potential mechanisms that have been implicated in depression and suicide. Firstly, PUFAs, cholesterol, and estrogen can interact to influence structure and function of membrane microdomains ("lipid rafts"), with potential regulatory effects on inflammation and signal transduction, including monoaminergic signaling. Secondly, PUFAs bind to and activate peroxisome proliferator-activated receptors (PPARs), nuclear receptors that regulate gene expression, with resultant effects on inflammation and bioenergetics. Thirdly, PUFAs are both a target for and a hormetic regulator of oxidative stress. Critical to a greater understanding of lipid status as a suicide risk predictor and treatment target will be studies that map genomic and phenotypic characteristics of individuals whose emotional state is affected most by lipid status. Also important will be a more nuanced understanding of lipid-lipid interactions and the differential roles of lipid subclasses on suicide risk.