We applaud the article by Mukamal and colleagues1 linking higher BMI to lower suicide risk. However, note that we previously reported the inverse connection of BMI to suicide.2 Indeed, we showed that this was part of a broader set of relationships.
Moreover, we had predicted this association. We theorized that markers of insulin resistance—including high BMI—might be linked to reduced risk of suicide. Why? Free fatty acid levels are elevated in insulin resistance. Free fatty acids compete with and displace tryptophan from binding to serum albumin, thus increasing the fraction of tryptophan that is free, and that can cross the blood-brain barrier where it is the substrate for the rate-limiting reaction in serotonin formation. Thus, we theorized that more insulin resistance may portend higher central serotonin levels and fewer suicides. Greater insulin sensitivity, analogously, may predict greater suicide risk.
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