Helene Bach, Ph.D., Columbia University
Standard Research Grant (2008): $63,750
Expression of Truncated Isoform of Neuronal Tryptophan Hydroxylase in the Brainstem of Depressed Suicides
Abstract: Past research has shown a deficit of serotonin in the brains of persons who die by suicide. This postmortem study aims to determine whether this deficit is due to an overabundance of a defective truncated isoform of the serotonin biosynthetic enzyme, trytophan hydroxylase (TPH2), which limits the brain’s ability to synthesize serotonin. The proposed research will measure the concentration and distribution of both the truncated (defective) and full-length (functional) isoform of TPH2 in the dorsal and median raphe nuclei from 10 matched pairs of depressed suicide victims and normal controls. Diagnoses will be made by psychological autopsy and all decedents will have clear toxicological screens. The investigators hypothesize that suicide victims will show an increased amount of truncated TPH2 expression in the dorsal and median raphe, compared to normal controls. Targeting this likely cause of serotonin deficiency in depressed suicide victims would have clear implications for the development of therapeutic medications for individuals suffering from major depression. This grant project was supported by Dr. Saul Siegel.