Levels of Tyrosine Hydroxylase Protein are Elevated in Locus Coeruleus of Suicide Victims

Abstract

Alterations in brain norepinephrine (NE) have been implicated in depression, bipolar disorders, and schizophrenia. The locus coeruleus (LC) is the principal source of brain NE, and the biosynthesis of NE is controlled by tyrosine hydroxylase (TH), the expression of which can be influenced by environmental factors such as stress and by psychoactive drugs. In the present study, quantitative blot immunolabeling techniques were used to determine if the levels of TH in LC of suicide victims were altered. In tissue sections taken at a single rostral-caudal level of LC from 9 pairs of antidepressant-free suicide victims and age-matched, sudden death controls, there was a greater amount of TH protein in the sections from suicide victims in each of the 9 matched pairs (x̄ = 136% of control; range, 108% to 172%). By contrast, there were no differences in the levels of neuron-specific enolase (range, 90% to 114%) or in the numbers of neuromelanin-containing cells in adjacent sections. Similar results were obtained when tissue punches of LC from the sections were analyzed. Additional studies analyzing punches taken at several rostral-caudal levels of LC from control subjects and suicide victims, for whom psychological autopsy data are available, are currently underway.