1. ¹Department of Neuroscience, New York State Psychiatric Institute, New York, NY, USA
2. ²Department of Psychiatry, Columbia College of Physicians and Surgeons, New York, NY, USA
3. ³Department of Anatomy and Cell Biology, Columbia College of Physicians and Surgeons, New York, NY, USA

Correspondence: Professor V Arango, Department of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, Box 42, New York, NY 10032, USA, Tel: +1 212 543 5440; Fax: +1 212 543 6017; E-mail: varango@neuron.cpmc.columbia.edu

⁴Current address: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, PA, USA

Received 10 February 2005; Revised 5 August 2005; Accepted 11 August 2005; Published online 28 September 2005.

Abstract

Major depressive disorder (MDD) and suicide are associated with deficient serotonergic neurotransmission. Tryptophan hydroxylase (TPH) is the rate-limiting biosynthetic enzyme for serotonin. Previously, we reported elevated levels of TPH protein in the dorsal raphe nucleus (DRN) of depressed suicides and now examine expression of neuronal TPH2 mRNA in a cohort of matched controls and depressed suicides (n=11 pairs). DRN TPH2 mRNA was measured by densitometric analysis of autoradiograms from in situ hybridization histochemistry experiments. TPH2 mRNA is confirmed as the raphe-specific isoform of TPH in human brain, and is expressed in neurons throughout the anteroposterior extent of the DRN and median raphe nucleus (MRN). TPH2 mRNA expression correlates with TPH protein distribution in the DRN, and has a negative correlation with age. In drug-free suicides, TPH2 expression is 33% higher in the DRN and 17% higher in the MRN as compared to matched nonpsychiatric controls. Higher levels of TPH2 mRNA were found throughout the entire extent of the rostrocaudal axis of the DRN, and were not specific to any single subnucleus. Higher TPH2 mRNA expression may explain more TPH protein observed in depressed suicides and reflect a homeostatic response to deficient brain serotonergic transmission.