Study Report

CitationBach-Mizrachi, 2006 PubMed
Full InfoBach-Mizrachi, H., Underwood, M.D., Kassir, S.A., Bakalian, M.J., Sibille, E., Tamir, H., Mann, J.J. and Arango, V. (2006) Neuronal tryptophan hydroxylase mRNA expression in the human dorsal and median raphe nuclei: major depression and suicide. Neuropsychopharmacology, 31, 814-824.

Hypothesis or Background 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
Sample Informationa cohort of matched controls and depressed suicides (n = 11 pairs)
Method DetailDRN TPH2 mRNA was measured by densitometric analysis of autoradiograms from in situ hybridization histochemistry experiments
Method Keywordsimmunocytochemical analysis
ResultTPH2 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.
ConclusionsHigher TPH2 mRNA expression may explain more TPH protein observed in depressed suicides and reflect a homeostatic response to deficient brain serotonergic transmission.

Relationships reported by Bach-Mizrachi, 2006