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Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides

Molecular Psychiatry volume 13, pages 507–513 (2008)Cite this article

Abstract

Deficient levels of serotonin are associated with suicide and depression. Paradoxically, in the dorsal raphe nucleus (DRN) there are more serotonin neurons and more neuronal tryptophan hydroxylase-2 (TPH2) expression postmortem in depressed suicides. In this study, we sought to determine whether greater TPH2 expression in depressed suicides was the result of more TPH2 expression per neuron. In situ hybridization and computer-assisted image analysis were performed on tissue sections throughout the extent of the raphe nuclei at the level of silver grains per neuron to systematically quantify TPH2 neuronal expression. Depressed suicides have 26.5% more TPH2 grain density per neuron in the DRN compared with matched controls (P=0.04). The difference in grain density is greater at mid- and caudal anatomical levels across the rostrocaudal axis of the DRN. Densitometric analysis of TPH2 expression in the DRN subnuclei showed that higher expression levels were observed at posterior anatomical levels of depressed suicides (121% of control in the caudal subnucleus). Higher TPH2 expression in depressed suicides may explain more TPH2 protein and reflect a homeostatic response to deficient serotonin levels in the brains of depressed suicides. Localized changes in TPH2 expression in specific subnuclei of the DRN suggest that the serotonergic compensatory mechanism in depression and suicide is specifically regulated within the DRN and has implications for regions innervated by this subnucleus.

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Acknowledgements

We thank Mihran J Bakalian, Suham A Kassir and Jennifer Lau for technical assistance. The work was supported by PHS grants MH40210, MH62185 and MH64168, the American Foundation for Suicide Prevention and the Diane Goldberg Foundation.

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Authors and Affiliations

  1. Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, USA

    H Bach-Mizrachi, M D Underwood, A Tin, S P Ellis, J J Mann & V Arango

  2. Department of Psychiatry, Columbia College of Physicians and Surgeons, New York State Psychiatric Institute,

    H Bach-Mizrachi, M D Underwood, S P Ellis, J J Mann & V Arango

  3. Columbia University, New York, NY, USA

    H Bach-Mizrachi, M D Underwood, S P Ellis, J J Mann & V Arango

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  1. H Bach-Mizrachi
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Correspondence to V Arango.

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Bach-Mizrachi, H., Underwood, M., Tin, A. et al. Elevated expression of tryptophan hydroxylase-2 mRNA at the neuronal level in the dorsal and median raphe nuclei of depressed suicides. Mol Psychiatry 13, 507–513 (2008). https://doi.org/10.1038/sj.mp.4002143

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