Document Detail


More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides.
MedLine Citation:
PMID:  15804496     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Deficient serotonin neurotransmission in suicide is indicated by reduced brainstem serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), fewer 5-HT(1A) autoreceptors and reduced cortical serotonin transporter binding in suicide victims. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of 5-HT, and alterations in TPH could explain some of these findings. We sought to determine the amount of TPH immunoreactivity (TPH-IR) in the dorsal (DRN) and median (MRN) raphe nuclei in suicides and controls. Brainstems of suicide victims and controls (n = 11 pairs) were collected at autopsy, matched for age, sex and postmortem interval, frozen and sectioned (20 microm). Immunoautoradiography, using an antibody to label TPH, was performed, slides exposed to film and autoradiograms quantified by a computer-based image analysis system. We examined sections every 1000 microm throughout the whole length of the nucleus, performing statistical analysis only on those subjects for whom the raphe was complete (n = 8 pairs). TPH-IR (microCi/g) was higher in suicides than controls (S: 300.8 +/- 70.8 vs. C: 259.6 +/- 40.7, t = 2.57, df = 7, P = 0.04) in the dorsal raphe nucleus (DRN), and not different between suicides and controls (S: 251.3 +/- 44.2 vs. C: 235.9 +/- 27.4, t = 1.49, df = 7, P = 0.18) in the MRN. DRN TPH-IR was higher in male suicide victims (MS) compared to male controls (MC; MS: 318.4 +/- 54.4 vs. MC: 271.9 +/- 22.5, t = 2.66, df = 6, P = 0.03). The analysis of TPH-IR area and density at each DRN rostrocaudal levels showed higher area and density in suicides compared to controls in the rostral DRN and lower area and density in the caudal DRN. TPH-IR, an index of the amount of TPH enzyme, in the DRN is higher in depressed suicides. More TPH may be an upregulatory homeostatic response to impaired serotonin release or less autoreceptor activation. Alternatively, the serotonin impairment in suicide may be due to hypofunctional serotonin-synthesizing enzyme.
Authors:
Maura Boldrini; Mark D Underwood; J John Mann; Victoria Arango
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Brain research     Volume:  1041     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-04     Completed Date:  2005-09-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  19-28     Citation Subset:  IM    
Affiliation:
Department of Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Autopsy
Brain Stem / enzymology
Case-Control Studies
Depressive Disorder / enzymology*
Female
Humans
Immunohistochemistry
Male
Middle Aged
Raphe Nuclei / enzymology*
Serotonin / metabolism*
Suicide*
Tryptophan Hydroxylase / analysis*
Grant Support
ID/Acronym/Agency:
MH40210/MH/NIMH NIH HHS; MH62185/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
50-67-9/Serotonin; EC 1.14.16.4/Tryptophan Hydroxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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