Increased mRNA expression of cytochrome oxidase in dorsal raphe nucleus of depressive suicide victims

Abstract

Suicidal behavior is a problem with important social repercussions. Some groups of the population show a higher risk of suicide; for example, depression, alcoholism, psychosis or drug abuse frequently precedes suicidal behavior. However, the relationship between metabolic alterations in the brain and premorbid clinical symptoms of suicide remains uncertain. The serotonergic and noradrenergic systems have frequently been, implicated in suicidal behavior and the amount of serotonin in the brain and CSF of suicide victims has been found to be low compared with normal subjects. However, there are contradictory results regarding the role of noradrenergic neurons in the mediation of suicide attempts, possibly reflecting the heterogeneity of conditions that lead to a common outcome. In the present work we focus on the subgroup of suicide victims that share a common diagnosis of major depression. Based on post-mortem studies analyzing mRNA expression by in situ hybridization, serotonergic neurons from the dorsal raphe nucleus (DRN) from depressive suicide victims are seen to over-express cytochrome oxidase mRNA. However, no corresponding changes were found in the expression of tyrosine hydroxylase (TH) mRNA in the noradrenergic neurons of the Locus Coeruleus (LC). These results suggest that, despite of the low levels of serotonin described in suicide victims, the activity of DRN neurons could increase in the suicidally depressed, probably due to the over activation of serotonin re-uptake. No alteration was found in noradrenergic neurons, suggesting that they play no crucial role in the suicidal behavior of depressive patients.

Keywords:

• depression
• suicidal behavior
• dorsal raphe nucleus
• noradrenergic neurons

Acknowledgements

This work has been supported by grants from: Spanish Ministry of Science (SAF 2002 11675E), Fundación Séneca (FS/05662/PI/07) and CIBERNED (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas). The authors would also like to thank Mr P Thomas for comments and language suggestions on this manuscript. Finally, the authors declare that there is no conflict of interests in the present work.