The International Journal of Neuropsychopharmacology

Research Article

Brain-derived neurotrophic factor and tyrosine kinase B receptor signalling in post-mortem brain of teenage suicide victims

Ghanshyam N. Pandeya1 c1, Xinguo Rena1, Hooriyah S. Rizavia1, Robert R. Conleya2, Rosalinda C. Robertsa2 and Yogesh Dwivedia1

a1 Department of Psychiatry, University of Illinois at Chicago, College of Medicine, Chicago, IL, USA

a2 Maryland Psychiatric Research Center, Baltimore, MD, USA

Abstract

Teenage suicide is a major public health concern, but its neurobiology is not very well understood. Stress and major mental disorders are major risk factors for suicidal behaviour, and it has been shown that brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) are not only regulated by stress but are also altered in these illnesses. We therefore examined if BDNF/TrkB signalling is altered in the post-mortem brain of teenage suicide victims. Protein and mRNA expression of BDNF and of TrkB receptors were determined in the prefrontal cortex (PFC), Brodmann's Area 9 (BA 9), and hippocampus obtained from 29 teenage suicide victims and 25 matched normal control subjects. Protein expression was determined using the Western blot technique; mRNA levels by a quantitative RT–PCR technique. The protein expression of BDNF was significantly decreased in the PFC of teenage suicide victims compared with normal control subjects, whereas no change was observed in the hippocampus. Protein expression of TrkB full-length receptors was significantly decreased in both PFC and hippocampus of teenage suicide victims without any significant changes in the truncated form of TrkB receptors. mRNA expression of both BDNF and TrkB was significantly decreased in the PFC and hippocampus of teenage suicide victims compared with normal control subjects. These studies indicate a down-regulation of both BDNF and its receptor TrkB in the PFC and hippocampus of teenage suicide victims, which suggests that stress and altered BDNF may represent a major vulnerability factor in teenage suicidal behaviour.

(Received August 16 2007)

(Reviewed October 11 2007)

(Revised April 04 2008)

(Accepted April 15 2008)

(Online publication July 09 2008)

Correspondence:

c1 Address for correspondence: G. N. Pandey, Ph.D., The Psychiatric Institute, University of Illinois at Chicago, 1601 West Taylor Street, Chicago, IL 60612, USA. Tel.: (312) 413-4540 Fax: (312) 413-4547 E-mail: Gnpandey@psych.uic.edu