PMID- 12912764
OWN - NLM
STAT- MEDLINE
DCOM- 20030910
LR  - 20230817
IS  - 0003-990X (Print)
IS  - 0003-990X (Linking)
VI  - 60
IP  - 8
DP  - 2003 Aug
TI  - Altered gene expression of brain-derived neurotrophic factor and receptor 
      tyrosine kinase B in postmortem brain of suicide subjects.
PG  - 804-15
AB  - BACKGROUND: Suicide is a major public health concern. Although authors of many 
      studies have examined the neurobiological aspects of suicide, the molecular 
      mechanisms associated with suicidal behavior remain unclear. Brain-derived 
      neurotrophic factor (BDNF), one of the most important neurotrophins, after 
      binding with and activating receptor tyrosine kinase B (trk B), is directly 
      involved in many physiological functions in the brain, including cell survival 
      and synaptic plasticity. The present study was performed to examine whether the 
      expression of BDNF and/or trk B isoforms was altered in postmortem brain in 
      subjects who commit suicide (hereafter referred to as suicide subjects) and 
      whether these alterations were associated with specific psychopathologic 
      conditions. METHODS: These studies were performed in prefrontal cortex in 
      Brodmann area 9 and hippocampus obtained in 27 suicide subjects and 21 
      nonpsychiatric control subjects. Levels of messenger RNA and protein levels of 
      BDNF and trk B were determined with competitive reverse transcriptase-polymerase 
      chain reaction and Western blot technique, respectively. The level of 
      neuron-specific enolase messenger RNA as a neuronal marker was also determined in 
      these brain areas. RESULTS: Messenger RNA levels of BDNF and trk B were 
      significantly reduced, independently and as a ratio to neuron-specific enolase, 
      in both prefrontal cortex and hippocampus in suicide subjects, as compared with 
      those in control subjects. These reductions were associated with significant 
      decreases in the protein levels of BDNF and of full-length trk B but not trk B's 
      truncated isoform. These changes were present in all suicide subjects regardless 
      of psychiatric diagnosis and were unrelated to postmortem interval, age, sex, or 
      pH of the brain. CONCLUSIONS: Given the importance of BDNF in mediating 
      physiological functions, including cell survival and synaptic plasticity, our 
      findings of reduced expression of BDNF and trk B in postmortem brain in suicide 
      subjects suggest that these molecules may play an important role in the 
      pathophysiological aspects of suicidal behavior.
FAU - Dwivedi, Yogesh
AU  - Dwivedi Y
AD  - Psychiatric Institute, Department of Psychiatry, University of Illinois at 
      Chicago, 60612, USA. ydwivedi@psych.uic.edu
FAU - Rizavi, Hooriyah S
AU  - Rizavi HS
FAU - Conley, Robert R
AU  - Conley RR
FAU - Roberts, Rosalinda C
AU  - Roberts RC
FAU - Tamminga, Carol A
AU  - Tamminga CA
FAU - Pandey, Ghanshyam N
AU  - Pandey GN
LA  - eng
GR  - KO1MH01836/MH/NIMH NIH HHS/United States
GR  - R01MH48153/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arch Gen Psychiatry
JT  - Archives of general psychiatry
JID - 0372435
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 4.2.1.11 (Phosphopyruvate Hydratase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Cause of Death
MH  - Female
MH  - Gene Expression/*physiology
MH  - Hippocampus/*pathology
MH  - Humans
MH  - Male
MH  - Maryland
MH  - Mental Disorders/genetics/pathology
MH  - Middle Aged
MH  - Phosphopyruvate Hydratase/genetics
MH  - Prefrontal Cortex/*pathology
MH  - Protein Isoforms/genetics
MH  - RNA, Messenger/genetics
MH  - Receptor, trkB/*genetics
MH  - Reference Values
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Suicide
EDAT- 2003/08/13 05:00
MHDA- 2003/09/11 05:00
CRDT- 2003/08/13 05:00
PHST- 2003/08/13 05:00 [pubmed]
PHST- 2003/09/11 05:00 [medline]
PHST- 2003/08/13 05:00 [entrez]
AID - 60/8/804 [pii]
AID - 10.1001/archpsyc.60.8.804 [doi]
PST - ppublish
SO  - Arch Gen Psychiatry. 2003 Aug;60(8):804-15. doi: 10.1001/archpsyc.60.8.804.