Conference paper
THE ROLE OF BRAIN-DERIVED NEUROTROPHIC FACTOR IN THE PATHOPHYSIOLOGY OF SUICIDAL BEHAVIOR
Alja Videtič Paska
; University of Ljubljana, Faculty of Medicine, Institute of Biochemistry, Ljubljana, Slovenia
Tomaž Zupanc
; University of Ljubljana, Faculty of Medicine, Institute of Forensic Medicine, Ljubljana, Slovenia
Peter Pregelj
; University of Ljubljana, Faculty of Medicine, Department of Psychiatry, Ljubljana, Slovenia ; University Psychiatric Hospital Ljubljana, Ljubljana, Slovenia
Abstract
Suicidal behaviour is a major public health concern. It is known that the pathogenesis of suicidal behaviour involves altered
neural plasticity, resulting in the aberrant stress response of the central nervous system to environmental factors. Indeed, altered
brain structure and function was found in suicide victims. Neurotrophins are growth factors that are involved in the regulation of
structural, synaptic, and morphological plasticity and in the modulation of the strength and number of synaptic connections and
neurotransmission. Brain-derived neurotrophic factor (BDNF) the most studied and the most widely distributed among
neurotrophins binds to a tropomyosin-related kinase B (TrkB) receptor and to a pan75 neurotrophins receptor. It has been reported
that BDNF production is decreased in all patients with suicidal behaviour and in all suicide victims regardless of a psychiatric
diagnosis. It was also found that the mRNA and protein level of BDNF was significantly lower in both the prefrontal cortex and the
hippocampus of suicide subjects. Different mechanisms could be involved in the regulation of BDNF gene expression, among which
epigenetic mechanisms seem to play a key role. However, also for a functional polymorphism (rs6265) Val66Metit has been shown
that the Met allele is associated with the reduced BDNF activity. Further, a recent meta-analysis including 12 studies showed a trend
for the Met-carrying genotypes and Met allele conferring risk for suicide. Among included studies, our study with the largest sample
size, indicated that the combined Met/Met and Met/Val genotypes of the BDNF Val66Met variant could be the risk factor for violent
suicide in female subjects and for suicide in victims exposed to childhood trauma. In accordance with previous reports, our findings
demonstrate that aberrant regulation of BDNF synthesis is associated with suicidal behaviour.
Keywords
suicide; Brain-Derived Neurotrophic Factor; Tropomyosin-related kinase B; suicidal behaviour; polymorphism
Hrčak ID:
266708
URI
Publication date:
26.8.2013.
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