Brain-derived neurotrophic factor and suicide pathogenesis

Abstract

Abstract Suicide is a major public health concern. The etiology and pathogenic mechanisms associated with suicidal behavior are poorly understood. Recent research on the biological perspective of suicide has gained momentum and appears to provide a promising approach for identifying potential risk factors associated with this disorder. One of the areas that have gained the most attention in suicide research is the role of brain-derived neurotrophic factor (BDNF), which participates in many physiological functions in the brain, including synaptic and structural plasticity. Several studies consistently show that expression of BDNF is reduced in blood cells of suicidal patients and in brains of subjects who committed suicide. Recent studies also demonstrate abnormalities in the functioning of BDNF, because its cognate receptors (tropomycin receptor kinase B and pan75 neurotrophin receptor) are abnormally active and/or expressed in the post-mortem brains of suicide subjects. There is further evidence of the role of BDNF in suicide as numerous studies show a strong association of suicidal behavior with BDNF functional polymorphism. Overall, it appears that abnormalities in BDNF signaling may serve as an important biological risk factor in the etiology and pathogenesis of suicide.

Figure 1. Postulated hypothesis for the role of BDNF and p75^NTR in suicidal behavior

Reductions in BDNF and TrkB and upregulation of pro-BDNF and p75^NTR may cause altered structural and neural plasticity, which may be crucial in the etiology and pathogenesis of suicidal behavior. Abbreviations: BDNF, brain-derived neurotrophic factor; LTD, long-term depression; LTP, long-term potentiation; p75^NTR, pan 75 neurotrophin receptor; TrkB, tropomycin receptor kinase B.