Brain-derived neurotrophic factor: role in depression and suicide

Abstract

Depression and suicidal behavior have recently been shown to be associated with disturbances in structural and synaptic plasticity. Brain-derived neurotrophic factor (BDNF), one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons and in synaptic plasticity. Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. In addition, antidepressants up-regulate the expression of BDNF. This has led to the proposal of the “neurotrophin hypothesis of depression”. Increasing evidence demonstrates that suicidal behavior is also associated with lower expression of BDNF, which may be independent from depression. Recent genetic studies also support a link of BDNF to depression/suicidal behavior. Not only BDNF, but abnormalities in its cognate receptor tropomycin receptor kinase B (TrkB) and its splice variant (TrkB.T1) have also been reported in depressed/suicidal patients. It has been suggested that epigenetic modulation of the Bdnf and Trkb genes may contribute to their altered expression and functioning. More recently, impairment in the functioning of pan75 neurotrophin receptor has been reported in suicide brain specimens. pan75 neurotrophin receptor is a low-affinity neurotrophin receptor that, when expressed in conjunction with low availability of neurotropins/Trks, induces apoptosis. Overall, these studies suggest the possibility that BDNF and its mediated signaling may participate in the pathophysiology of depression and suicidal behavior. This review focuses on the critical evidence demonstrating the involvement of BDNF in depression and suicide.

Sleep and Behavior in Cross-Fostering Rats: Developmental and Sex Aspects

“…Adenosine and brain-derived neurotrophic factor (BDNF) have been proposed to participate in both regulation of sleep and depression. [7][8][9][10][11] The gender differences in the prevalence of mental disorders are large: major depression and anxiety disorder are approximately twice as common in women as in men. 12,13 While there is only modest evidence of sex differences in sleep parameters verified with EEG, 14 the epidemiological studies frequently demonstrate a large difference in sleep complains between the sexes, showing that females in all age groups report more sleep complaints than males.…”

Epigenetic regulation of BDNF expression according to antidepressant response

“…1 The neurotrophin hypothesis of depression postulates that stress and depression are associated with decreased BDNF expression that can be reversed by antidepressant treatment. 2 The goal of the present study was to investigate the effect of antidepressant treatment on the epigenetic regulation of BDNF in major depressive disorder (MDD).…”

Brain-derived neurotrophic factor and suicidal behavior in adolescents

“…[11][12][13][14] Neurotrophic factors promote neuronal survival, regulate many aspects of neuronal development and function, including synapse formation and synaptic plasticity. [15] Of various neurotrophic factors, BDNF has attracted a lot of interest because it is involved in the pathophysiology of many psychiatric disorders associated with suicidal behavior including depression, posttraumatic stress, schizophrenia, and obsessivecompulsive disorder.…”