Brain-derived neurotrophic factor and suicidal behavior in patients with posttraumatic stress disorder

Abstract

Brain-derived neurotrophic factor and suicidal behavior in patients with posttraumatic stress disorder Fator neurotrófico derivado do encéfalo e comportamento suicida em pacientes com transtorno de estresse pós-traumáticoPosttraumatic stress disorder (PTSD) is a severe illness affecting a substantial part of the population in both Western and developing countries. Many individuals suffering from PTSD display suicidal behavior. The association between PTSD and suicidal behavior has been observed both in clinical and in general population samples and is irrespective of the type of trauma that led to PTSD. The neurobiology of suicidal behavior in individuals of PTSD is not clear and is subject of research. 1 Brain-derived neurotrophic factor (BDNF) may be involved in the neurobiology of suicidal behavior in PTSD because of its potential role in the pathophysiology of stress-related disorders.BDNF is one of mammalian neurotrophins which are homodimeric proteins. Mammalian neurotrophins also include nerve growth factor, neurotrophin (NT) 3 and NT 4/5. BDNF is involved in neuronal growth, phenotypic maturation, morphological plasticity, and synthesis of proteins for differentiated functioning of neurons and synaptic functioning.Multiple lines of evidence suggest that BDNF function is dysregulated in PTSD.2-4 A recent study has demonstrated significantly lower plasma BDNF levels in PTSD patients compared to healthy control subjects.2 Stressors regulate the expression of BDNF. It has been demonstrated that animals showing ongoing behavioral disturbances after stress showed BDNF downregulation and neurotrophic tyrosine kinase receptor, type 2 (TrkB) upregulation in a subregion of the hippocampus, compared with controls.3 Chronic stress or prolonged exposure to glucocorticoids decrease BDNF levels and damage hippocampal functioning, by producing dendritic retraction, restructuring, and disconnection.4 Postmortem brain studies in suicidal subjects with or without depression, studies of levels of BDNF in blood cells/plasma of suicidal patients, and genetic association studies linking BDNF to suicide suggest that suicidal behavior may be associated with a decrease in BDNF functioning.5 A postmortem study found that mRNA level of BDNF was significantly reduced, independently and as a ratio to neuron-specific enolase, in both the prefrontal cortex and hippocampus of suicide subjects compared with nonpsychiatric healthy control subjects.5 Interestingly, the decrease in expression of BDNF was present in all suicide subjects regardless of psychiatric diagnosis.It is not clear whether abnormal BDNF function is a marker of PTSD itself, or a marker of a neural vulnerability to PTSD. It is reasonable to hypothesize that reduced BDNF function increases vulnerability to PTSD and traumatic stress further decreases BDNF function. If BDNF dysregulation contributes to the pathophysiology of PTSD and suicidal behavior, it may underlie both conditions. If BDNF dysregulation is mostly a result of traumatic stress, it is logical to suggest tha...

Peripheral blood levels of brain-derived neurotrophic factor in patients with post-traumatic stress disorder (PTSD): A systematic review and meta-analysis

“…A number of 27 records did not measure the BDNF level. We excluded 13 additional studies due to the following reasons: four articles for being non-diagnostic [16][17][18][19], two for not being original studies [20,21], and the other two due to insufficient data [12,22]. Five more studies were also excluded due to measuring BDNF in CSF [23], investigating on small sample size [24], using animal samples [25], using replicated data [12], and having no control group [26].…”