Neurotrophins and Psychiatric Disorders

Abstract

Increasing number of studies has during the last decade linked neurotrophic factors with the pathophysiology of neuropsychiatric disorders and with the mechanisms of action of drugs used for the treatment of these disorders. In particular, brain-derived neurotrophic factor BDNF and its receptor TrkB have been connected with the pathophysiology in mood disorders, and there is strong evidence that BDNF signaling is critically involved in the recovery from depression with both pharmacological and psychological means. Neurotrophins play a central role in neuronal plasticity and network connectivity in developing adult brain, and recent evidence links plasticity and network rewiring with mood disorders and their treatment. Therefore, neurotrophins should not be seen as happiness factors but as critical tools in the process where brain networks are optimally tuned to environment, and it is against this background that the effects of neurotrophins on neuropsychiatric disorders should be looked at.

Nerve Growth Factor(s) Mediated Hypothalamic Pituitary Axis Activation Model in Stress Induced Genesis of Psychiatric Disorders

“…Increasing number of studies is linking neurotrophins or NGFs, and stress to the pathophysiology of psychiatric disorders (104)(105)(106). NGFs work as a homeostatic interface between organism and environment which is robust to get disrupted from ordinary perturbations of daily life and helps the organism to adapt to the changing survival conditions (107).…”

“…NGFs show activity and stress based synthesis in various brain regions involved in stress response regulation (1,105,114) and the involved brain regions are known to differentially regulate HPA axis. For example, prefrontal cortex and hippocampus are known to inhibit but amygdala excites it (115).…”

Functional Role of BDNF Production from Unique Promoters in Aggression and Serotonin Signaling

“…An important but unanswered question is why multiple transcripts encode an identical BDNF protein and whether BDNF produced from individual promoters regulates specific BDNF-dependent functions. As a secreted neurotrophic factor, BDNF regulates diverse biological functions that range from neuronal survival and differentiation during development to synaptic plasticity and cognitive behavior in the adult (Andero et al, 2014;Autry and Monteggia, 2012;Castren, 2014;Chao et al, 2006;Lu, 2003). Mice engineered to disrupt BDNF signaling display several phenotypes, including hyperphagia-induced obesity, enhanced aggression, changes in cognitive behavior, and blunted response to antidepressant treatments (Autry et al, 2011;Chan et al, 2006;Ito et al, 2011;Lyons et al, 1999;Monteggia et al, 2004;Monteggia et al, 2007;Sakata et al, 2013).…”

Nerve Growth Factor(s) Mediated Hypothalamic Pituitary Adrenal Axis Dysregulation Model in Stress Induced Genesis of Psychiatric Disorders

“…Increasing number of studies are linking NGFs, and stress to the pathophysiology of psychiatric disorders (104)(105)(106). NGFs work as a homeostatic interface between organism and environment which is too robust to get disrupted from ordinary perturbations of daily life and helps the organism to adapt to the changing conditions (107).…”

“…NGFs show activity and stress based synthesis in various brain regions involved in stress response regulation (1,105,115) and the involved brain regions are known to differentially regulate HPA axis. For example, prefrontal cortex and hippocampus are known to inhibit but amygdala excites it (116).…”