The Role of Brain-Derived Neurotrophic Factor in Comorbid Depression: Possible Linkage with Steroid Hormones, Cytokines, and Nutrition

Abstract

Increasing evidence demonstrates a connection between growth factor function (including brain-derived neurotrophic factor, BDNF), glucocorticoid levels (one of the steroid hormones), and the pathophysiology of depressive disorders. Because both BDNF and glucocorticoids regulate synaptic function in the central nervous system, their functional interaction is of major concern. Interestingly, alterations in levels of estrogen, another steroid hormone, may play a role in depressive-like behavior in postpartum females with fluctuations of BDNF-related molecules in the brain. BDNF and cytokines, which are protein regulators of inflammation, stimulate multiple intracellular signaling cascades involved in neuropsychiatric illness. Pro-inflammatory cytokines may increase vulnerability to depressive symptoms, such as the increased risk observed in patients with cancer and/or autoimmune diseases. In this review, we discuss the possible relationship between inflammation and depression, in addition to the cross-talk among cytokines, BDNF, and steroids. Further, since nutritional status has been shown to affect critical pathways involved in depression through both BDNF function and the monoamine system, we also review current evidence surrounding diet and supplementation (e.g., flavonoids) on BDNF-mediated brain functions.

Molecular network of neuronal autophagy in the pathophysiology and treatment of depression

“…Brain-derived neurotrophic factor (BDNF) plays an essential role in neuronal plasticity, and downregulation of its expression/function is reproduced in a variety of animal models of MDD [54] . Indeed, the neuroprotective effect of BDNF not only prevents apoptosis by inhibiting caspase activation but also promotes neuron survival through modulation of autophagy [55] .…”

Depression in cancer: The many biobehavioral pathways driving tumor progression

“…Finally, cascades associated with the activation of the aforementioned pathways appear to lead to excitotoxic neural damage, a reduced expression of brain derived neurotrophic factor (BDNF) and consequently to a disruption of mechanisms subserving neural plasticity 53,54 . In addition, oxidative stress may reduce the activity of 5,6,7,8-tetrahydrobiopterin (BH4), which is a co-factor for several aromatic amino acid monooxygenases and is rate-limiting for the biosynthesis of the neurotransmitter serotonin and the catecholamines dopamine, epinephrine and norepinephrine 55 .…”

The complex neurobiology of resilient functioning after child maltreatment

“…Increases in pro-inflammatory cytokines and glucocorticoid systems have each been associated with structural changes in brain regions crucial for emotion regulation and stress response (i.e. lower PFC and hippocampal volumes and larger amygdala volumes (Andrea Danese & McEwen, 2012;Davidson, 2002;Etkin, Egner, & Kalisch, 2011;Gunnar & Quevedo, 2007;Sonia J Lupien, McEwen, Gunnar, & Heim, 2009;Bruce S McEwen, 2005;Numakawa et al, 2014;van Velzen et al, 2016). These regions are also implicated in neuroimaging studies of CM that utilized Magnetic Resonance Imaging (MRI) to investigate CM-related brain structures.…”