Brain-Derived Neurotrophic Factor Serum Levels and Genotype: Association with Depression during Interferon-α Treatment

Abstract

Depression has been associated with inflammation, and inflammation may both influence and interact with growth factors such as brainderived neurotrophic factor (BDNF). Both the functional Val66Met BDNF polymorphism (rs6265) and BDNF levels have been associated with depression. It is thus plausible that decreased BDNF could mediate and/or moderate cytokine-induced depression. We therefore prospectively employed the Beck Depression Inventory-II (BDI-II), the Hospital Anxiety and Depression Scale (HADS), and the Montgomery-Asberg Depression Rating Scale (MADRS) in 124 initially euthymic patients during treatment with interferon-alpha (IFN-a), assessing serum BDNF and rs6265. Using mixed-effect repeated measures, lower pretreatment BDNF was associated with higher depression symptoms during IFN-a treatment (F 144,17.2 ¼ 6.8; Po0.0001). However, although the Met allele was associated with lower BDNF levels (F 1,83.0 ¼ 5.0; P ¼ 0.03), it was only associated with increased MADRS scores (F 4,8.9 ¼ 20.3; Po0.001), and not the BDI-II or HADS. An exploratory comparison of individual BDI-II items indicated that the Met allele was associated with suicidal ideation, sadness, and worthlessness, but not neurovegetative symptoms. Conversely, the serotonin transporter promoter polymorphism (5-HTTLPR) short allele was associated with neurovegetative symptoms such as insomnia, poor appetite and fatigue, but not sadness, worthlessness, or suicidal ideation. IFN-a therapy further lowered BDNF serum levels (F 4,37.7 ¼ 5.0; P ¼ 0.003), but this decrease occurred regardless of depression development. The findings thus do not support the hypothesis that decreasing BDNF is the primary pathway by which IFN-a worsens depression. Nonetheless, the results support the hypothesis that BDNF levels influence resiliency against developing inflammatory cytokine-associated depression, and specifically to a subset of symptoms distinct from those influenced by 5-HTTLPR. Neuropsychopharmacology (2013) 38, 985-995;

A Follow-Up Study of 50 Chronic Hepatitis C Patients: Adiponectin as a Resilience Biomarker for Major Depression

“…BDNF was also known to be a resilience biomarker for IFN-associated MD in CHC patients [12]. Our study failed to replicate this finding, but we reported for the first time that adiponectin may also be a resilience biomarker for MD in CHC patients.…”

“…brain-derived neurotrophic factor (BDNF), tumor necrosis factor (TNF)-α, its soluble variant (sTNFR2), IL-23 and RANTES, associated with neuropsychiatric symptoms (depression, anxiety, fatigue and/or pain) [11]. In patients with CHC, BDNF has been shown to influence resilience to depression during IFN-based therapies [12]. However, variation in either BDNF or other inflammatory mediators investigated to date does not fully explain the substantial heterogeneity associated with the risk of developing IFN-induced depression.…”

Job performance in chronic hepatitis C virus patients treated with pegylated interferon-α2b plus ribavirin: an observational study

“…The loss of work performance increases with infection and with IFN treatment. Behavioral responses to cytokines can benefit an organism by promoting conservation of energy and allocation of resources to combat infection or recovery from injury along with behaviors that may elicit care giving from others [40,41].…”

Biochemical Studies of Hippocampal Gene Expression of Brain-Derived Neurotropic Factor and Toll-Like Receptor-4 in Diabetic Rats Exposed to Chronic Stress: Effects of Antidepressant Drugs

“…Pro-inflammatory cytokines negatively regulate hippocampal BDNF expression and signal transduction [44]. There is a bidirectional relationship between BDNF and cytokines with a plausible role for this interaction in the etiology of major depressive disorders [45]. Accordingly, administration of lipopolysaccharide (LPS), a major bacterial TLR-4 ligand, caused cognitive impairment in animal models through increased expression of pro-inflammatory cytokines alongside a reduction in BDNF levels in the hippocampus [40].…”