Brain-Derived Neurotrophic Factor (BDNF) protein levels in anxiety disorders: systematic review and meta-regression analysis

Abstract

Background: Brain-Derived Neurotrophic Factor (BDNF) is a neurotrophin that is involved in the synaptic plasticity and survival of neurons. BDNF is believed to be involved in the pathogenesis of several neuropsychiatric disorders. As findings of BDNF levels in anxiety disorders have been inconsistent, we undertook to conduct a systematic review and meta-analysis of studies that assessed BDNF protein levels in these disorders.Methods: We conducted the review using electronic databases and searched reference lists of relevant articles for any further studies. Studies that measured BDNF protein levels in any anxiety disorder and compared these to a control group were included. Effect sizes of the differences in BDNF levels between anxiety disorder and control groups were calculated.Results: Eight studies with a total of 1179 participants were included. Initial findings suggested that BDNF levels were lower in individuals with any anxiety disorder compared to those without [Standard Mean Difference (SMD) = −0.94 (−1.75, −0.12), p ≤ 0.05]. This was, however, dependent on source of BDNF protein [plasma: SMD = −1.31 (−1.69, −0.92), p ≤ 0.01; serum: SMD = −1.06 (−2.27, 0.16), p ≥ 0.01] and type of anxiety disorder [PTSD: SMD = −0.05 (−1.66, 1.75), p ≥ 0.01; OCD: SMD = −2.33 (−4.21, −0.45), p ≤ 0.01].Conclusion: Although BDNF levels appear to be reduced in individuals with an anxiety disorder, this is not consistent across the various anxiety disorders and may largely be explained by the significantly lowered BDNF levels found in OCD. Results further appear to be mediated by differences in sampling methods. Findings are, however, limited by the lack of research in this area, and given the potential for BDNF as a biomarker of anxiety disorders, it would be useful to clarify the relationship further.

Circulating Brain-Derived Neurotrophic Factor Has Diagnostic and Prognostic Value in Traumatic Brain Injury

“…Understanding the temporal variations in BDNF expression will be an important first step towards further elucidating the biological functions of BDNF in TBI and recovery. It is also possible that since decreased BDNF levels are found in patients with anxiety, 55 major depressive disorder, 56 and schizophrenia, 57 low BDNF values on the day of injury identifies subjects at risk for these conditions (whether previously recognized or otherwise) and predisposes this population to incomplete recovery. Although circulating BDNF may originate from the hippocampus, cerebral cortex, and basal forebrain, 58 it also may be derived from other cellular sources, including platelets, 59,60 smooth muscle cells, 35,61 and vascular endothelial cells.…”

“…Decreased circulating BDNF levels have been implicated in other non-TBI conditions including anxiety, 55 major depressive disorder, 56 schizophrenia, 57 and Alzheimer's disease. 66 However, these studies did not account for other potential confounders, such as age and gender.…”

No gene-by-environment interaction of BDNF Val66Met polymorphism and childhood maltreatment on anxiety sensitivity in a mixed race adolescent sample

“…Compared with the Val66 allele, the Met66 allele is associated with a decrease in activity-dependent secretion of BDNF (Egan et al, 2003). BDNF has received attention due to its evident role in anxiety and mood disorders (Angelucci et al, 2014; Hemmings et al, 2008; Li, Chang, & Xiao, 2016; Martinowich et al, 2007; Molendijk et al, 2014; Suliman, Hemmings, & Seedat, 2013), although findings have been inconsistent across studies (Frustaci, Pozzi, Gianfagna, Manzoli, & Boccia, 2008; Hong, Liou, & Tsai, 2012; Lam, Cheng, Hong, & Tsai, 2004; Minelli et al, 2011; Notaras et al, 2015; Surtees et al, 2007; Wang et al, 2015). …”

Effect of Brain Derived Neurotrophic Factor, In Relation to Diet and Lifestyle Factors, for Prevention of Neuropsychiatric and Vascular Diseases and Diabetes

“…Majority of the BDNF (70-80%) is derived from brain but it is normally found in the liver, pancreas, small intestine and arterial cells, indicating its role in the brain-body connections. The synaptic plasticity and survival of neurons may be modulated by BDNF concentration [12]. BDNF appears to be involved in the pathogenesis of several cardio-metabolic and neuropsychiatric disorders, indicating that it is important in brainbody interactions [10][11][12][13][14][15][16][17].…”

“…It is proposed that BDNF levels also may have periodicity showing lower levels in the morning with increase in the day as a compensatory mechanism. Neurotrophins are considered to play a major role in neural function including survival, development, and plasticity [10,12]. This review reports the scientific evidence available on neuro-hormonal and environmental triggers of BDNF in relation to CVDs, anxiety disorders and type 2 diabetes.…”