ReviewA meta-analytic review of the effects of exercise on brain-derived neurotrophic factor
Introduction
There is a wealth of evidence that exercise improves both cognition (Roig et al., 2013, Smith et al., 2010) and mood (Josefsson et al., 2014, Rethorst and Trivedi, 2013, Stathopoulou et al., 2006), with evidence suggesting that brain-derived neurotrophic factor (BDNF) activity may mediate these effects (Erickson et al., 2012, Heyman et al., 2012, van Praag et al., 2005, Vaynman et al., 2004). BDNF is a protein found in high concentrations in the central nervous system, primarily in the brain regions of the hippocampus, cerebral cortex, hypothalamus, and cerebellum (Murer et al., 2001). Central BDNF can cross the blood–brain barrier and therefore be stored in other areas of the body; however, BDNF can also be produced by tissues in the periphery, making it difficult to identify in humans whether BDNF changes in serum levels result from changes in central or peripheral BDNF (Erickson et al., 2012, Murer et al., 2001). BDNF has been implicated in neural development and functioning, including neurogenesis, dendritic growth, and long-term potentiation of neurons (Altar, 1999, Gorski et al., 2003, Huang et al., 1999, Lu et al., 2005). Non-quantitative reviews from both the animal and human literature (Huang et al., 2014, ∗Zoladz and Pilc, 2010) provide evidence that BDNF increases following exercise in rodents and acute and programmed aerobic exercise in humans. Animal models provide more consistent evidence for exercise-induced upregulation of BDNF, given the ability to measure BDNF centrally; however, studies indicate that peripheral (serum and plasma) and central BDNF levels are correlated in mouse models (Angelucci et al., 2011, Karege et al., 2002), with some evidence for similar associations in humans (Krabbe et al., 2007). There is also tentative evidence that peripheral levels of BDNF may have central effects (Schmidt and Duman, 2010). Given the evidence for BDNF increases, exercise can be viewed as a potential strategy for inducing BDNF activity for application to the enhancement of mood or cognition.
Indeed, individual studies have demonstrated the effect of higher BDNF levels on numerous cognitive processes. For example, higher BDNF levels have been associated with better spatial (Erickson et al., 2009, ∗Rex et al., 2006), episodic (Egan et al., 2003), recognition (Komulainen et al., 2008, Whiteman et al., 2014), and verbal memory (Grassi-Oliveira et al., 2008) as well as better hippocampal functioning (Erickson et al., 2012). In addition, decreased levels of BDNF, particularly in older adults, have been associated with hippocampal atrophy and may contribute to memory impairment, which may be linked to cognitive challenges experienced in Alzheimer's (Erickson et al., 2012, Murer et al., 2001).
Qualitative reviews (e.g., Huang et al., 2014, ∗Zoladz and Pilc, 2010) present significant evidence that exercise enhances BDNF levels; however, they do not provide the magnitude or reliability of this effect. The goal of the present quantitative meta-analytic investigation was to document the level and reliability of the effect of exercise on changes in BDNF activity in humans. Three distinct paradigms have been used to study this effect: (1) changes in BDNF levels across a single session of acute exercise, (2) changes in BDNF levels across a session of exercise following a program of regular exercise (showing changes in BDNF release following repeated bouts of exercise), and (3) changes in resting BDNF levels following a program of regular exercise. Each of these was examined separately due to evidence that the effects of exercise on BDNF vary across paradigms (Huang et al., 2014). In the current meta-analysis, potential moderators (e.g., sex, age, assay type, diagnostic status, and exercise frequency) of the effect of exercise on BDNF were investigated.
Section snippets
Search strategy
Studies published in English through February 2013 were identified using the search engines PubMed, PsycINFO, and Google Scholar. The following search terms were used in combination: brain-derived neurotrophic factor, BDNF, exercise, and physical activity. Reference sections of identified articles and relevant reviews were also examined to detect articles not captured by this search.
Study selection and data abstraction
Identified studies were selected for inclusion in analyses based on the following criteria: (1) focus on a human
Trial flow
A total of 61 studies was initially identified as likely meeting inclusion criteria; evaluation of these studies resulted in a final sample for analysis that included 29 studies (see Fig. 1). Studies were excluded when sufficient data were not available (following several contact attempts with authors), when outcomes were not based on BDNF levels following a bout of exercise, or when BDNF genotypes rather than levels were assessed.
Table 1 displays the characteristics of the 29 studies,
Discussion
This meta-analysis provides reliable evidence that both acute and regular exercise have a significant impact on BDNF levels. Evidence from 14 studies indicated that a single session of exercise increases BDNF levels, reflecting a moderate effect size. Moreover, regular exercise intensifies the magnitude of these effects with increased BDNF responsivity, reflecting a moderate effect size, following a regular program of exercise relative to those completing acute exercise alone. Both of these
Acknowledgment
The first author's contribution to this work was supported by grant F31 MH100773 from the National Institute of Mental Health.
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All references marked with an asterisk were included in the meta-analysis.