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Journal of Clinical and
Basic Psychosomatics BDNF in psychotherapy

3. Discussion which the latter two may be causally related. Although it is
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reasonable to assume that the reverse process may be true,
Given the limited information obtained, we lack a that is, a reduction in the consequences of stressful events
clear set of findings that support the main hypothesis: through psychotherapy may normalize BDNF function,
increased BDNF function is associated with an effective this assumption also implies a deficit in BDNF activity in
psychotherapeutic response in anxiety and depression. patients undergoing treatment. A review of meta-analyses
Where significant effects are identified, they may indicates that in terms of blood BDNF levels in individuals
associate treatment efficacy with an increase in BDNF with MDD, this may be true. 51
concentrations or function, although this is not always
the case. The single positive genetic finding, showing an Associations or correlations between BDNF markers
association of the heterozygous genotype with response, and outcomes do not indicate a causal or mechanistic role
does not clearly support this interpretation, indicating of BDNF in psychotherapy. Although that is a possible
very little consistency between studies. Many reasons may interpretation, alternative theories suggest reverse
underlie the variability between the findings. causality, in which the neurobiological effects of effective
psychotherapy – potentially through the normalization
Methodological factors are a likely major concern. of HPA axis function and/or a reduction in inflammatory
While it is considered that over 99% of blood BDNF activation – result in disinhibition of BDNF production.
resides in platelet stores, most investigations of plasma Such theoretical processes are consistent with our
concentrations report findings that are typically 5% of understanding of the relationship between stress and
concentrations in serum. This is likely to reflect the release BDNF; however, they do not explain the mechanism
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of platelet stores into the plasma in some participants, behind the initial effects of psychotherapy on symptoms.
which in turn will contribute to higher variances, as
demonstrated in the methodological study of Gejl et al. A further possibility is that observed BDNF changes
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These authors also highlighted the importance of other are epiphenomena associated with one or more of the
variables such as storage time and centrifugation protocol various behavioral, social, and physiological consequences
in both plasma and serum preparation. In many of the of a successful psychotherapeutic intervention. Two such
reviewed articles, such technical information, along with secondary consequences might be increases in physical
temperatures, delays before centrifugation, and so on, are activity and improved dietary intake. Notably, poor
incompletely reported, making replication difficult. activity and diet contribute to the somatic symptoms of
depression. The effects of physical activity and exercise
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The origins of circulating BDNF are unclear. Although on peripheral BDNF levels have been studied extensively,
many of the studies have implied that it derives from the particularly because BDNF, in addition to its effects on
brain, evidence is very limited and open to criticism. maintaining normal neuronal function, also plays an
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Other organs contain and rely on BDNF, which is likely to important role in the maintenance of cardiovascular
contribute to circulating concentrations and confound the health. Furthermore, interest in the role of diet and the
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interpretation of any changes, as indicated below.
gut microbiota in depression and its treatment outcomes
In contrast, BDNF genotypes, particularly those of has been increasing, with some evidence showing that
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rs6265, have known effects on the cellular disposition this can affect peripheral BDNF.
and function of the resultant protein. This has established Studies in healthy subjects have shown that increases
consequences on the brain, with both anatomical and in physical activity, particularly aerobic exercise, result
functional correlates. Furthermore, it is a genetic factor in increases in peripheral BDNF levels, 55,56 which occur
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and therefore unmodifiable; any association found is likely without any neurological correlation. These effects are
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to be causal, in contrast to blood-derived BDNF measures.
greater in the plasma than in the serum BDNF, and the
How might psychotherapy influence or be influenced limited evidence suggests sex differences, with stronger
by these various measures of BDNF? One hypothetical changes in men. Similarly, food intake can affect blood
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mechanism can be simply described as stress reduction. BDNF, with elevations associated with various dietary
The stress response, involving an increase in cortisol supplements, notably polyphenol-containing foods.
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secretion mediated by the hypothalamic–pituitary– Physical activity and diet are examples of potentially
adrenal (HPA) axis, is often chronically dysfunctional important confounders that may be difficult, if not
in affective and anxiety disorders. Stress can lead to impossible, to control in studies of therapeutic responses
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various physiological changes in addition to the activation in psychiatric illness. The possibility that changes in BDNF
of the HPA axis; this includes increases in cortisol and might correlate with improvements in somatic symptoms
proinflammatory cytokines and reductions in BDNF, of rather than those directly associated with brain function
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Volume 3 Issue 1 (2025) 26 doi: 10.36922/jcbp.4461