One of the most well-studied genetic variants in the BDNF gene is the SNP rs6265. The variant that a person carries for this SNP has been reported to affect how much BDNF their brain produces. Because BDNF is believed to be critical for many important processes – such as neurogenesis and synaptic plasticity – this genetic variation could potentially have a variety of significant effects on various aspects of physical health and mental well-being. In this post, we’ll discuss what some of the latest science has to say about some of the effects that may be associated with certain genotypes for this SNP. Read on to learn more! What Is The rs6265 Variant?
In our previous post on the BDNF gene SNP rs6265 , we discussed how certain variants in this gene may influence the amount of BDNF a person produces, as well as some of the potential mechanisms that might be responsible for these differences.
If you missed that post, we highly recommend starting there first – you can find it by clicking here .
Additionally, if you want a more detailed breakdown of exactly what BDNF is and why it’s important, we recommend checking out our comprehensive post on BDNF here .
In this post, we’ll turn to discussing some of the scientific findings that have associated each of the different rs6265 genotypes with more complex effects, which may, in turn, affect various aspects of physiological and psychological health!
You can use SelfDecode to find out what your genotype is.
However, once again keep in mind the limitations and caveats we discussed in the previous post! These findings are all just associations , and these links have not been demonstrated to be directly causative yet. Therefore, just because you have a certain genotype does not automatically mean that you will have any of the traits or conditions that have been associated with that genotype.
With that in mind, let’s see what the science has to say about what the different genotypes for the BDNF SNP rs6265 could potentially mean!
A number of studies have investigated the relationship between this BDNF variant and body weight/obesity.
For example, in men, carriers of the ‘CC’ genotype for rs6265 have been reported to have roughly twice the risk of being overweight compared to people with one or more ‘T’ alleles. However, this same study reported the opposite association in women, where carriers of the ‘CC’ genotype were reported to be up to 50% less likely to be overweight, compared to carriers of one or more ‘T’ alleles [ 1 ]. The results of this study may, therefore, suggest that some of this BDNF variant’s effects may be sex-specific, and more research will be needed to fully tease these nuances out.
Relatedly, some early evidence suggests that rs6265 may influence the effects of certain diets on overall body weight. For example, one study reported that among men with the ‘CC’ genotype, those who consumed diets rich in poly-unsaturated fatty acids (PUFAs) tended to weigh significantly less than ‘CC’ carriers with other diets [ 1 ]. This may suggest that people who carry the ‘CC’ genotype may be more likely to benefit from a high-PUFA diet.
This same study also reported a similar trend among women with the ‘CC’ genotype, although this effect was smaller, and ultimately failed to reach statistical significance [ 1 ]. This may suggest that this association, too, is sex-specific.
While these early findings are promising, much more research will still be needed before any firm conclusions can be made about the effect of this particular BDNF variant on overall body weight.
Preliminary findings from some early studies may suggest that BDNF variants – such as rs6265 – may also play a key role in how the body and brain respond to stress .
For example, one study has reported that men with the ‘CC’ genotype showed a larger increase in salivary levels of the “stress hormone” cortisol compared to men with one or more ‘T’ alleles [ 2 ].
Relatedly, another study has also reported that carriers of the ‘T’ allele for rs6265 showed significantly less stress-related activity in the HPA axis compared to people with the ‘CC’ genotype [ 2 ].
While these initial findings might seem to suggest that carriers of the ‘CC’ genotype might be relatively more sensitive to stress in general, at least one additional study has actually reported the opposite effect! According to this study, ‘CC’ carriers were reported to actually show less stress-induced anxiety-like behaviors compared to people with the ‘TT’ genotype [ 3 ].
Overall, while some early evidence suggests a potential relationship between rs6265 genotype and the stress response, the complicated and sometimes-contradictory nature of the findings so far indicates that this relationship may be quite complex, and will most likely need a lot more intensive research before we can fully understand the nuances behind it. BDNF and Stress: Potential Mechanisms
If there is a potential link between BDNF and stress, what might the nature of this relationship be, and what mechanisms might be responsible?
Some clues come from animal studies. For example, injections of BDNF into the hypothalamus of animals led to increased production of the stress-related hormone CRH , and activated the brain’s HPA axis [ 4 ].
In other words, increased BDNF in the hypothalamus may stimulate the stress response (via CRH), whereas reduced expression of BDNF, in general, has been associated with a somewhat suppressed stress response (again via CRH).
However, research from other stress-related mechanisms suggests that the main “stress hormone” cortisol sometimes “shuts off” the stress response by decreasing BDNF levels in the hypothalamus. When cortisol levels are not regulated properly – which can sometimes occur in response to both chronic or severe acute stress – CRH levels can also become dysregulated (elevated), which causes the stress response to be chronically activated [ 4 ].
If BDNF also acts on the stress response by increasing CRH levels, this may potentially explain why people who produce more BDNF (i.e. the ‘CC’ genotype) might tend to be more sensitive to stress.