Friday, 7 November 2014

Treating depression: exercise or anti-inflammatory meds?

Reiterating my primary caveat on this blog about not giving anything that looks, sounds or smells like medical and/or clinical advice, I'm bringing three papers to the research blogging table today, all published in the JAMA journal family and all talking about depression / depressive symptoms.
See my hat... @ Wikipedia 

First up is the paper by Ole Köhler and colleagues [1] reviewing "the antidepressant and possible adverse effects of anti-inflammatory interventions". Some media interest in this study can be found here. For those who might not know, there is a growing 'feeling' that the various links being made between inflammation or inflammatory mechanisms and psychiatry (see here) may well also extend into the area of depression or depressive symptoms. Far be it from me to say that inflammation and depression is a 'done deal' in scientific terms, but when reading research papers with titles like: 'So depression is an inflammatory disease, but where does the inflammation come from?' by Michael Berk and colleagues [2] (open-access) one kinda gets the impression that quite a lot of opinion has already come down on the side of a probable link.

The Köhler paper looked at the combined peer-reviewed literature on the use of various anti-inflammatory medication strategies previously trialled "in adults with depressive symptoms, including those who fulfilled the criteria for depression" including the use of "nonsteroidal anti-inflammatory drugs (NSAIDs)" and "cytokine inhibitors". Cytokines, inflammation and psychology is a topic which has graced this blog on previous occasions (see here). The authors concluded that whilst there is quite a bit more to do in this area: "This study supports a proof-of-concept concerning the use of anti-inflammatory treatment in depression. Identification of subgroups that could benefit from such treatment might be warranted". Touché.

Next up are the papers by Snehal M. Pinto Pereira and colleagues [3] and Umar Toseeb and colleagues [4] both talking about a possible role for physical activity and exercise when it comes to the presentation of depression. The results were a little mixed; Pinto Pereira et al concluding that during adult life "activity may alleviate depressive symptoms in the general population" as a function of "a trend of fewer depressive symptoms with more frequent activity". By contrast, Toseeb et al looking at physical activity (PA) "and depressive symptoms during 3 years of adolescence" noted no "longitudinal association between objectively measured PA and the development of depressive symptoms". Indeed they quite prominently recorded a lack of support for PA being protective against developing depressive-type symptoms in their teenage group.

There are some differences in the way that the Pinto Pereira and Toseeb research groups went about looking at their respective cohorts and the differences in age between their participants is certainly worth noting. Just correlating two variables is also likely to omit other significant factors (such as inflammation!) which might also show some involvement in the onset or continuation of depression/depressive symptoms. That being said I hark back to other reviews on this topic such as the meta-analysis by Mammen & Faulkner [5] as detailing the bigger picture, denoting some "promising evidence that any level of PA, including low levels (e.g., walking <150 minutes/weeks), can prevent future depression".

If we are to assume that anti-inflammatory medication and physical activity (at least for some) can impact on depression or depressive symptoms, the next question really needs to be: what could unite these two findings if anything? Yes, anti-inflammatory meds impact on inflammatory processes, but does this mean that exercise could be doing the same? I found quite a bit of peer-reviewed literature in this area talking about acute and chronic exercise and its short- and long-term effects on inflammation and inflammatory markers (see here for a summary). The long-and-short of it is that nobody really knows at present and, once again, there is quite a lot of merit for the N=1 in this area of study.

I might however also advance a couple of other ideas potentially worth looking into. First is the impact that inflammation / anti-inflammatory techniques and exercise have on an important region: the gut microbiota. Those trillions of wee beasties which reside in our deepest, darkest recesses doing so much more than just helping us digest our food are seemingly cropping up everywhere these days (see here for example). The idea that certain elements of our bacterial passengers might also show involvement with something like depression in a sort of gut-brain axis manner is by no means a new concept as per previous discussions on this blog (see here). Research hinting that exercise may also impact on the gut microbiota [6] particularly when it comes to the diversity of bacteria to be present, offers something a glimpse into how exercise may provide effects. Gut bacteria diversity and depression is however still wanting in research terms...

Second up, and potentially related to the gut microbiota [7] is the introduction of some epigenetic effect from both anti-inflammatory strategies and exercise when it comes to depression. The science of epigenetics has again been something of a talking point on this blog (see here and see here) from quite a few behavioural perspectives down the years. The idea being that above and beyond your structural genome, there is an added layer of chemical complexity pertinent to the switching on or off of genes which might influence risk for all manner of things. Hype aside, there is growing evidence looking at epigenetic mechanisms being potentially pertinent to depression [8] (open-access) although the precise hows and whys remain somewhat elusive. At the same time, the epigenetics of exercise is also an up-coming area [9] albeit with further investigation needed. Marrying the two concepts together - the epigenetics of exercise and depression - might be a good research idea because at present, there is something of a void in this area. That being said, the epigenetics of immune functions is an area of some note (see here).

I really hope that I've not gone beyond my blogging remit with this post in emphasising the potential links between depression, inflammation and physical activity. By no means did I intend to boil something like depression down to just a lack of exercise or inflammation running amok, given the complexity of the condition and the seemingly many ways that one can arrive at the condition. Similar things were noted in a recent post on zinc and depression (see here). At the very least, I'd like to think my musings are nothing like as sweeping as suggesting that major depression is "an infectious disease" [10]. I do however think that the further moves by disciplines like psychiatry to understanding conditions like depression as potential 'whole body' conditions (either in causation or manifestation) brings us closer to understanding how one might further alleviate the often severe symptoms of depression and, to some degree, potentially mitigate signs and symptoms before they ever get the chance to severely impact on a person's life.

Music to close, and what else but Physical by Olivia Newton-John.


[1] Köhler O. et al. Effect of Anti-inflammatory Treatment on Depression, Depressive Symptoms, and Adverse Effects. JAMA Psychiatry. 2014. October 15.

[2] Berk M. et al. So depression is an inflammatory disease, but where does the inflammation come from? BMC Med. 2013; 11: 200.

[3] Pinto Pereira SM. et al. Depressive Symptoms and Physical Activity During 3 Decades in Adult Life. JAMA Psychiatry. 2014. October 15.

[4] Toseeb U. et al. Exercise and Depressive Symptoms in Adolescents. JAMA Pediatrics. 2014. October 13.

[5] Mammen G. & Faulkner G. Physical activity and the prevention of depression: a systematic review of prospective studies. Am J Prev Med. 2013 Nov;45(5):649-57.

[6] Clarke SF. et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014 Jun 9. pii: gutjnl-2013-306541.

[7] Stilling RM. et al. Microbial genes, brain & behaviour - epigenetic regulation of the gut-brain axis. Genes Brain Behav. 2014 Jan;13(1):69-86.

[8] Vialou V. et al. Epigenetic Mechanisms of Depression and Antidepressants Action. Annu Rev Pharmacol Toxicol. 2013; 53: 59–87.

[9] Ntanasis-Stathopoulos J. et al. Epigenetic regulation on gene expression induced by physical exercise. J Musculoskelet Neuronal Interact 2013; 13(2):133-146

[10] Canli T. Reconceptualizing major depressive disorder as an infectious disease. Biology of Mood & Anxiety Disorders 2014, 4:10.

---------- Ole Köhler, Michael E. Benros, Merete Nordentoft, Michael E. Farkouh, Rupa L. Iyengar, Ole Mors, & Jesper Krogh (2014). Effect of Anti-inflammatory Treatment on Depression, Depressive Symptoms, and Adverse Effects JAMA Psychiatry : doi:10.1001/jamapsychiatry.2014.1611 Snehal M. Pinto Pereira, Marie-Claude Geoffroy, & Christine Power (2014). Depressive Symptoms and Physical Activity During 3 Decades in Adult Life JAMA Psychiatry : doi:10.1001/jamapsychiatry.2014.1240 Toseeb, U., Brage, S., Corder, K., Dunn, V., Jones, P., Owens, M., St Clair, M., van Sluijs, E., & Goodyer, I. (2014). Exercise and Depressive Symptoms in Adolescents JAMA Pediatrics DOI: 10.1001/jamapediatrics.2014.1794