PCOS, DOGMA and autism with a pinch of salt

I really have to stop doing this. Speculating. Taking a few scoops of relatively small scale research, often in quite disparate areas and making a meal out of them. I don't know if it is the freedom of a lack of peer-review that follows with blogging or just my silly brain making mountains out of molehills, but tenuous links seem to be coming thick and fast at the moment. Perhaps I need a break and some sunshine...

But just before I do, and with a rather large pinch of salt in hand...

Polycystic ovary syndrome (PCOS) has been coming to my attention a few times over the last few days. I readily admit that my knowledge of PCOS is fairly limited, but from what I understand here is a condition which is said to affect anywhere from round about 6% to 10-12% of women. I wouldn't wish to provide a definitive definition of PCOS aside from the fact that it is an endocrine disorder defined by an imbalance in the androgenic sex hormones (hyperandrogenism) which affects ovulation. I should point out that endocrine disorder is not to be confused with endocrine disruptor as per some recent discussions on phthalates and autism.

What else to say about PCOS? Well, there is a suggestion of association with lifestyle-related health conditions such as type-2 diabetes, high blood pressure and weight gain / obesity. This is something I remember seeing on a TV program recently - the Food Hospital - which quite nicely explained how insulin resistance might lead to PCOS, and how higher levels of insulin being produced leads to higher levels of testosterone. I'll come back to testosterone shortly.

Indeed the potential elevation of such lifestyle conditions brings me to the first paper which caught my eye; a speculative paper by Tremellen & Pearce* in a speculative journal. Tremellen & Pearce make an interesting (speculative) suggestion that Dysbiosis Of Gut Microbiota (DOGMA) might be implicated in cases of PCOS. I was always going to be drawn to this paper, simply because (a) who wouldn't with an acronym like DOGMA and (b) it making mention of a mechanism which seems to be coming up time and time again whereby gut bacterial disturbances lead to the so-called leaky gut (gut hyperpermeability) which allows passage of bits of gut bacteria into places they shouldn't really be found which in turn switches the immune system into 'eye of Sauron' mode with potential onward effects on health. The recent Sutterella-autism paper suggested something quite similar. The authors speculate that the immune activation resulting from detection of these foreign bodies interferes with insulin receptor functioning which starts the cascade of rising insulin levels and PCOS as a possible end-point. I'm not really in a position to argue for or against this immune-insulin link but have blogged before about a potential link between diabetes, inflammation and gut permeability. Make of that what you will.

The second paper in this grand speculative post is this one by Palomba and colleagues** looking at offspring of women with PCOS in terms of their scores on various measures of autistic traits. MJ over at Autism Jabberwocky recently discussed everyone's favourite sweeping autism generalisation theory 'the Extreme Male Brain Theory' which has graced previous posts on this blog before. The connection between PCOS and autism (apparently) is testosterone and how the sex hormone biological fingerprint might confer some risk for autistic traits. Interestingly Palomba and co. reported higher levels of autistic traits in children of mums with PCOS compared to non-PCOS controls. Interesting also that female offspring of mums with PCOS seemed to be the ones who quote: "seem to have a higher risk for PDDs".

The final piece [bear with me] of this jagged little post goes back to that very interesting paper by Brent Williams and colleagues*** on carbohydrate metabolism and gut dysbiosis in a small group of children with autism which was discussed here and here. To reiterate: issues with the 'starting material' for enzymes used to process carbohydrates in cases of autism and potential signs of gut bacteria dysbiosis. No specific mention of gut permeability issues, but the words 'maldigestion' and 'malabsorption' are used a few times.

Taken as a whole and with quite a few pinches of salt, I'm speculating on a few things with this post. So for example, dysbiosis is a starting point; where, for whatever reason, disturbances to gut bacteria begin a cycle of physiological changes eventually resulting in elevated levels of insulin and further elevations in testosterone in PCOS. I know some people will look at a concept like dysbiosis and think that it is something fresh out of the 'alt-med' camp complete with lashings of new-age, tofu tomfoolery. The fact of the matter however is that DOGMA(!) is quite a widely reported phenomenon and not just the stuff of fluffy organic dreams.

A second speculation is that, accepting a link between increasing insulin levels and increasing testosterone levels, albeit not necessarily the only way that testosterone levels can be increased, one questions the possibility that testosterone levels could be artificially inflated by environment or lifestyle means (as per this recent study) and what implications this might have for the testosterone-autism hypothesis. Understanding that not every woman with PCOS will have a child with autism, I do wonder about the recent obesity-autism hypothesis and whether there may be grounds for a study looking at maternal insulin and testosterone levels as a function of offspring risk of autism. When saying this I am also sensitive to the fact that maternal obesity / signs of metabolic syndrome are not a universal connection in autism and that quite a few mums (and dads) with children with autism might be getting a little tired of all the 'risks' being reported in relation to autism.

I think I've exhausted my salt supplies with the speculation in this post. Readers are advised that nothing should be taken as fact in this post aside from the results presented in the peer-reviewed journals. I am truly interested to see how the work in these various areas advances and whether issues like DOGMA are indeed able to crack some of the other dogma present in autism and other research circles.

To finish, some Salt-n-Peppa going easy on the salt please.

* Tremellen K & Pearce K. Dysbiosis of Gut Microbiota (DOGMA) - A novel theory for the development of Polycystic Ovarian Syndrome. Medical Hypotheses. April 2012

** Palomba S. et al. Pervasive developmental disorders in children of hyperandrogenic women with polycystic ovary syndrome: a longitudinal case-control study. Clinical Endocrinology. May 2012.
DOI: 10.1111/j.1365-2265.2012.04443.x

*** Williams B. et al. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS ONE. September 2011.