Sunday, 4 March 2012

Antibiotics and autism: friend or foe?

Ear @ Paul Whiteley
An interesting headline caught my eye recently: 'Scientists shocked to find antibiotics alleviate symptoms of schizophrenia'. I'm cautiously intrigued. Intrigued enough to post this entry on antibiotics in relation to autism spectrum conditions with some potential overlap with the 'shocking' headline.

Bacteria is something which has cropped up quite a bit on this blog and its derivative. Most of the more intriguing posts have concerned the trillion or so bacteria residing in our deepest, darkest bowels alongside various suggestions on how such bacteria might (a) have quite a close connection to our health and wellbeing or (b) how different types of bacteria might be more prevalent in certain groups.

In amongst some of the discussions, some mention of the use of antibiotics (antimicrobials if you wish) has also been made. With autism spectrum conditions particularly in mind, the surprising effects from certain types of antibiotic use has been noted. I refer for example, to this study by Sandler and colleagues* which suggested that administration of quite a powerful antibiotic, the glycopeptide antibiotic vancomycin, seemed to tie in with some short-term improvements in various facets of behaviour seen in autism. The authors speculated on a gut flora-brain connection which, in light of subsequent findings, might eventually turn out to have been quite a good forecast.

Backing up slightly I perhaps should mention a few things. As any good Doctor / Pharmacist will tell you, the term 'antibiotics' is a bit of a catch-all for a large group of medications targeting various, different kinds of bacteria. So as one might imagine, treating cellulitis thought to be due to staphylococcal infection will involve a different antibiotic compared with cellulitis caused by streptococcal infection. Not all bacteria are created equal; the trick is to link bacteria to antibiotic. I should also point out that generally speaking, antibiotics tend not to be very selective in the bacteria they target; thinking shock-and-awe rather than precision bombing when it comes to bacterial destruction of like-minded species. That and the fact like many of our medications, there may be more effects than those merely detailed on the patient information leaflet.

An interesting study has surfaced suggesting that antibiotic administration, a certain type of antibiotic called D-cycloserine (not chirality again), might have some interesting effects on some behaviours linked to autism. The study by Deutsch and colleagues** carried out on BALB/c mice who might share some characteristics relevant to autism, suggested that the social behaviours of young mice were "attenuated" following D-cycloserine administration. In effect, mice were observed to become more social. The authors suggested that the effects were more central, in that cycloserine is known to act on the NMDA receptor.

Not for the first time has D-cycloserine turned up in autism research circles. On that occasion suggesting that administration to people with autism, not mice, again targeted one of the core symptoms of autism, the sociability side of things. Indeed looking around the research landscape, D-cycloserine seems to have developed a bit of a following for quite a few, behaviourally-related conditions including OCD and schizophrenia albeit not universally so and not necessarily with sociability in mind. Not bad for a drug more commonly used to treat TB.

A possible role for other antibiotics in cases of autism litter the research landscape. Paribello and colleagues*** discussed the possible usefulness of minocycline - the same antibiotic listed in the headline at the start of this post - and Fragile X syndrome; something which has cropped up again fairly recently. I note that minocycline is one of the drugs of choice for spirochaete infections potentially taking us back to some 'speculations' on Lyme disease (if we were to stick to its normal action). Indeed there is further speculation about this Lyme connection in this article by Kuhn and colleagues**** recently published.

Several interesting studies indeed, but antibiotics are potentially a bit of a double-edged sword with regards to autism. I say this because of the various suggestions linking a medical history of antibiotic use to autism particularly where ear infections (otitis media) seem to be frequent. I know, I know, correlation/association does not imply causation and all that; nevertheless, I tread very carefully with the reports detailing a possible connection (and their retort).

We are all told that we should be cutting back on our antibiotic use as bacteria become more and more resistant to them. The scariest scenario is that of conditions such as tuberculosis (TB) becoming totally resistant to our antibacterial defences leaving us with lots of potential problems. With this in mind, the long-term use of specific antibiotics for some cases of autism is probably not going to be a strategy that most people would desire or want. That, and the potential longer term side-effects of antibiotic administration which might compound existing peripheral issues noted in cases of autism, means that other intervention strategies need to be identified.

Not being a bacteriologist or anything related I can't speculate much further aside from asking about two related issues: (1) how about competition rather than eradication? and (2) set yuck factor to 10 but what about the growing interest in bacterial transplantation as a potential area of investigation?

To finish, paying homage to the spooky appearance of fireballs in the sky over England and Mars being so close, Jeff Wayne and Eve of the War. You might not be alone... (although Martian invaders are probably not about to take over Earth just yet).

* Sandler R. et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. Journal of Child Neurology. 2000; 15: 429-435.

** Deutsch SI. et al. d-cycloserine improves sociability and spontaneous stereotypic behaviors in 4-week old mice. Brain Research. 2011

*** Paribello C. et al. Open-label add-on treatment trial of minocycline in fragile X syndrome. BMC Neurology. 2010; 10: 91.

**** Kuhn M. et al. Long term antibiotic therapy may be an effective treatment for children co-morbid with Lyme disease and Autism Spectrum Disorder. Medical Hypotheses. February 2012.