Lyme and soda: hold the autism risk?

I've talked about the mighty tick previously on this blog and some speculation on how a tick harbouring the bacteria Borrelia burgdorferi (or a close relation) bites and transmits said bacteria to humans which can lead to Lyme disease and whether this might be implicated in some cases of autism.

 Tickety boo @ Wikipedia  

The suggestion from that post was that whilst the data was speculative and relatively sparse at that time on whether Lyme disease is common in cases of autism or indeed could 'cause' autism, there might be some room to test one or two hypotheses regarding a possible link between the two conditions.

Two years on, I'm happy to report that someone has finally looked at the possibility of a connection in the form of a letter by Mary Ajamian and colleagues* published in the journal JAMA. The results: no link between Lyme disease and autism in a sizeable cohort of children/young adults with autism or indeed Lyme disease and control participants.

The ins-and-outs of the study have been quite widely reported, for example with headlines like: 'Autism-Lyme Correlation Debunked' and 'Autism And Lyme Disease Link Is Bunk, Study Says'. Using a two-tiered assay based on initial screening for antibodies to B.burgdorferi (IgG and IgM) and Western blotting for antibodies in suspect cases, the authors were systematically able to test for signs of infection and found pretty much nothing.

Interestingly, the authors are quoted as saying that their study, whilst well-powered and based on the US CDC advice for screening for Lyme disease, might not necessarily spell the end of any association between Lyme disease and autism. To quote from this news source: "The researchers also pointed out that their analysis did not address the question of whether Lyme disease might cause autism-like behavioral deficits". That for example earlier infection during infancy or even in-utero might be linked to cases of autism was not part and parcel of the Ajamian study. Certainly with all the recent speculation turning to the earliest time of life being linked to autism risk - think folate and valproate for example - I don't think we are in a position to yet discount such possibilities. That and the renewed focus on the tetracyclines with autism in mind (used to treat Lyme disease).

But....

The Ajamian study must be seen as compelling evidence that no current infection pertinent to Lyme disease exists in cases of autism or controls, or at least the cases that were under investigation. I know infection is still quite a hot potato when it comes to autism risk (remembering this study by Hornig and colleagues** and all that XMRV overspill into autism spectrum disorders) bearing in mind the continued speculation on all those possible in-utero exposures whether viral or bacterial. I would bring you back to that most classical of autism risk factors - congenital rubella as per the study by Chess and colleagues*** - as evidence that external agents might be associated with autism onset and how the wider search for potentially linked pathogens should not be tarnished by the latest findings.

Update (10/05/13) And just a few days later... Lack of serum antibodies against Borrelia burgdorferi in children with autism by Burbelo and colleagues****.

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* Ajamian M. et al. Serologic markers of Lyme Disease in children with autism. JAMA. 2013; 309: 1771-1773.

** Hornig M. et al. Lack of association between measles virus vaccine and autism with enteropathy: a case-control study. PLoS ONE. 2008; 3: e3140.

*** Chess S. et al. Behavioral consequences of congenital rubella. J Pediatr. 1978; 93: 699-703.

**** Burbelo PD. et al. Lack of serum antibodies against Borrelia burgdorferi in children with autism. Clin Vaccine Immunol. May 2013.

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Mary Ajamian, Barry E. Kosofsky, Gary P. Wormser, Anjali M. Rajadhyaksha, & Armin Alaedini (2013). Serologic Markers of Lyme Disease in Children With Autism JAMA, 309 (17), 1771-1773

Tick, tick, tick...boom

Despite the very dramatic title of this post, I am not going to be discussing explosives nor even the Will Smith (not forgetting Jazzy Jeff) song which carried such lyrical swagger, but rather a few things related to the small but mighty tick (and no, not that tick either). For those of a squeamish disposition who prefer not to see creepy-crawlies and their various effects on body parts, I would perhaps suggest not clicking on this link (or even worse this link) which describes, in quite some detail, how the tick and its bite is potentially linked to a condition called Lyme disease.

For those who didn't click on the link but are still curious, Lyme disease is an inflammatory disease which occurs when a tick harbouring the bacteria Borrelia burgdorferi bites and transmits said bacteria to humans. The name Lyme comes from the place Lyme, USA where an outbreak of the disease leading to a cluster of cases of juvenile arthritis led to the first comprehensive description. The symptoms can include things like lethargy, fever, headaches, muscle pain and in more serious cases, joint inflammation and changes to behaviour. This last symptom relating to behaviour is a little non-descript although some people have speculated that this could include autistic-like behaviours. Bacteria affecting behaviour also conjours up some interesting links with the many and varied posts made on this blog relating to how external organisms might be able to affect our presented behaviour; but I digress.

Looking on the web, there is quite a lot of interest in a possible connection between Lyme disease and lots of different conditions. Chronic, persistent Lyme disease has found some overlap with conditions such as Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME) and fibromyalgia (FM) given the described similarities in symptoms. Indeed, there is some evidence that Lyme disease may co-exist alongside conditions such as FM, although a universally causative relationship has not yet been established. As mentioned, a particular form of arthritis is one of the more serious symptoms associated with Lyme disease but there are a variety of other effects linked to the nervous system for example.

Autism has also been speculatively linked to Lyme disease, although I would perhaps emphasise the 'speculatively' side of things. The evidence for an association is sparse to say the least, and currently non-existent (at least in PubMed listed journals) in terms of data on things like serological co-morbidity and any potential effects on autistic symptoms following infection or treatment for Lyme disease. That being said, the prescribed treatment schedule for Lyme disease utilising antibiotics such as the tetracyclines has found some initial favour in the management of symptoms in autism-linked conditions such as Fragile X syndrome albeit tied into potential effects outside of antimicrobial activity.

Although the data is sparse, there is some common sense reason for looking at the potential involvement of Lyme disease in some cases of autism. As per my comments in previous posts, autism is not protective of developing other conditions/diseases/infections, so one could perhaps see that a child with autism walking in woodland with their parents would be at equal risk of being bitten by a tick as everyone else. Whether or not there would be some increased likelihood of being bitten is not known. Gestational Lyme disease, diagnosed on the presence of anti-Borrelia burgdorferi antibodies, can be associated with adverse neonatal and post-natal outcomes for the infant. This, despite the fact, that pregnancy might actually provide some protective immunological effects. Some of the adverse outcomes described by Nadal and colleagues show some possible connection to autism (hyperbilirubinaemia, hypotonia, macrocephaly) but it is altogether a different thing to say that such outcomes related to autism might be caused by secondary Lyme disease. Further research would perhaps be required.

I appreciate that for some people thinking about ticks and what they could do is spine-tingling stuff. Suffice to say that the risk of getting a tick bite is pretty low assuming that a few precautions are taken, not least keeping away from tick hotspots (long grass off the beaten track where deer may roam).