Saturday, 31 May 2014

Cytomegalovirus and autism

Today I'm talking on the topic of cytomegalovirus infection and autism following the paper by Sakamoto and colleagues [1] and their conclusion on: "the involvement of congenital CMV [cytomegalovirus] infection in a portion of children with ASD [autism spectrum disorder]".
Do you mind?  @ Wikipedia 

Cytomegalovirus (CMV) belongs to a family of viruses called herpesviruses which includes chicken pox and shingles. It is a pretty common virus insofar as an estimated 50-80% of the over 40s in the United States are infected with CMV according to the CDC. The various descriptions of CMV have tended to suggest that for many people, CMV infection seems to have little effect on day-to-day health and wellbeing assuming no presence of any underlying disease or state affecting the immune system for example. As with other herpesviruses however, CMV has the ability to lie dormant (latent) in the body, avoiding detection by the immune system. Reactivation of the virus can occur, as seen with other herpesviruses, notably shingles.

CMV is not however always so benign. Where a woman for example, contracts a CMV infection for the first time during pregnancy or in the months before conception, the infection can spread to the developing foetus, something called congenital CMV infection. This can often have serious consequences for offspring health and development. Seroprevalence rates for CMV in pregnant women have been estimated to be quite high particularly when ethnicity is taken into account [2].

The Sakamoto paper adds to quite a long history of research looking at a possible connection between congenital CMV infection and the presentation of autism (see here). Examining blood and/or tissue samples (yes, including those gold mines of information, the neonatal bloodspots) for 27 children diagnosed with ASD, researchers went looking for the DNA of CMV, that is the genetic blueprint of the virus. DNA was preferable to the presence of just antibodies to the virus, which could be there purely because maternal antibodies to CMV will to some extent be reflected in newborn infants. "CMV DNA was detected in two (7.4%) of the 27 children" researchers reported, and interestingly, aside from the presentation of autism, none of the more classical indicators of congenital CMV infection were observed in these children such as hearing loss or epilepsy (see here).

Whilst one has to be a little bit careful in saying that congenital CMV infection 'causes' autism, I do find the association to be a potentially important one. I note from some of the earlier work in this area, specifically that of Gene Stubbs [3] there was a recommendation that: "Physicians who find autistic symptoms in very young children might include cytomegalovirus in their differential to document the presence or absence of a correlation". Likewise the paper by Markowitz [4] similarly hinted "that congenital viral infection may be an important cause of infantile autism". In that case there was also some discussion that "over time improvement was noted" in behavioural presentation in line with what would be expected from an infection-based model of symptoms.

From a cold, objective science perspective, cases of congenital CMV infection with autism presentation also offer a potentially valuable insight into mechanism and intervention. Yamashita and colleagues [5] talked about "subependymal cysts and the later development of AD [autistic disorder]" as one research avenue. Whether such features directly link to the presence of autism or autistic behaviours or other presentation talked about in the case reports discussed by the authors is not yet known. Similarly, Engman and colleagues [6] talked about cerebral cortical malformations being more frequently detected in cases of congenital CMV infection. Various directions for autism research are provided.

The question of 'treating' congenital CMV infection also arises, and what effect this might have on the presentation of autism or autistic traits. I note another paper from Stubbs and colleagues [7] talked about the use of "Transfer factor immunotherapy" in one child to "improve his specific immunocompetence to cytomegalovirus thereby either containing the effects of the virus or eradicating the virus". I'm not making any recommendations or anything about this course of action particularly when one considers some of the history of transfer factor and autism, but following a pattern of treatment of the condition where autism is not mentioned [8] the use of something like an anti-viral might be an area in need of further research investigations, particularly where circulating anti-CMV antibodies persist [9]. As Binstock [10] noted: "immune impairments and atypical infections may be treatable" when it comes to autism, as they might be when it comes to other conditions and other viral infections (again with no medical or clinical advice given or intended).

Music to close. The North-East of England is really pulling in the acts this year. The Kings of Leon play Newcastle this evening, and so I leave you with perhaps their most famous song to date about something being on fire... socks perhaps?

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[1] Sakamoto A. et al. Retrospective diagnosis of congenital cytomegalovirus infection in children with autism spectrum disorder but no other major neurologic deficit. Brain Dev. 2014 Apr 22. pii: S0387-7604(14)00094-1.

[2] Pembrey L. et al. Seroprevalence of cytomegalovirus, Epstein Barr virus and varicella zoster virus among pregnant women in Bradford: a cohort study. PLoS One. 2013 Nov 27;8(11):e81881.

[3] Stubbs EG. Autistic symptoms in a child with congenital cytomegalovirus infection. J Autism Child Schizophr. 1978 Mar;8(1):37-43.

[4] Markowitz PI. Autism in a child with congenital cytomegalovirus infection. J Autism Dev Disord. 1983 Sep;13(3):249-53.

[5] Yamashita Y. et al. Possible association between congenital cytomegalovirus infection and autistic disorder. J Autism Dev Disord. 2003 Aug;33(4):455-9.

[6] Engman ML. et al. Congenital cytomegalovirus infection: the impact of cerebral cortical malformations. Acta Paediatr. 2010 Sep;99(9):1344-9.

[7] Stubbs EG. et al. Transfer factor immunotherapy of an autistic child with congenital cytomegalovirus. J Autism Dev Disord. 1980 Dec;10(4):451-8.

[8] Lombardi G. et al. Congenital cytomegalovirus infection: treatment, sequelae and follow-up. J Matern Fetal Neonatal Med. 2010 Oct;23 Suppl 3:45-8.

[9] Kawashti MI. et al. Possible immunological disorders in autism: concomitant autoimmunity and immune tolerance. Egypt J Immunol. 2006;13(1):99-104.

[10] Binstock T. Intra-monocyte pathogens delineate autism subgroups. Med Hypotheses. 2001 Apr;56(4):523-31.

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ResearchBlogging.org Sakamoto A, Moriuchi H, Matsuzaki J, Motoyama K, & Moriuchi M (2014). Retrospective diagnosis of congenital cytomegalovirus infection in children with autism spectrum disorder but no other major neurologic deficit. Brain & development PMID: 24768169