Immunological effects from risperidone treatment in autism

The findings from Jai Eun Choi and colleagues [1] suggesting that use of the antipsychotic risperidone may impact on levels of certain cytokines - messenger cells of the immune system - in some cases of autism spectrum disorder (ASD) grabbed my attention recently. I've always been pretty interested in the complexity of the immune system when it comes to something like autism (see here) as well as the various examples of how many of the medications used to 'manage' aspects of autism appear to have quite a few more biological effects over and above those listed on the patient information leaflet. Think melatonin for example, and what a molecular handyperson this pharmaceutic has turned out to be (see here).

Could it be magic... @ Wikipedia 

The Choi paper worked on the assumption that use of risperidone and other antipsychotics have previously been shown to correlate with changes to serum levels of certain cytokines as per examples of work in the area of schizophrenia [2] and here [3]. Some of this research even hinted that part of the reason why antipsychotics might 'work' in some cases of schizophrenia was to do with their potential effect on "the inflammatory-like situation" present [4]. Certainly it's been noted before on this blog how inflammation may very well play some role when it comes to psychiatry (see here) particularly in light of some of the research on the various inflammatory markers (see here) accepting the chicken-and-egg question of what comes first: inflammation or symptoms?

Anyhow, based on a small-ish sample (n=45), Choi et al looked at plasma levels of "27 different cytokines" both before risperidone treatment was introduced and after 8 weeks on the drug. Interestingly the words 'responders' and 'nonresponders' were included in the analyses undertaken to look for any changes/trends following antipsychotic use (something which I think more studies should head towards). As it happens, "2 of the 27 plasma cytokines showed statistically significant decreases in median levels" - eotaxin and monocyte chemoattractant protein-1 (MCP-1). Further, when those responders and non-responders were separated out "the median values of interleukin (IL)-5 were significantly higher (p=0.005) in the overall responder group than in nonresponders".

Obviously one has to be a little bit guarded about the conclusions reached from this fairly small and fairly short study. Whilst risperidone does have a place in the medicines cabinet for some people with autism (see here), paediatric use (as was the case in the Choi study) is not without risks as per a recent entry on the SFARI website (see here). The guidance from NICE here in the UK (well, England at least) also mentioned how cautious physicians must be when using antipsychotics "for behaviour that challenges" with autism in mind.

I was quite interested in the Choi findings particularly that of the elevations in IL-5 in the responder group. I'm no expert on IL-5 but some light reading around the topic (see here) seems to imply that elevations of this cytokine are probably not going to be a great thing from the point of view of their involvement in the activation of eosinophils [5]. I've talked before on this blog about some of the work looking at eosinophils and autism (see here) and some potentially interesting correlations with other research (see here). I'd perhaps like to see more about this correlation in future studies particularly building on other findings in relation to IL-5 and autism [6] (open-access here) including as part of being a risk factor for offspring autism [7] (open-access here).

Insofar as the eotaxin and MCP-1 findings, well, again there is probably a lot more work to do on these compounds as a function of their mention in other autism research [8] (open-access here). The paper by Paul Ashwood [9] (who incidentally was an author on the Choi paper) looking at Fragile X syndrome (FXS) with and without autism also caught my eye: "significant differences were observed between the FXS group with autism and the FXS without autism for IL-6, eotaxin, MCP-1" as another avenue for further study.

So then... somewhere the drinks are free (or should that be all-inclusive).

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[1] Choi JE. et al. Change in Plasma Cytokine Levels During Risperidone Treatment in Children with Autism. J Child Adolesc Psychopharmacol. 2014 May 14.

[2] Zhang XY. et al. Changes in serum interleukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia. J Clin Psychiatry. 2004 Jul;65(7):940-7.

[3] Kim DJ. et al. Effect of risperidone on serum cytokines. Int J Neurosci. 2001;111(1-2):11-9.

[4] Cazzullo CL. et al. Cytokine profiles in schizophrenic patients treated with risperidone: a 3-month follow-up study. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Jan;26(1):33-9.

[5] Takatsu K. & Nakajima H. IL-5 and eosinophilia. Curr Opin Immunol. 2008 Jun;20(3):288-94.

[6] Suzuki K. et al. Plasma cytokine profiles in subjects with high-functioning autism spectrum disorders. PLoS One. 2011;6(5):e20470.

[7] Goines PE. et al. Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: A case-control study. Mol Autism. 2011 Aug 2;2:13.

[8] Ashwood P. et al. Associations of impaired behaviors with elevated plasma chemokines in autism spectrum disorders. J Neuroimmunol. 2011 Mar;232(1-2):196-9.

[9] Ashwood P. et al. Plasma cytokine profiles in Fragile X subjects: is there a role for cytokines in the pathogenesis? Brain Behav Immun. 2010 Aug;24(6):898-902.

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Choi JE, Widjaja F, Careaga M, Bent S, Ashwood P, & Hendren RL (2014). Change in Plasma Cytokine Levels During Risperidone Treatment in Children with Autism. Journal of child and adolescent psychopharmacology PMID: 24828014