"Anti-Candida albicans IgG antibodies in children with autism spectrum disorders"

The quote titling this post - "Anti-Candida albicans IgG antibodies in children with autism spectrum disorders" - reflects the title of the paper by Paul Ashwood & Heather Hughes [1] who set out to "determine if children with ASD [autism spectrum disorder] exhibit elevations in antibodies that target C. albicans, indicating current or previous overgrowth of this fungal species." Such work is based on the still developing idea that "individuals with ASD have significant aberrations in the composition of their gut microbiota, known as dysbiosis" and part of that dysbiosis might also stretch to fungal as well as bacterial species.

Candida albicans also known as C. albicans is described as a 'opportunistic pathogenic yeast' quite readily observed in quite a large proportion of 'healthy adults'. For most people, this yeast does not cause any issues. On occasion however, C. albicans can lead to problems, particularly among those who are described as 'immunocompromised'. This is not the first time that C. albicans has been examined in the context of autism. Granted, the studies so far have been relatively small scale [2] and in requirement of follow-up [3] but this topic is no stranger to the peer-reviewed science literature. The Ashwood & Hughes paper should also be viewed in the context of other science discussions from this authorship group [4]; indeed several [5].

So: "We measured anti-C. albicans immunoglobulin (IgG) in plasma from eighty children enrolled in the UC Davis MIND Institute CHARGE study." IgG antibodies, represent 'immune status' with regards to a history of encountering specific pathogens. So, being positive to "anti-C. albicans immunoglobulin (IgG)" means that someone has been exposed to C. albicans at some point in their lifetime and retained something of an 'immune memory' to it. This subsequently means that your immune system is 'primed' in case that specific pathogen is encountered once again.

Results: "Plasma anti-C. albicans antibody positivity was found in 36.5% (19/52) of children with ASD. Anti-C. albicans antibodies in typically developing controls was (14.3%; 4/28)." I'm sure that you can see the disparity between the groups, bearing in mind that this was not an 'all-or-nothing' finding in relation to the separation of the groups. I should also mention that researchers also reported that gastrointestinal (GI) symptoms, also examined in this cohort, did not seemingly play a role in C. albicans antibody positivity.

Where next for this area of investigation? Well, alongside perhaps taking these results into consideration with other findings from this research group (see here), the authors mention that "exploring fungal composition within the gut as well as metabolic byproducts of yeast species such as d-arabinitol and ethanol, and identifying associations these might have with behaviors in ASD" could be one direction. In light of other independent research (see here), I'd say that was a sensible next step to take.

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[1] Ashwood P. & Hughes HK. Brief Report: Anti-Candida albicans IgG antibodies in children with autism spectrum disorders. Front. Psychiatry. 2018. Nov 26.

[2] Ekiel A. et al. Intestinal microflora of autistic children. Med Dosw Mikrobiol. 2010;62(3):237-43.

[3] Iovene MR. et al. Intestinal Dysbiosis and Yeast Isolation in Stool of Subjects with Autism Spectrum Disorders. Mycopathologia. 2017 Apr;182(3-4):349-363.

[4] Hughes HK. et al. The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders. Curr Neurol Neurosci Rep. 2018 Sep 24;18(11):81.

[5] Hughes HK. et al. Immune Dysfunction and Autoimmunity as Pathological Mechanisms in Autism Spectrum Disorders. Front. Cell. Neurosci. 2018.

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Putting Money on autoimmunity and autism

Go to Jail, go directly to jail... @ Wikipedia  

I owe a debt of gratitude to Natasa who brought me to the very short and very pay-walled communication by McDougle & Carlezon* discussing neuroinflammation and autism. Whilst the open-accessing of research is seemingly discussed in bulk these days, we are not quite there yet in making science free and accessible to all hence I can't refer you to the full-text paper at this time unfortunately.

No mind, the McDougle communication is brief but discusses some interesting themes, some of which have appeared before on this blog including:

• Kanner's original descriptions of autism describing so much more than just behaviour (see this post)
• The issue of autoimmunity and autism tracking back to the topic of today's post, the paper by John Money and colleagues** from 1971.
• And how mention of the paper that should not be mentioned (in my best Harry Potter voice) reflects the fact "that at least some subtypes [of autism] represent whole-body disorders, offering exciting new possibilities for therapy".

I'm not 100% sure if it is the same person or not but the psychologists out there might recognise the name John Money in relation to the very sad case of the late David Reimer. A quick scan through the scientific literature based on the name Money and other authors listed on the the 1971 paper leads me to believe it is the same person who undertook work on gender identity and who championed the chemical castration of certain types of offenders. I offer no opinion on these ideas by the way.

I've previously done a review of some older research before on this blog and in particular the wonderfully descriptive article by Mary Goodwin and colleagues (see this post) on the very earliest days of the gut-brain axis in cases of autism. Readers should consider this post of a similar ilk and indeed published in the same year and by the same journal.

Money and colleagues present a family study with a few interesting points noted:

• The particular family was one seen at The Johns Hopkins Hospital in Baltimore, USA.
• It presents on a case of autism presenting in a boy called Tommy also diagnosed with Addison's disease and moniliasis - fungal infection related to Candida to you and me.
• Tommy had several brothers (x3), 2 of whom also showed various signs and symptoms of autoimmune diseases including those found with Tommy. 
• The early presentation of Tommy has some interesting features. He was overdue, presented with jaundice, had poor weight gain, issues with bone age and quite a few issues related to his diagnosis of Addison's disease. Tonsilitis with convulsions and coma with seizures "attributed to hypogylcaemia" were all in his clinical notes. 
• His psychological development is equally interesting, going from a child who reportedly smiled at 3 weeks (remember he was overdue) and cooed at 5 weeks to a child with "an air of preoccupation and a secret smile".
• Tommy's siblings were not diagnosed with autism but similarly presented with some notable traits. One of the siblings, Peter, was mis-diagnosed with coeliac (celiac) disease though later diagnosed with malabsoprtion in addition to hypomagnesia. He also presented with rapid hair loss aged 16 years. His psychological report mentions quite a lot of attention-seeking behaviour as well as him being prone to depressive episodes and ideations about suicide. 
• Another sibling, Theodore, was described as presenting with hypocalcemia and eventually diagnosed with diabetes. Behaviour was described as 'autistic' at some points in his development, as well as being reported as "hyperactive, disruptive, short in attention span and imitative". 
• All this was set against a family history of ulcerative colitis (UC) (maternal).

I know some people will probably read through all this and perhaps think its all just coincidence. One family history which, in the grand scheme of things, means very little to the millions of cases of autism past, present and future. Indeed also with only one of the brothers formally diagnosed with autism. I have to say however that accepting the heterogeneity present in autism(s), I'm not one of those people. Simply because quite a few elements of the cases described by Money et al have been mentioned in subsequent research literature with autism in mind pointing to some possible connections.

Don't believe me? Well have a look at papers like this one from Mouridsen and colleagues on maternal UC linked to autism*** and this one from Paul Ashwood and Judy Van de Water**** on autoimmunity appearing alongside cases of autism. Indeed Money and colleagues were also seemingly not convinced that these patterns of presentation in the family was merely a random act either, accepting that science is all about probability rather than absolutes. 

I was also drawn to some discussion made in the paper which referenced the work of the late Curt Dohan, he of the gluten-schizophrenia hypothesis. It appears that Money and colleagues might have had some personal communication with Dohan about their results and indeed how Dohan had "reported finding autoimmune antibody formation to brain and gut tissues in patients with schizophrenic-like symptoms and celiac disease". I don't want to make mountains out of molehills but one does wonder whether there might be a link with cases of autism as per the more recent tissue transglutaminase antibodies findings and perhaps even the folate receptor autoantibodies research. Although by no means am I suggesting autism is schizophrenia or vice-versa, we do know that the two conditions have been known to overlap and there's no reason to suspect that biology, genetics and even epigenetics might not also.

I'm going to finish with another quote from the Money paper: "it is quite possible that the patient's progressive withdrawal into autism, after a perhaps auspicious beginning, represents a developmental deterioration dependent on internal autoimmunizing factors rather than psychosocial factors". Sentiments that at least McDougle & Carlezon seem to be taking quite seriously.

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* McDougle CJ. & Carlezon WA. Neuroinflammation and autism: toward mechanisms and treatments. Neuropsychopharmacology. 2013; 38: 241-242.

** Money J. Autism and autoimmune disease: a family study. J Autism Child Schizophr. 1971; 1: 146-160.

*** Mouridesen SE. et al. Autoimmune diseases in parents of children with infantile autism: a case-control study. Dev Med Child Neurol. 2007; 49: 429-432.

**** Ashood P. & Van de Water J. Is autism an autoimmune disease? Autoimmun Rev. 2004; 3: 557-562.

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Money J, Bobrow NA, & Clarke FC (1971). Autism and autoimmune disease: a family study. Journal of autism and childhood schizophrenia, 1 (2), 146-60 PMID: 5172389