Sex-specific immune response to Candida albicans in schizophrenia and beyond

I have quite a bit of time for the various members of the Stanley Division of Developmental Neurovirology at Johns Hopkins on this blog. Not least because of the interesting work of one researcher in particular - Emily Severance - as a name behind some potentially very important research on how food, infection and immune function might come together in complicated conditions such as [some] schizophrenia and [some] bipolar disorder (see here and see here).

Continuing their 'gut-brain' theme (oh, yes) new research from Prof/Dr Severance and colleagues [1] has been published observing that "sex-specific C. albicans immune responses were evident in psychiatric disorder subsets." C. albicans refers to Candida albicans, a fungus that I'm sure most people will have heard of at one time or another if not only as a function of those TV adverts for preparations to combat C. albicans when tied into yeast infection.

On this most recent occasion, researchers were testing the idea of "C. albicans as a new candidate infectious disease target for studies of schizophrenia and bipolar disorder" as a extension of other research talking about 'bacterial dysbioses' potentially contributing "to C. albicans overgrowth by failing to provide the competition needed to keep the fungus in check." If you're furrowing your brow about the thought that the trillions of wee beasties that call us home (the gut microbiome) might exert an effect on behavioural or psychiatric presentation, relax yourself slightly: interest is growing in this area [2] following on from other investigations in other areas (see here).

So, researchers: "measured and compared IgG antibodies directed against this fungus in two psychiatric cohorts: one composed of 261 people with schizophrenia, 270 with bipolar disorder and 277 individuals without a history of psychiatric disorder; the other cohort was composed of 139 people with first-episode schizophrenia, 78 of whom were antipsychotic naive." They also examined cognitive symptoms and took into account various factors that might act as confounders onwards to the idea that IgG antibodies to C. albicans *might* be considered a risk factor for either schizophrenia or bipolar disorder.

Results: well it wasn't as straight-forward as blanket saying that the presence of IgG antibodies (seropositivity) or quantitative levels of these antibodies to C. albicans equals schizophrenia or bipolar disorder (or not-schizophrenia or not-bipolar disorder). There was nothing statistically significant between the various groupings in the cohorts included for study. But... when the groups were categorised according to sex (gender), researchers reported "significant elevations of C. albicans IgG in males with schizophrenia and bipolar disorder compared with male controls."

Further analyses suggested that there may be some 'associations' with other variables examined across the sexes when it came to those IgG antibodies ("females with schizophrenia who were C. albicans IgG-seropositive performed more poorly on these [cognitive] tests than did females with schizophrenia who were C. albicans IgG-seronegative or than female controls") and it appeared that antipsychotic medication use did little to impact on the findings. The bottom line: "antibodies directed against the opportunistic fungal pathogen, C. albicans, were elevated in distinct subsets of individuals with psychiatric disorders" and minus any sweeping generalisations, a research agenda incorporating brain, immune function, gut and also contents of the gut could be indicated in future study. This of course set among the idea that schizophrenia might be better represented by the more plural 'schizophrenias'.

Some of the media around this study and its findings are perhaps a little 'sensational' as per the headline asking: Is a sexually transmitted yeast infection making people mentally ill? I perhaps wouldn't go as far as that at the moment given that C. albicans is present in everyone(?) and overgrowth of such a yeast is not necessarily due to sex or related activities. Yes, certain sexual diseases can manifest as psychological symptoms but an important basis of the Severance study is that intrinsic factors such as gut dysbiosis might start a chain reaction whereby C. albicans is able to flourish and becomes rather more systemic and pathogenic linked to the presentation of behavioural symptoms. Or at least that is part of the hypothesis requiring further testing...

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[1] Severance EG. et al. Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder. npj Schizophrenia 2016; 2: 16018.

[2] Dinan TG. et al. Genomics of schizophrenia: time to consider the gut microbiome? Mol Psychiatry. 2014 Dec;19(12):1252-7.

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Severance, E., Gressitt, K., Stallings, C., Katsafanas, E., Schweinfurth, L., Savage, C., Adamos, M., Sweeney, K., Origoni, A., Khushalani, S., Leweke, F., Dickerson, F., & Yolken, R. (2016). Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder npj Schizophrenia, 2 DOI: 10.1038/npjschz.2016.18