Maternal complement C1q and offspring psychosis

"In conclusion, exposure to maternal C1q activity during pregnancy may be a risk factor for the development of schizophrenia and psychosis in offspring". That was the primary observation made by Emily Severance and colleagues [1] at Johns Hopkins, extending their scientific interest in immune system involvement being potentially linked to psychiatry [2].

"Serve the public trust, protect the innocent,
uphold the law"

I've already talked about Dr Severance's previous research forays into complement factor C1q and psychiatry on this blog (see here) and how C1q seropositivity was pretty significantly associated with both recent and non-recent onset schizophrenia in their cohort. Said complexing of C1q also turning up food components (gluten and casein) as potentially being involved [3] which has rumbles of Dohan's hypothesis [4] mixed in.

The most recent Severance paper takes things another stage further by trying to "determine if maternal C1q was associated with offspring schizophrenia and psychosis". Archived serum samples provided during pregnancy were therefore analysed for 55 "matched case-control" pairs of mothers - mothers with offspring who went on to develop psychoses as adults and those with offspring who were asymptomatic from such psychiatric issues. "IgG markers of C1q, bovine milk casein, egg ovalbumin, and wheat gluten were measured". Authors reported that: "C1q was significantly elevated in case mothers" and in that case group, where offspring developed psychoses: "C1q was significantly correlated with antibodies to both food and infectious antigens: gluten..., herpes simplex virus type 2..., and adenovirus".

Accepting that the total number of participants included in this latest trial was relatively small, also relying on archived samples collected as part of the US Collaborative Perinatal Project (CPP) [5], these are interesting results. That both food and infectious agent antigens seemed to correlate with C1q adds to other interesting work by Dr Severance and colleagues on, for example, the protozoan Toxoplasma gondii potentially joining forces with food antigens (see here) in some fashion. I don't know enough about the processes potentially involved in any relationship to provide any definitive answers as to the hows and whys but one hazards a guess that something like an effect on gastrointestinal barrier function might play some role [6].

This and other research from people such as the late Paul Patterson [7] continue to drive home the notion that maternal infection, or rather the immune processes and consequence of infection during pregnancy, seem to be able to influence later life outcomes for offspring. We still need to know more about the specific biological processes involved in any relationship including the rising scientific star that is epigenetics [8] (something covered in a recent blog post) and also how subsequent life events (whether biological, social or psychological) contribute to any psychiatric diagnosis. Whether for certain people or groups of people, there may be some merit at looking further at gastrointestinal (GI) functions (see here) or even dietary changes (see here) is perhaps something else worth investing a little more research time and effort into too...

Ben Folds Five to close...

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[1] Severance EG. et al. Maternal complement C1q and increased odds for psychosis in adult offspring. Schizophrenia Res. 2014. 4 September.

[2] Severance EG. et al. Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling. Schizophr Res. 2014 Jul 14. pii: S0920-9964(14)00319-3.

[3] Severance EG. et al. Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia. Neurobiol Dis. 2012 Dec;48(3):447-53.

[4] Dohan FC. Genetic hypothesis of idiopathic schizophrenia: its exorphin connection. Schizophr Bull. 1988;14(4):489-94.

[5] Klebanoff MA. The Collaborative Perinatal Project: a 50-year retrospective. Paediatr Perinat Epidemiol. 2009 Jan;23(1):2-8.

[6] Nouri M. et al. Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells. PLoS One. 2014 Sep 3;9(9):e106335.

[7] Brown AS. & Patterson PH. Maternal infection and schizophrenia: implications for prevention. Schizophr Bull. 2011 Mar;37(2):284-90.

[8] Tang B. et al. Epigenetic changes at gene promoters in response to immune activation in utero. Brain Behav Immun. 2013 May;30:168-75.

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Emily G. Severance, Kristin L. Gressitt, Stephen L. Buka, Tyrone D. Cannon, & Robert H. Yolken (2014). Maternal complement C1q and increased odds for psychosis in adult offspring Schizophrenia Research : 10.1016/j.schres.2014.07.053