Part 2: Is there a relationship between parasitic infections and psychosis?
In my previous post I discussed how cats can infect you with T. gondii and how these infections are linked to changes in mental health. If you're curious about cat-loving mice, sexually transmitted food poisoning or where this story all began make sure to go back and read part one! And now, as promised, here is a continuation of that discussion in regards to genetic factors in schizophrenia and T. gondii infection.
Genetic Factors
In every psychological disorders class you learn about the genetics of schizophrenia. You are taught about the classic the twin studies and how risk increases when you have affected relatives on your mother’s side of the family. But where do these genetic factors really fit into the schizophrenia and T. gondii connection?
This is where we must not only consider the infectious agent, but also the way the body’s immune system responds. It is uncommon for toxoplasma to cause symptomatic disease in healthy individuals because the immune system should be able to suppress the tachyzoites, leading to the creation of dormant cysts [1].
The data emerging from genome wide analyses suggests that variations notable in schizophrenia have roles in both nervous system and immune system function [2]. This leaves room for genetics to impact our susceptibility to the infection and the way we deal with the infection. One example is the impact of the interferon gamma response, which helps to suppress T. gondii infection [3]. T. gondii is actually capable of rendering macrophages unresponsive to IFN-gamma [4].
Histocompatibility genes also play a role with HLA-DQ3 giving greater and HLA-DQ1 lesser susceptibility [3]. Additionally, the Disrupted in Schizophrenia 1 (DISC1) genes have been shown in mice to interact with Toxoplasma infection to produce cognitive changes not otherwise seen in those with the genes alone [5].
All these studies reveal an interplay between genetics, immune function and T. gondii infection. But is it solely the inheritance of certain genes related to immune function or could there be a more direct inheritance of “schizophrenia”?
One of the most curious aspects of Toxoplasma I’ve read about was seen in mouse studies: the ability to be transmitted through the placenta for as many as five generations [6]!!! How incredible is that? This gives the false impression of genetic heritability.
Stay tuned for my final post in this series on the relationships between psychosis, cognitive changes, T. gondii and schizophrenia.
References:
Torda, A. Are cats really the source? 30, 743–748 (2001).
Avramopoulos, D. et al. Infection and inflammation in schizophrenia and bipolar disorder: a genome wide study for interactions with genetic variation. PLoS One 10, e0116696 (2015).
Carruthers, V. B. & Suzuki, Y. Effects of Toxoplasma gondii infection on the brain. Schizophr. Bull. 33, 745–751 (2007).
Lang, C. et al. Impaired chromatin remodelling at STAT1-regulated promoters leads to global unresponsiveness of Toxoplasma gondii-infected macrophages to IFN-γ. PLoS Pathog. 8, e1002483 (2012).
Kannan, G. & Pletnikov, M. V. Toxoplasma gondii and cognitive deficits in schizophrenia: An animal model perspective. Schizophr. Bull. 38, 1155–1161 (2012).
Torrey, E. F., Bartko, J. J., Lun, Z. R. & Yolken, R. H. Antibodies to Toxoplasma gondii in patients with schizophrenia: A meta-analysis. Schizophr. Bull. 33, 729–736 (2007).
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