Clinical studies frequently report that patients with major mental
illness such as schizophrenia and bipolar disorder have co-morbid
physical conditions, suggesting that systemic alterations affecting both
brain and peripheral tissues might underlie the disorders. Numerous
studies have reported elevated levels of anti-Toxoplasma gondii (T.
gondii) antibodies in patients with major mental illnesses, but the
underlying mechanism was unclear. Using multidisciplinary
epidemiological, cell biological, and gene expression profiling
approaches, we report here multiple lines of evidence suggesting that a
major mental illness-related susceptibility factor, Disrupted in
schizophrenia (DISC1), is involved in host immune responses against T.
gondii infection. Specifically, our cell biology and gene expression
studies have revealed that DISC1 Leu607Phe variation, which changes
DISC1 interaction with activating transcription factor 4 (ATF4),
modifies gene expression patterns upon T. gondii infection. Our
epidemiological data have also shown that DISC1 607 Phe/Phe genotype was
associated with higher T. gondii antibody levels in sera. Although
further studies are required, our study provides mechanistic insight
into one of the few well-replicated serological observations in major
mental illness.
illness such as schizophrenia and bipolar disorder have co-morbid
physical conditions, suggesting that systemic alterations affecting both
brain and peripheral tissues might underlie the disorders. Numerous
studies have reported elevated levels of anti-Toxoplasma gondii (T.
gondii) antibodies in patients with major mental illnesses, but the
underlying mechanism was unclear. Using multidisciplinary
epidemiological, cell biological, and gene expression profiling
approaches, we report here multiple lines of evidence suggesting that a
major mental illness-related susceptibility factor, Disrupted in
schizophrenia (DISC1), is involved in host immune responses against T.
gondii infection. Specifically, our cell biology and gene expression
studies have revealed that DISC1 Leu607Phe variation, which changes
DISC1 interaction with activating transcription factor 4 (ATF4),
modifies gene expression patterns upon T. gondii infection. Our
epidemiological data have also shown that DISC1 607 Phe/Phe genotype was
associated with higher T. gondii antibody levels in sera. Although
further studies are required, our study provides mechanistic insight
into one of the few well-replicated serological observations in major
mental illness.
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