ArticlePloS one2015
Infection and inflammation in schizophrenia and bipolar disorder: a genome wide study for interactions with genetic variation.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 3 of them syntheses that pooled it.
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Who cites it
64 citing papers in PubMed, 3 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- The association between antibodies to neurotropic pathogens and bipolar disorder : A study in the Dutch Bipolar (DB) Cohort and meta-analysis.Translational psychiatry · 2019Pooled it
- Genome-wide association study in two populations to determine genetic variants associated with Toxoplasma gondii infection and relationship to schizophrenia risk.Progress in neuro-psychopharmacology & biological psychiatry · 2019Pooled it
- The interaction between cannabis use and the Val158Met polymorphism of the COMT gene in psychosis: A transdiagnostic meta - analysis.PloS one · 2018Pooled it
- Exploring the roots of schizophrenia: Current research and future directions (Review).Experimental and therapeutic medicine · 2026Review
- A review of post-GWAS studies in schizophrenia.Translational psychiatry · 2025Review
- Association of TNF and TLR2 genes with blood parameter levels in Mexican patients with schizophrenia.BMC psychiatry · 2025Article
- Recent findings and future directions for the intersection of genetic and environmental contributions to schizophrenia.Genomic psychiatry : advancing science from genes to society · 2025Article
- Seroprevalence and Associated Risk Factors ofBiomedicines · 2024Article
- The Pathophysiological Underpinnings of Gamma-Band Alterations in Psychiatric Disorders.Life (Basel, Switzerland) · 2024Review
- Maternal immune activation induces sex-dependent behavioral differences in a rat model of schizophrenia.Frontiers in psychiatry · 2024Article
- Higher Levels of C-reactive Protein Are Associated With Higher Cortical Surface Area and Lower Cortical Thickness in Youth With Bipolar Disorder.The international journal of neuropsychopharmacology · 2023Article
- Increased Striatal Presynaptic Dopamine in a Nonhuman Primate Model of Maternal Immune Activation: A Longitudinal Neurodevelopmental Positron Emission Tomography Study With Implications for Schizophrenia.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2023Article
- Therapeutic Implications of the Microbial Hypothesis of Mental Illness.Current topics in behavioral neurosciences · 2023Review
- Effect of Cytomegalovirus Infection on the Central Nervous System: Implications for Psychiatric Disorders.Current topics in behavioral neurosciences · 2023Article
- Toll-Like Receptor (Neuropsychiatric disease and treatment · 2023Article
- The relationship between COVID-19, depressive disorder, and anxiety: a bidirectional Mendelian randomization study.Frontiers in psychiatry · 2023Article
- First-episode mania after COVID-19: A case series in Iran.Frontiers in psychiatry · 2023Article
- Effect of Cytomegalovirus on the Immune System: Implications for Aging and Mental Health.Current topics in behavioral neurosciences · 2023Article
- Analysis of the association between MICA gene polymorphisms and schizophrenia.Journal of clinical laboratory analysis · 2022Article
- Immune Activation in Pregnant Rats Affects Brain Glucose Consumption, Anxiety-like Behaviour and Recognition Memory in their Male Offspring.Molecular imaging and biology · 2022Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Inflammation and maternal or fetal infections have been suggested as risk factors for schizophrenia (SZ) and bipolar disorder (BP). It is likely that such environmental effects are contingent on genetic background. Here, in a genome-wide approach, we test the hypothesis that such exposures increase the risk for SZ and BP and that the increase is dependent on genetic variants. We use genome-wide genotype data, plasma IgG antibody measurements against Toxoplasma gondii, Herpes simplex virus type 1, Cytomegalovirus, Human Herpes Virus 6 and the food antigen gliadin as well as measurements of C-reactive protein (CRP), a peripheral marker of inflammation. The subjects are SZ cases, BP cases, parents of cases and screened controls. We look for higher levels of our immunity/infection variables and interactions between them and common genetic variation genome-wide. We find many of the antibody measurements higher in both disorders. While individual tests do not withstand correction for multiple comparisons, the number of nominally significant tests and the comparisons showing the expected direction are in significant excess (permutation p=0.019 and 0.004 respectively). We also find CRP levels highly elevated in SZ, BP and the mothers of BP cases, in agreement with existing literature, but possibly confounded by our inability to correct for smoking or body mass index. In our genome-wide interaction analysis no signal reached genome-wide significance, yet many plausible candidate genes emerged. In a hypothesis driven test, we found multiple interactions among SZ-associated SNPs in the HLA region on chromosome 6 and replicated an interaction between CMV infection and genotypes near the CTNNA3 gene reported by a recent GWAS. Our results support that inflammatory processes and infection may modify the risk for psychosis and suggest that the genotype at SZ-associated HLA loci modifies the effect of these variables on the risk to develop SZ.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.