ArticlePloS one2015
Combined effect of TLR2 gene polymorphism and early life stress on the age at onset of bipolar disorders.
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 29 papers, 2 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- Altered functional activity in bipolar disorder: A comprehensive review from a large-scale network perspective.Brain and behavior · 2021Pooled it
- Interactions Between Variation in Candidate Genes and Environmental Factors in the Etiology of Schizophrenia and Bipolar Disorder: a Systematic Review.Molecular neurobiology · 2018Pooled it
- The Toll-Like Receptor Signalling Pathway Is Altered in iPSC-Derived Cortical Networks From People With Bipolar Disorder.Bipolar disorders · 2026Article
- Toll-Like Receptor (Neuropsychiatric disease and treatment · 2023Article
- Article
- Social and environmental variables as predictors of mania: a review of longitudinal research findings.Discover mental health · 2022Review
- Identification of inflammatory subgroups of schizophrenia and bipolar disorder patients with HERV-W ENV antigenemia by unsupervised cluster analysis.Translational psychiatry · 2021Article
- Toll-like receptor 4 methylation grade is linked to depressive symptom severity.Translational psychiatry · 2021Article
- Bipolar disorder: Trimodal age-at-onset distribution.Bipolar disorders · 2021Review
- Childhood Maltreatment in Bipolar Disorders.Current topics in behavioral neurosciences · 2021Article
- Toll-like receptor 2 (TLR2)-deficiency impairs male mouse recovery from a depression-like state.Brain, behavior, and immunity · 2020Article
- The genetics of bipolar disorder.Molecular psychiatry · 2020Review
- The Devastating Clinical Consequences of Child Abuse and Neglect: Increased Disease Vulnerability and Poor Treatment Response in Mood Disorders.The American journal of psychiatry · 2020Review
- Polymorphisms in Inflammatory Genes Modulate Clinical Complications in Patients With Sickle Cell Disease.Frontiers in immunology · 2020Article
- Gene-Environment Interactions in Psychiatry: Recent Evidence and Clinical Implications.Current psychiatry reports · 2019Review
- Article
- Epidemiology and risk factors for bipolar disorder.Therapeutic advances in psychopharmacology · 2018Review
- Infectious and immunogenetic factors in bipolar disorder.Acta psychiatrica Scandinavica · 2017Review
- Timeline of Intergenerational Child Maltreatment: the Mind-Brain-Body Interplay.Current psychiatry reports · 2017Review
- Is Toxoplasma gondii a Trigger of Bipolar Disorder?Pathogens (Basel, Switzerland) · 2017Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD), particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2) and 4 (TLR4), major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ) in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified), genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02). Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts.
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