title: Effects of IL1B single nucleotide polymorphisms on depressive and anxiety symptoms are determined by severity and type of life stress.
abstract: Interleukin-1β is one of the main mediators in the cross-talk between the immune system and the central nervous system. Higher interleukin-1β levels are found in mood spectrum disorders, and the stress-induced expression rate of the interleukin-1β gene (IL1B) is altered by polymorphisms in the region. Therefore we examined the effects of rs16944 and rs1143643 single nucleotide polymorphisms (SNPs) within the IL1B gene on depressive and anxiety symptoms, as measured by the Brief Symptom Inventory, in a Hungarian population sample of 1053 persons. Distal and proximal environmental stress factors were also included in our analysis, namely childhood adversity and recent negative life-events. We found that rs16944 minor (A) allele specifically interacted with childhood adversity increasing depressive and anxiety symptoms, while rs1143643's minor (A) allele showed protective effect against depressive symptoms after recent life stress. The genetic main effects of the two SNPs were not significant in the main analysis, but the interaction effects remained significant after correction for multiple testing. In addition, the effect of rs16944 A allele was reversed in a subsample with low-exposure to life stress, suggesting a protective effect against depressive symptoms, in the post hoc analysis. In summary, both of the two IL1B SNPs showed specific environmental stressor-dependent effects on mood disorder symptoms. We also demonstrated that the presence of exposure to childhood adversity changed the direction of the rs16944 effect on depression phenotype. Therefore our results suggest that it is advisable to include environmental factors in genetic association studies when examining the effect of the IL1B gene.
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, Budapest, Hungary; MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4, Budapest, Hungary. Electronic address: thadeous.smith@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Kovacs
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, Budapest, Hungary; MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4, Budapest, Hungary.
authors.forename: Nora
authors.initials: N
authors.lastname: Eszlari
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, Budapest, Hungary; MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Petschner
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, Budapest, Hungary.
authors.forename: Dorottya
authors.initials: D
authors.lastname: Pap
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, Budapest, Hungary; MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4, Budapest, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Vas
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, Budapest, Hungary; National Institute of Oncology, Rath Gyorgy u. 7-9, Budapest, Hungary; PhD School of Mental Health Sciences, Semmelweis University, Balassa u. 6, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, Budapest, Hungary; MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4, Budapest, Hungary; Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Kútvölgyi u.4, Budapest, Hungary.
authors.forename: Xenia
authors.initials: X
authors.lastname: Gonda
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, Budapest, Hungary; MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4, Budapest, Hungary; Neuroscience and Psychiatry Unit, University Manchester, Manchester M13 9PT, United Kingdom; MTA-SE-NAP B Genetic Brain Imaging Migraine Research Group, Hungarian Academy of Sciences, Semmelweis University, Nagyvarad ter 4, Budapest, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Juhasz
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, Budapest, Hungary; MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Nagyvarad ter 4, Budapest, Hungary.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Bagdy
mesh_terms: D000293:Adolescent; D000328:Adult; D000069586:Adult Survivors of Child Adverse Events / Q000706:statistics & numerical data*; D001008:Anxiety Disorders / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D003866:Depressive Disorder / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013315:Stress, Psychological / Q000453:epidemiology; D055815:Young Adult
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta
keywords: Anxiety; Cytokines; Depression; Interleukin-1β; Stress