Interaction between childhood maltreatment on immunogenetic risk in depression: Discovery and replication in clinical case-control samples

Brain, Behavior, and Immunity

Volume 67, January 2018, Pages 203-210


















aSchool of Psychology, Faculty of Social and Behavioural Sciences, Flinders University, Adelaide, SA, Australia

bFlinders Centre for Innovation in Cancer, School of Medicine, Flinders University, PO Box 2100, Adelaide, SA 5001, Australia

cMRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK

dDepartment of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK

eDepartment of Psychology, Goldsmiths, University of London, London, UK

fCentre for Psychiatry, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK

gMRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK

hDepartment of Psychiatry, University of Münster, Münster, Germany

iDiscipline of Psychiatry, School of Medicine, The University of Adelaide, Adelaide, SA, Australia

jDepartment of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada

Received 24 April 2017, Revised 1 August 2017, Accepted 30 August 2017, Available online 1 September 2017. rights and content


•Gene-environment study focusing on comprehensive analysis of immune candidate genes.

•Interaction with childhood maltreatment in predicting recurrent depression.

•Loci identified in the discovery sample taken forward to an independent replication sample.

•Two loci present some evidence for replication in IL-6 and CRP.

•These loci should be targeted for replication in further studies internationally in the future.


Major depressive disorder (MDD) is a prevalent disorder with moderate heritability. Both MDD and interpersonal adversity, including childhood maltreatment, have been consistently associated with elevated inflammatory markers. We investigated interaction between exposure to childhood maltreatment and extensive genetic variation within the inflammation pathway (CRPIL1bIL-6IL11TNFTNFR1, and TNFR2) in relation to depression diagnosis. The discovery RADIANT sample included 262 cases with recurrent DSM-IV/ICD-10 MDD, and 288 unaffected controls. The replication Münster cohort included 277 cases with DSM-IV MDD, and 316 unaffected controls. We identified twenty-five single nucleotide polymorphisms (SNPs) following multiple testing correction that interacted with childhood maltreatment to predict depression in the discovery cohort. Seven SNPs representing independent signals (rs1818879, rs1041981, rs4149576, rs616645, rs17882988, rs1061622, and rs3093077) were taken forward for replication. Meta-analyses of the two samples presented evidence for interaction with rs1818879 (IL6) (RD = 0.059, SE = 0.016, p < 0.001), with the replication Münster sample approaching statistical significance in analyses restricted to recurrent MDD and controls following correction for multiple testing (q = 0.066). The CRP locus (rs3093077) showed a similar level of evidence for interaction in the meta-analysis (RD = 0.092, SE = 0.029, p = 0.002), but less compelling evidence in the replication sample alone (recurrent MDD q = 0.198; all MDD q = 0.126). Here we present evidence suggestive of interaction with childhood maltreatment for novel loci in IL-6 (rs1818879) and CRP (rs3093077), increasing risk of depression. Replication is needed by independent groups, targeting these specific variants and interaction with childhood maltreatment on depression risk.

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About S. R. Zelenz 117 Articles
S.R. Zelenz has worked in education for 20 years. Working with students from all walks of life, cultures, races, and social diversity, Zelenz’s research in Educational Leadership led to finding a better way to approach learning for students with trauma histories. Many were juvenile offenders, gang members, diagnosed with varying behavioral disorders, or had family histories of violence, murder, or narcissistic parenting. This research could not be effectively accomplished without further understanding: how epigenetic trauma inheritance may be impacting these students; how brain development from trauma may be impacting their behavioral and emotional development; as well as deep understanding of psychology and its varying classifications for behavioral and personality disorders. The goal is to find solutions for changing the conversation and making a real difference for these students. She has also worked with nonprofits of varying focus areas for the last 25 years. Her undergraduate degree in Arts Administration and Music prepared her for managing nonprofits of any size as well as procuring funding so that they can achieve their goals. Pairing her nonprofit background with her education background, she has been able to make a difference for over 200 nonprofits worldwide, written curriculum for schools across the globe, and assisted many arts organizations through performance and management.