Early life Adversity,functional connectivity and cognitive performance in Schizophrenia: The mediating role of IL-6 |
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| Affiliation: | 1. Centre for Neuroimaging, Cognition and Genomics (NICOG), School of Psychology, National University of Ireland, Galway, Ireland;2. Pharmacology & Therapeutics, National University of Ireland, Galway, Ireland;3. Department of Psychology, National College of Ireland, Dublin, Ireland;4. School of Natural Sciences, National University of Ireland, Galway, Ireland;5. Department of Psychiatry, Trinity Centre for Health Sciences, St. James’s Hospital, Dublin, Ireland;6. Department of Psychiatry, Clinical Science Institute, National University of Ireland, Galway, Ireland;1. Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India;2. Department of Psychiatry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India;3. Department of Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India;4. Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India;5. Department of Psychiatry, Sri Manakula Vinayagar Medical College Hospital, Puducherry, India;1. Parnassia Psychiatric Institute, Kiwistraat 43, 2552 DH The Hague, The Netherlands;2. Erasmus Medical Center Rotterdam, Department of Immunology, PO Box 2040, 3000 CA Rotterdam, The Netherlands;3. Health E-Solutions, Westplein 11, 3016 BM Rotterdam, The Netherlands;4. VU University, Department of Clinical Psychology, de Boelelaan 1105, 1081 HV Amsterdam, The Netherlands;5. Erasmus Medical Center Rotterdam, Department of Psychiatry, PO Box 2040, 3000 CA Rotterdam, The Netherlands;6. University of Groningen, University Medical Center Groningen, Department of Psychiatry, PO Box 30.001, 9700 RB Groningen, The Netherlands;7. Columbia University, Mailman School of Public Health, Department of Epidemiology, 722 West 168th Street, NY 10032, New York, NY, USA;1. School of Social Work, University of Maryland, Baltimore, USA;2. Department of Psychology, The College of William & Mary, USA;3. Department of Psychology, University of Maryland, Baltimore County, USA;1. The University of Queensland, Rural Clinical School, School of Medicine, 152, West St., Toowoomba, QLD 4350, Australia;2. 424 General Military Hospital of Thessaloniki, Psychiatric Department, Thessaloniki Ring Road, 56429 Efkarpia, Thessaloniki, Greece;3. International Business Machines Corporation, New Orchard Road, Armonk, New York 10504 USA;4. 2nd Psychiatric Department, Aristotle University of Thessaloniki, 196 Lagkadast, Stavroupoli 564 29, Thessaloniki, Greece;1. Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India;2. Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India;3. Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India;4. Deakin University, School of Medicine, IMPACT Strategic Research Centre, Geelong, Victoria, Australia;5. Orygen, The Centre of Excellence in Youth Mental Health, The Department of Psychiatry and the Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Australia;1. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Australia;2. Department of Psychiatry, The University of Melbourne, Australia;3. Translational Clinical Psychology Research Unit, Institute for Social Neuroscience, Australia;4. Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick NSW 2031, Australia;5. School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia;6. Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, NY 13210, USA;7. Departments of Medical Genetics, Psychiatry, Physiology & Pharmacology, University of Calgary, Calgary, AB, Canada;8. Department of Psychiatry, University of Münster, Germany;9. Orygen, National Centre of Excellence in Youth Mental Health, Melbourne, Australia;10. North Western Mental Health, Melbourne Health, Parkville, VIC Australia;11. Florey Institute for Neurosciences and Mental Health, Parkville, VIC Australia;12. Centre for Mental Health, Faculty of Health, Arts and Design, School of Health Sciences, Swinburne University, Melbourne, Australia;13. Department of Biomedical Engineering, Melbourne School of Engineering, The University of Melbourne;14. Department of Medicine, Royal Melbourne Hospital, Royal Parade, Melbourne, Australia |
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| Abstract: | ObjectiveExposure to childhood trauma (CT) is associated with cognitive impairment in schizophrenia, and deficits in social cognition in particular. Here, we sought to test whether IL-6 mediated the association between CT and social cognition both directly, and sequentially via altered default mode network (DMN) connectivity.MethodsThree-hundred-and-eleven participants (104 patients and 207 healthy participants) were included, with MRI data acquired in a subset of n = 147. CT was measured using the childhood trauma questionnaire (CTQ). IL-6 was measured in both plasma and in toll like receptor (TLR) stimulated whole blood. The CANTAB emotion recognition task (ERT) was administered to assess social cognition, and cortical connectivity was assessed based on resting DMN connectivity.ResultsHigher IL-6 levels, measured both in plasma and in toll-like receptor (TLR-2) stimulated blood, were significantly correlated with higher CTQ scores and lower cognitive and social cognitive function. Plasma IL-6 was further observed to partly mediate the association between higher CT scores and lower emotion recognition performance (CTQ total: βindirect −0.0234, 95% CI: −0.0573 to −0.0074; CTQ physical neglect: βindirect = −0.0316, 95% CI: −0.0741 to −0.0049). Finally, sequential mediation was observed between plasma IL-6 levels and DMN connectivity in mediating the effects of higher CTQ on lower social cognitive function (βindirect = −0.0618, 95% CI: −0.1523 to −0.285).ConclusionThis work suggests that previous associations between CT and social cognition may be partly mediated via an increased inflammatory response. IL-6′s association with changes in DMN activity further suggest at least one cortical network via which CT related effects on cognition may be transmitted. |
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