Childhood trauma, IL-6 and weaker suppression of the default mode network (DMN) during theory of mind (ToM) performance in schizophrenia

King, Sinead, Mothersill, David, Holleran, Laurena, Patlola, Saahithh, McManus, Ross, Kenyon, Marcus, McDonald, Colm, Hallahan, Brian, Corvin, Aiden, Morris, Derek W., Kelly, John P., McKernan, Declan and Donohoe, Gary (2022) Childhood trauma, IL-6 and weaker suppression of the default mode network (DMN) during theory of mind (ToM) performance in schizophrenia. Brain, Behavior, and Immunity - Health, 26. ISSN 2666-3546

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Abstract

Background
Both low-grade systemic inflammation and functional connectivity of the default mode network (DMN) during rest have recently been observed to mediate the association between childhood trauma (CT) and behavioural performance on an emotion recognition task. Whether inflammation also mediates the association between CT and functional connectivity of the DMN during social cognitive task performance is unknown.

Methods
51 patients with schizophrenia (SZ) or schizoaffective disorder (SZA) and 176 healthy participants completed a theory of mind (ToM) task during fMRI. IL-6 was measured in plasma using ELISA. DMN connectivity was measured during performance of the fMRI ToM task. To examine DMN connectivity, we selected 4 a priori seeds of the DMN, i.e., the medial prefrontal cortex (PFC), right lateral parietal (LP), left LP, and posterior cingulate cortex (PCC) according to the Harvard-Oxford Cortical and Subcortical Atlas (http://www.cma.mgh.harvard.edu/fsl_atlas.html) as implemented in CONN.

Results
Patients showed significantly increased DMN connectivity compared to healthy participants between each of the four seeds of the DMN and with other clusters in the brain. Across the entire sample, higher levels of IL-6 predicted increased connectivity between the mPFC and regions encompassing the cerebellum (<.001 FWE). IL-6 mediated the association between physical neglect and weaker suppression of the posterior cingulate cortex (PCC) DMN seed -left precentral and postcentral gyrus (βINDIRECT = .0170, CI: 0.0008 to.0506) connectivity during ToM performance.

Discussion
This is the first study to our knowledge that provides evidence that higher plasma IL-6 mediates the association between higher childhood neglect and increased DMN connectivity during ToM task performance. Consistent with our previous study that IL-6 mediated the association between early life stress exposure and reduced connectivity of the DMN during rest, here IL-6 mediated the association between early life stress and increased connectivity of the DMN during ToM based cognitive processing. These findings suggest a biological mechanism for how chronic stress impacts social cognitive processing.

Item Type:	Article
Subjects:	B Philosophy. Psychology. Religion > Psychology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry B Philosophy. Psychology. Religion > Psychology > Child psychology B Philosophy. Psychology. Religion > Psychology > Cognitive psychology
Divisions:	School of Business > Staff Research and Publications
Depositing User:	Clara Chan
Date Deposited:	01 Nov 2022 12:59
Last Modified:	03 Nov 2022 16:30
URI:	https://norma.ncirl.ie/id/eprint/5833

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