Inflammation-Related Functional and Structural Dysconnectivity as a Pathway to Psychopathology


Author: David R Goldsmith1, Mandakh Bekhbat1, Neeti D Mehta2, Jennifer C Felger3

Affiliation: <sup>1</sup> Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.

<sup>2</sup> Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia; Neuroscience Graduate Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, Georgia.

<sup>3</sup> Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia; Winship Cancer Institute, Emory University, Atlanta, Georgia. Electronic address: jfelger@emory.edu.
Conference/Journal: Biol Psychiatry
Date published: 2023 Mar 1
Other:
 Volume ID: 93   ,  Issue ID: 5   ,  Pages: 405-418   ,  Special Notes: doi: 10.1016/j.biopsych.2022.11.003.   ,  Word Count: 243  
    Findings from numerous laboratories and across neuroimaging modalities have consistently shown that exogenous administration of cytokines or inflammatory stimuli that induce cytokines disrupts circuits and networks involved in motivation and motor activity, threat detection, anxiety, and interoceptive and emotional processing. While inflammatory effects on neural circuits and relevant behaviors may represent adaptive responses promoting conservation of energy and heightened vigilance during immune activation, chronically elevated inflammation may contribute to symptoms of psychiatric illnesses. Indeed, biomarkers of inflammation such as cytokines and acute phase reactants are reliably elevated in a subset of patients with unipolar or bipolar depression, anxiety-related disorders, and schizophrenia and have been associated with differential treatment responses and poor clinical outcomes. A growing body of literature also describes higher levels of endogenous inflammatory markers and altered, typically lower functional or structural connectivity within these circuits in association with transdiagnostic symptoms such as anhedonia and anxiety in psychiatric and at-risk populations. This review presents recent evidence that inflammation and its effects on the brain may serve as one molecular and cellular mechanism of dysconnectivity within anatomically and/or functionally connected cortical and subcortical regions in association with transdiagnostic symptoms. We also discuss the need to establish reproducible methods to assess inflammation-associated dysconnectivity in relation to behavior for use in translational studies or biomarker-driven clinical trials for novel pharmacological or behavioral interventions targeting inflammation or its effects on the brain.



Keywords: Anhedonia; Anxiety; Depression; Functional connectivity; Inflammation; Interoception; fMRI.



PMID: 36725140 DOI: 10.1016/j.biopsych.2022.11.003