Author: Giovanni O1, Laura BH2, Ricard N3, Zoe M4, David MH5, Myriam C3, Dolors G6, Javier C5, Lucile C7, Xavier F4, Jesus P2, Ricard S6, Rocio MS8
Affiliation: <sup>1</sup>Department of Psychiatry and Psychology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain; Department of Medicine, Faculty of Medicine, and Institute of Neuroscience, University of Barcelona (UB), Barcelona, Spain.
<sup>2</sup>MRI Research Unit, Department of Radiology, Hospital del Mar, CIBERSAM, G21, Barcelona, Spain.
<sup>3</sup>Department of Psychiatry and Psychology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
<sup>4</sup>Liver Unit, Hospital Clinic, IDIBAPS, Centro Investigacion Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.
<sup>5</sup>Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense de Madrid, CIBERSAM, Imas12, IUINQ, Madrid, Spain.
<sup>6</sup>Liver Section, Hospital del Mar, Parc de Salut Mar, Grup de Recerca Hepatológica, FIMIM, Universitat Autónoma de Barcelona, Barcelona, Spain.
<sup>7</sup>INRA, Laboratory of Nutrition and Integrative Neurobiology (NutriNeuro), UMR 1286, F-33076 Bordeaux, France; University of Bordeaux, Laboratory of Nutrition and Integrative Neurobiology (NutriNeuro), UMR 1286, F-33076 Bordeaux, France.
<sup>8</sup>Department of Psychiatry and Psychology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigacion Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain; Department of Medicine, Faculty of Medicine, and Institute of Neuroscience, University of Barcelona (UB), Barcelona, Spain. Electronic address: rmsantos@clinic.ub.es.
Conference/Journal: Brain Behav Immun.
Date published: 2019 Mar 11
Other:
Pages: S0889-1591(18)30821-3 , Special Notes: doi: 10.1016/j.bbi.2019.03.008. [Epub ahead of print] , Word Count: 337
BACKGROUND: Sickness behavioral changes elicited by inflammation may become prolonged and dysfunctional in patients with chronic disease, such as chronic hepatitis C (CHC). Neuroimaging studies show that the basal ganglia and insula are sensitive to systemic inflammation.
AIM: To elucidate the clinical and neurobiological aspects of prolonged illnesses in patients with CHC.
METHODS: Thirty-five CHC patients not treated with interferon-α or other antiviral therapy, and 30 control subjects matched for age and sex, were evaluated for perceived stress (perceived stress scale; PSS), depression (PHQ-9), fatigue and irritability through a visual analog scale (VAS), as well as serum levels of interleukin-6 (IL-6), prostaglandin E2 (PGE2) and oxidative stress markers. Functional MRI was performed, measuring resting-state functional connectivity using a region-of-interest (seed)-based approach focusing on the bilateral insula, subgenual anterior cingulate cortex and bilateral putamen. Between-group differences in functional connectivity patterns were assessed with two-sample t-tests, while the associations between symptoms, inflammatory markers and functional connectivity patterns were analyzed with multiple regression analyses.
RESULTS: CHC patients had higher PSS, PHQ-9 and VAS scores for fatigue and irritability, as well as increased IL-6 levels, PGE2 concentrations and antioxidant system activation compared to controls. PSS scores positively correlated with functional connectivity between the right anterior insula and right putamen, whereas PHQ-9 scores correlated with functional connectivity between most of the seeds and the right anterior insula. PGE2 (positively) and IL-6 (negatively) correlated with functional connectivity between the right anterior insula and right caudate nucleus and between the right ventral putamen and right putamen/globus pallidus. PGE2 and PSS scores accounted for 46% of the variance in functional connectivity between the anterior insula and putamen.
CONCLUSIONS: CHC patients exhibited increased perceived stress and depressive symptoms, which were associated with changes in inflammatory marker levels and in functional connectivity between the insula and putamen, areas involved in interoceptive integration, emotional awareness, and orientation of motivational state.
Copyright © 2019. Published by Elsevier Inc.
KEYWORDS: Basal ganglia; IL-6; depression; functional connectivity; hepatitis C virus; inflammation; insula; interoception; perceived stress; prostaglandin E(2); sickness behavior
PMID: 30872094 DOI: 10.1016/j.bbi.2019.03.008