Association of chronic inflammation and perceived stress with abnormal functional connectivity in brain areas involved with interoception in hepatitis C patients.
Brain, Behavior, and Immunity. 2019-08-01; 80: 204-218
DOI: 10.1016/j.bbi.2019.03.008
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Oriolo G(1), Blanco-Hinojo L(2), Navines R(1), Mariño Z(3), Martín-Hernández
D(4), Cavero M(1), Gimenez D(5), Caso J(4), Capuron L(6), Forns X(3), Pujol
J(2), Sola R(5), Martin-Santos R(7).
Author information:
(1)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.
(2)MRI Research Unit, Department of Radiology, Hospital del Mar, CIBERSAM, G21,
Barcelona, Spain.
(3)Liver Unit, Hospital Clinic, IDIBAPS, Centro Investigacion Biomédica en Red
de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona,
Barcelona, Spain.
(4)Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad
Complutense de Madrid, CIBERSAM, Imas12, IUINQ, Madrid, Spain.
(5)Liver Section, Hospital del Mar, Parc de Salut Mar, Grup de Recerca
Hepatológica, FIMIM, Universitat Autónoma de Barcelona, Barcelona, Spain.
(6)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.
(7)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:
.
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.
DOI: 10.1016/j.bbi.2019.03.008
PMID: 30872094 [Indexed for MEDLINE]