Interferon and anti-TNF therapies differentially modulate amygdala reactivity which predicts associated bidirectional changes in depressive symptoms.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
21
10
2019
accepted:
15
05
2020
revised:
24
04
2020
pubmed:
28
5
2020
medline:
1
2
2022
entrez:
28
5
2020
Statut:
ppublish
Résumé
A third of patients receiving Interferon-α (IFN-α) treatment for Hepatitis-C develop major depressive disorder (MDD). Conversely, anti-Tumor Necrosis Factor (TNF) therapies improve depression providing key empirical support for the "inflammatory theory" of depression. Heightened amygdala reactivity (particularly to negatively valanced stimuli) is a consistent finding within MDD; can predict treatment efficacy and reverses following successful treatment. However, whether IFN-α and anti-TNF enhance/attenuate depressive symptoms through modulation of amygdala emotional reactivity is unknown. Utilizing a prospective study design, we recruited 30 patients (mean 48.0 ± 10.5 years, 21 male) initiating IFN-α treatment for Hepatitis-C and 30 (mean 50.4 ± 15.7 years, 10 male) anti-TNF therapy for inflammatory arthritis. All completed an emotional face-processing task during fMRI and blood sampling before and after their first IFN-α (4-h) or anti-TNF (24-h) injection and follow-up psychiatric assessments for 3 months of treatment. IFN-α significantly increased depression symptoms (Hamilton Depression Rating Scale HAM-D) at 4 weeks (p < 0.001) but not 4-h after first dose (p > 0.1). Conversely, anti-TNF significantly improved depressive symptoms (Hospital Anxiety and Depression Rating Scale HADS) at both 24-h (P = 0.015) and 12 weeks (p = 0.018). In support of our a-priori hypothesis, both IFN-α and anti-TNF significantly modulated amygdala reactivity with IFN-α acutely enhancing right amygdala responses to sad (compared with neutral) faces (p = 0.032) and anti-TNF conversely decreasing right amygdala reactivity (across emotional valence) (p = 0.033). Furthermore, these changes predicted IFN-induced increases in HAM-D 4 weeks later (R
Identifiants
pubmed: 32457424
doi: 10.1038/s41380-020-0790-9
pii: 10.1038/s41380-020-0790-9
pmc: PMC8589643
doi:
Substances chimiques
Interferon-alpha
0
Tumor Necrosis Factor Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5150-5160Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P008747/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 093881/Z/10/Z
Pays : United Kingdom
Informations de copyright
© 2020. The Author(s).
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