Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Depression, Anxiety, and Chronic Fatigue Symptoms in Acute Rheumatoid Arthritis are Associated with Immune-inflammatory, Autoimmune, Endogenous Opioid System and Lactosylceramide Signaling Pathways: A Nomothetic Network Approach

Version 1 : Received: 26 September 2021 / Approved: 27 September 2021 / Online: 27 September 2021 (16:30:00 CEST)

How to cite: Smesam, H.; Qazmooz, H.; Khayoon, S.; Al-Hakeim, H.; Maes, M. Depression, Anxiety, and Chronic Fatigue Symptoms in Acute Rheumatoid Arthritis are Associated with Immune-inflammatory, Autoimmune, Endogenous Opioid System and Lactosylceramide Signaling Pathways: A Nomothetic Network Approach. Preprints 2021, 2021090455 (doi: 10.20944/preprints202109.0455.v1). Smesam, H.; Qazmooz, H.; Khayoon, S.; Al-Hakeim, H.; Maes, M. Depression, Anxiety, and Chronic Fatigue Symptoms in Acute Rheumatoid Arthritis are Associated with Immune-inflammatory, Autoimmune, Endogenous Opioid System and Lactosylceramide Signaling Pathways: A Nomothetic Network Approach. Preprints 2021, 2021090455 (doi: 10.20944/preprints202109.0455.v1).

Abstract

Background. Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disorder which affects the joints in the wrists, fingers, and knees. RA is often associated with depressive and anxiety symptoms as well as chronic fatigue syndrome (CFS)-like symptoms.Aim. To examine the association between depressive symptoms (measured with the Beck Depression Inventory, BDI), anxiety (Hamilton Anxiety Rating Scale, HAMA), and CFS-like (Fibro-fatigue Scale) symptoms and immune-inflammatory, autoimmune, and endogenous opioid system (EOS) markers, and lactosylceramide in RA. Methods. The serum biomarkers were assayed in fifty-nine RA and fifty-nine patients without increased psychopathology (PP) and fifty healthy controls.Results. There were highly significant correlations between the BDI, FF, and HAMA scores and severity of RA, as assessed with the DAS28-4, clinical and disease activity indices, the number of tenders and swollen joints, and patient and evaluator global assessment scores. A common latent vector (reflective model) could be extracted from the PP and RA-severity scales, which showed excellent psychometric properties. Partial least squares analysis showed that 69.7% of the variance in this common core underpinning PP and RA symptoms could be explained by the regression on immune-inflammatory pathways, rheumatoid factor, anti-citrullinated protein antibodies, CD17, and mu-opioid receptor levels. Conclusions. Depression, anxiety, and CFS-like symptoms due to RA are reflective manifestations of the phenome of RA and are mediated via the effects of the same immune-inflammatory, autoimmune, and EOS pathways and lactosylceramide that underpin the pathophysiology of RA. These PP symptoms are clinical manifestations of the pathophysiology of RA.

Keywords

inflammation; neuro-immune; cytokines; major depression; chronic fatigue syndrome; affective disorders

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