Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to Acute Rheumatoid Arthritis: A Precision Nomothetic Psychiatry Analysis

Abstract

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. This paper examines the association between depressive symptoms (measured with the Beck Depression Inventory, BDI), anxiety (Hamilton Anxiety Rating Scale, HAMA), CFS-like (Fibro-fatigue Scale) symptoms and immune–inflammatory, autoimmune, and endogenous opioid system (EOS) markers, and lactosylcer-amide (CD17) in RA. The serum biomarkers were assayed in 118 RA and 50 healthy controls. Results were analyzed using the new precision nomothetic psychiatry approach. We found 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 tender and swollen joints, and patient and evaluator global assessment scores. Partial least squares analysis showed that 69.7% of the variance in this common core underpinning psychopathology and RA symptoms was explained by immune–inflammatory pathways, rheumatoid factor, anti-citrullinated protein antibodies, CD17, and mu-opioid receptor levels. We constructed a new endophenotype class comprising patients with very high immune–inflammatory markers, CD17, RA, affective and CF-like symptoms, and tobacco use disorder. We extracted a reliable and replicable latent vector (pathway phenotype) from immune data, psychopathology, and RA-severity scales. Depression, anxiety, and CFS-like symptoms due to RA are manifestations of the phenome of RA and are mediated by the effects of the same immune–inflammatory, autoimmune, and other pathways that underpin the pathophysiology of RA.

Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to Long COVID: A precision nomothetic approach

“…This indicates that shared pathways may underpin the physio-affective phenome of the acute as well as chronic phases of the illness. Previously, we observed intertwined associations between increased levels of affective and physiosomatic symptoms not only in acute COVID-19 but also in, for example, schizophrenia, rheumatoid arthritis and major depression (Kanchanatawan et al, 2019;Maes et al, 2021;Smesam et al, 2022;Almulla et al, 2020). Since our previous study (Al-Jassas et al, 2022) and the current study were performed using different study samples, we were unable to examine whether patients with acute physio-affective symptoms present the same symptoms in Long COVID.…”

“…Hence, hypoxia and inflammation in acute COVID-19 may be accompanied by overexpression of HIFs which may further fuel the immune-inflammatory disorders leading to Long COVID. Moreover, hypoxia may cause increases in reactive oxygen and nitrogen species (Solaini et al, 2010), leading to oxidative damage, which is implicated in the pathophysiology of depression, fatigue and anxiety (Maes et al, 2011a;Morris and Maes, 2014). Furthermore, different areas of the brain, mainly the structures that take part in affective disorders, namely the amygdala, hippocampus, anterior cingulate cortex, and prefrontal cortex (Aryutova and Stoyanov, 2021) were found to be influenced by hypoxia (Shankaranarayana Rao et al, 1999;Alchanatis et al, 2005).…”

Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to LONG COVID: a precision nomothetic approach

“…This indicates that shared pathways may underpin the physio-affective phenome of the acute as well as chronic phases of the illness. Previously, we observed intertwined associations between increased levels of affective and physiosomatic symptoms not only in acute COVID-19 but also in, for example, schizophrenia, rheumatoid arthritis, and major depression (Kanchanatawan, Sriswasdi et al 2019, Almulla, Al-Hakeim et al 2020, Maes, Andrés-Rodríguez et al 2021, Smesam, Qazmooz et al 2022). Since our previous study (Al-Jassas, Al-Hakeim et al 2022) and the current study were performed using different study samples, we were unable to examine whether patients with acute physio-affective symptoms present the same symptoms in Long COVID.…”

Ceramides in Autoimmune Rheumatic Diseases: Existing Evidence and Therapeutic Considerations for Diet as an Anticeramide Treatment

“…Similarly, greater sphingomyelinase activity was observed in the serum of patients with RA compared to healthy controls [ 80 ]. In a more recent study, greater serum LactCer levels were observed in patients with RA compared to controls [ 86 ]. LactCer activates the reactive oxygen species (ROS) and cytosolic phospholipase A 2 (cPLA 2 a), releasing arachidonic acid, a known inflammation mediator [ 68 ].…”