key: cord-0909146-w2obrjw5
authors: Senra, Hugo
title: Bidirectional Associations and Common Inflammatory Biomarkers in COVID-19 and Mental Health Disorders: a window of opportunity for future research?
date: 2021-03-03
journal: Brain Behav Immun Health
DOI: 10.1016/j.bbih.2021.100237
sha: 5c2a5dd8b6e6eeed63d97f3f81f83b20c2faf320
doc_id: 909146
cord_uid: w2obrjw5

nan

The new coronavirus disease has drawn the interest of mental health and 36 neuroscience research, with emerging literature illustrating potential psychiatric and 37 neurological manifestations following the COVID-19 infection [1] [2] [3] [4] . Recently, it was published 38 a large retrospective cohort study conducted in US with a sample of 62 354 patients 39 suggesting a bidirectional association between COVID-19 and psychiatric disorders, 40 particularly anxiety and mood disorders 4 . In this study, the diagnosis of COVID-19 was 41 independently associated with greater risk for psychiatric disorders, in the following 14 to 90 42 days, when compared with other acute conditions (e.g. influenza, respiratory infection, skin 43 infection, fracture). Additionally, a psychiatric diagnosis confirmed in the previous year (prior 44 to the infection) was associated with 65% increased risk for subsequent COVID-19 infection.

Findings were robust after sensitivity analysis accounting for other potential confounders such 46 as race and other comorbidities.

The novelty here is the reciprocal association found between psychiatric disorders and 48 an acute infection such as COVID-19. Prior to the pandemic era, a bidirectional relationship 49 had been mainly hypothesized and found between depression and chronic inflammatory The neurobiological literature has robustly suggested the occurrence of immunologic 55 dysregulations entailing inflammatory processes in several psychiatric disorders 8 . There is 56 growing evidence that an increased expression of pro-inflammatory cytokines, particularly 57 interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), occurs in psychiatric disorders 8-58 11 , including generalized anxiety disorder 9 , major depressive disorder 10 , and post-traumatic 59 stress disorder 11 . A recent large cohort study using network analysis suggested that IL-6 might 60 be a key inflammatory marker in depression 12 . IL-6 is a cytokine known to play a mediating 61 role in the regulation of inflammatory and immunological responses, and in hematopoiesis 13 .

The underlying mechanisms of pro-inflammatory responses in depression remain unclear, 63 although recent research has proposed that inflammation might be triggered by prolonged 64 exposures to psychological stress via dysregulation of peripheral myeloid cells and brain-65 resident microglia 8, 14 .

The occurrence of pathogenic inflammatory processes in COVID-19 patients has been 67 well-documented 15, 16 . These inflammatory manifestations are known to result from virus-infection, a dysregulated immune response involving an excessive cytokine release, 70 frequently called "cytokine storm", has been described 16 immunological and inflammatory processes for the comorbidity of both conditions. There is 96 current evidence that increased serum levels of some inflammatory biomarkers such as IL-6 97 and C-reactive protein are a risk factor for subsequent depression, shown by longitudinal 98 research 20 . Finally, as we mentioned before, elevated levels of IL-6 have been associated with 99 poor outcomes among COVID-19 patients 17, 18 .

In light of recent findings presented, the hypothesis of a synergistic relationship 101 between depression and COVID-19 can be raised, where inflammatory manifestations in 19. This hypothesis takes us to the question of whether such common inflammatory 104 manifestations would also be present between depression and some chronic inflammatory 105 illnesses. Previous research has robustly suggested that depression is highly comorbid with 106 chronic illnesses 5-7,21 , being depression itself a potential risk factor for subsequent incidence 107 of chronic illnesses 7 . In 2018, a large longitudinal study had highlighted that depression can 108 have a predictive effect on the incidence of chronic illness up to 10 years later, including 109 coronary heart disease, lung disease, arthritis, and osteoporosis 7 . Other longitudinal studies 110 have robustly showed a reciprocal association between depression and some chronic 111 inflammatory diseases, particularly stroke, diabetes, and cardiovascular disease [5] [6] [7] 21, 22 . 

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