Cytokine secretion and the risk of depression development in patients with connective tissue diseases

Abstract

Research in the past two decades has revolutionized our understanding of depressive illnesses. Proinflammatory cytokines have become a point of interest in the interconnecting areas of neuropsychiatric and autoimmune diseases. The cytokine hypothesis of depression suggests that pro‐inflammatory cytokines play a primary role in the mediation of the pathophysiological characteristics of major depression, in which an inflammatory process may be induced by external and internal stressors, such as psychological and inflammatory diseases, respectively. The higher prevalence of depression, particularly in patients with chronic autoimmune connective tissue disorders (CTD), suggests that depression may present a dysfunctional adaptation of cytokine‐induced sickness, which could manifest in times of an exacerbated activation of the innate immune system. Inflammation is thought to contribute to the development of clinical depression through its ability to induce sickness behaviors corresponding to the neurovegetative features of depression, through the dysregulation of the hypothalamic–pituitary–adrenal axis, alterations in neurotransmitter synthesis and reuptake, and through its involvement in the neuroprogression pathways. This review explores the complex interrelationships in which inflammatory responses alter neuroendocrine and neuropsychological regulation contributing to depressive symptoms in CTD. The prevalence and characteristics of depression, and its correlation to the levels of inflammatory cytokines and disease activity among different CTD will be reviewed.

Low social and family well-being is associated with greater RAGE ligand s100A8/A9 and interleukin-1 beta levels in metastatic breast cancer patients

“…For example, IL-1β has been reported to induce “sickness behavior” since it can activate the hypothalamic-pituitary-adrenal axis and is a potent regulator of serotonin transporter gene indicating that this interleukin may have a role in the biology of depression ( Licinio and Wong, 1999 ). Besides psychosocial stress, inflammatory diseases can induce depression as well ( Grygiel-Górniak et al., 2019 ). Another facet of sickness behavior may involve social and behavioral withdrawal ( Dantzer, 2018 ; DiSabato et al., 2021 ) suggesting that social isolation and decreased social interactions may accompany elevations in IL-1β.…”

The prevalence and impact of depression in primary systemic vasculitis: a systematic review and meta-analysis

“…In systemic lupus erythematosus, where long-term glucocorticoids are also used, the prevalence of depression was reported to be 30-39% [32]. Glucocorticoids have well-known psychiatric side effects, but they also reduce inflammation which has been hypothesised to contribute to depressive symptoms [3,33]. Hinojosa-Azaola et al reported nearly sevenfold higher odds of requiring prednisolone ≥ 10 mg/day among those with depression [27].…”

Antioxidant and Anti-inflammatory Mechanisms of Neuroprotection by Ursolic Acid: Addressing Brain Injury, Cerebral Ischemia, Cognition Deficit, Anxiety, and Depression

“…This relationship is even more prevalent under depressive conditions as inflammatory pathways are activated in depressed patients [64] or in experimental animals [65, 66]. The relationship between inflammatory diseases and depression has also been extensively reviewed and includes cytokine-mediated depression development in patients with connective tissues [67], neuroinflammation in cognitive impairment under psychiatric conditions (e.g., major depressive disorder, bipolar disorder, schizophrenia, and posttraumatic stress disorder) [68], central and peripheral inflammation as the link between depressive disorders and metabolic syndrome [69], and anti-inflammatory intervention as means of managing depressive disorders [70]. Oxidative stress is similarly a major component of anxiety pathology although whether it is the cause or a pathological consequence of the disease is still in need of further research.…”