A chicken and egg scenario in psychoneuroimmunology: Bidirectional mechanisms linking cytokines and depression

Rengasamy, Manivel; Marsland, Anna L.; Spada, Meredith; Hsiung, Kimberly; Kovats, Tessa; Price, Rebecca B.

doi:10.1016/j.jadr.2021.100177

Cited by 12 publications

(7 citation statements)

References 217 publications

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“…The excessive production of cytokines, the signaling molecules of the immune system, affects neurocircuitry in the basal ganglia and anterior cingulate cortex, the functioning of the HPA axis, synaptic plasticity, and neurotransmission, leading to behavioral alterations, mood changes, and the impairment of cognitive functions characteristic of depression. The behavioral effects of cytokines are largely mediated through the activation of the inflammatory signaling pathways that regulate the production of monoamines, glutamate, neuropeptides, and BDNF [ 146 , 147 , 148 , 149 ].…”

Section: Neuropathological Mechanisms Underlying the Development Of D...mentioning

confidence: 99%

Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder

Jembrek

Oršolić

Karlović

et al. 2023

IJMS

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Major depressive disorder is one of the most common mental illnesses that highly impairs quality of life. Pharmacological interventions are mainly focused on altered monoamine neurotransmission, which is considered the primary event underlying the disease’s etiology. However, many other neuropathological mechanisms that contribute to the disease’s progression and clinical symptoms have been identified. These include oxidative stress, neuroinflammation, hippocampal atrophy, reduced synaptic plasticity and neurogenesis, the depletion of neurotrophic factors, and the dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis. Current therapeutic options are often unsatisfactory and associated with adverse effects. This review highlights the most relevant findings concerning the role of flavonols, a ubiquitous class of flavonoids in the human diet, as potential antidepressant agents. In general, flavonols are considered to be both an effective and safe therapeutic option in the management of depression, which is largely based on their prominent antioxidative and anti-inflammatory effects. Moreover, preclinical studies have provided evidence that they are capable of restoring the neuroendocrine control of the HPA axis, promoting neurogenesis, and alleviating depressive-like behavior. Although these findings are promising, they are still far from being implemented in clinical practice. Hence, further studies are needed to more comprehensively evaluate the potential of flavonols with respect to the improvement of clinical signs of depression.

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Section: Neuropathological Mechanisms Underlying the Development Of D...mentioning

confidence: 99%

Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder

Jembrek

Oršolić

Karlović

et al. 2023

IJMS

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“…Among patients with cancer, inflammation has frequently been associated with both tumor progression and depression. Bidirectional brain-immune relationships are marked by elevated blood levels of inflammatory cytokines (eg, IL-6, TNF-α) . The pathophysiologic mechanisms connecting these factors is under investigation .…”

Section: Introductionmentioning

confidence: 99%

“…Bidirectional brain-immune relationships are marked by elevated blood levels of inflammatory cytokines (eg, IL-6, TNF-α). [6][7][8] The pathophysiologic mechanisms connecting these factors is under investigation. 9 Elevated inflammatory cytokines have been noted as a prelude to depressive episodes among people with major depressive disorder 10,11 and are believed to contribute to mechanisms of depression onset and poorer antidepressant treatment response.…”

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confidence: 99%

Depressive Symptoms, Systemic Inflammation, and Survival Among Patients With Head and Neck Cancer

Cash,

Albert,

Palmer

et al. 2024

JAMA Otolaryngol Head Neck Surg

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ImportancePatients with head and neck cancer experience high rates of depression. Depression and systemic inflammation have been found to be associated in numerous cancer types, often independently from disease status. Depression-related inflammation may elevate the risks for poor tumor response to treatment and early mortality, and comprises a mechanism by which depression is associated with survival in head and neck cancer.ObjectiveTo assess mediation pathways incorporating pretreatment depressive symptoms, pretreatment inflammation, and tumor response posttreatment on overall survival among patients with head and neck cancer.Design, Setting, and ParticipantsThis was a prospective observational cohort study of patients with head and neck cancer treated in a single multidisciplinary head and neck cancer clinic from May 10, 2013, to December 30, 2019, and followed up for 2 years. Data analysis was performed from June 29, 2022, to June 23, 2023.ExposuresPatient-reported depressive symptoms using the Patient Health Questionnaire−9 item (PHQ−9) at treatment planning; pretreatment hematology workup for systemic inflammation index (SII) score; and clinical data review for tumor response (complete vs incomplete) and overall survival.Main OutcomesTwo-year overall survival.ResultsThe total study cohort included 394 patients (mean [SD] age, 62.5 [11.5] years; 277 [70.3%] males) with head and neck cancer. Among 285 patients (72.3%) who scored below the clinical cutoff for depression on the PHQ−9, depressive symptoms were significantly associated with inflammation (partial r, 0.168; 95% CI, 0.007-0.038). In addition, both depression and inflammation were associated with early mortality (PHQ−9: hazard ratio [HR], 1.04; 95% CI, 1.02-1.07; SII: HR, 1.36; 95% CI, 1.08-1.71). The depression-survival association was fully mediated by inflammation (HR, 1.28; 95% CI, 1.00-1.64). Depressive symptoms were also associated with poorer tumor response (odds ratio, 1.05; 95% CI, 1.01-1.08), and the depression-survival association was partially mediated by tumor response (HR, 9.44; 95% CI, 6.23-14.32). Systemic inflammation was not associated with tumor response.ConclusionsIn this cohort study, systemic inflammation emerged as a novel candidate mechanism of the association of depression with mortality. Tumor response partially mediated effects of depression on mortality, replicating prior work. Thus, depression stands out as a highly feasible target for renewed clinical attention. Even mild symptoms of depression during the treatment-planning phase may be associated with higher systemic inflammation in addition to poorer tumor response to treatment and survival outcomes; therefore, depression should be clinically addressed.

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“…In humans, there is a relationship between having mental disorders and higher levels of proinflammatory cytokines (e.g., TNF-alpha, interleukin-6) that can activate the inflammatory response system [ 7 ]. This relationship appears bidirectional, as higher levels of these cytokines also increase the risk of depression [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Psychiatric medications and the risk of autoimmune and immune-mediated inflammatory diseases: A systematic review and meta-analysis of observational studies

Larivuo

Laukkala²,

Nevalainen³

et al. 2023

PLoS ONE

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Background Pharmacovigilance reports have suggested that certain commonly used medications may trigger autoimmune diseases (ADs) and immune-mediated inflammatory diseases (IMIDs). We systematically reviewed the literature to evaluate whether psychiatric medication use is associated with ADs and IMIDs. Methods The protocol was registered in PROSPERO (CRD42022296524) before the start of the study. We searched Medline Ovid and Scopus up to November 28th, 2021, for comparative studies, with any psychiatric medication as exposure and ADs and IMIDs as outcomes. Meta-analysis was performed using DerSimonian-Laird random-effects modeling. The PRISMA 2020 guidelines were followed in reporting. Study-level risk of bias was assessed using the Newcastle-Ottawa Scale, and the overall certainty of evidence using GRADE. Results There were 7,265 citations from which 31 studies were eligible, all from high-income countries, covering 15 distinct immune diseases. The evidence for the association between selective serotonin reuptake inhibitor (SSRI) use and higher risk of microscopic colitis (meta-OR 2.60, 95% CI 1.05–6.39, I2 97.5%, 6 studies) was of low certainty. A subgroup analysis by the histological type of microscopic colitis showed a statistically significant association only with lymphocytic colitis (meta-OR 2.88, 95% CI 2.60–3.18, I2 00.00%, three studies). In two case-control studies, SSRI use had no significant association with psoriasis (meta-OR 0.80, 95% CI 0.58–1.10, I2 82.4%). The risk of acute pancreatitis was slightly increased with exposure to SSRIs (meta-OR 1.13, 95% CI 1.01–1.26, I2 00.0%), as was the risk of bullous pemphigoid after exposure to antipsychotics (meta-OR 1.79, 95% CI 1.17–2.73, I2 0%). Conclusions We reviewed the literature on whether psychiatric medications associate with the risk of ADs and IMIDs and concluded that, despite several signals, the credibility of evidence remains low at best. Prospective cohort studies would be needed as the next step to confirm the suggestions of increased risk.

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A chicken and egg scenario in psychoneuroimmunology: Bidirectional mechanisms linking cytokines and depression

Cited by 12 publications

References 217 publications

Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder

Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder

Depressive Symptoms, Systemic Inflammation, and Survival Among Patients With Head and Neck Cancer

Psychiatric medications and the risk of autoimmune and immune-mediated inflammatory diseases: A systematic review and meta-analysis of observational studies

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