Extra-axial inflammatory signal and its relationship to peripheral and central immunity in depression DOI Creative Commons
Brandi Eiff, Edward T. Bullmore, Menna R. Clatworthy

et al.

Brain, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Although both central and peripheral inflammation have been observed consistently in depression, the relationship between two remains obscure. Extra-axial immune cells may play a role mediating connection immunity. This study investigates potential roles of calvarial bone marrow parameningeal spaces interactions immunity depression. PET was used to measure regional TSPO expression skull parameninges as marker inflammatory activity. correlated with brain cytokine concentrations cohort enriched for heightened comprising 51 individuals depression 25 healthy controls. The findings reveal complex Facial parietal showed significant associations confluence sinuses also linked markers. Group-dependent elevations within occipital were found be significantly associated inflammation. Significant activity skull, parameninges, parenchyma periphery highlight venous pivotal sites interactions.

Language: Английский

Peripheral and central immune system crosstalk in Alzheimer disease — a research prospectus DOI Open Access
Brianne M. Bettcher, Malú G. Tansey, Guillaume Dorothée

et al.

Nature Reviews Neurology, Journal Year: 2021, Volume and Issue: 17(11), P. 689 - 701

Published: Sept. 14, 2021

Language: Английский

Citations

285
Microglia in neuroimmunopharmacology and drug addiction DOI
Hongyuan Li, Linda R. Watkins, Xiaohui Wang

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(6), P. 1912 - 1924

Published: Feb. 2, 2024

Language: Английский

Citations

17
Inflammation‐driven brain and gut barrier dysfunction in stress and mood disorders DOI
Ellen Doney, Alice Cadoret, Laurence Dion‐Albert

et al.

European Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 55(9-10), P. 2851 - 2894

Published: April 20, 2021

Regulation of emotions is generally associated exclusively with the brain. However, there evidence that peripheral systems are also involved in mood, stress vulnerability vs. resilience, and emotion-related memory encoding. Prevalence mood disorders such as major depression, bipolar disorder, post-traumatic disorder increasing our modern societies. Unfortunately, 30%-50% individuals respond poorly to currently available treatments highlighting need further investigate biology gain mechanistic insights could lead innovative therapies. Here, we provide an overview inflammation-related mechanisms regulation responses discovered using animal models. If clinical studies available, discuss translational value these findings including limitations. Neuroimmune depression maladaptive have been receiving attention, thus, first part centered on inflammation dysregulation brain circulating cytokines disorders. Next, recent supporting a role for inflammation-driven leakiness blood-brain gut barriers emotion highlighted. Stress-induced exacerbated fragilizes which become hyperpermeable through loss integrity altered biology. At level, this be dysbiosis, imbalance microbial communities, alteration gut-brain axis central production mood-related neurotransmitter serotonin. Novel therapeutic approaches anti-inflammatory drugs, fast-acting antidepressant ketamine, probiotics directly act described here improving disorder-associated symptomatology. Discovery biomarkers has challenging quest psychiatry, end by listing promising targets worth investigation.

Language: Английский

Citations

86
Treatment-Resistant Depression Revisited: A Glimmer of Hope DOI Open Access

Angelos Halaris,

Emilie Sohl, Elizabeth A. Whitham

et al.

Journal of Personalized Medicine, Journal Year: 2021, Volume and Issue: 11(2), P. 155 - 155

Published: Feb. 23, 2021

Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder worldwide. It causes individual suffering, loss of productivity, increased health care costs and high suicide risk. Current pharmacologic interventions fail to produce at least partial response approximately one third these patients, remission obtained in 30% patients. This known as Treatment-Resistant Depression (TRD). The burden TRD exponentially increases the longer it persists, with higher risk impaired functional social functioning, vast losses quality life significant somatic morbidity suicidality. Different approaches have been suggested utilized, but results not encouraging. In this review article, we present new identify correct potential TRD, thereby reducing its prevalence overall disease entity. We will address contributory factors most which can be investigated many laboratories routine tests. discuss endocrinological aberrations, notably, hypothalamic-pituitary-adrenal (HPA) axis dysregulation thyroid gonadal dysfunction. role Vitamin D contributing depression. Pharmacogenomic testing being increasingly used determine Single Nucleotide Polymorphisms Cytochrome P450, Serotonin Transporter, COMT, folic acid conversion (MTHFR). As immune system recognized potentially major factor measurement C-reactive protein (CRP) select biomarkers, where available, guide combination treatments anti-inflammatory agents (e.g., selective COX-2 inhibitors) reversing treatment resistance. focus on established emerging test procedures, biomarkers non-biologic assessments apply personalized medicine effectively manage resistance general specifically.

Language: Английский

Citations

76
Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression DOI Creative Commons
Noha Althubaity, Julia Schubert, Daniel Martins

et al.

NeuroImage Clinical, Journal Year: 2021, Volume and Issue: 33, P. 102926 - 102926

Published: Dec. 27, 2021

Recent studies have shown that choroid plexuses (CP) may be involved in the neuro-immune axes, playing a role interaction between central and peripheral inflammation. Here we aimed to investigate CP volume alterations depression their associations with inflammation.51 depressed participants (HDRS score > 13) 25 age- sex-matched healthy controls (HCs) from Wellcome Trust NIMA consortium were re-analysed for study. All underwent full cytokine profiling simultaneous [11C]PK11195 PET/structural MRI imaging measuring neuroinflammation respectively.We found significantly greater subjects compared HCs (t(76) = +2.17) was positively correlated PET binding anterior cingulate cortex (r 0.28, p 0.02), prefrontal 0.24, 0.04), insular but not inflammatory markers: CRP levels 0.07, 0.53), IL-6 -0.08, 0.61), TNF-α -0.06, 0.70). The 0.34, 0.005). Integration of transcriptomic data Allen Human Brain Atlas brain map depicting correlations significant gene enrichment several pathways neuroinflammatory response.This result supports hypothesis changes barriers cause reduction solute exchanges blood CSF, disturbing homeostasis ultimately contributing inflammation depression. Given anomalies been recently detected other disorders, these results specific might extend conditions component.

Language: Английский

Citations

76
Ketamine’s effect on inflammation and kynurenine pathway in depression: A systematic review DOI Creative Commons
Emma I Kopra, Valeria Mondelli, Carmine M. Pariante

et al.

Journal of Psychopharmacology, Journal Year: 2021, Volume and Issue: 35(8), P. 934 - 945

Published: June 26, 2021

Background: Ketamine is a novel rapid-acting antidepressant with high efficacy in treatment-resistant patients. Its exact therapeutic mechanisms of action are unclear; however, recent years its anti-inflammatory properties and subsequent downstream effects on tryptophan (TRP) metabolism have sparked research interest. Aim: This systematic review examined the effect ketamine inflammatory markers TRP–kynurenine (KYN) pathway metabolites patients unipolar bipolar depression animal models depression. Methods: MEDLINE, Embase, PsycINFO databases were searched October 2020 (1806 to 2020). Results: Out 807 initial results, nine human studies 22 rodents met inclusion criteria. Rodent provided strong support for ketamine-induced decreases pro-inflammatory cytokines, namely interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α indicated TRP metabolism, including enzyme indoleamine 2,3-dioxygenase (IDO). Clinical evidence was less robust heterogeneity between sample characteristics, but most experiments demonstrated peripheral inflammation IL-1β, TNF-α. Preliminary also found reduced activation neurotoxic arm KYN pathway. Conclusion: appears induce at least proportion depressed Suggestions future include investigation central nervous system examination clinical relevance changes.

Language: Английский

Citations

59
Sickness behaviour and depression: An updated model of peripheral-central immunity interactions DOI Creative Commons
Federico Turkheimer, Mattia Veronese, Valeria Mondelli

et al.

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 111, P. 202 - 210

Published: April 17, 2023

Current research into mood disorders indicates that circulating immune mediators participating in the pathophysiology of chronic somatic have potent influences on brain function. This paradigm has brought to fore use anti-inflammatory therapies as adjunctive standard antidepressant therapy improve treatment efficacy, particularly subjects do not respond medication. Such new practice requires biomarkers tailor these those most likely benefit but also validated mechanisms action describing interaction between peripheral immunity and function optimize target intervention. These are generally studied preclinical models try recapitulate human disease, MDD, through peripherally induced sickness behaviour. In this proposal paper, after an appraisal data rodent their adherence clinical cohorts, we put forward a modified model periphery-brain interactions goes beyond currently established view microglia cells drivers depression. Instead, suggest that, for patients with mild levels inflammation, barriers primary actors disease resistance. We then highlight gaps novel lines research.

Language: Английский

Citations

34
Inflammation as a mediator between adverse childhood experiences and adult depression: A meta-analytic structural equation model DOI Creative Commons
Andrea Zagaria,

Valeria Fiori,

Mariacarolina Vacca

et al.

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 357, P. 85 - 96

Published: April 25, 2024

Exposure to adverse childhood experiences (ACEs) confers a higher risk of developing depression in adulthood, yet the mediation inflammation remains under debate. To test this model, we conducted systematic review and two-stage structural equation modelling meta-analysis studies reporting correlations between ACEs before age 18, inflammatory markers severity adulthood. Scopus, Pubmed, Medline, PsycInfo, CINAHL were searched up 2 October 2023. Twenty-two data on C-reactive protein (CRP, n = 12,935), interleukin-6 (IL-6, 4108), tumour necrosis factor-α (TNF-α, 2256) composite measures (n 1674) included. Unadjusted models revealed that CRP (β 0.003, 95 % LBCI 0.0002 0.0068), IL-6 0.001 0.006), 0.009, 0.004 0.018) significantly mediated association adult depression. The effects no longer survived after adjusting for BMI; however, serial model BMI sequentially 0.002, 0.0005 0.0046), accounting 14.59 9.94 variance depressive symptoms, respectively. Due cross-sectional nature assessment findings should be approached with caution; results suggest complex interactions psychoneuroimmunological metabolic factors underlie adulthood

Language: Английский

Citations

12
Systemic inflammatory regulators and 7 major psychiatric disorders: A two-sample Mendelian randomization study DOI
Xinzhen Chen, Ting Yao,

Jinliang Cai

et al.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2022, Volume and Issue: 116, P. 110534 - 110534

Published: Feb. 9, 2022

Language: Английский

Citations

35
Astroglial Connexin 43-Mediated Gap Junctions and Hemichannels: Potential Antidepressant Mechanisms and the Link to Neuroinflammation DOI
Lan Lei,

Y Wang,

Die Hu

et al.

Cellular and Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 43(8), P. 4023 - 4040

Published: Oct. 24, 2023

Language: Английский

Citations

17