Major depressive disorder: hypothesis, mechanism, prevention and treatment

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 9, 2024

Abstract Worldwide, the incidence of major depressive disorder (MDD) is increasing annually, resulting in greater economic and social burdens. Moreover, pathological mechanisms MDD underlying effects pharmacological treatments for are complex unclear, additional diagnostic therapeutic strategies still needed. The currently widely accepted theories pathogenesis include neurotransmitter receptor hypothesis, hypothalamic-pituitary-adrenal (HPA) axis cytokine neuroplasticity hypothesis systemic influence but these cannot completely explain mechanism MDD. Even it hard to adopt only one reveal MDD, thus recent years, great progress has been made elucidating roles multiple organ interactions identifying novel approaches multitarget modulatory strategies, further revealing disease features Furthermore, some newly discovered potential targets studied antidepressants have attracted widespread attention, reagents even approved clinical treatment methods such as phototherapy acupuncture effective improvement symptoms. In this work, we comprehensively summarize latest research on diagnosis preventive medicines, well related trials.

Language: Английский

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Major depressive disorder

Nature Reviews Disease Primers, Journal Year: 2023, Volume and Issue: 9(1)

Published: Aug. 24, 2023

Language: Английский

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Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: May 11, 2023

In a subset of patients, chronic exposure to stress is an etiological risk factor for neuroinflammation and depression. Neuroinflammation affects up 27% patients with MDD associated more severe, chronic, treatment-resistant trajectory. Inflammation not unique depression has transdiagnostic effects suggesting shared underlying psychopathologies metabolic disorders. Research supports association but necessarily causation Putative mechanisms link dysregulation the HPA axis immune cell glucocorticoid resistance resulting in hyperactivation peripheral system. The extracellular release DAMPs DAMP-PRR signaling creates feed forward loop that accelerates central inflammation. Higher plasma levels inflammatory cytokines, most consistently interleukin IL-1β, IL-6, TNF-α, are correlated greater depressive symptomatology. Cytokines sensitize axis, disrupt negative feedback loop, further propagate reactions. Peripheral inflammation exacerbates (neuroinflammation) through several including disruption blood-brain barrier, cellular trafficking, activation glial cells. Activated cells chemokines, reactive oxygen nitrogen species into extra-synaptic space dysregulating neurotransmitter systems, imbalancing excitatory inhibitory ratio, disrupting neural circuitry plasticity adaptation. particular, microglial toxicity plays role pathophysiology neuroinflammation. Magnetic resonance imaging (MRI) studies show reduced hippocampal volumes. Neural dysfunction such as hypoactivation between ventral striatum ventromedial prefrontal cortex underlies melancholic phenotype Chronic administration monoamine-based antidepressants counters response, delayed therapeutic onset. Therapeutics targeting mediated immunity, generalized specific pathways, nitro-oxidative have enormous potential advance treatment landscape. Future clinical trials will need include system perturbations biomarker outcome measures facilitate novel antidepressant development. this overview, we explore correlates elucidate pathomechanisms development biomarkers therapeutics.

Language: Английский

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Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 423 - 423

Published: Feb. 28, 2024

The involvement of central and peripheral inflammation in the pathogenesis prognosis major depressive disorder (MDD) has been demonstrated. increase pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, IL-18, TNF-α) individuals with depression may elicit neuroinflammatory processes inflammation, mechanisms that, turn, can contribute to gut microbiota dysbiosis. Together, neuroinflammation dysbiosis induce alterations tryptophan metabolism, culminating decreased serotonin synthesis, impairments neuroplasticity-related mechanisms, glutamate-mediated excitotoxicity. This review aims highlight inflammatory (neuroinflammation, dysbiosis) involved pathophysiology MDD explore novel anti-inflammatory therapeutic approaches for this psychiatric disturbance. Several lines evidence have indicated that addition antidepressants, physical exercise, probiotics, nutraceuticals (agmatine, ascorbic acid, vitamin D) possess effects their antidepressant properties. Further studies are necessary benefits these alternative therapies MDD.

Language: Английский

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Exploring the Role of Neuroplasticity in Development, Aging, and Neurodegeneration

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(12), P. 1610 - 1610

Published: Nov. 21, 2023

Neuroplasticity refers to the ability of brain reorganize and modify its neural connections in response environmental stimuli, experience, learning, injury, disease processes. It encompasses a range mechanisms, including changes synaptic strength connectivity, formation new synapses, alterations structure function neurons, generation neurons. plays crucial role developing maintaining function, learning memory, as well recovery from injury adaptation changes. In this review, we explore vast potential neuroplasticity various aspects across lifespan context disease. Changes aging significance cognitive later life will also be reviewed. Finally, discuss common mechanisms associated with age-related neurodegenerative processes (including protein aggregation accumulation, mitochondrial dysfunction, oxidative stress, neuroinflammation) how these can mitigated, at least partially, by non-invasive non-pharmacologic lifestyle interventions aimed promoting harnessing neuroplasticity.

Language: Английский

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Molecular basis underlying changes of brain entropy and functional connectivity in major depressive disorders after electroconvulsive therapy

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(3)

Published: March 1, 2024

Abstract Introduction Electroconvulsive therapy (ECT) is widely used for treatment‐resistant depression. However, it unclear whether/how ECT can be targeted to affect brain regions and circuits in the dynamically regulate mood cognition. Methods This study entropy (BEN) measure irregular levels of systems 46 major depressive disorder (MDD) patients before after treatment. Functional connectivity (FC) was further adopted reveal changes functional couplings. Moreover, transcriptomic neurotransmitter receptor data were genetic molecular basis BEN connectivities. Results Compared pretreatment, posterior cerebellar lobe (PCL) significantly decreased FC between PCL right temporal pole (TP) increased MDD we found that these closely associated with genes' expression profiles involved MAPK signaling pathway, GABAergic synapse, dopaminergic synapse correlated receptor/transporter density 5‐HT, norepinephrine, glutamate, etc. Conclusion These findings suggest loops cerebellum TP are crucial regulation cognition, which provides new evidence antidepressant effects potential mechanism leading cognitive impairment.

Language: Английский

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Syringa oblata Lindl Extract Alleviated Corticosterone-Induced Depression via the cAMP/PKA–CREB–BDNF Pathway

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119274 - 119274

Published: Jan. 1, 2025

Language: Английский

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Melanin-like polydopamine nanoparticles mediating anti-inflammatory and rescuing synaptic loss for inflammatory depression therapy

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Feb. 10, 2023

Inflammatory depression is closely related to neuroinflammation. However, current anti-inflammatory drugs have low permeability cross blood-brain barrier with difficulties reaching the central nervous system provide therapeutic effectiveness. To overcome this limitation, nano-based drug delivery technology was used synthesize melanin-like polydopamine nanoparticles (PDA NPs) (~ 250 nm) which can barrier. Importantly, PDA NPs abundant phenolic hydroxyl groups function as excellent free radical scavengers attenuate cell damage caused by reactive oxygen species or acute inflammation. In vitro experiments revealed that exhibited antioxidative properties. Next, we aimed investigate effect of on inflammatory through intraperitoneal injection lipopolysaccharide-induced model in mice. significantly reversed depression-like behavior. also found reduce peripheral and inflammation induced LPS, showing alleviated splenomegaly, reduced serum cytokines, inhibited microglial activation restored synaptic loss. Various showed had good biocompatibility both vivo vitro. Our work suggested may be biocompatible nano-drugs treating but their clinical application requires further study.

Language: Английский

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Shared biological mechanisms of depression and obesity: focus on adipokines and lipokines

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: June 29, 2023

Depression and obesity are both common disorders currently affecting public health, frequently occurring simultaneously within individuals, the relationship between these is bidirectional. The association depression highly co-morbid tends to significantly exacerbate metabolic related depressive symptoms. However, neural mechanism under mutual control of largely inscrutable. This review focuses particularly on alterations in systems that may mechanistically explain vivo homeostatic regulation link, such as immune-inflammatory activation, gut microbiota, neuroplasticity, HPA axis dysregulation well neuroendocrine regulators energy metabolism including adipocytokines lipokines. In addition, summarizes potential future treatments for raises several questions need be answered research. will provide a comprehensive description localization biological connection better understand co-morbidity depression.

Language: Английский

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Exercise as an antidepressant: exploring its therapeutic potential

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 12, 2023

The COVID-19 pandemic has increased the prevalence of depressive disorders worldwide, requiring alternative treatments beyond medication and psychotherapy. Exercise positive effects on brain; therefore, it emerged as a promising therapeutic option for individuals with depression. Considerable research involving humans animals offers compelling evidence to support mental health benefits physical activity or exercise mediated by regulation complex theoretical paradigms. However, challenges such conducting long-term follow-up assessments considering individual characteristics remain in human studies despite extensive efforts. While animal provide valuable insights into potential its impact outcomes related depression anxiety rodents exposed different stress paradigms, translating findings requires careful evaluation. More is needed establish precise prescription guidelines better understand relationship between disorders. Therefore, this concise review explores supporting intervention an antidepressant treatment underlying mechanisms.

Language: Английский

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