Aug 2026· Biomolecules· Vol 16· 0 citations· 122 references
Medicine
TL;DR
Patients with preexisting mood disorders may enter surgery in a biologically sensitized neuroimmune state, lowering the threshold for exaggerated neuroinflammatory responses and postoperative cognitive dysfunction, according to a review of convergent pathophysiologic pathways.
Abstract
Perioperative neurocognitive disorders (PND) encompass a spectrum of cognitive impairments occurring across the surgical period and are associated with significant morbidity, delayed recovery, and reduced quality of life. Although established risk factors include advanced age, cardiovascular disease, and preexisting cognitive impairment, the contribution of mood disorders to PND susceptibility remains incompletely understood. This review systematically examines the neurobiological overlap between mood disorders, particularly major depressive disorder (MDD) and bipolar disorder, and PND, with emphasis on shared biomolecular mechanisms. We identify convergent pathophysiologic pathways including hypothalamic–pituitary–adrenal (HPA) axis dysregulation, chronic neuroinflammation, NF-κB-mediated cytokine signaling, microglial priming, tryptophan–kynurenine pathway dysregulation, and brain-derived neurotrophic factor (BDNF) suppression. These mechanisms collectively suggest that patients with preexisting mood disorders may enter surgery in a biologically sensitized neuroimmune state, lowering the threshold for exaggerated neuroinflammatory responses and postoperative cognitive dysfunction. Recognition of mood disorders as modifiable perioperative vulnerability states may inform preoperative risk stratification, guide anesthetic and analgesic management, and support the development of targeted interventions to reduce postoperative cognitive complications and improve surgical outcomes.
Chronic pain, sleep disturbances, and mental health disorders such as anxiety and depression disorders frequently co-occur, forming a self-reinforcing cycle that impairs daily functioning and quality of life. Chronic pain is driven by peripheral and central sensitization, the latter sustained by reciprocal microglial–astrocytic crosstalk and maladaptive neuroplasticity. Poor sleep amplifies pain through inflammation and circadian disruption. Imbalances in serotonin, dopamine, and norepinephrine, together with limbic alterations and HPA axis dysregulation, contribute to comorbid anxiety and depression. Elevated pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α), NF-κB-driven neuroinflammation, and mitochondrial oxidative stress serve as key molecular links. Building on previous evidence, this review presents an updated triadic, mechanism-based framework describing the reciprocal reinforcement among chronic pain, sleep disturbances, and anxiety and depressive disorders. Consequently, therapeutic strategies targeting inflammatory cytokines, microglial and astrocytic activation, neurotransmitter imbalance, and psychological dysfunction may help address these shared neuroimmune and neuroplastic mechanisms underlying these interconnected disorders.
Boris Burnjaković, Harrison Moy, Aleksandar Sič et al.· International Journal of Mol...· 0 citations
A comprehensive understanding of neuroinflammatory mechanisms may provide new opportunities for developing targeted therapeutic interventions and improving clinical outcomes in psychiatric disorders, including patient stratification and enable precision psychiatry.
P. Karwa, Vaibhav Parekar, Sarthak Buttepatil et al.· Current pharmaceutical desig...· 1 citation
Clinical evidence suggests that structured, individualized, and supervised exercise programs may improve mood, cognition, mobility, fatigue, fatigue, and quality of life in individuals with long COVID; however, careful pacing and symptom-contingent adaptation are essential in long COVID to avoid post-exertional symptom exacerbation.
G. Verrienti· Exploration of Neuroscience· 0 citations
Overall, the findings suggest that neuroinflammation represents a promising and increasingly actionable target for biomarker-guided, personalized psychiatric care.
Zvikomborero Murimbechi· World Journal of Advanced Re...· 0 citations
Background Depression is increasingly recognized as a multisystem disorder involving interconnected neuroinflammatory, neuroendocrine, metabolic and gut–brain mechanisms rather than isolated neurotransmitter abnormalities. Emerging evidence suggests that dysregulation of cytokine activity, hypothalamic–pituitary–adrenal (HPA) axis function, oxidative stress, mitochondrial dysfunction and gut microbiota collectively contribute to depressive pathophysiology. This review aimed to synthesise current evidence on these biological interactions and evaluate the potential role of nutritional modulation in influencing these pathways. Summary A PRISMA-informed systematic review was conducted using PubMed, Scopus, Web of Science, Embase, PsycINFO and Google Scholar for studies published between 2010 and 2025. Thirty-five eligible studies were included. The evidence demonstrates a self-reinforcing biological network in which chronic stress activates the HPA axis, leading to glucocorticoid receptor resistance, increased pro-inflammatory cytokines, neuroinflammation, oxidative stress and gut microbiota dysbiosis. These interconnected mechanisms contribute to depressive symptoms and may perpetuate disease progression. Nutritional interventions, including Mediterranean dietary patterns, omega-3 fatty acids, dietary fibre, probiotics, polyphenols and selected micronutrients, consistently showed potential to reduce inflammation, regulate HPA axis activity, improve gut microbial balance and mitigate oxidative stress. Key Message Depression should be conceptualised as a complex multisystem disorder driven by dynamic interactions among immune, endocrine, metabolic and microbiota-related pathways. Nutritional modulation represents a promising adjunctive strategy capable of targeting these interconnected biological mechanisms. Future longitudinal and interventional studies integrating multi-omics approaches are needed to validate causal pathways and develop personalised nutrition-based interventions for depression.
Saranya Ts, Ş. Yücel, Sandeep Kumar Gupta et al.· Annals of Neurosciences· 0 citations
Cortisol, regulated by the hypothalamic-pituitary-adrenal (HPA) axis, is critical for stress response, metabolism, and immune function. Its dysregulation is increasingly implicated in neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). This review synthesizes evidence on cortisol's role in neurodegenerative disorders, exploring its mechanisms, clinical implications, and therapeutic potential. This study analyzed preclinical models, clinical studies, and biomarker data to elucidate cortisol's impact on neurodegeneration. Key mechanisms include glucocorticoid and mineralocorticoid receptor-mediated effects on synaptic plasticity, neuroinflammation, and oxidative stress. In AD, elevated cortisol accelerates cognitive decline, hippocampal atrophy, and amyloid-β accumulation. In PD, higher cortisol levels correlate with gait dysfunction and dopaminergic neuron loss. HD shows variable cortisol profiles, with early hypocortisolism shifting to hypercortisolism in later stages, linked to depression. In ALS, elevated cortisol hastens disease progression and neuroinflammation. In MS, HPA axis hyperactivity is associated with cognitive deficits and lesion activity, though it may support remyelination. Chronic stress exacerbates these effects across disorders, promoting neuronal vulnerability. Cortisol dysregulation is a significant contributor to neurodegenerative pathology, acting as both a biomarker and therapeutic target. Emerging interventions, including glucocorticoid receptor antagonists, cortisol synthesis inhibitors, and stress reduction strategies, show promise in mitigating neuronal damage. Personalized, stage-specific therapies and longitudinal studies are needed to optimize cortisol-targeted treatments for neurodegenerative diseases.
Reza Hooshyari Ardakani, Mohadeseh Dashtaki, Seyed-Mahdi Mohamadi-Zarch et al.· CNS and Neurological Disorde...· 0 citations
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