Neuroprogression in substance use disorders: Integrating molecular mechanisms, brain circuitry, biomarkers, and implications for clinical staging and service design.

Molecular and Cellular Mechanisms Linking Mood Disorders, HPA Axis Dysregulation, and Neurocognitive Inflammation to Perioperative Neurocognitive Disorders

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.

Biological Embedding of Adverse Childhood Experiences: Neurobiological and Immune Mechanisms Linking Early-Life Stress to Addiction Vulnerability.

Neuroinflammation in major depressive disorder: Mechanisms, biomarkers, and emerging therapeutic targets

Major depressive disorder (MDD) affects an estimated 280 million people worldwide and remains a leading cause of disability. The monoamine hypothesis, and later the neuroplasticity hypothesis, transformed treatment but leave a substantial share of patients with delayed response, partial remission, or outright treatment resistance. Over the past two decades, evidence has accumulated that a subset of MDD is driven by chronic, low-grade neuroinflammation rather than, or in addition to, monoaminergic deficits. This review synthesizes current evidence on the neuroimmune mechanisms involved in MDD microglial activation, pro-inflammatory cytokine signaling, blood–brain barrier disruption, oxidative stress, kynurenine pathway dysregulation, and impaired neuroplasticity and examines how these mechanisms are captured by peripheral, central, neuroimaging, and emerging molecular biomarkers. It then reviews therapeutic strategies that target inflammation directly (minocycline, celecoxib, TNF-α antagonists), indirectly (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), ketamine), or through lifestyle modification (exercise, diet, sleep), with attention to why inflammation-stratified trials have outperformed unstratified ones. Across mechanisms, biomarkers, and treatment response, a consistent pattern emerges: neuroinflammation does not simply co-occur with depression, it may mark a biologically distinct, identifiable subtype roughly a quarter to a third of patients with elevated high-sensitivity C-reactive protein (hsCRP) or IL-6 for whom anti-inflammatory or immune-modulating strategies produce disproportionate benefit. Overall, the findings suggest that neuroinflammation represents a promising and increasingly actionable target for biomarker-guided, personalized psychiatric care.

Pharmacological Insights in to Schizophrenia: Neurochemical Dysregulation, Disease Mechanisms and Future Therapeutic Strategies

Current understanding of the clinical features, etiological factors, biological mechanisms, and pharmacological management of schizophrenia is summarized, while emerging therapeutic targets that may guide future research and drug development are outlined.

Neuroinflammatory pathways linking pain and rehabilitation outcomes in schizophrenia: a narrative review.

INTRODUCTION Schizophrenia is a chronic and disabling neuropsychiatric disorder traditionally defined by psychotic and cognitive symptoms. Increasing evidence suggests that neuroinflammatory mechanisms contribute to its pathophysiology and may also underlie common but underrecognized somatic manifestations. These include altered pain perception, characterized by both diminished sensitivity and chronic pain, with important implications for functional outcomes and rehabilitation. AREAS COVERED This narrative review examines clinical, preclinical, and translational studies addressing the role of neuroinflammation in schizophrenia, with a specific focus on microglial and astrocytic activation, cytokine signaling, oxidative stress pathways, and their interactions with central pain processing circuits. The review was informed by targeted searches of PubMed, Scopus, Web of Science, and Google Scholar, covering articles published from database inception to January 2026, with emphasis on studies relevant to pain modulation, symptom expression, and neurobiological heterogeneity in schizophrenia. EXPERT OPINION Neuroinflammation represents a biologically plausible link between core schizophrenia pathology and altered pain perception. Recognition of pain as an integrated component of disease biology, rather than a secondary complaint, may improve clinical assessment and treatment planning. Investigating and targeting neuroinflammatory pathways holds promise for personalized interventions that address neuropsychiatric symptoms and pain, potentially enhancing rehabilitation outcomes and quality of life.

Exercise and brain health in long COVID: mechanisms and therapeutic implications for neuropsychiatric disorders

Psychiatric and neurological disorders represent a major global health burden, often characterized by chronic disability and incomplete response to pharmacological treatments. The emergence of long COVID has further contributed to this challenge, introducing persistent neuropsychiatric and neurological sequelae, including cognitive impairment, fatigue, mood disturbances, and autonomic dysfunction, that overlap with mechanisms observed in established brain disorders. This narrative review synthesizes current evidence on exercise as a multimodal therapeutic strategy for individuals with long COVID and pre-existing or COVID-related psychiatric and neurological conditions. Exercise may exert broad effects across interconnected biological systems, potentially enhancing neuroplasticity and neurotrophic signaling, modulating neuroinflammation and immune responses, improving mitochondrial function and energy metabolism, supporting cerebrovascular health, regulating stress physiology and autonomic balance, and influencing the gut–brain axis. These mechanisms are thought to converge on shared pathophysiological pathways implicated in depression, anxiety, bipolar disorder, schizophrenia, post-traumatic stress disorder, neurodegenerative diseases, stroke, epilepsy, and post-viral syndromes. Clinical evidence suggests that structured, individualized, and supervised exercise programs may improve mood, cognition, mobility, fatigue, and quality of life. However, careful pacing and symptom-contingent adaptation are essential in long COVID to avoid post-exertional symptom exacerbation. Although high-quality randomized trials remain limited, exercise appears to be a promising, low-risk, and potentially scalable component of multidisciplinary rehabilitation in long COVID-related brain disorders.