Brain, behavior, & immunity - health最新文献

Introduction: Investigating the psychological impact caused by the interruption of social interactions on university students during the pandemic is essential, with a view to developing strategies to preserve mental health and academic performance.

Objective: To analyze the impact of social isolation during the COVID-19 pandemic on the mental health of university students and propose recommendations for the post-pandemic period.

Method: This systematic review was conduced in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in the International Prospective Register of Systematic Reviews (PROSPERO). Database searches were performed up to December 2024 in PubMed, EMBASE, Web of Science, Scopus, CINAHL, and PsycNET, using the terms "COVID-19," "social isolation," "mental health," and "college students." Studies were excluded if they focused on non-college populations, other causes of social isolation, physical health, or specific designs.

Results: The initial search identified 3051 records and 68 studies were included in this review, with sample off 177,537 university students. Anxiety was the most commonly investigated variable (79.4%), followed by depression (75%) and stress (42.6%). Less frequently, studies highlighted the increase in alcohol and drug consumption and suicidal ideation. Some authors also investigated sleep quality, relating insomnia and emotional changes with the reduction in physical exercise. Anxiety symptoms related to online learning directly impacted academic performance. The assessment of the risk of bias showed that of the 68 studies included, 34 had a low risk of bias, 30 had a moderate risk of bias, and 4 had a high risk of bias.

Conclusion: This study highlights the negative impact of the COVID-19 pandemic on the mental health of college students, particularly in relation to symptoms of anxiety, depression, and stress. Post-pandemic interventions should prioritize fostering healthy habits, such as ensuring quality sleep, engaging in moderate physical activity, and raising mental health awareness. Additionally, universities should implement proactive support systems to cultivate a safe and inclusive environment for students.

Objective: To determine whether a panel of immune markers adds significant information to known correlates of risk of dementia and cognitive impairment.

Background: The impact of immune mechanisms on dementia risk is incompletely characterized.

Design/methods: A subsample of the Northern Manhattan Study, a prospective cohort study in the racially/ethnically diverse population of New York City, underwent comprehensive neuropsychological testing up to three times, at approximately 5-year intervals. Cognitive outcomes were adjudicated as no cognitive impairment, mild cognitive impairment (MCI), or dementia. Immune markers were assessed using a multiplex immunoassay on plasma samples collected at the time of the first neuropsychological test. Least absolute shrinkage and selection operator (LASSO) techniques were employed to yield a panel of immune markers linearly related to the outcome of dementia/MCI vs. no cognitive impairment. Nested logistic regression models were run to determine the independent association of the immune marker panel with dementia/MCI after adjusting for other predictors of risk.

Results: Among 1179 participants (mean age 70.0 ± 8.9 years, 60% women, 68% Hispanic), immune markers improved model fit above demographic and vascular risk factors (p-value for likelihood ratio test <0.0001) as correlates of MCI/dementia. Individual immune markers found to be associated with dementia/MCI were C-X-C Motif Chemokine Ligand 9 (CXCL9) and C-C Motif Chemokine Ligand 2 (CCL2). The effect of the immune markers was comparable to traditional risk factors, with CCL2 (per SD) having almost the same effect as 1 year of aging and CXCL9 (per SD) showing approximately twice this magnitude.

Conclusion: Immune markers are associated with cognitive decline and dementia outcomes in a multi-ethnic cohort. More work is needed to further characterize these associations and determine therapeutic strategies. (Funded by the National Institute of Health/National Institute of Neurological Disorders and Stroke; grant number R01 29993 (Sacco/Elkind)).

Image 1.

Duchenne muscular dystrophy (DMD), an X-linked neuromuscular disorder, characterised by progressive immobility, chronic inflammation and premature death, is caused by the loss of the mechano-transducing signalling molecule, dystrophin. In non-contracting cells, such as neurons, dystrophin is likely to have a functional role in synaptic plasticity, anchoring post-synaptic receptors. Dystrophin-expressing hippocampal neurons are key to cognitive functions such as emotions, learning and the consolidation of memories. In the context of disease-induced chronic inflammation, we have explored the role of the pleiotropic cytokine, interleukin (IL)-6 in hippocampal dysfunction using immunofluorescence, electrophysiology and metabolic measurements in dystrophic mdx mice. Hippocampal long-term potentiation (LTP) of the Schaffer collateral-CA1 projections was suppressed in mdx slices. Given the importance of mitochondria-generated ATP in synaptic plasticity, reduced maximal respiration in the CA1 region may impact upon this process. Consistent with a role for IL-6 in this observation, early LTP was suppressed in dystrophin-expressing wildtype slices exposed to IL-6. In dystrophic mdx mice, exposure to IL-6 suppressed mitochondrial-mediated basal metabolism in CA1, CA3 and DG hippocampal regions. Furthermore, blocking IL-6-mediated signalling by administering neutralising monoclonal IL-6 receptor antibodies intrathecally, normalised LTP in mdx mice. The impact of dystrophin loss from the hippocampus was associated with modified cellular bioenergetics, which underpin energy-driven processes such as the induction of LTP. The additional challenge of pathophysiological levels of IL-6 resulted in altered cellular bioenergetics, which may be key to cognitive deficits associated with the loss of dystrophin.

Interest in preventative dietary interventions for human health has increasingly focused on the endocannabinoid (eCB)-like compound palmitoylethanolamide (PEA), a bioactive lipid mediator with anti-inflammatory, analgesic, and neuroprotective properties. This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020-compliant systematic review aimed at collecting and comprehensively discussing all available data from Randomized Controlled Trials (RCTs) evaluating the efficacy and tolerability of PEA supplementation across human illnesses in patient populations. Overall, 48 eligible outputs from 47 RCTs were extracted, covering neuropsychiatric (n = 15), neurological (n = 17), somatic (n = 13), and visceral (n = 11) disturbances, as well as PEA effects on blood/plasma or other tissue biomarkers (n = 10). The strongest evidence emerged from RCTs exploring PEA impact on pain management and measures of general wellbeing, especially in its ultramicronized/micronized or cold-water dispersible formulations, showing good tolerability compared to controls. Also, alongside symptom improvement, PEA demonstrated to modulate biomarkers early altered in the initial phases of an illness or contributing to its progression, suggesting a disease-modifying potential. This systematic review provided a comprehensive overview of the therapeutic potential of PEA across RCTs, highlighting its versatility either as monotherapy or add-on treatment for various clinical conditions.

A proposed contributor to Alzheimer's disease (AD) pathology is the induction of neuroinflammation due to tau and beta-amyloid protein accumulation causing neuronal injury and dysfunction. Dysregulation of lipid mediators derived from polyunsaturated fatty acids may contribute to this inflammatory response in the brain of patients with AD, yet the literature has not yet been systematically reviewed. A systematic search was conducted in Medline, Embase and PsychINFO for articles published up to April 22, 2024. Papers were included if they measured levels of lipid mediators and/or enzymes involved in their production in post-mortem brain samples from patients with AD and control without neurological disease. A total of 50 relevant studies were identified. Despite heterogeneity in the results, pro-inflammatory lipid mediators, including 5-, 11-, 12- and 15-hydroxyeicosatetraenoic acid oxylipins and prostaglandin D2, were significantly higher, while anti-inflammatory lipoxin A4 and DHA-derived docosanoids were significantly lower in brains of patients with AD compared to control (16 studies). Thirty-seven articles reported on enzymes, with 32 reporting values for enzyme level changes between AD and controls. Among the 32 articles, the majority reported on levels of cyclooxygenase (COX) (18/32), with fewer studies reporting on phospholipase (8/32), lipoxygenase (LOX) (4/32) and prostaglandin E synthase (4/32). Enzyme levels also exhibited variability in the literature, with a trend towards elevated expression of enzymes involved in the pro-inflammatory response, including COX and LOX enzymes. Overall, these results are consistent with the involvement of neuroinflammation in the pathogenesis of AD measured by lipid mediators. However, the specific contribution of each lipid metabolite and enzymes to either the progression or persistence of AD remains unclear, and more research is required.

Background: Electroconvulsive therapy (ECT) is a highly efficacious intervention for severe and intractable depression. Evidence suggests ECT provokes an initial acute inflammatory response that subsequently decreases with repeated administration. However, relationships between inflammatory changes and clinical effects are unclear. Improved understanding of these processes may provide critical insight into effective intervention for treatment-resistant depression (TRD).

Methods: Plasma inflammatory markers were assessed at pre-treatment (T1), after the second ECT session (T2), and after ECT index series completion (post-treatment/T3) in TRD (n = 40). Changes were examined over time and in association with post-treatment Responder/Non-responder status (≥50% reduction in global depression severity) and percent change in affective, cognitive and neurovegetative depressive symptom domains.

Results: C-reactive protein (CRP) and interleukin-6 (IL-6) increased from pre-treatment to T2, and decreased from T2 to post-treatment. Neither early (%T2-T1) nor total (%T1-T3) change in inflammation predicted clinical outcomes, however, the interaction between early/acute inflammatory response and post-treatment inflammation (relative to baseline) was associated with clinical outcomes. Larger initial increases in IL-6 predicted greater reductions in both affective and cognitive symptoms in subjects with higher post-treatment IL-6; those with lower post-treatment IL-6 trended toward the opposite. The same was found between changes in CRP and neurovegetative symptoms.

Conclusions: Though preliminary, these results demonstrate how processes involved in the acute inflammatory response to ECT may differentially influence clinical outcomes depending on overall trajectory of inflammation following ECT. Findings also highlight the importance of examining symptom-specific changes in depression when studying treatment mechanisms, rather than relying solely on global measures of severity.

Schizophrenia is a chronic psychiatric disorder characterized by a variety of symptoms broadly categorized into positive, negative, and cognitive domains. Its etiology is multifactorial, involving a complex interplay of genetic, neurobiological, and environmental factors, and its neurobiology is associated with abnormalities in different neurotransmitter systems. Due to this multifactorial etiology and neurobiology, leading to a wide heterogeneity of symptoms and clinical presentations, current antipsychotic treatments face challenges, underscoring the need for novel therapeutic approaches. Recent studies have revealed differences in the gut microbiome of individuals with schizophrenia compared to healthy controls, establishing an intricate link between this disorder and gastrointestinal health, and suggesting that microbiota-targeted interventions could help alleviate clinical symptoms. Therefore, this meta-analysis investigates whether gut microbiota manipulation can ameliorate psychotic outcomes in patients with schizophrenia receiving pharmacological treatment. Nine studies (n = 417 participants) were selected from 81 records, comprising seven randomized controlled trials and two open-label studies, all with a low risk of bias, included in this systematic review and meta-analysis. The overall combined effect size indicated significant symptom improvement following microbiota treatment (Hedges' g = 0.48, 95% CI = 0.09 to 0.88, p = 0.004, I² = 62.35%). However, according to Hedges' g criteria, the effect size was small (approaching moderate), and study heterogeneity was moderate based on I² criteria. This review also discusses clinical and preclinical studies to elucidate the neural, immune, and metabolic pathways by which microbiota manipulation, particularly with Lactobacillus and Bifidobacterium genera, may exert beneficial effects on schizophrenia symptoms via the gut-brain axis. Finally, we address the main confounding factors identified in our systematic review, highlight key limitations, and offer recommendations to guide future high-quality trials with larger participant cohorts to explore microbiome-based therapies as a primary or adjunctive treatment for schizophrenia.

Delirium is a highly prevalent neuropsychiatric syndrome characterised by acute and fluctuating impairments in attention and cognition. Mechanisms driving delirium are poorly understood but it has been suggested that blood cytokines and chemokines cross the blood brain barrier during delirium, directly impairing brain function. It is not known whether these molecules reach higher brain levels when the blood cerebrospinal fluid barrier (BCSFB) is impaired. Here, in human hip-fracture patients, we tested the influence of BCSFB integrity on CSF levels of chemokines and assessed their association with delirium. CSF levels of IP-10, eotaxin, eotaxin 3 and TARC showed weak to moderate correlations with BCSFB permeability, as measured by the Q_albumin ratio, while MCP1, IL-8, MIP1α and MIP1β showed no significant correlation. Chemokines were not associated with delirium in univariate analysis or when stratified on dementia status, but exploratory analyses showed that elevated Eotaxin (CCL11) and MIP1α (CCL3) were associated with prevalent delirium. Modelling acute systemic inflammation, we used bacterial LPS (250 μg/kg) or sterile laparotomy surgery in mice to demonstrate de novo synthesis of chemokines at the choroid plexus (CP) and microvasculature. Gene expression data showed CP-enriched expression of Il1b, Tnfa, Cxcl1 and Ccl3 in both models and immunohistochemistry showed cytokine and chemokine synthesis in CP stromal (IL-1β, CCL2/MCP1) or epithelial cells (CXCL10/IP-10) cells and at the microvasculature. Larger studies are required to confirm these human findings on chemokine associations with BCSFB permeability and prevalent delirium. Preclinical studies are warranted to determine whether chemokines might play a role in the pathophysiology of delirium.