Increased risk of COVID‐19 infection and mortality in people with mental disorders: analysis from electronic health records in the United States

World Psychiatry, Journal Year: 2020, Volume and Issue: 20(1), P. 124 - 130

Published: Oct. 7, 2020

Concerns have been expressed that persons with a pre‐existing mental disorder may represent population at increased risk for COVID‐19 infec­tion and higher likelihood of adverse outcomes the infection, but there is no systematic research evidence in this respect. This study assessed impact recent (within past year) diagnosis – including attention‐deficit/hyperactivity (ADHD), bipolar disorder, depression schizophrenia on infection related mortality hospitalization rates. We analyzed nation‐wide database electronic health records 61 million adult patients from 360 hospitals 317,000 providers, across 50 states US, up to July 29, 2020. Patients had significantly an effect strongest (adjusted odds ratio, AOR=7.64, 95% CI: 7.45‐7.83, p<0.001) (AOR=7.34, 6.65‐8.10, p<0.001). Among African Americans than Caucasians, ethnic disparity (AOR=3.78, 3.58‐3.98, Women disorders males, gender ADHD (AOR=2.03, 1.73‐2.39, both death rate 8.5% (vs. 4.7% among 27.4% 18.6% These findings identify individuals as being which further exacerbated women, having frequency some infection. highlights need address modifiable vulnerability factors prevent delays care provision population.

Language: Английский

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Brain–gut–microbiota axis in depression: A historical overview and future directions

Brain Research Bulletin, Journal Year: 2022, Volume and Issue: 182, P. 44 - 56

Published: Feb. 11, 2022

Depression is the most common mental disorder and a leading cause of disability worldwide. Despite abundant research, precise mechanisms underlying pathophysiology depression remain elusive. Accumulating evidence from preclinical clinical studies suggests that alterations in gut microbiota, microbe-derived short-chain fatty acids, D-amino acids metabolites play key role via brain–gut–microbiota axis, including neural immune systems. Notably, axis might crucial susceptibility versus resilience rodents exposed to stress. Vagotomy reported block depression-like phenotypes after fecal microbiota transplantation "depression-related" microbiome, suggesting vagus nerve influences through axis. In this article, we review recent findings regarding discuss its potential as therapeutic target for depression.

Language: Английский

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Molecular pathways of major depressive disorder converge on the synapse

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(1), P. 284 - 297

Published: Oct. 6, 2022

Abstract Major depressive disorder (MDD) is a psychiatric disease of still poorly understood molecular etiology. Extensive studies at different levels point to high complexity numerous interrelated pathways as the underpinnings depression. systems under consideration include monoamines, stress, neurotrophins and neurogenesis, excitatory inhibitory neurotransmission, mitochondrial dysfunction, (epi)genetics, inflammation, opioid system, myelination, gut-brain axis, among others. This review aims illustrating how these multiple signaling may interact provide more comprehensive view MDD’s neurobiology. In particular, considering pattern synaptic activity closest physical representation mood, emotion, conscience we can conceptualize, each pathway or system will be scrutinized for links neurotransmission. Models neurobiology MDD discussed well future actions improve understanding treatment options.

Language: Английский

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Early-life inflammation promotes depressive symptoms in adolescence via microglial engulfment of dendritic spines

Neuron, Journal Year: 2021, Volume and Issue: 109(16), P. 2573 - 2589.e9

Published: July 6, 2021

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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Guts Imbalance Imbalances the Brain: A Review of Gut Microbiota Association With Neurological and Psychiatric Disorders

Frontiers in Medicine, Journal Year: 2022, Volume and Issue: 9

Published: March 31, 2022

Over the last 10 years, there has been a growing interest in relationship between gut microbiota, brain, and neurologic-associated affections. As multiple preclinical clinical research studies highlight microbiota’s potential to modulate general state of health state, it goes without saying that microbiota plays significant role neurogenesis, mental cognitive development, emotions, behaviors, progression neuropsychiatric illnesses. Gut produces important biologic products that, through gut-brain axis, are directly connected with appearance evolution neurological psychiatric disorders such as depression, anxiety, bipolar disorder, autism, schizophrenia, Parkinson’s disease, Alzheimer’s dementia, sclerosis, epilepsy. This study reviews recent on link microbiome’s shaping development most common Moreover, special attention is paid use probiotic formulations non-invasive therapeutic opportunity for prevention management neuropsychiatric-associated

Language: Английский

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New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications

World Psychiatry, Journal Year: 2023, Volume and Issue: 22(1), P. 4 - 24

Published: Jan. 14, 2023

Psychiatric genetics has made substantial progress in the last decade, providing new insights into genetic etiology of psychiatric disorders, and paving way for precision psychiatry, which individual profiles may be used to personalize risk assessment inform clinical decision‐making. Long recognized heritable, recent evidence shows that disorders are influenced by thousands variants acting together. Most these commonly occurring, meaning every a each disorder, from low high. A series large‐scale studies have discovered an increasing number common rare robustly associated with major disorders. The most convincing biological interpretation findings implicates altered synaptic function autism spectrum disorder schizophrenia. However, mechanistic understanding is still incomplete. In line their extensive epidemiological overlap, appear exist on continua share large degree one another. This provides further support notion current diagnoses do not represent distinct pathogenic entities, ongoing attempts reconceptualize nosology. also influences range behavioral somatic traits diseases, including brain structures, cognitive function, immunological phenotypes cardiovascular disease, suggesting shared potential importance. Current polygenic score tools, predict susceptibility illness, yet provide clinically actionable information. likely improve coming years, they eventually become part practice, stressing need educate clinicians patients about use misuse. review discusses key possible applications, suggests future directions.

Language: Английский

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Tetramethylpyrazine: A review on its mechanisms and functions

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 150, P. 113005 - 113005

Published: April 25, 2022

Ligusticum chuanxiong Hort (known as Chuanxiong in China, CX) is one of the most widely used and long-standing medicinal herbs China. Tetramethylpyrazine (TMP) an alkaloid active components CX. Over past few decades, TMP has been proven to possess several pharmacological properties. It treat a variety diseases with excellent therapeutic effects. Here, characteristics molecular mechanism recent years are reviewed, emphasis on signal-regulation TMP. This review shows that many physiological functions, including anti-oxidant, anti-inflammatory, anti-apoptosis properties; autophagy regulation; vasodilation; angiogenesis mitochondrial damage suppression; endothelial protection; reduction proliferation migration vascular smooth muscle cells; neuroprotection. At present, treating cardiovascular, nervous, digestive system conditions, cancer, other conditions achieved good curative The involves multiple targets, pathways, bidirectional regulation. is, thus, promising drug great research potential.

Language: Английский

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Association Between Systemic Inflammation and Individual Symptoms of Depression: A Pooled Analysis of 15 Population-Based Cohort Studies

American Journal of Psychiatry, Journal Year: 2021, Volume and Issue: 178(12), P. 1107 - 1118

Published: Oct. 14, 2021

Evidence from anti-inflammatory drug trials for the treatment of depression has been inconsistent. This may be ascribed to differing symptom-specific effects inflammation. Accordingly, authors explored associations between systemic inflammation and an array individual symptoms across multiple studies.This random-effects pooled analysis included 15 population-based cohorts 56,351 individuals age 18 years older. Serum or plasma concentrations C-reactive protein (CRP) interleukin-6 (IL-6) were measured at baseline. Using validated self-report measures, 24 depressive ascertained in cross-sectional studies, and, seven cohorts, also assessed follow-up (mean period, 3.2 years).The prevalence ranged 1.1% (suicidal ideation) 21.5% (sleep problems). In analyses, higher CRP robustly associated with increased risk experiencing four physical (changes appetite, felt everything was effort, loss energy, sleep problems) one cognitive symptom (little interest doing things). These remained after adjustment sociodemographic variables, behavioral factors, chronic conditions; sex- age-stratified analyses; longitudinal when using IL-6 as inflammatory marker interest; depressed individuals; excluding chronically ill individuals. For exclusively emotional (bothered by things, hopelessness about future, fearful, life had a failure), overall evidence strongly against association inflammation.These findings suggest rather than generalized on depression. Future exploring regimens benefit targeting presenting profiles characterized distinct inflammation-related symptoms.

Language: Английский

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Accelerated biological aging and risk of depression and anxiety: evidence from 424,299 UK Biobank participants

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 20, 2023

Theory predicts that biological processes of aging may contribute to poor mental health in late life. To test this hypothesis, we evaluated prospective associations between age and incident depression anxiety 424,299 UK Biobank participants. We measured from clinical traits using the KDM-BA PhenoAge algorithms. At baseline, participants who were biologically older more often experienced depression/anxiety. During a median 8.7 years follow-up, with at increased risk depression/anxiety (5.9% increase per standard deviation [SD] acceleration, 95% confidence intervals [CI]: 3.3%-8.5%; 11.3% SD CI: 9.%-13.0%). Biological-aging-associated was independent additive genetic by genome-wide-association-study-based polygenic scores. Advanced represent potential factor for midlife adults target assessment intervention.

Language: Английский

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