Novel and emerging treatments for major depression

The Lancet, Journal Year: 2022, Volume and Issue: 401(10371), P. 141 - 153

Published: Dec. 16, 2022

Language: Английский

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Causal role of immune cells in schizophrenia: Mendelian randomization (MR) study

BMC Psychiatry, Journal Year: 2023, Volume and Issue: 23(1)

Published: Aug. 15, 2023

Complex immune-brain interactions that affect neural development, survival and function might have causal therapeutic implications for psychiatric illnesses. However, previous studies examining the association between immune inflammation schizophrenia (SCZ) yielded inconsistent findings.Comprehensive two-sample Mendelian randomization (MR) analysis was performed to determine cell signatures SCZ in this study. Based on publicly available genetic data, we explored associations 731 risk. A total of four types (median fluorescence intensities (MFI), relative (RC), absolute (AC), morphological parameters (MP)) were included. Comprehensive sensitivity analyses used verify robustness, heterogeneity, horizontal pleiotropy results.After FDR correction, had no statistically significant effect immunophenotypes. It worth mentioning some phenotypes with unadjusted low P-values, including FSC-A NKT (β = 0.119, 95% CI 0.044 ~ 0.194, P 0.002), DN (CD4-CD8-) %T 0.131, 0.054 0.208, 9.03 × 10- 4), SSC-A lymphocytes 0.136, 0.059 0.213, 5.43 4). The IgD transitional estimated 0.127 (95% 0.051 0.203, 1.09 3). also a IgD+ %B 0.130, 0.207, 8.69 DP (CD4+CD8+) 8.05 Furthermore, immunophenotypes identified be significantly associated risk: naive CD4+ (OR 0.986, 0.979 0.992, 1.37 5), HLA DR CD14- CD16- 0.738 0.642 0.849, 2.00 CD33dim DR+ CD11b- AC 0.631, 0.529 0.753, 3.40 7) activated & resting Treg % CD4 0.937, 0.906 0.970, 1.96 4).Our study has demonstrated close connection cells by means, thus providing guidance future clinical research.

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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Microglial over-pruning of synapses during development in autism-associated SCN2A-deficient mice and human cerebral organoids

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(8), P. 2424 - 2437

Published: March 18, 2024

Language: Английский

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The brain structure, inflammatory, and genetic mechanisms mediate the association between physical frailty and depression

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 23, 2024

Abstract Cross-sectional studies have demonstrated strong associations between physical frailty and depression. However, the evidence from prospective is limited. Here, we analyze data of 352,277 participants UK Biobank with 12.25-year follow-up. Compared non-frail individuals, pre-frail frail individuals increased risk for incident depression independent many putative confounds. Altogether, account 20.58% 13.16% cases by population attributable fraction analyses. Higher risks are observed in males younger than 65 years their counterparts. Mendelian randomization analyses support a potential causal effect on Associations also inflammatory markers, brain volumes, Moreover, these regional volumes three markers—C-reactive protein, neutrophils, leukocytes—significantly mediate Given scarcity curative treatment high disease burden, identifying modifiable factors depression, such as frailty, needed.

Language: Английский

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Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review

Molecular Neurobiology, Journal Year: 2022, Volume and Issue: 59(10), P. 6460 - 6501

Published: Aug. 13, 2022

Abstract Evidence from clinical, preclinical, and post-mortem studies supports the inflammatory/immune hypothesis of schizophrenia pathogenesis. Less evident is link between inflammatory background two well-recognized functional structural findings pathophysiology: dopamine-glutamate aberrant interaction alteration dendritic spines architecture, both believed to be “quantal” elements cortical-subcortical dysfunctional network. In this systematic review, we tried capture major linking inflammation, glutamate-dopamine interaction, post-synaptic changes under a direct inverse translational perspective, paramount picture that at present lacking. The effects on dopaminergic function appear bidirectional: inflammation influences dopamine release, acts as regulator discrete processes involved in such dysregulated interleukin kynurenine pathways. Furthermore, glutamate strongly supported by clinical aimed exploring overactive microglia patients maternal immune activation models, indicating impaired regulation reduced N-methyl-D-aspartate receptor (NMDAR) function. addition, an inflammatory/immune-induced density scaffold proteins, crucial for downstream NMDAR signaling synaptic efficacy, has been demonstrated. According these findings, significant increase plasma markers found compared healthy controls, associated with cortical integrity connectivity, relevant cognitive deficit schizophrenia. Finally, altered responses raises questions regarding potential new therapeutic strategies specifically those forms are resistant canonical antipsychotics or unresponsive clozapine.

Language: Английский

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MicroRNA schizophrenia: Etiology, biomarkers and therapeutic targets

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 146, P. 105064 - 105064

Published: Jan. 25, 2023

Language: Английский

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Inflammation and the Potential Implication of Macrophage-Microglia Polarization in Human ASD: An Overview

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2703 - 2703

Published: Jan. 31, 2023

Autism spectrum disorder (ASD) is a heterogeneous collection of neurodevelopmental disorders, difficult to diagnose and currently lacking treatment options. The possibility finding reliable biomarkers useful for early identification would offer the opportunity intervene with strategies improve life quality ASD patients. To date, there are many recognized risk factors development ASD, both genetic non-genetic. Although epigenetic may play critical role, extent their contribution still under study. On other hand, non-genetic include pollution, nutrition, infection, psychological states, lifestyle, all together known as exposome, which impacts mother’s fetus’s life, especially during pregnancy. Pathogenic non-pathogenic maternal immune activation (MIA) autoimmune diseases can cause various alterations in fetal environment, also contributing etiology offspring. Activation monocytes, macrophages, mast cells microglia high production pro-inflammatory cytokines indeed neuroinflammation, latter involved ASD’s onset development. In this review, we focused on factors, connection between inflammation, macrophage polarization syndrome, MIA, involvement microglia.

Language: Английский

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Inflammatory subgroups of schizophrenia and their association with brain structure: A semi-supervised machine learning examination of heterogeneity

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 113, P. 166 - 175

Published: July 8, 2023

Immune system dysfunction is hypothesised to contribute structural brain changes through aberrant synaptic pruning in schizophrenia. However, evidence mixed and there a lack of inflammation its effect on grey matter volume (GMV) patients. We that inflammatory subgroups can be identified the will show distinct neuroanatomical neurocognitive profiles. The total sample consisted 1067 participants (chronic patients with schizophrenia n = 467 healthy controls (HCs) 600) from Australia Schizophrenia Research Bank (ASRB) dataset, together 218 recent-onset external Benefit Minocycline Negative Symptoms Psychosis: Extent Mechanism (BeneMin) dataset. HYDRA (HeterogeneitY DiscRiminant Analysis) was used separate HC define disease-related based markers. Voxel-based morphometry inferential statistics were explore GMV alterations deficits these subgroups. An optimal clustering solution revealed five main groups separable HC: Low Inflammation, Elevated CRP, IL-6/IL-8, IFN-γ, IL-10 an adjusted Rand index 0.573. When compared controls, IL-6/IL-8 cluster showed most widespread, including anterior cingulate, reduction. IFN-γ least reduction impairment cognitive performance. CRP Inflammation clusters dominated younger may not merely case low vs high, but rather are pluripotent, heterogeneous mechanisms at play which could reliably accessible, peripheral measures. This inform successful development targeted interventions.

Language: Английский

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Neuroinflammation and Schizophrenia: New Therapeutic Strategies through Psychobiotics, Nanotechnology, and Artificial Intelligence (AI)

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(4), P. 391 - 391

Published: April 6, 2024

The prevalence of schizophrenia, affecting approximately 1% the global population, underscores urgency for innovative therapeutic strategies. Recent insights into role neuroinflammation, gut–brain axis, and microbiota in schizophrenia pathogenesis have paved way exploration psychobiotics as a novel treatment avenue. These interventions, targeting gut microbiome, offer promising approach to ameliorating psychiatric symptoms. Furthermore, advancements artificial intelligence nanotechnology are set revolutionize psychobiotic development application, enhance their production, precision, effectiveness. This interdisciplinary heralds new era management, potentially transforming patient outcomes offering beacon hope those afflicted by this complex disorder.

Language: Английский

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