Inflammation and Brain Structure in Schizophrenia and Other Neuropsychiatric Disorders

JAMA Psychiatry, Год журнала: 2022, Номер 79(5), С. 498 - 498

Опубликована: Март 30, 2022

Importance

Previous in vitro and postmortem research suggests that inflammation may lead to structural brain changes via activation of microglia and/or astrocytic dysfunction a range neuropsychiatric disorders.

Objective

To investigate the relationship between structures vivo explore transcriptome-driven functional basis with relevance mental illness.

Design, Setting, Participants

This study used multistage linked analyses, including mendelian randomization (MR), gene expression correlation, connectivity analyses. A total 20 688 participants UK Biobank, which includes clinical, genomic, neuroimaging data, 6 brains from neurotypical individuals Allen Human Brain Atlas (AHBA), RNA microarray data. Data were extracted February 2021 analyzed March October 2021.

Exposures

Genetic variants regulating levels activity circulating interleukin 1 (IL-1), IL-2, IL-6, C-reactive protein (CRP), brain-derived neurotrophic factor (BDNF) as exposures MR

Main Outcomes Measures

imaging measures, gray matter volume (GMV) cortical thickness (CT), outcomes. Associations considered significant at multiple testing–corrected threshold ofP < 1.1 × 10⁻⁴. Differential AHBA data was modeled regions mapped areas analyses; genes tested for biological disease overrepresentation annotation databases protein-protein interaction networks.

Results

Of Biobank sample, 10 828 (52.3%) female, mean (SD) age 55.5 (7.5) years. In genetically predicted IL-6 associated GMV middle temporal cortex (zscore, 5.76;P = 8.39 10⁻⁹), inferior (z score, 3.38;P 7.20 10⁻⁵), fusiform 4.70;P 2.60 10⁻⁷), frontal −3.59;P 3.30 10⁻⁵) together CT superior region −5.11;P 3.22 10⁻⁷). No associations found IL-1, CRP, or BDNF after correction comparison. 5 (83%) male, 42.5 (13.4) Brain-wide coexpression analysis showed highly interconnected network preferentially expressed gyrus (MTG), further formed connected (enrichment test expected vs observed given prevalence degree interactions STRING database: 43 nodes/30 edges 8 expected; node degree, 1.4; genome-wide significance,P 4.54 10⁻⁹). MTG differentially functionally enriched processes schizophrenia, autism spectrum disorder, epilepsy.

Conclusions Relevance

this study, determined structure potentially affects implicated developmental disorders, schizophrenia autism.

Язык: Английский

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Selected Biomarkers of Depression: What Are the Effects of Cytokines and Inflammation?

International Journal of Molecular Sciences, Год журнала: 2022, Номер 24(1), С. 578 - 578

Опубликована: Дек. 29, 2022

Depression is one of the leading mental illnesses worldwide and lowers quality life many. According to WHO, about 5% population suffers from depression. Newer studies report a staggering global prevalence 27.6%, it rising. Professionally, depression belonging affective disorders psychiatric illness, category major depressive disorder (MDD) comprises various diagnoses related persistent disruptive mood disorders. Due this fact, imperative find way assess quantitatively using specific biomarker or panel biomarkers that would be able reflect patients' state effects therapy. Cytokines, hormones, oxidative stress markers, neuropeptides are studied in association with The latest research into inflammatory cytokines shows their relationship etiology causative. There stronger cytokine reactions pathogens stressors If combined other predisposing factors, responses lead prolonged processes, dysregulation axes, stress, pain, changes, anxiety, This review focuses on most recent data as markers concerning roles its pathogenesis, possible use diagnosis management, different levels bodily fluids, similarities animal studies. However, not isolated pathophysiologic mechanisms Their only part whole pathway.

Язык: Английский

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Balancing the Mind: Toward a Complete Picture of the Interplay between Gut Microbiota, Inflammation and Major Depressive Disorder

Brain Research Bulletin, Год журнала: 2024, Номер 216, С. 111056 - 111056

Опубликована: Авг. 24, 2024

The intricate interplay existing between gut microbiota and homeostasis extends to the realm of brain, where emerging research underscores significant impact on mood regulation overall neurological well-being vice-versa, with inflammation playing a pivotal role in mediating these complex interactions. This comprehensive review explores inflammation, alterations microbiota, their major depressive disorder (MDD). It provides cohesive framework for puzzle pieces this triad, emphasizing recent advancements understanding inflammatory states' contribution features. Two directions communication brain depression are discussed, serving as potential modulator. Therapeutic implications were discussed well, drawing insights from interventional studies effects probiotics bacterial composition symptoms. Ultimately, will attempt provide complete valuable future therapeutic interventions MDD.

Язык: Английский

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The Effects of Dietary Advanced Glycation End-Products on Neurocognitive and Mental Disorders

Nutrients, Год журнала: 2022, Номер 14(12), С. 2421 - 2421

Опубликована: Июнь 10, 2022

Advanced glycation end products (AGEs) are glycated proteins or lipids formed endogenously in the human body consumed through diet. Ultra-processed foods and some culinary techniques, such as dry cooking methods, represent main sources drivers of dietary AGEs. Tissue accumulation AGEs has been associated with cellular aging implicated various age-related diseases, including type-2 diabetes cardiovascular disease. The current review summarizes literature examining associations between neurocognitive mental health disorders. Studies indicate that elevated circulating cross-sectionally poorer cognitive function longitudinally increase risk developing dementia. Additionally, preliminary studies show higher skin AGE may be disorders, particularly depression schizophrenia. Potential mechanisms underpinning effects include oxidative stress neuroinflammation, which both key pathogenetic underlying neurodegeneration Decreasing intake improve neurological disorder outcomes. However, more sophisticated prospective analytical approaches required to verify directionality extent a mediator linking unhealthy patterns

Язык: Английский

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An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes

JAMA Psychiatry, Год журнала: 2022, Номер 79(7), С. 667 - 667

Опубликована: Май 4, 2022

Certain psychiatric and immune-related disorders are reciprocal risk factors. However, the nature of these associations is unclear.

Язык: 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, Год журнала: 2023, Номер 113, С. 166 - 175

Опубликована: Июль 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.

Язык: Английский

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Childhood maltreatment influences adult brain structure through its effects on immune, metabolic, and psychosocial factors

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(16)

Опубликована: Апрель 9, 2024

Childhood maltreatment (CM) leads to a lifelong susceptibility mental ill-health which might be reflected by its effects on adult brain structure, perhaps indirectly mediated metabolic, immune, and psychosocial systems. Indexing these systemic factors via body mass index (BMI), C-reactive protein (CRP), rates of trauma (AT), respectively, we tested three hypotheses: (H1) CM has direct or indirect trauma, BMI, CRP; (H2) CRP are all independently related structure; (H3) childhood structure in parallel CRP, AT. Using path analysis data from

Язык: Английский

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Genetic evidence for causal effects of immune dysfunction in psychiatric disorders: where are we?

Translational Psychiatry, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 26, 2024

Abstract The question of whether immune dysfunction contributes to risk psychiatric disorders has long been a subject interest. To assert this hypothesis plethora correlative evidence accumulated from the past decades; however, variety technical and practical obstacles impeded on cause-effect interpretation these data. With advent large-scale omics technology advanced statistical models, particularly Mendelian randomization, new studies testing old are accruing. Here we synthesize findings genomics genetic causal inference role in major reconcile data with pre-omics findings. By reconciling evidences, aim identify key gaps propose directions for future field.

Язык: Английский

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Major Depressive Disorder: Existing Hypotheses about Pathophysiological Mechanisms and New Genetic Findings

Genes, Год журнала: 2022, Номер 13(4), С. 646 - 646

Опубликована: Апрель 6, 2022

Major depressive disorder (MDD) is a common mental generally characterized by symptoms associated with mood, pleasure and effectiveness in daily life activities. MDD ranked as major contributor to worldwide disability. The complex pathogenesis of not yet understood, this cause failure develop new therapies recurrence. Here we summarize the literature on existing hypotheses about pathophysiological mechanisms MDD. We describe different approaches undertaken understand molecular mechanism using genetic data. Hundreds loci have now been identified large genome-wide association studies (GWAS). these how they provided information biological processes, cell types, tissues druggable targets that are enriched for risk genes. detail our understanding correlations causal relationships between many psychiatric non-psychiatric disorders traits. highlight challenges studies, including complexity genetics diverse populations need study rare variants gene-environment interactions.

Язык: Английский

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The human physiology of well-being: A systematic review on the association between neurotransmitters, hormones, inflammatory markers, the microbiome and well-being

Neuroscience & Biobehavioral Reviews, Год журнала: 2022, Номер 139, С. 104733 - 104733

Опубликована: Июнь 11, 2022

To understand the pathways through which well-being contributes to health, we performed a systematic review according Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines on association between physiological markers in four categories, neurotransmitters, hormones, inflammatory markers, microbiome. We identified 91 studies. Neurotransmitter studies (knumber of studies=9) reported only possible positive serotonin well-being. For hormone (k = 48), lower momentary cortisol level was related higher (meta-analytic r −0.06), steeper diurnal slope levels. Inflammatory marker 36) negative or non-significant relations with well-being, meta-analytic estimates respectively −0.07 −0.05 C-reactive protein interleukin-6. Microbiome 4) inconsistent associations different bacteria abundance The results indicate but small roles serotonin, cortisol, explaining differences limited other microbiome require further research. Future directions complete picture factors underlying are proposed.

Язык: Английский

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