Microglia-neuron interactions in schizophrenia

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: March 6, 2024

Multiple lines of evidence implicate increased neuroinflammation mediated by glial cells to play a key role in neurodevelopmental disorders such as schizophrenia. Microglia, which are the primary innate immune brain, crucial for refinement synaptic circuitry during early brain development pruning and regulation plasticity adulthood. Schizophrenia risk factors genetics or environmental influences may further be linked activation microglia, an increase pro-inflammatory cytokine levels inflammasome resulting overall elevated neuroinflammatory state patients. Synaptic loss, one central pathological hallmarks schizophrenia, is believed due excess removal synapses activated primarily affecting glutamatergic neurons. Therefore, it investigate microglia-neuron interactions, has been done multiple studies focusing on post-mortem tissues, imaging, animal models patient iPSC-derived 2D culture systems. In this review, we summarize major findings patients vivo vitro context neuron-microglia interactions schizophrenia secondly discuss potential anti-inflammatory treatments alleviation positive, negative, cognitive symptoms.

Language: Английский

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Immunophenotypes in psychosis: is it a premature inflamm-aging disorder?

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(9), P. 2834 - 2848

Published: March 26, 2024

Immunopsychiatric field has rapidly accumulated evidence demonstrating the involvement of both innate and adaptive immune components in psychotic disorders such as schizophrenia. Nevertheless, researchers are facing dilemmas discrepant findings immunophenotypes outside inside brains patients, discovered by recent meta-analyses. These discrepancies make interpretations interrogations on their roles psychosis remain vague even controversial, regarding whether certain cells more activated or less so, they causal consequential, beneficial harmful for psychosis. Addressing these issues is not at all trivial, either brain an enormously heterogeneous plastic cell population, falling into a vast range lineages subgroups, functioning differently malleably context-dependent manners. This review aims to overview currently known patients with psychosis, provocatively suggest premature "burnout" inflamm-aging initiated since organ development potential primary mechanism behind pathogenesis disorders.

Language: Английский

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Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 118, P. 287 - 299

Published: March 8, 2024

Recent findings link cognitive impairment and inflammatory-immune dysregulation in schizophrenia (SZ) bipolar (BD) spectrum disorders. However, heterogeneity translation between the periphery central (blood-to-brain) mechanisms remains a challenge. Starting with large SZ, BD healthy control cohort (n = 1235), we aimed to i) identify candidate peripheral markers 25) associated domains 9) elucidate heterogenous immune-cognitive patterns, ii) evaluate regulation of using human induced pluripotent stem cell (iPSC)-derived astrocytes neural progenitor cells 10), iii) marker messenger RNA expression leukocytes microarray available data from subsample main 776), RNA-sequencing deconvolution analysis postmortem brain samples 474) CommonMind Consortium (CMC). We identified transdiagnostic subgroups based on covariance (measures speed verbal learning) reflecting inflammatory response (CRP, sTNFR1, YKL-40), innate immune activation (MIF) extracellular matrix remodelling (YKL-40, CatS). Of there was considerable variance secretion YKL-40 iPSC-derived SZ compared HC. Further, provide evidence dysregulated genes encoding related signalling pathways high neuroinflammatory subgroup samples. Our suggest relationship activity impairment, highlight as potential functioning individuals severe mental illness.

Language: Английский

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Electroretinographic dysfunction, insulin resistance, and childhood trauma in early-course psychosis: A case-control exploratory study

Biomarkers in Neuropsychiatry, Journal Year: 2024, Volume and Issue: 10, P. 100088 - 100088

Published: March 13, 2024

Electroretinographic dysfunction is observed in psychosis, with a-wave and b-wave amplitudes potentially serving as biomarkers. Insulin resistance (IR) childhood trauma (CT) have also been associated psychosis-spectrum disorders, particularly schizophrenia. early-course psychosis (EP) lacks exploration. This case-control exploratory study aimed to understand electroretinographic EP its relationship IR CT. The involved healthy controls (n=13) individuals (n=14) included photopic scotopic flash-electroretinography (fERG), blood collection for assessment, the Childhood Trauma Questionnaire (CTQ). Data were analyzed using SPSS v.29.0. Case-control differences across fERG conditions explored repeated-measures ANCOVA (3 flash X 2 groups) adjusted gender age. Sub-analyses Fisher's, Mann-Whitney, partial correlations, logistic linear regressions. Compared controls, participants showed (1) lower amplitudes, specifically left eye under P1 condition, (2) greater odds IR, (3) higher CTQ scores. was a score P2b amplitude. A amplitude when adjusting interacting effect IR. These findings suggest CT are explanatory markers EP. may dysregulate hypothalamic-pituitary-adrenal axis, increasing risk of experiencing later-life psychosis. might be biomarker contributing neurodegeneration cone post-synaptic cells. Further investigations needed.

Language: Английский

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Inflammation is associated with avolition and reduced resting state functional connectivity in corticostriatal reward circuitry in patients with schizophrenia

Neuropsychopharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Language: Английский

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Disturbed Functional Connectivity Between Anterior Default Mode and Sensory Processing Regions Is Linked to Peripheral Inflammatory Markers and Psychopathology in Schizophrenia

Schizophrenia Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: April 23, 2025

Abstract Background and Hypothesis Both elevated inflammatory markers aberrant functional connectivity have been detected in patients with schizophrenia, but there is limited knowledge on the relationship between two phenomena. Some positive symptoms may arise from external misattribution of self-generated actions mediated by decoupling default mode network (DMN) sensory processing regions. Since anterior DMN also exhibits bidirectional interaction immune system, we hypothesized its would be associated as well burden symptomatology. Study Design Resting-state magnetic resonance imaging, diffusion tensor imaging (DTI), clinical laboratory data (serum concentrations interleukin-6 C-reactive protein) were collected within a neuroimaging trial schizophrenia. Neuroimaging assessed applying seed-to-voxel region-of-interest-to-region-of-interest analyses DTI tractography. Associations behavioral studied employing regression analyses. Results For both markers, consistent pattern hypo-connectivity emerged different brain regions involved self-monitoring. The strongest association was for right parietal operculum which not explained structural integrity respective white matter tract. Finally, this connection correlated negative symptoms. Conclusions Our findings reveal mechanistically plausible neurobiological link inflammation psychopathology

Language: Английский

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Deep retinal layer microvasculature alterations in schizophrenia

Biomarkers in Neuropsychiatry, Journal Year: 2024, Volume and Issue: 10, P. 100084 - 100084

Published: Feb. 3, 2024

A subset of individuals with schizophrenia (SZ) are thought to have a microvascular component their illness studies demonstrating alterations in retinal superficial, deep, and choroidal microvasculature networks. However, the direction location these differed across studies. In recent study, we reported that SZ demonstrated lower superficial layer density than healthy control (HC) group. The current study investigated characteristics deep vascular SZ, including examining consistency findings two layers. We included 28 diagnosis or schizoaffective disorder, 37 HCs. Optical coherence tomography angiography (OCTA) data was collected measure perfusion density, skeletonized vessel diameter index, fractal dimension. conducted between-group comparisons examine differences OCTA variables between HC groups. trend analysis determine if reflected linear according age length Spearman correlations were associations density. Individuals significantly bilateral as well left eye Results showed indices decreased duration, older lowest values younger controls highest for all at least one eye. Lower also associated layer. Overall, results suggest present multiple layers they may be useful visual system biomarkers neurovascular changes disorder.

Language: Английский

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White matter microstructural and inflammation-based subgroups in bipolar disorder II depression differentiate in depressive and psychotic symptoms

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 368, P. 493 - 502

Published: Sept. 17, 2024

Language: Английский

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Inflammation-related abnormal dynamic brain activity correlates with cognitive impairment in first-episode, drug-naïve major depressive disorder

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 366, P. 217 - 225

Published: Aug. 27, 2024

Language: Английский

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Longitudinal course of inflammatory-cognitive subgroups across first treatment severe mental illness and healthy controls

Psychological Medicine, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 11

Published: Oct. 2, 2024

Abstract Background While inflammation is associated with cognitive impairment in severe mental illnesses (SMI), there substantial heterogeneity and evidence of transdiagnostic subgroups across schizophrenia (SZ) bipolar (BD) spectrum disorders. There however, limited knowledge about the longitudinal course this relationship. Methods Systemic (C-Reactive Protein, CRP) cognition (nine domains) was measured from baseline to 1 year follow-up first treatment SZ BD ( n = 221), healthy controls (HC, 220). Linear mixed models were used evaluate changes separately CRP domains specific diagnostic status (SZ, BD, HC). Hierarchical clustering applied on entire sample investigate inflammatory-cognitive subgroups. Results no case-control differences or change follow-up. We confirm previous observations at both time-points domain stability/improvement over time regardless status. identified differing demographics clinical severity. Despite improvement cognition, symptoms functioning, higher – lower subgroup (75% SZ; 48% BD; 38% HC) had sustained more symptoms, functioning (SMI only) This comparison a (25% SZ, 52% 62% HC), where SMI participants showed HC level positive course. Conclusions Our findings support heterogenous that are stable time, may benefit targeted interventions.

Language: Английский

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