Homotopic functional connectivity disruptions in schizophrenia and their associated gene expression

NeuroImage, Journal Year: 2024, Volume and Issue: 289, P. 120551 - 120551

Published: Feb. 20, 2024

It has been revealed that abnormal voxel-mirrored homotopic connectivity (VMHC) is present in patients with schizophrenia, yet there are inconsistencies the relevant findings. Moreover, little known about their association brain gene expression profiles. In this study, transcription-neuroimaging analyses using data from Allen Human Brain Atlas and case-control VMHC differences both discovery (meta-analysis, including 9 studies a total of 386 357 controls) replication (separate group-level comparisons within two datasets, 258 287 phases were performed to identify genes associated alterations. Enrichment conducted characterize biological functions specific identified genes, Neurosynth decoding analysis was examine correlation between cognitive-related processes alterations schizophrenia. phases, schizophrenia exhibited consistent changes compared controls, which correlated series processes; meta-regression illness duration negatively abnormalities cerebellum postcentral/precentral gyrus. The patterns stably 1287 enriched for fundamental like regulation cell communication, nervous system development, communication. addition, these overexpressed astrocytes immune cells, extensive cortical regions wide developmental time windows. findings may contribute more comprehensive understanding molecular mechanisms underlying

Language: Английский

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New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment

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

Published: May 10, 2024

Schizophrenia (SZ) is a complex neuropsychiatric disorder associated with severe cognitive dysfunction. Although research has mainly focused on forebrain abnormalities, emerging results support the involvement of cerebellum in SZ physiopathology, particularly Cognitive Impairment Associated (CIAS). Besides its role motor learning and control, implicated cognition emotion. Recent suggests that structural functional changes are linked to deficits various domains including attention, working memory, decision-making. Moreover, cerebellar dysfunction related altered circuit activities connectivity brain regions processing. This review delves into CIAS. We initially consider major alterations CIAS, addressing impairments neurotransmitter systems, synaptic plasticity, connectivity. then focus recent findings showing several mechanisms also communication impaired. evidence implicates as key component circuits underpinning CIAS physiopathology. Further studies warranted might open new perspectives toward understanding physiopathology effective treatment these disorders.

Language: Английский

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The circadian system: A neglected player in neurodevelopmental disorders

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 60(2), P. 3858 - 3890

Published: May 30, 2024

Abstract Patients with neurodevelopmental disorders, such as autism spectrum disorder, often display abnormal circadian rhythms. The role of the system in these disorders has gained considerable attention over last decades. Yet, it remains largely unknown how disruptions occur and to what extent they contribute disorders' development. In this review, we examine dysregulation observed patients animal models disorders. Second, explore whether rhythm constitute a risk factor for from studies humans model organisms. Lastly, focus on impact psychiatric medications rhythms potential benefits chronotherapy. literature reveals that altered sleep–wake cycles melatonin rhythms/levels heterogeneous manner, organisms used study appear support dysfunction may be an inherent characteristic Furthermore, pre‐clinical clinical evidence indicates disruption at environmental genetic levels behavioural changes Finally, suggest medications, particularly those prescribed attention‐deficit/hyperactivity disorder schizophrenia, can have direct effects chronotherapy leveraged offset some side effects. This review highlights is likely core pathological feature further research required elucidate relationship.

Language: Английский

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Developmental perspectives on the origins of psychotic disorders: The need for a transdiagnostic approach

Development and Psychopathology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 11

Published: Feb. 26, 2024

Research on serious mental disorders, particularly psychosis, has revealed highly variable symptom profiles and developmental trajectories prior to illness-onset. As Dante Cicchetti pointed out decades before the term "transdiagnostic" was widely used, pathways psychopathology emerge in a system involving equifinality multifinality. Like most other psychological psychosis is associated with multiple domains of risk factors, both genetic environmental, there are many transdiagnostic that can lead psychotic syndromes. In this article, we discuss our current understanding heterogeneity etiology its implications for approaches conceptualizing research. We highlight need examining factors at levels increase emphasis as key etiologic subtypes. This will be increasingly feasible now large, longitudinal datasets becoming available researchers have access more sophisticated analytic tools, such machine learning, which identify homogenous subtypes ultimate goal enhancing options treatment preventive intervention.

Language: Английский

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Co-expression of prepulse inhibition and schizophrenia genes in the mouse and human brain

Neuroscience Applied, Journal Year: 2024, Volume and Issue: 3, P. 104075 - 104075

Published: Jan. 1, 2024

Schizophrenia is a complex psychiatric disorder with genetic and phenotypic heterogeneity. Accumulating rare genome-wide association study (GWAS) common risk variant information has yet to yield robust mechanistic insight. Leveraging large-scale gene deletion mouse phenomic data thus potential functionally interrogate prioritize human disease genes. To this end, we applied cross-species network-based approach parse an extensive set (188 genes) associated disrupted prepulse inhibition (PPI), endophenotype. Integrating PPI genes high-resolution brain transcriptomic data, identified functional coherent co-expression modules through hierarchical clustering weighted network analysis (WGCNA). In two modules, converged based on telencephalic patterning. The neuronal were highly expressed in cingulate cortex- hippocampus; implicated synaptic function neurotransmission overlapped the greatest proportion of variants. Concordant neuroanatomical patterning revealed novel core Schizophrenia-relevant consistent Omnigenic hypothesis traits. Among other discussed, developmental post-synaptic scaffold TANC2 (Tetratricopeptide repeat, ankyrin repeat coiled-coil containing 2) emerged from both networks as driver altering PPI. Aspects comorbidity heterogeneity are also explored. Overall, provides framework galvanizes value preclinical genetics existing candidate druggable targets.

Language: Английский

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Dysfunction of the NMDA Receptor in the Pathophysiology of Schizophrenia and/or the Pathomechanisms of Treatment-Resistant Schizophrenia

Biomolecules, Journal Year: 2024, Volume and Issue: 14(9), P. 1128 - 1128

Published: Sept. 6, 2024

For several decades, the dopamine hypothesis contributed to discovery of numerous typical and atypical antipsychotics was sole for pathophysiology schizophrenia. However, neither nor antipsychotics, other than clozapine, have been effective in addressing negative symptoms cognitive impairments, which are indices prognostic disability outcomes Following development therapeutic targets expanded beyond blockade D2 serotonin 5-HT2A receptors explore partial agonism receptor modulation new targets, such as D3, 5-HT1A, 5-HT7, metabotropic glutamate receptors. Despite these efforts, date, psychiatry has not successfully developed with antipsychotic properties proven be superior those clozapine. The hypothesis, another regarding pathophysiology/pathomechanism schizophrenia, proposed based on clinical findings that N-methyl-D-aspartate (NMDAR) antagonists, phencyclidine ketamine, induce schizophrenia-like psychotic episodes. Large-scale genome-wide association studies (GWASs) revealed approximately 30% risk genes schizophrenia (the total number over one hundred) encode proteins associated glutamatergic transmission. These supported validation inspired by NMDAR antagonists. Additionally, genetic suggest is possibly a syndrome complicated pathomechanisms affected multiple biological vulnerabilities. most extensively investigated hypothesis. Studies possibility functional abnormalities play important roles no derived from yet approved treatment or treatment-resistant Considering increasing evidence supporting potential pro-cognitive effects agents lack sufficient medications treat impairments previous setbacks cannot preclude research into novel modulators. Given this background, emphasize importance dysfunction pathomechanism and/or review introduces transmission NMDAR.

Language: Английский

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Somatic mosaicism in schizophrenia brains reveals prenatal mutational processes

Science, Journal Year: 2024, Volume and Issue: 386(6718), P. 217 - 224

Published: Oct. 10, 2024

Germline mutations modulate the risk of developing schizophrenia (SCZ). Much less is known about role mosaic somatic in context SCZ. Deep (239×) whole-genome sequencing (WGS) brain neurons from 61 SCZ cases and 25 controls postmortem identified occurring during prenatal neurogenesis. showed increased variants open chromatin, with CpG transversions (CpG>GpG) T>G at transcription factor binding sites (TFBSs) overlapping a result not seen controls. Some these alter gene expression, including genes involved neurodevelopment. Although mutational processes can reflect difference factors indirectly disease, developmental TFBSs could also potentially contribute to

Language: Английский

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What is the neurobiology of schizophrenia?

CNS Spectrums, Journal Year: 2024, Volume and Issue: 30(1)

Published: Oct. 30, 2024

Abstract Schizophrenia spectrum disorders are brain diseases that developmental dementias (dementia praecox). Their pathology begins in utero with psychosis most commonly becoming evident adolescence and early adulthood. It is estimated they afflict the U.S. population at a prevalence rate of approximately 0.8%. Genetic studies indicate these about 80% determined by genes 20% environmental risk factors. Inheritance polygenic some 270 gene loci having been identified as contributing to for schizophrenia. Interestingly, many polymorphisms involved formation maturation. The genetic epigenetic risks give rise which neuroblasts migrate abnormally, assume abnormal locations orientations, vulnerable excessive neuronal synaptic loss, resulting overt psychotic illness. illness trajectory schizophrenia then one loss mass related number active exacerbations duration untreated In this context, molecules such dopamine, glutamate, serotonin play critical roles respect positive, negative, cognitive domains Acutely, antipsychotics ameliorate illness, especially positive signs symptoms. long-term effects antipsychotic medications have debated; however, bulk imaging data suggest slow but do not reverse Long-acting injectable (LAI) appear superior regard. Clozapine remains “gold standard” managing treatment-resistant

Language: Английский

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Concerns over investigating the effect of air pollutants on disease risk utilizing Mendelian randomization

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 487, P. 137251 - 137251

Published: Jan. 16, 2025

Language: Английский

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Comprehensive Insights into Schizophrenia Causes Treatments and Prevention

Theoretical and Natural Science, Journal Year: 2025, Volume and Issue: 89(1), P. 57 - 63

Published: Jan. 15, 2025

With the significant improvement in material life recent years, people now focus more on status and well-being of spiritual life. The discovery diagnosis schizophrenia, a severe mental disorder, thus came into attention. Current studies have centered causes associations, which are often combined with symptoms schizophrenia. As consequence, scientists developed various treatments. Some scholars suggested control prevention methods, but many them remained uninformative unimplemented account real factors. study combines most available information gives general overview schizophrenia as an influential disorder. mechanism certain genes or alleles inherited from ancestors unpleasant grown-up environments that can affect risk getting is analyzed. Treatment approaches referring to pharmacologic, psychotherapeutic, other commonly mentioned ones included. techniques correlate health literacy, governance participation parental environment advocated. meaning this review lies proposing summarized thesis for investigating present methods indicating inadequacies. In consideration shortcomings medical care public system, it expected future research inquire innovative treatments strategies.

Language: Английский

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