Network-Based Spreading of Gray Matter Changes Across Different Stages of Psychosis

JAMA Psychiatry, Год журнала: 2023, Номер 80(12), С. 1246 - 1246

Опубликована: Сен. 20, 2023

Psychotic illness is associated with anatomically distributed gray matter reductions that can worsen progression, but the mechanisms underlying specific spatial patterning of these changes unknown.

Язык: Английский

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Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 24, 2025

Abstract Schizophrenia spectrum disorders (SSD) involve disturbances in the integration of perception, emotion and cognition. The corticolimbic system is an interacting set cortical subcortical brain regions critically involved this process. Understanding how neural circuitry molecular mechanisms within may contribute to development not only positive symptoms but also negative cognitive deficits SSD has been a recent focus intense research, as latter are adequately treated by current antipsychotic medications more strongly associated with poorer functioning long-term outcomes. This review synthesises developments examining dysfunction pathophysiology SSD, on neuroimaging advances related novel methodologies that enable data across different scales. We then integrate these findings inform identification therapeutic preventive targets for symptomatology. A range pharmacological interventions have shown initial promise correcting improving negative, treatment-resistant symptoms. discuss challenges opportunities still limited translation research into clinical practice. argue our knowledge role can be improved combining multiple modalities examine hypotheses spatial temporal scales, experimental utilising large-scale consortia advance biomarker identification. Translation practice will aided consideration optimal intervention timings, biomarker-led patient stratification, selective medications.

Язык: Английский

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Neuroimaging Biomarkers for Drug Discovery and Development in Schizophrenia

Biological Psychiatry, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Schizophrenia is a chronic mental illness that affects up to 1% of the population. While efficacious therapies are available for positive symptoms, effective treatment cognitive and negative symptoms remains an unmet need after decades research. New developments in field neuroimaging accelerating our knowledge gain regarding underlying pathophysiology schizophrenia psychosis spectrum disorders, inspiring new targets drug development. However, no validated qualified biomarkers currently support development therapeutics. This review summarizes current use technology clinical psychotic disorders. As exemplified by programs target NMDA receptor hypofunction, results play critical role discovery establishing engagement dose selection. Furthermore, pharmacological may provide response allow early decision making proof-of-concept studies leverage challenge models healthy volunteers. That said, while predictive starting be evaluated patient populations, they continue limited role. Novel approaches data acquisition analysis aid establishment at individual level future. Nevertheless, various gaps addressed establish them as "fit purpose"

Язык: Английский

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Decoding Schizophrenia: How AI-Enhanced fMRI Unlocks New Pathways for Precision Psychiatry

Brain Sciences, Год журнала: 2024, Номер 14(12), С. 1196 - 1196

Опубликована: Ноя. 27, 2024

Schizophrenia, a highly complex psychiatric disorder, presents significant challenges in diagnosis and treatment due to its multifaceted neurobiological underpinnings. Recent advancements functional magnetic resonance imaging (fMRI) artificial intelligence (AI) have revolutionized the understanding management of this condition. This manuscript explores how integration these technologies has unveiled key insights into schizophrenia’s structural neural anomalies. fMRI research highlights disruptions crucial brain regions like prefrontal cortex hippocampus, alongside impaired connectivity within networks such as default mode network (DMN). These alterations correlate with cognitive deficits emotional dysregulation characteristic schizophrenia. AI techniques, including machine learning (ML) deep (DL), enhanced detection analysis patterns, surpassing traditional methods precision. Algorithms support vector machines (SVMs) Vision Transformers (ViTs) proven particularly effective identifying biomarkers aiding early diagnosis. Despite advancements, variability methodologies disorder’s heterogeneity persist, necessitating large-scale, collaborative studies for clinical translation. Moreover, ethical considerations surrounding data integrity, algorithmic transparency, patient individuality must guide AI’s psychiatry. Looking ahead, AI-augmented holds promise tailoring personalized interventions, addressing unique dysfunctions, improving therapeutic outcomes individuals convergence neuroimaging computational innovation heralds transformative era precision

Язык: Английский

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Associations between epilepsy-related polygenic risk and brain morphology in childhood

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 17, 2025

A bstract Temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is associated a complex genetic architecture, but the translation from risk factors to brain vulnerability remains unclear. Here, we examined associations between epilepsy-related polygenic scores for HS (PRS-HS) and structure in large sample of neurotypical children, correlated these signatures case-control findings multicentric cohorts patients TLE-HS. Imaging-genetic analyses revealed PRS-related cortical thinning temporo-parietal fronto-central regions, strongly anchored distinct functional structural network epicentres. Compared disease-related effects derived cohorts, correlates PRS-HS mirrored atrophy epicentre patterns By identifying potential pathway disease mechanisms, our provide new insights into underpinnings alterations TLE-HS highlight imaging-genetic biomarkers early stratification personalized interventions.

Язык: Английский

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Mendelian randomization analyses uncover causal relationships between brain structural connectome and risk of psychiatric disorders

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

Abstract Growing evidence suggests abnormalities of brain structural connectome in psychiatric disorders, but the causal relationships remain underexplored. We conducted bidirectional two-sample Mendelian randomization (MR) analyses to investigate links between 206 white-matter connectivity phenotypes (n = 26,333, UK Biobank) and 13 major disorders 14,307 1,222,882). Forward MR identified effects genetically predicted five on six with associations being significant or suggestive. For instance, left-hemisphere frontoparietal control network right-hemisphere default mode was significantly negatively associated autism spectrum disorder risk, while increased hippocampus linked decreased anorexia nervosa cannabis use risk. Reverse revealed suggestively risk two four different phenotypes. example, susceptibility found be visual pallidum. These findings offer new insights into etiology highlight potential biomarkers for early detection prevention at level.

Язык: Английский

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Connectome architecture for gray matter atrophy and surgical outcomes in temporal lobe epilepsy

Epilepsia, Год журнала: 2025, Номер unknown

Опубликована: Март 8, 2025

Temporal lobe epilepsy (TLE) has been recognized as a network disorder with widespread gray matter atrophy. However, the role of connectome architecture in shaping morphological alterations and identifying atrophy epicenters remains unclear. Furthermore, individualized modeling their potential clinical applications have not well established. This study aims to explore how correlates normal architecture, identify epicenters, employ approach evaluate impact different epicenter patterns on surgical outcomes patients TLE. utilized anatomic MRI data from 126 refractory TLE who underwent anterior temporal lobectomy 60 healthy controls (HCs), along normative functional structural data, investigate relationship between volume (GMV) changes or connectivity. Two models were employed epicenters: data-driven evaluating nodal neighbor rankings, diffusion model (NDM) simulating spread pathology seed regions. K-means clustering was applied patient-tailored uncover distinct subtypes. Our findings indicate that pattern is constrained primarily by connectivity rather than Using connectome, we pinpointed hippocampus adjacent temporo-limbic regions key epicenters. The revealed significant variability distribution, allowing us categorize them into two Notably, subtype 2, localized ipsilateral pole medial lobe, exhibited significantly higher seizure-free rates compared 1, whose situated frontocentral These highlight central TLE-related changes. Individualized may enhance decisions improve prognostic stratification management.

Язык: Английский

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Common and unique white matter fractional anisotropy patterns in patients with schizophrenia with medication-resistant auditory verbal hallucinations: a retrospective tract-based spatial statistics study

Schizophrenia, Год журнала: 2025, Номер 11(1)

Опубликована: Март 20, 2025

Auditory verbal hallucinations (AVHs) are experienced by the majority of patients with schizophrenia and often resistant to treatment antipsychotic agents. White matter (WM) tract abnormalities associated AVH efficacy. Using a retrospective design, 115 AVHs, 48 medication-resistant AVHs 67 treatable 70 healthy controls (HCs) were selected from database our cohort study for 5-year follow-up assessment. WM integrity was measured using tract-based spatial statistics (TBSS) at baseline after 5 years agent treatment. The fractional anisotropy (FA) value used demonstrate alterations in HCs. Our data demonstrated that showed significantly greater FA values corpus callosum (CC) fasciculus corticospinal post-treatment compared HCs, but difference CC no longer significant group exhibited superior longitudinal Compared HC group, visual radiation In groups, common noted, as observed group. At same time, distinct fasciculus, which may contribute whereas both AVHs. decrease posterior observation baseline. summary, treatment-resistant have tract.

Язык: Английский

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Dynamic modular dysregulation in multilayer networks underlies cognitive and clinical deficits in first-episode schizophrenia

Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Association of Cortical Atrophy Patterns With Clinical Phenotypes and Histopathological Findings in Patients With Rasmussen Syndrome

Neurology, Год журнала: 2025, Номер 104(10)

Опубликована: Май 2, 2025

Automated MRI analyses have identified variable patterns of cortical atrophy in Rasmussen syndrome. In this study, we aim to identify imaging phenotypes syndrome, clinically characterize these phenotypes, and validate imaging-based approach through histopathologic analysis. For retrospective case-control individuals with syndrome diagnosed according the European Consensus Statement at least one 3D T1-weighted scan (<20 years after onset) were from University Hospital Bonn (1995-2023). Healthy controls selected databases Bonn, Charité Berlin, Human Connectome Project. Disease epicenters, describing brain regions highly connected regions, mapped individually using network-based modeling. Subtypes k-means clustering. Neuropsychological test results neuropathologic biopsies ascertained, correlations between subtype-specific maps normative (enhancing neuro genetics meta analysis [ENIGMA] neuromaps toolbox) used profiles epicenter susceptibility. The study incorporated 54 (median age MRI: 18 years, range 2-61, 65% female) 270 healthy 26.5 3-61, 49% female). Four distinct subtypes (temporoparietal, centrotemporal, frontal, bilateral). Individuals centrotemporal subtype younger onset 5.5 years) than temporoparietal 11.5 p = 0.02) frontal 6 subtypes. Most severe neuropsychological impairment was observed for subtypes, occurred preferentially hubs (r -0.28, 0.006; r -0.30, 0.02). susceptibility associated higher thickness -0.57, 0.005), lower myelin content 0.47, 0.02), cerebral blood flow 0.42, 0.03), volume 0.57, 0.006), oxygen metabolism 0.01). Brain showing strong inflammation taken likely whereas weaker came less epicenters (p 0.04). Using as a model, mapping individual disease evidence. With further validation, could potentially be guide biopsy site selection, inform treatment decisions, improve outcome prognoses.

Язык: Английский

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