Atypical brain maturation in psychosis is associated with long-term cognitive decline and symptom progression

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

ABSTRACT Background Clinical progression during psychosis has been closely associated with grey matter abnormalities resulting from atypical brain development. However, the complex interplay between psychopathology and neurodiversity challenges identifying neuroanatomical features that anticipate long-term cognitive symptomatic decline. Here, we collected MRI, cognitive, data 165 healthy controls 357 drug-naïve or minimally medicated FEP individuals were followed up 1,3,5 10 years after first episode. (1778 MRI scans assessments in total). Using normative modelling, derived subject-specific centile scores for cortical volume to investigate deviations their relationship deterioration. The association maps further characterized by examining cytoarchitectural neurobiological attributes using atlases. Aims To longitudinal exploring outcomes, as well underpinnings. Results centiles showed a widespread reduction at treatment initiation, analysis showing an increase time, indicating convergence toward normal maturation trajectories. Interestingly, this effect was reduced highly individuals. Additionally, found impairments experienced early stages correlated mitigated time. Positive symptomatology negatively regional centiles, higher benefited most treatment. Cytoarchitectural analyses revealed related FEP, function, specific molecular features, such serotonin receptor densities heteromodal areas. Conclusions Collectively, these findings underscore potential use of centile-based modelling better understanding how development contributes clinical neurodevelopmental conditions.

Language: Английский

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Disrupted Hierarchical Functional Brain Organization in Affective and Psychotic Disorders: Insights from Functional Brain Gradients

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Patients with psychosis and depression show widespread alterations in brain resting-state functional connectivity (rs-FC), affecting both sensory higher-order regions. In this study, we investigate disruptions the hierarchical organization of networks patients psychotic affective disorders. We derived gradients, low dimensional representations rs-FC that capture cortical hierarchy, a large patient sample including clinical high-risk for (CHR-P) patients, recent-onset (ROP) (ROD) healthy controls (HC). examined regional alterations, network-level differentiation their relationship to symptoms. addition, linked case-control differences receptor expression maps explore underlying neurobiological mechanisms. All groups exhibited visual-to-sensorimotor gradient, while only ROP showed association-to-sensory gradient. CHR-P lower values ventral attention network. Additionally, combined higher somatomotor network, reduced gradient range altered between-network dispersion. ROD within-network dispersion attentional range. Correlational analysis revealed weak associations measures functioning, visual dysfunctions cognition. Furthermore maps, suggesting involvement neurotransmitter systems these disruptions. Our findings reveal transdiagnostic disease-specific organization. These indicate deficits integration across psychiatric diseases, highlighting role disease processes.

Language: Английский

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Cortical differences across psychiatric disorders and associated common and rare genetic variants

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Genetic studies have identified common and rare variants increasing the risk for neurodevelopmental psychiatric disorders (NPDs). These also been shown to influence structure of cerebral cortex. However, it is unknown whether cortical differences associated with genetic are linked they confer NPDs. To answer this question, we analyzed thickness (CT) surface area (SA) NPDs, in ∼33000 individuals from general population clinical cohorts, as well ENIGMA summary statistics 8 Rare NPDs were preferentially total SA, while mean CT. Larger effects on CT, but not observed NPD medicated subgroups. At regional level, sensorimotor areas, showed higher association areas. We show that schizophrenia- bipolar-disorder- SNPs positive negative effect sizes SA suggesting their aggregated cancel out additive polygenic models. Overall, CT do relate those across individual may be critical non-genetic factors, such medication lived experience disorder.

Language: Английский

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Longitudinal trajectories of resilient psychosocial functioning link to ongoing cortical myelination and functional reorganization during adolescence

Published: Jan. 25, 2024

Adolescence is a period of dynamic brain remodeling and susceptibility to psychiatric risk factors, mediated by the protracted consolidation association cortices. Here, we investigated whether intra-individual trajectories psychosocial functioning relative environmental stressor exposure - including adverse life events, dysfunctional family settings, socio-economic status are tied myeloarchitectural maturation down-stream effects on intrinsic function. To this end, employed longitudinal myelin-sensitive Magnetic Transfer (MT) resting-state imaging in NSPN cohort (aged 14-26y). Developing towards more resilient was linked increasing myelination anterolateral prefrontal cortex, which exhibited stabilized functional connectivity. Studying depth-specific intracortical MT profiles cortex-wide synchronization maturation, further observed wide-spread re-configuration cortices paralleled attenuated reorganization with increasingly outcomes. Together, resilient/susceptible showed considerable change reflected multi-modal cortical refinement processes at local system-level.

Language: Английский

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Molecular signatures of cortical expansion in the human foetal brain

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

Published: Nov. 8, 2024

Abstract The third trimester of human gestation is characterised by rapid increases in brain volume and cortical surface area. Recent studies have revealed a remarkable molecular diversity across the prenatal cortex but little known about how this translates into differential rates expansion observed during gestation. We present digital resource, μBrain, to facilitate knowledge translation between anatomical descriptions brain. Using we evaluate signatures preferentially-expanded regions, quantified utero using magnetic resonance imaging. Our findings demonstrate spatial coupling areal differences timing neurogenesis neocortical identify genes, upregulated from mid-gestation, that are highly expressed rapidly expanding neocortex implicated genetic disorders with cognitive sequelae. μBrain atlas provides tool comprehensively map early development domains, model systems resolution scales.

Language: Английский

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