The genetic architecture of the human cerebral cortex

Science, Journal Year: 2020, Volume and Issue: 367(6484)

Published: March 19, 2020

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify variants affect structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed surface area and average thickness whole 34 regions with functional specializations. identified 199 significant found enrichment for influencing total within regulatory elements are active during prenatal development, supporting radial unit hypothesis. Loci regional cluster near genes in Wnt signaling pathways, which progenitor expansion areal identity. Variation structure genetically correlated function, Parkinson's disease, insomnia, depression, neuroticism, attention deficit hyperactivity disorder.

Language: Английский

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Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(11), P. 1569 - 1581

Published: Oct. 27, 2022

Abstract Neurotransmitter receptors support the propagation of signals in human brain. How receptor systems are situated within macro-scale neuroanatomy and how they shape emergent function remain poorly understood, there exists no comprehensive atlas receptors. Here we collate positron emission tomography data from more than 1,200 healthy individuals to construct a whole-brain three-dimensional normative 19 transporters across nine different neurotransmitter systems. We found that profiles align with structural connectivity mediate function, including neurophysiological oscillatory dynamics resting-state hemodynamic functional connectivity. Using Neurosynth cognitive atlas, uncovered topographic gradient overlapping distributions separates extrinsic intrinsic psychological processes. Finally, both expected novel associations between cortical abnormality patterns 13 disorders. replicated all findings an independently collected autoradiography dataset. This work demonstrates chemoarchitecture shapes brain structure providing new direction for studying multi-scale organization.

Language: Английский

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Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects

American Journal of Psychiatry, Journal Year: 2018, Volume and Issue: 176(2), P. 119 - 128

Published: Oct. 19, 2018

Although lower brain volume has been routinely observed in individuals with substance dependence compared nondependent control subjects, the regions exhibiting have not consistent across studies. In addition, it is clear whether a common set of are involved regardless used or some effects specific. Resolution these issues may contribute to identification clinically relevant imaging biomarkers. Using pooled data from 14 countries, authors sought identify general and substance-specific associations between regional volumes.Brain structure was examined mega-analysis previously published 23 laboratories, including 3,240 individuals, 2,140 whom had on one five substances: alcohol, nicotine, cocaine, methamphetamine, cannabis. Subcortical cortical thickness defined by FreeSurfer were subjects when all sampled categories combined, as well separately, while controlling for age, sex, site, total intracranial volume. Because extensive alcohol dependence, secondary contrast also performed substances except alcohol. An optimized split-half strategy assess reliability findings.Lower many dependence. The greatest associated use disorder. A affected related general, substance, included insula medial orbitofrontal cortex. Furthermore, support vector machine multivariate classification volumes successfully classified nicotine relative subjects.The results indicate that range different shares neural substrate differential patterns could serve useful biomarkers nicotine.

Language: Английский

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Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3–90 years

Human Brain Mapping, Journal Year: 2021, Volume and Issue: 43(1), P. 431 - 451

Published: Feb. 17, 2021

Delineating the association of age and cortical thickness in healthy individuals is critical given with cognition behavior. Previous research has shown that robust estimates between brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 aged 3-90 years Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes thickness. We fractional polynomial (FP) regression quantify thickness, computed normalized growth centiles using parametric Lambda, Mu, Sigma method. Interindividual variability was estimated meta-analysis one-way analysis variance. For most regions, their highest value observed childhood. Age showed a negative association; slope steeper up third decade life more gradual thereafter; notable exceptions this general pattern were entorhinal, temporopolar, anterior cingulate cortices. largest temporal frontal regions across lifespan. its FP combinations explained 59% variance These results may form basis further investigation on normative deviation significance for behavioral cognitive outcomes.

Language: Английский

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Linking RDoC and HiTOP: A new interface for advancing psychiatric nosology and neuroscience

Clinical Psychology Review, Journal Year: 2021, Volume and Issue: 86, P. 102025 - 102025

Published: March 24, 2021

Language: Английский

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Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

JAMA Psychiatry, Journal Year: 2020, Volume and Issue: 78(1), P. 47 - 47

Published: Aug. 26, 2020

Importance

Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these is not well understood.

Objective

To determine neurobiologic correlates of between cases and controls 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum (ASD), bipolar (BD), major depressive (MDD), obsessive-compulsive (OCD), schizophrenia.

Design, Setting, Participants

Profiles were generated using T1-weighted magnetic resonance images. Similarity interregional profiles cell-specific gene expression those the investigated each disorder. Next, principal component analysis was used to reveal a shared profile difference Analysis for coexpression, clustering, enrichment genes associated with disorders conducted. Data conducted June December 2019. included 145 cohorts drawn from ENIGMA consortium. numbers as follows: ADHD: 1814 1602; ASD: 1748 1770; BD: 1547 3405; MDD: 2658 3572; OCD: 2266 2007; schizophrenia: 2688 3244.

Main Outcomes Measures

Interregional controls.

Results

A total 12 721 15 600 controls, ranging ages 2 89 years, this study. specific pyramidal (CA1) cells, astrocytes (except BD), microglia OCD); collectively, gene-expression 3 cell types explain 25% 54% variance thickness. Principal (48% explained); 1 that pyramidal-cell (explaining 56% variation). Coexpression analyses clusters: (1) prenatal cluster enriched involved neurodevelopmental (axon guidance) processes (2) postnatal synaptic activity plasticity-related processes. These clusters all

Conclusions Relevance

In study, multiple implicate common role development functioning cerebral cortex

Language: Английский

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White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA-Epilepsy study

Brain, Journal Year: 2020, Volume and Issue: 143(8), P. 2454 - 2473

Published: June 5, 2020

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging common epilepsy syndromes, including temporal lobe epilepsy, extratemporal and genetic generalized epilepsy. Our goal was rank the most robust matter microstructural differences across within syndromes multicentre sample adult patients. Diffusion-weighted MRI were analysed from 1069 healthy controls 1249 patients: with hippocampal sclerosis (n = 599), normal 275), 182) non-lesional 193). A harmonized protocol using tract-based spatial statistics used derive skeletonized maps fractional anisotropy mean diffusivity for each participant, fibre tracts segmented diffusion atlas. Data correct scanner-specific variations measures batch-effect correction tool (ComBat). Analyses covariance, adjusting age sex, examined between syndrome tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower observed small medium effect sizes, especially corpus callosum, cingulum external capsule. There also less increases diffusivity. Syndrome-specific pronounced patients ipsilateral parahippocampal capsule, smaller effects other tracts. Individuals showed similar pattern greater than contralateral abnormalities, but marked those sclerosis. Patients had reductions corona radiata increased anterior radiata. Earlier seizure onset longer disease duration associated extent We demonstrate major association, commissural, projection fibres study Overall, differing severity syndromes. These further define spectrum yielding more detailed insights into pathological substrates that may explain cognitive psychiatric co-morbidities be guide biomarker studies treatment outcomes and/or research.

Language: Английский

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ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing

Translational Psychiatry, Journal Year: 2020, Volume and Issue: 10(1)

Published: May 29, 2020

Abstract A key objective in the field of translational psychiatry over past few decades has been to identify brain correlates major depressive disorder (MDD). Identifying measurable indicators processes associated with MDD could facilitate detection individuals at risk, and development novel treatments, monitoring treatment effects, predicting who might benefit most from treatments that target specific mechanisms. However, despite intensive neuroimaging research towards this effort, underpowered studies a lack reproducible findings have hindered progress. Here, we discuss work ENIGMA Major Depressive Disorder (MDD) Consortium, which was established address issues poor replication, unreliable results, overestimation effect sizes previous studies. The Consortium currently includes data 45 study cohorts 14 countries across six continents. primary aim is structural functional alterations can be reliably detected replicated worldwide. secondary goal investigate how demographic, genetic, clinical, psychological, environmental factors affect these associations. In review, summarize disease working group date future directions. We also highlight challenges benefits large-scale sharing for mental health research.

Language: Английский

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JuSpace: A tool for spatial correlation analyses of magnetic resonance imaging data with nuclear imaging derived neurotransmitter maps

Human Brain Mapping, Journal Year: 2020, Volume and Issue: 42(3), P. 555 - 566

Published: Oct. 20, 2020

Abstract Recent studies have shown that drug‐induced spatial alteration patterns in resting state functional activity as measured using magnetic resonance imaging (rsfMRI) are associated with the distribution of specific receptor systems targeted by respective compounds. Based on this approach, we introduce a toolbox (JuSpace) allowing for cross‐modal correlation MRI‐based measures nuclear derived estimates covering various neurotransmitter including dopaminergic, serotonergic, noradrenergic, and GABAergic (gamma‐aminobutric acid) neurotransmission. We apply JuSpace to two datasets Parkinson's disease patients (PD) risperidone‐induced changes rsfMRI cerebral blood flow (CBF). Consistently predominant neurodegeneration dopaminergic serotonergic system PD, find significant associations between alterations PD (D2) (5‐HT1b). Risperidone induced CBF were correlated its main targets systems. provides biologically meaningful framework linking neuroimaging underlying information.

Language: Английский

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Psychiatric diagnosis and treatment in the 21st century: paradigm shifts versus incremental integration

World Psychiatry, Journal Year: 2022, Volume and Issue: 21(3), P. 393 - 414

Published: Sept. 8, 2022

Psychiatry has always been characterized by a range of different models and approaches to mental disorder, which have sometimes brought progress in clinical practice, but often also accompanied critique from within without the field. Psychiatric nosology particular focus debate recent decades; successive editions DSM ICD strongly influenced both psychiatric practice research, led assertions that psychiatry is crisis, advocacy for entirely new paradigms diagnosis assessment. When thinking about etiology, many researchers currently refer biopsychosocial model, this approach received significant critique, being considered some observers overly eclectic vague. Despite development evidence-based pharmacotherapies psychotherapies, current evidence points treatment gap research-practice health. In paper, after considering we discuss proposed novel perspectives recently achieved prominence may significantly impact research future: neuroscience personalized pharmacotherapy; statistical nosology, assessment research; deinstitutionalization community health care; scale-up psychotherapy; digital phenotyping therapies; global task-sharing approaches. We consider extent transitions practices reflect hype or hope. Our review indicates each contributes important insights allow hope future, provides only partial view, any promise paradigm shift field not well grounded. conclude there crucial advances that, despite progress, considerable need further improvements intervention; such will likely be specific shifts rather incremental iterative integration.

Language: Английский

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