Chromatin accessibility during human first-trimester neurodevelopment DOI Creative Commons
Camiel C.A. Mannens, Lijuan Hu, Peter Lönnerberg

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Abstract The human brain develops through a tightly organized cascade of patterning events, induced by transcription factor expression and changes in chromatin accessibility. Although gene across the developing has been described at single-cell resolution 1 , similar atlases accessibility have primarily focused on forebrain 2–4 . Here we describe paired entire during first trimester (6–13 weeks after conception). We defined 135 clusters used multiomic measurements to link candidate cis -regulatory elements expression. number accessible regions increased both with age along neuronal differentiation. Using convolutional neural network, identified putative functional factor-binding sites enhancers characterizing subtypes. applied this model linked ESRRB elucidate its activation mechanism Purkinje cell lineage. Finally, linking disease-associated single nucleotide polymorphisms elements, validated pathogenic mechanisms several diseases midbrain-derived GABAergic neurons as being most vulnerable major depressive disorder-related mutations. Our findings provide more detailed view key regulatory underlying emergence types comprehensive reference for future studies related neurodevelopment.

Language: Английский

An overview of clustering methods with guidelines for application in mental health research DOI Creative Commons
Caroline X. Gao, Dominic E. Dwyer, Ye Zhu

et al.

Psychiatry Research, Journal Year: 2023, Volume and Issue: 327, P. 115265 - 115265

Published: May 27, 2023

Cluster analyzes have been widely used in mental health research to decompose inter-individual heterogeneity by identifying more homogeneous subgroups of individuals. However, despite advances new algorithms and increasing popularity, there is little guidance on model choice, analytical framework reporting requirements. In this paper, we aimed address gap introducing the philosophy, design, advantages/disadvantages implementation major that are particularly relevant research. Extensions basic models, such as kernel methods, deep learning, semi-supervised clustering, clustering ensembles subsequently introduced. How choose common issues well methods for pre-clustering data processing, evaluation validation then discussed. Importantly, also provide general workflow To facilitate different algorithms, information R functions libraries.

Language: Английский

Citations

55
A shared neural basis underlying psychiatric comorbidity DOI Creative Commons
Chao Xie, Shitong Xiang, Chun Shen

et al.

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(5), P. 1232 - 1242

Published: April 24, 2023

Abstract Recent studies proposed a general psychopathology factor underlying common comorbidities among psychiatric disorders. However, its neurobiological mechanisms and generalizability remain elusive. In this study, we used large longitudinal neuroimaging cohort from adolescence to young adulthood (IMAGEN) define neuropsychopathological (NP) across externalizing internalizing symptoms using multitask connectomes. We demonstrate that NP might represent unified, genetically determined, delayed development of the prefrontal cortex further leads poor executive function. also show be reproducible in multiple developmental periods, preadolescence early adulthood, generalizable resting-state connectome clinical samples (the ADHD-200 Sample STRATIFY & ESTRA Project). conclusion, identify neural basis mental health disorders, bridging multidimensional evidence behavioral, genetic substrates. These findings may help develop new therapeutic interventions for comorbidities.

Language: Английский

Citations

52
Massively parallel reporter assay investigates shared genetic variants of eight psychiatric disorders DOI
Sool Lee, Jessica C. McAfee, Jiseok Lee

et al.

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

Published: Jan. 1, 2025

Language: Английский

Citations

2
Reviewing the genetics of heterogeneity in depression: operationalizations, manifestations and etiologies DOI Creative Commons
Na Cai, Karmel W. Choi, Eiko I. Fried

et al.

Human Molecular Genetics, Journal Year: 2020, Volume and Issue: 29(R1), P. R10 - R18

Published: June 9, 2020

Abstract With progress in genome-wide association studies of depression, from identifying zero hits ~16 000 individuals 2013 to 223 more than a million 2020, understanding the genetic architecture this debilitating condition no longer appears be an impossible task. The pressing question now is whether recently discovered variants describe etiology single disease entity. There are myriad ways measure and operationalize depression severity, major depressive disorder as defined Diagnostic Statistical Manual Mental Disorders-5 can manifest 10 based on symptom profiles alone. Variations developmental timing, comorbidity environmental contexts across samples further add heterogeneity. big data increasingly enabling genomic discovery psychiatry, it timely ever explicitly disentangle contributions what likely ‘depressions’ rather depression. Here, we introduce three sources heterogeneity: operationalization, manifestation etiology. We review recent efforts identify subtypes using clinical data-driven approaches, examine differences contexts, argue that heterogeneity operationalizations considerable source inconsistency. Finally, offer recommendations considerations for field going forward.

Language: Английский

Citations

134
Neurodevelopmental pathways in bipolar disorder DOI
Stefan Kloiber, Joshua D. Rosenblat, M. Ishrat Husain

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2020, Volume and Issue: 112, P. 213 - 226

Published: Feb. 5, 2020

Language: Английский

Citations

97
Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure DOI Creative Commons
Martine Hoogman, Daan van Rooij, Marieke Klein

et al.

Human Brain Mapping, Journal Year: 2020, Volume and Issue: 43(1), P. 37 - 55

Published: May 18, 2020

Abstract Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) autism spectrum (ASD) over the past decades. Two of main shortcomings neuroimaging literature these disorders are small sample sizes employed heterogeneity methods used. In 2013 2014, ENIGMA‐ADHD ENIGMA‐ASD working groups were respectively, founded a common goal address limitations. Here, we provide narrative review thus far completed still ongoing projects groups. Due an implicitly hierarchical psychiatric diagnostic classification system, fields ADHD ASD have developed largely isolation, despite considerable overlap occurrence disorders. The collaboration between ‐ASD seeks bring efforts two closer together. outcomes case–control studies subcortical cortical structures showed that volumes similarly affected ADHD, albeit effect sizes. Cortical analyses identified unique differences each disorder, but also two, specifically thickness. Ongoing work is examining alternative research questions, such as laterality, prediction status, anatomical heterogeneity. brief, great strides made toward fulfilling aims ENIGMA collaborations, while new ideas follow‐up continue include more imaging modalities (diffusion MRI resting‐state functional MRI), collaborations other large databases, samples dual diagnoses.

Language: Английский

Citations

96
Pervasively Thinner Neocortex as a Transdiagnostic Feature of General Psychopathology DOI
Adrienne L. Romer, Maxwell L. Elliott, Annchen R. Knodt

et al.

American Journal of Psychiatry, Journal Year: 2020, Volume and Issue: 178(2), P. 174 - 182

Published: June 30, 2020

Objective: Neuroimaging research has revealed that structural brain alterations are common across broad diagnostic families of disorders rather than specific to a single psychiatric disorder. Such overlap in the correlates mental mirrors already well-documented phenotypic comorbidity symptoms and diagnoses, which can be indexed by general psychopathology or p factor. The authors hypothesized if drives convergence disorders, then 1) there should few associations unique any one family 2) with factor those for broader families. Methods: Analyses were conducted on MRI data collected from 861 members population-representative Dunedin Multidisciplinary Health Development Study at age 45. Results: high scores three (externalizing, internalizing, thought disorder) exhibited highly overlapping patterns reduced global widely distributed parcel-wise neocortical thickness. thickness nearly identical associated Conclusions: A pattern pervasively appears all forms may represent transdiagnostic feature psychopathology. As been documented regard underlying not exhibit specificity, continued pursuit such limit progress toward more effective strategies etiological understanding, prevention, intervention.

Language: Английский

Citations

79
Coexpression network architecture reveals the brain-wide and multiregional basis of disease susceptibility DOI
Christopher Hartl, Gokul Ramaswami,

William G. Pembroke

et al.

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(9), P. 1313 - 1323

Published: July 22, 2021

Language: Английский

Citations

75
The iPSYCH2015 Case-Cohort sample: updated directions for unravelling genetic and environmental architectures of severe mental disorders DOI Creative Commons
Jonas Bybjerg‐Grauholm, Carsten Bøcker Pedersen, Marie Bækvad‐Hansen

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: Dec. 2, 2020

Abstract The Lundbeck Foundation Integrative Psychiatric Research (iPSYCH) consortium has almost doubled its Danish population-based Case–Cohort sample (iPSYCH2012). newly updated cohort, named iPSYCH2015, expands the study base with 56,233 samples, to a combined total of 141,265 samples. cohort is nested within population born between 1981 and 2008 Case-Cohort design including 50,615 controls. We added more cases existing phenotypes identified with, schizophrenia (N new =4,131/N =8,113), autism =8,056 / N =24,975), attention-deficit/hyperactivity disorder =10,026/N =29,668) affective =13,999/N =40,482) which subset bipolar (N- =1,656/N =3,819). also two additional focus phenotypes, spectrum (N=16,008) post-partum (N=3,421). In total, expanded iPSYCH2015 consists 93,608 unique individuals in case groups For expansion, DNA was extracted amplified from dried blood spots samples stored Neonatal Screening Biobank genotyped using Illumina Global Array. retrieval rate 95%, genotyping success 92% (97% retrieved). follow-up period by three years, data such as longitudinal information on health, prescribed medicine, social socioeconomic information.

Language: Английский

Citations

74
Genome-wide landscape of RNA-binding protein target site dysregulation reveals a major impact on psychiatric disorder risk DOI
Christopher Y. Park, Jian Zhou, Aaron K. Wong

et al.

Nature Genetics, Journal Year: 2021, Volume and Issue: 53(2), P. 166 - 173

Published: Jan. 18, 2021

Language: Английский

Citations

67