ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

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

Published: March 20, 2020

Abstract This review summarizes the last decade of work by ENIGMA ( E nhancing N euro I maging G enetics through M eta A nalysis) Consortium, a global alliance over 1400 scientists across 43 countries, studying human brain in health and disease. Building on large-scale genetic studies that discovered first robustly replicated loci associated with metrics, has diversified into 50 working groups (WGs), pooling worldwide data expertise to answer fundamental questions neuroscience, psychiatry, neurology, genetics. Most WGs focus specific psychiatric neurological conditions, other study normal variation due sex gender differences, or development aging; still develop methodological pipelines tools facilitate harmonized analyses “big data” (i.e., epigenetic data, multimodal MRI, electroencephalography data). These international efforts have yielded largest neuroimaging date schizophrenia, bipolar disorder, major depressive post-traumatic stress substance use disorders, obsessive-compulsive attention-deficit/hyperactivity autism spectrum epilepsy, 22q11.2 deletion syndrome. More recent formed anxiety suicidal thoughts behavior, sleep insomnia, eating irritability, injury, antisocial personality conduct dissociative identity disorder. Here, we summarize ENIGMA’s activities ongoing projects, describe successes challenges encountered along way. We highlight advantages collaborative coordinated for testing reproducibility robustness findings, offering opportunity identify systems involved clinical syndromes diverse samples genetic, environmental, demographic, cognitive, psychosocial factors.

Language: Английский

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Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples

American Journal of Psychiatry, Journal Year: 2019, Volume and Issue: 176(7), P. 531 - 542

Published: April 24, 2019

Objective: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related ADHD using large-scale studies. Methods: Cortical thickness surface area (based on the Desikan–Killiany atlas) were compared between case subjects (N=2,246) control (N=1,934) for children, adolescents, separately ENIGMA-ADHD, a consortium 36 centers. To assess familial effects measures, subjects, unaffected siblings, NeuroIMAGE study (N=506) compared. Associations scale from Child Behavior Checklist measures determined pediatric population sample (Generation-R, N=2,707). Results: In ENIGMA-ADHD sample, lower values found ADHD, mainly frontal, cingulate, temporal regions; largest significant effect was total (Cohen’s d=−0.21). Fusiform gyrus pole also ADHD. Neither nor differences adolescent or adult groups. Familial seen several regions. an overlapping set regions, area, but not thickness, associated problems Generation-R sample. Conclusions: Subtle widespread adolescents confirming involvement frontal cortex highlighting deserving further attention. Notably, behave like endophenotypes families linked symptoms population, extending evidence that behaves as continuous trait population. Future longitudinal should clarify individual lifespan trajectories lead nonsignificant findings groups despite presence diagnosis.

Language: Английский

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A large-scale genome-wide association study meta-analysis of cannabis use disorder

The Lancet Psychiatry, Journal Year: 2020, Volume and Issue: 7(12), P. 1032 - 1045

Published: Oct. 20, 2020

BackgroundVariation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) is associated with negative outcomes, including increased risk of psychopathology. The aim the study was conduct large genome-wide association (GWAS) identify novel variants disorder.MethodsTo this GWAS meta-analysis associations loci, we used samples from Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, deCODE (20 916 case samples, 363 116 control total), contrasting cases controls. To examine overlap between 22 traits interest (chosen because previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised chronotype] disorder), linkage disequilibrium score regression calculate correlations.FindingsWe identified two significant loci: chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) 8 (near CHRNA2 EPHX2, SNP rs4732724; OR 0·89, 0·86–0·93, p=6·46 10−9). Cannabis were genetically correlated (rg 0·50, p=1·50 10−21), but they showed significantly different 12 tested, suggesting at least partially underpinnings disorder. positively other psychopathology, ADHD, major depression, schizophrenia.InterpretationThese findings support theory that shared there distinction disorder.FundingNational Institute Mental Health; National on Alcohol Abuse Alcoholism; Drug Abuse; Center for Personalized Medicine Centre Integrative Sequencing; European Commission, Horizon 2020; Child Health Human Development; Research Council New Zealand; Aging; Wellcome Trust Case Control Consortium; UK Innovation Medical (UKRI MRC); Brain & Behavior Foundation; Deafness Other Communication Disorders; Services Administration (SAMHSA); Biomedical Imaging Bioengineering; (NHMRC) Australia; Tobacco-Related Disease Program University California; Families Borderline Personality Disorder (Beth Rob Elliott) 2018 NARSAD Young Investigator Grant; Foundation (Cure Kids); Canterbury Zealand Lottery Grants Board; Otago; Carney Pharmacogenomics; James Hume Bequest Fund; Institutes Health: Genes, Environment Initiative; Cancer Institute; William T Grant Australian Council; Virginia Tobacco Settlement VISN 1 4 Illness Research, Education, Clinical Centers US Department Veterans Affairs; 5th Framework Programme (FP-5) GenomEUtwin Project; Lundbeck NIH-funded Shared Instrumentation S10RR025141; Translational Sciences Award grants; Neurological Stroke; Heart, Lung, Blood General Sciences.

Language: Английский

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Polysubstance use in the U.S. opioid crisis

Molecular Psychiatry, Journal Year: 2020, Volume and Issue: 26(1), P. 41 - 50

Published: Nov. 13, 2020

Abstract Interventions to address the U.S. opioid crisis primarily target use, misuse, and addiction, but because includes multiple substances, specificity of interventions may limit their ability broader problem polysubstance use. Overlap opioids with other substances ranges from shifts among used across lifespan simultaneous co-use that span similar disparate pharmacological categories. Evidence suggests nonmedical users quite commonly use drugs, this contributes increasing morbidity mortality. Reasons for adding include enhancement high (additive or synergistic reward), compensation undesired effects one drug by taking another, negative internal states, a common predisposition is related all substance consumption. But consumption itself have unique effects. To achieve maximum benefit, addressing overlap needed spectrum prevention treatment interventions, overdose reversal, public health surveillance, research. By patterns reasons people mix research be enhanced.

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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Psychopathy

Nature Reviews Disease Primers, Journal Year: 2021, Volume and Issue: 7(1)

Published: July 8, 2021

Language: Английский

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Educational attainment, structural brain reserve and Alzheimer’s disease: a Mendelian randomization analysis

Brain, Journal Year: 2022, Volume and Issue: 146(5), P. 2059 - 2074

Published: Oct. 31, 2022

Abstract Higher educational attainment is observationally associated with lower risk of Alzheimer’s disease. However, the biological mechanisms underpinning this association remain unclear. The protective effect education on disease may be mediated via increased brain reserve. We used two-sample Mendelian randomization to explore putative causal relationships between attainment, structural reserve as proxied by MRI phenotypes and Summary statistics were obtained from genome-wide studies (n = 1 131 881), late-onset (35 274 cases, 59 163 controls) 15 measures grey or white matter macro- micro-structure derived diffusion (nmax 33 211). conducted univariable analyses investigate bidirectional associations (i) disease; (ii) imaging-derived phenotypes; (iii) Multivariable was assess whether structure risk. Genetically inversely (odds ratio per standard deviation increase in genetically predicted years schooling 0.70, 95% confidence interval 0.60, 0.80). There positive four cortical metrics (standard units change imaging phenotype one schooling): surface area 0.30 (95% 0.20, 0.40); volume 0.29 0.37); intrinsic curvature 0.18 0.11, 0.25); local gyrification index 0.21 0.31)]; inverse intracellular fraction [−0.09 −0.15, −0.03)] hyperintensities [−0.14 −0.23, −0.05)]. levels area, positively [standard respective phenotype: 0.13 0.10, 0.16); 0.15 0.19) 0.12 0.04, 0.19)]. found no evidence did not attenuate after adjusting for multivariable analyses. Our results provide support a risk, well potential micro-structure. we find that these markers affect other included present study, alternative mechanisms.

Language: Английский

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Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders

Molecular Psychiatry, Journal Year: 2020, Volume and Issue: 26(9), P. 4839 - 4852

Published: May 28, 2020

Abstract Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between and structure using structural MRI ( n = 6420) genetic data 3907) from ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical subcortical abnormalities in both mass-univariate multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations lower temporo-frontal thickness (maximum Cohen´s d (left fusiform gyrus) −0.33). observed regional distribution effect size reductions revealed considerable similarities corresponding patterns previously published studies neuropsychiatric disorders. A higher polygenic risk score correlated occipital surface area. In addition, a significant age-by-obesity interaction on emerged driven by older participants. Our findings suggest neurobiological under physiological pathological conditions.

Language: Английский

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What we learn about bipolar disorder from large‐scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group

Human Brain Mapping, Journal Year: 2020, Volume and Issue: 43(1), P. 56 - 82

Published: July 29, 2020

Abstract MRI‐derived brain measures offer a link between genes, the environment and behavior have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD underpowered, leading to varied results uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed 2012 empower discoveries, generate consensus findings inform future hypothesis‐driven BD. Through this effort, over 150 researchers from 20 countries 55 institutions pool data resources produce largest ever conducted. ENIGMA applies standardized processing analysis techniques large‐scale meta‐ mega‐analyses multimodal MRI improve replicability relating variation clinical genetic data. Initial reveal widespread patterns lower cortical thickness, subcortical volume disrupted white matter integrity associated with Findings also include mapping alterations common medications like lithium, symptom risk profiles provided further insights into pathophysiological mechanisms Here we discuss key working group, its ongoing projects directions for large‐scale, collaborative mental illness.

Language: Английский

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The neurobiology of drug addiction: cross-species insights into the dysfunction and recovery of the prefrontal cortex

Neuropsychopharmacology, Journal Year: 2021, Volume and Issue: 47(1), P. 276 - 291

Published: Aug. 18, 2021

Language: Английский

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