Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes

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

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

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

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

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)

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

First published: 29 July 2020MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.Christopher R. K. Ching .... Bernhard T. Baune ... et al

Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study

Article Open Access Published: 27 July 2020 Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study Johan H. Thygesen, Amelia Presman, […]Elvira Bramon Molecular Psychiatry (2020)Cite this article 561 Accesses 10 Altmetric Metricsdetails Abstract The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, <1% MAF) as well as known schizophrenia-associated CNVs in patients with psychotic disorders, their unaffected relatives and controls (N = 3428) from the Psychosis Endophenotypes International Consortium (PEIC). The carriers of specific schizophrenia-associated CNVs showed poorer performance than non-carriers in immediate (P = 0.0036) and delayed (P = 0.0115) verbal recall. We found suggestive evidence that carriers of schizophrenia-associated CNVs had poorer block design performance (P = 0.0307). We do not find any association between CNV burden and cognition. Our findings show that the known high-risk CNVs are not only associated with schizophrenia and other neurodevelopmental disorders, but are also a contributing factor to impairment in cognitive domains such as memory and perceptual reasoning, and act as intermediate biomarkers of disease risk

Famine food of vegetal origin consumed in the Netherlands during World War II

Background: Periods of extreme food shortages during war force people to eat food that they normally do not consider edible. The last time that countries in Western Europe experienced severe scarcities was during World War II. The so-called Dutch famine or Hunger Winter (1944-1945) made at least 25,000 victims. The Dutch government took action by opening soup kitchens and providing information on wild plants and other famine food sources in "wartime cookbooks." The Dutch wartime diet has never been examined from an ethnobotanical perspective. Methods: We interviewed 78 elderly Dutch citizens to verify what they remembered of the consumption of vegetal and fungal famine food during World War II by them and their close surroundings. We asked whether they experienced any adverse effects from consuming famine food plants and how they knew they were edible. We identified plant species mentioned during interviews by their local Dutch names and illustrated field guides and floras. We hypothesized that people living in rural areas consumed more wild species than urban people. A Welch t test was performed to verify whether the number of wild and cultivated species differed between urban and rural citizens. Results: A total number of 38 emergency food species (14 cultivated and 21 wild plants, three wild fungi) were mentioned during interviews. Sugar beets, tulip bulbs, and potato peels were most frequently consumed. Regularly eaten wild species were common nettle, blackberry, and beechnuts. Almost one third of our interviewees explicitly described to have experienced extreme hunger during the war. People from rural areas listed significantly more wild species than urban people. The number of cultivated species consumed by both groups was similar. Negative effects were limited to sore throats and stomachache from the consumption of sugar beets and tulip bulbs. Knowledge on the edibility of famine food was obtained largely by oral transmission; few people remembered the written recipes in wartime cookbooks. Conclusion: This research shows that 71years after the Second World War, knowledge on famine food species, once crucial for people's survival, is still present in the Dutch society. The information on famine food sources supplied by several institutions was not distributed widely. For the necessary revival of famine food knowledge during the 1940s, people needed to consult a small group of elders. Presumed toxicity was a major reason given by our participants to explain why they did not collect wild plants or mushrooms during the war

Incident acute coronary syndromes in chronic dialysis patients in the United States11The opinions are solely those of the authors and do not represent an endorsement by the Department of Defense or the National Institutes of Health. This is a U.S. Government work. There are no restrictions on its use.

Incident acute coronary syndromes in chronic dialysis patients in the United States.BackgroundPatients on dialysis have a disproportionately high rate of cardiovascular disease (CVD). However, the incidence and risk factors for incident acute coronary syndromes (ACS) have not been previously assessed in dialysis patients.MethodsWe analyzed the United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Study (DMMS) Wave II in a historical cohort study of ACS. Data from 3374 patients who started dialysis in 1996 with valid follow-up times were available for analysis, censored at the time of renal transplantation and followed until March 2000. Cox regression analysis was used to model factors associated with time to first hospitalization for ACS (ICD9 code 410.x or 411.x) adjusted for comorbidities, demographic factors, baseline laboratory values, blood pressures and cholesterol levels, type of vascular access, dialysis adequacy, and cardioprotective medications (angiotensin-converting enzyme inhibitors, calcium channel blockers, HMG-CoA reductase inhibitors (statins), beta blockers, and aspirin). Follow-up was 2.19 ± 1.14 years.ResultsThe incidence of ACS was 29/1000 person-years. Factors associated with ACS were older age, the extreme high and low ranges of serum cholesterol level, history of coronary heart disease (CHD), male gender, and diabetes. No cardioprotective medications including statins had a significant association with ACS in this study. However, medications known to reduce mortality after ACS were used in less than 50% of patients with known CHD at the start of the study, and statins were used in less than 10% of patients with CHD.ConclusionsDialysis patients had similar risk factors for ACS compared to the general population. Cardioprotective medications were not associated with a significant benefit, possibly due to their striking underutilization in this at-risk population