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

Abstract

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, attentiondeficit/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.

Large-scale Phenomic and Genomic Analysis of Brain Asymmetrical Skew

“…In addition, we found evidence for genetic correlation between horizontal brain skew and ASD, which may be consistent with the subtle but widespread alterations of regional cortical thickness asymmetry in ASD reported in a recent, large-scale study [69]. The automated measurement of global brain asymmetry that we have employed here will be feasible for large-scale meta-analysis-based studies of brain disorders, such as those carried out within consortia such as ENIGMA (http://enigma.ini.usc.edu/) [92,93].…”

Visual QC Protocol for FreeSurfer Cortical Parcellations from Anatomical MRI

“…Aiming to deliver a quick method to QC FreeSurfer outputs from multiple large datasets, the Enhancing Neuro ImaGing through Meta-Analysis (ENIGMA) consortium (Thompson et al 2020), developed an useful visual rating protocol for FS QC (denoted by ENQC) based on a set of batch processing scripts, visualizations embedded in html and manual ratings collected in a spreadsheet. ENQC is a practical approach to greatly expedite an otherwise tedious process by selecting four volumetric slices for inspection (see Figure 1, Panel A for an example slice).…”

Smaller limbic structures are associated with greater immunosuppression in over 1000 HIV-infected adults across five continents: Findings from the ENIGMA-HIV Working Group

“…Effects in limbic structures, as seen here, have been detected in a wide-range of clinical conditions studied in similar large-scale international efforts from the ENIGMA consortium. 26 Serious mental illnesses, such as depression or substance-use disorder, have a high prevalence in HIV+ individuals and may increase the risk of HIV transmission. 27 As we assessed individuals with and without these comorbidities, limbic associations detected in this study are not likely simply a reflection of such comorbid neuropsychiatric conditions.…”