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

The stressed and depressed brain

Penninx, B.W.J.H. [Promotor]Veltman, D.J. [Promotor]Schmaal, L. [Copromotor

Response inhibition and interference control in obsessive-compulsive spectrum disorders

Over the past twenty years, motor response inhibition and interference control have received considerable scientific effort and attention, due to their important role in behavior and the development of neuropsychiatric disorders. Results of neuroimaging studies indicate that motor response inhibition and interference control are dependent on cortical-striatal-thalamic-cortical (CSTC) circuits. Structural and functional abnormalities within the CSTC circuits have been reported for many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD) and related disorders, such as attention deficit hyperactivity disorder (ADHD), Tourette’s syndrome (TS) and trichotillomania. These disorders also share impairments in motor response inhibition and interference control, which may underlie some of their behavioral and cognitive symptoms. Results of task-related neuroimaging studies on inhibitory functions in these disorders show that impaired task performance is related to altered recruitment of the CSTC circuits. Previous research has shown that inhibitory performance is dependent upon dopamine, noradrenaline and serotonin signaling, neurotransmitters that have been implicated in the pathophysiology of these disorders. In this review we discuss the common and disorder-specific pathophysiological mechanisms of inhibition-related dysfunction in OCD and related disorders

Concurrent Validity and Reliability of Suicide Risk Assessment Instruments: A Meta-Analysis of 20 Instruments Across 27 International Cohorts

Objective: A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behavior. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. Method: Here, we examine this issue through two approaches: (a) an extensive literature search on the reliability and concurrent validity of the most commonly used instruments and (b) by pooling data (N ∼ 6,000 participants) from cohorts from the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Major Depressive Disorder and ENIGMA–Suicidal Thoughts and Behaviour working groups, to assess the concurrent validity of instruments currently used for assessing suicidal thoughts or behavior. Results: We observed moderate-to-high correlations between measures, consistent with the wide range (κ range: 0.15–0.97; r range: 0.21–0.94) reported in the literature. Two common multi-item instruments, the Columbia Suicide Severity Rating Scale and the Beck Scale for Suicidal Ideation were highly correlated with each other (r = 0.83). Sensitivity analyses identified sources of heterogeneity such as the time frame of the instrument and whether it relies on self-report or a clinical interview. Finally, construct-specific analyses suggest that suicide ideation items from common psychiatric questionnaires are most concordant with the suicide ideation construct of multi-item instruments. Conclusions: Our findings suggest that multi-item instruments provide valuable information on different aspects of suicidal thoughts or behavior but share a modest core factor with single suicidal ideation items. Retrospective, multisite collaborations including distinct instruments should be feasible provided they harmonize across instruments or focus on specific constructs of suicidality. © 2023 American Psychological Associatio

Effect of brain-derived neurotrophic factor genotype, gene expression and serum protein levels and childhood maltreatment on regional brain volume

Stress-related psychiatric disorders across the life spa

Volume of subcortical brain regions in social anxiety disorder: Mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE < 0.001; right: d = -0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood

Classification of suicidal thoughts and behaviour in children: results from penalised logistic regression analyses in the Adolescent Brain Cognitive Development study

BACKGROUND\nAIMS\nMETHOD\nRESULTS\nCONCLUSIONS\nDespite efforts to predict suicide risk in children, the ability to reliably identify who will engage in suicide thoughts or behaviours has remained unsuccessful.\nWe apply a novel machine-learning approach and examine whether children with suicide thoughts or behaviours could be differentiated from children without suicide thoughts or behaviours based on a combination of traditional (sociodemographic, physical health, social-environmental, clinical psychiatric) risk factors, but also more novel risk factors (cognitive, neuroimaging and genetic characteristics).\nThe study included 5885 unrelated children (50% female, 67% White, 9-11 years of age) from the Adolescent Brain Cognitive Development (ABCD) study. We performed penalised logistic regression analysis to distinguish between: (a) children with current or past suicide thoughts or behaviours; (b) children with a mental illness but no suicide thoughts or behaviours (clinical controls); and (c) healthy control children (no suicide thoughts or behaviours and no history of mental illness). The model was subsequently validated with data from seven independent sites involved in the ABCD study (n = 1712).\nOur results showed that we were able to distinguish the suicide thoughts or behaviours group from healthy controls (area under the receiver operating characteristics curve: 0.80 child-report, 0.81 for parent-report) and clinical controls (0.71 child-report and 0.76-0.77 parent-report). However, we could not distinguish children with suicidal ideation from those who attempted suicide (AUROC: 0.55-0.58 child-report; 0.49-0.53 parent-report). The factors that differentiated the suicide thoughts or behaviours group from the clinical control group included family conflict, prodromal psychosis symptoms, impulsivity, depression severity and history of mental health treatment.\nThis work highlights that mostly clinical psychiatric factors were able to distinguish children with suicide thoughts or behaviours from children without suicide thoughts or behaviours. Future research is needed to determine if these variables prospectively predict subsequent suicidal behaviour.Stress and Psychopatholog