ENIGMA-anxiety working group: Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Abstract

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.

Keywords: amygdala; anxiety disorders; genetics; limbic system; magnetic resonance imaging; neuroimaging; prefrontal cortex.

FIGURE 1

Overview of neurocircuitry involved in anxiety disorders. This schematic overview illustrates the subcortical (Figure 1a) and cortical (Figure 1b) regions that are part of the FreeSurfer pipeline (RRID:SCR_001847; http://surfer.nmr.mgh.harvard.edu). Regions involved in anxiety are colored based on the work on the neurocircuitry of anxiety disorders (Duval et al., 2015), implicating brain areas involved in sensory processing (occipital cortex, fusiform gyrus, thalamus; green), emotion generating and processing (striatum, amygdala, insula, dorsal anterior cingulate cortex; red) and emotion modulation regions (medial prefrontal cortex, hippocampus, dorsolateral prefrontal cortex, subgenual/rostral anterior cingulate cortex; blue). Note that other models of brain circuitry in anxiety, for example those described by (Brühl et al., ; Kolesar et al., 2019), are more extended and also involve other regions—most notably regions of the parietal cortex. Figure 1a (subcortical) Amy, Amygdala; Cau, Nucleus Caudatus; Hip, Hippocampus; NAcc, Nucleus Accumbens; Pa, Pallidum; Pu, Putamen; Tha, Thalamus. Figure 1b (cortical) CAcc, Caudal Anterior Cingulate Cortex; CMF, Caudal Middle Frontal; Cun, Cuneus; Ent, Entorhinal; FF, Fusiform; INS, Insula; IP, Inferior Parietal; Ist, Isthmus; IT, Inferior Temporal; Ling, Lingual; LOC, Lateral Occipital; LOF, Lateral Orbitofrontal; MOF, Medial Orbitofrontal; MT, Middle Temporal; OPER, Pars Opercularis; ORB, Pars Orbitalis; ParaC, Paracentral; ParaH, Parahippocampal; Pcc, Posterior Cingulate Cortex; PCun, precuneus; Peri, Pericalcarine; PoC; Postcentral; PreC, Precentral; RAcc, Rostral Anterior Cingulate Cortex; RMF, Rostral Middle Frontal; SF, Superior Frontal; SP, Superior Parietal; ST, Superior Temporal; SuM, Supramarginal; TRI, Pars Triangularis; TT, Transverse Temporal

FIGURE 2

Institutes participating in ENIGMA‐Anxiety—world map