On the other hand, subcategories of AD are often highly co-morbid with each other as well as with other emotional (internalizing) disorders ( 3). Recent overarching conceptualizations based on DSM-5 propose that AD can be placed along a fear– anxiety continuum ranging from excessive fear-based responses to imminent specific threats in fear-related anxiety disorders (FAD, including social anxiety disorders, SAD specific phobias, SP panic disorders, PD and agoraphobia, AG) to a rather diffuse anxious apprehension of events in anxiety-related anxiety disorders such as generalized anxiety disorder (GAD) ( 2). AD comprise a group of heterogeneous disorders that share features of excessive fear and anxiety ( 1). Targeting the disorder-specific neurostructural signatures could improve therapeutic efficacy.Īnxiety disorders (AD) constitute the most prevalent diagnostic group of mental disorder and cause considerable suffering, disability and economic cost. Unique clinical features characterizing anxiety-, fear-related and depressive disorders are reflected by disorder-specific neuroanatomical abnormalities. No shared structural abnormalities were found. While FAD showed less robust alterations in lingual gyrus ( p < 0.0025, uncorrected), this group presented intact frontal integrity. Both GAD and MDD (46 studies, 2,575 patients) exhibited decreased prefrontal volumes compared to controls and FAD. GAD (9 studies, 226 patients) showed disorder-specific decreased volumes in left insula ( z=-2.98, p FWE-corrected<0.05) and lateral/medial prefrontal cortex (z=-2.10, p FWE-corrected<0.05,) as well as increased right putamen volume ( z=1.86, p FWE-corrected<0.05) relative to FAD (10 SAD, 11 PD, 2 SP studies, 918 patients). Neurostructural abnormalities were assessed within each disorder group followed by quantitative comparison and conjunction analyses using Seed-based d-Mapping (SDM-PSI). The PubMed, Web of Knowledge, and Scopus databases were searched for case-control voxel-based morphometric studies through December, 2020 in GAD, fear-related anxiety disorders (FAD, i.e., social anxiety disorders, SAD specific phobias, SP panic disorders, PD and agoraphobia, AG) and major depressive disorder (MDD). Given that a neurobiological evaluation is lacking, we conducted a comparative neuroimaging meta-analysis of gray matter volume alterations to determine common and disorder-specific brain structural signatures in these disorders. While the DSM-5 nosology conceptualizes anxiety and fear-related disorders as an entity, dimensional psychopathology models suggest that generalized anxiety disorders (GAD) and major depression originate from an overarching “anxious-misery” factor whereas fear-related disorders originate from the “fear” factor. Internalizing disorders encompass anxiety, fear and depressive disorders.
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