Pathological fear, anxiety and negative affect exhibit distinct neurostructural signatures: evidence from psychiatric neuroimaging meta-analysis

Internalizing disorders encompass anxiety, fear and depressive disorders, which exhibit overlap at both conceptual and symptom levels. Given that a neurobiological evaluation is lacking, we conducted a Seed-based D-Mapping comparative meta-analysis including coordinates as well as original statistical maps to determine common and disorder-specific gray matter volume alterations in generalized anxiety disorder (GAD), fear-related anxiety disorders (FAD, i.e., social anxiety disorder, specific phobias, panic disorder) and major depressive disorder (MDD). Results showed that GAD exhibited disorder-specific altered volumes relative to FAD including decreased volumes in left insula and lateral/medial prefrontal cortex as well as increased right putamen volume. Both GAD and MDD showed decreased prefrontal volumes compared to controls and FAD. While FAD showed less robust alterations in lingual gyrus compared to controls, this group presented intact frontal integrity. No shared structural abnormalities were found. Our study is the first to provide meta-analytic evidence for distinct neuroanatomical abnormalities underlying the pathophysiology of anxiety-, fear-related and depressive disorders. These findings may have implications for determining promising target regions for disorder-specific neuromodulation interventions (e.g. transcranial magnetic stimulation or neurofeedback).