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

Abstract

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).

A Voxel-Based Morphometric Study of Gray Matter in Specific Phobia

“…Additionally, our results showed smaller OFC and insula volumes in individuals with phobias compared with non-fearful controls, which is consistent with previous studies [ 19 ]. An increased GMV of the OFC has been associated with a high capacity for emotional self-regulation [ 43 ].…”

“…Morphometric analysis revealed that a cluster of superior/medial frontal areas and ACC were diminished in phobic participants. In the same vein, decreased volumes in the lateral/medial PFC cortex have been found in GAD and panic disorder [ 19 , 26 ]. However, an increased volume in the left PFC, OFC, and ACC has been found when individuals with phobia were compared with non-fearful controls [ 30 ].…”

“…Thus, alterations in brain structures associated with dysfunctions in the processing and regulation of emotion, as well as fear conditioning processes, can be explored. In this regard, contradictory results have been found for both larger and smaller GMV in the areas traditionally linked to ADs [ 17 , 18 , 19 , 20 ]. Smaller subcortical and larger cortical GMVs have been associated with social anxiety disorder (SAD) compared with healthy controls [ 21 , 22 ].…”

“…A reverse pattern of larger subcortical and smaller cortical GMVs has also been reported [ 24 ]. Specifically, an increased right putamen volume, and decreased lateral/medial PFC and left insula volumes have been found in generalized anxiety disorder (GAD) compared with fear-related AD [ 19 ]. Furthermore, smaller volume and altered activity patterns of the ventromedial PFC have been observed in patients with ADs [ 25 ].…”

“…The smaller volume of subcortical areas, however, has been related to greater sensitivity to emotional stimuli and sustained emotional dysregulation that may lead to the progressive impairment of these areas [ 22 ]. Conversely, a smaller volume of cortical areas has been interpreted as deficits in top-down control [ 19 ], and a larger GMV of subcortical areas, such as the putamen, could facilitate the saliency of stimuli and be associated with fear conditioning [ 27 ].…”