Volumetric Associations Between Amygdala, Nucleus Accumbens, and Socially Anxious Tendencies in Healthy Women

Commentary: Gray Matter Structural Alterations in Social Anxiety Disorder: A Voxel-Based Meta-Analysis

“…We don't agree with this statement: Potts and colleagues indicate that there is “no statistically significant difference between social phobia patients and normal control subjects”; the “age-related reduction in putamen volumes in patients with social phobia that was greater than that seen in controls” (25) cannot be equated with the group difference reported in the present meta-analysis. Furthermore, it should be noted that recent work on putamen volume in SAD, which was probably not yet available at the time the meta-analysis was performed, implies changes in the opposite direction, namely increased GMV in the dorsal striatum in SAD (14, 16); these findings are supported by a positive relationship between social anxiety and GMV in the putamen in healthy women (26) and a positive correlation between the concept “intolerance of uncertainty” and putamen volume (27).…”

Subcortical brain volumes, cortical thickness and cortical surface area in families genetically enriched for social anxiety disorder – A multiplex multigenerational neuroimaging study

“…This result is in line with findings of a mega-analysis on 174 patients with SAD and 213 healthy control participants, showing larger GM volume in the dorsal striatum, including the pallidum and the putamen; in this study, the increase in GM was positively related to the level of self-reported social anxiety [ 60 ]. Recently, the positive relationship between social anxiety and volume of the dorsal striatum was replicated in a sample of healthy young women with a broad range of social anxiety levels [ 67 ], while a study on the structural correlates of ‘intolerance of uncertainty’, a psychological construct that is related to anxiety, indicated a positive relationship between intolerance of uncertainty and bilateral striatal volume, in particular the putamen and pallidum [ 176 ]. Interestingly, these findings and the increase in pallidum volume reported in the present work fit within the recent focus on the striatum as being an important structure in the anxiety circuitry of the brain [ 177 ] and are potentially reflective of the role of the pallidum and putamen in processing emotions and reward [ 178 ], as both processes have been shown to be associated with altered brain activation levels in these regions in patients with SAD [ 170 , [179] , [180] , [181] ].…”

“…Although it should be noted that the findings reported in these studies are heterogeneous (see Table 1 and review by Brühl and colleagues [ 65 ]), and have small effect sizes [ 60 ], a machine learning study was able to discriminate SAD-patients from healthy controls based on GM changes over the whole brain [ 66 ]. Furthermore, higher levels of social anxiety in healthy women were related to increased volumes of the amygdala, nucleus accumbens, and striatal regions like the putamen and caudate nucleus [ 67 ], while structural brain alterations have also been reported in anxious children and adolescents [ [68] , [69] , [70] , [71] , [72] ]. In addition, changes in brain structure have been reported in participants who were classified as being ‘behaviorally inhibited’ [ [73] , [74] , [75] , [76] , [77] , [78] , [79] ], which refers to the innate, temperamental trait associated with an increased vulnerability for developing SAD [ 80 ].…”

“…The structural brain phenotypes were established using the FreeSurfer software package (version 5.3) and we employed a hypothesis-driven region-of-interest (ROI) approach based on the results of previous studies. With respect to the subcortical volumes, we focused on the putamen and pallidum , based on the findings of a recent mega-analysis on SAD reporting increased GM related to SAD in these regions [ 60 ], which were recently replicated [ 67 ]. In addition, we investigated the association between social anxiety and volumes of the amygdala and hippocampus , given the fact that volumetric changes in these areas in SAD have been reported [ 52 , 53 , 61 ], although it should be noted that other studies were not able to replicate these effects (see for example [ 54 , 60 ] and Table 1 ).…”

Serotonin and early life stress interact to shape brain architecture and anxious avoidant behavior – a TPH2 imaging genetics approach

“…While reduced gray matter volumes in limbicprefrontal regions have been consistently reported in psychiatric disorders characterized by exaggerated anxiety and deficient emotion regulation (van Tol et al 2010;Bora et al 2012;Ahmed-Leitao et al 2016), associations between emotional functioning and limbic-prefrontal volumes in healthy subjects remain less clear, such that elevated anxiety has been associated with both, volumetric increases as well as decreases in this circuitry (e.g. Modi et al 2019; however, see Günther et al 2018). On the other hand, a growing number of studies consistently reported positive associations between aversive learning and volumetric indices in this circuit (Hartley et al 2011;Cacciaglia et al 2015;Winkelmann et al 2016) and trauma exposure in adulthood has been associated with volumetric increases of the amygdala and concomitantly facilitated aversive learning (Cacciaglia et al 2017).…”