Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

Groenewold, Nynke A.; Bas-Hoogendam, Janna Marie; Amod, Alyssa R.; Laansma, Max A.; Velzen, Laura S. van; Aghajani, Moji; Hilbert, Kevin; Oh, Hyuntaek; Salas, Ramiro; Jackowski, Andrea Parolin; Pan, Pedro Mário; Salum, Giovanni Abrahão; Blair, James; Blair, Karina S.; Hirsch, Joy; Pantazatos, Spiro P.; Schneier, Franklin R.; Talati, Ardesheer; Roelofs, Karin; Volman, Inge; Blanco‐Hinojo, Laura; Cardoner, Narcı́s; Pujol, Jesús; Beesdo‐Baum, Katja; Ching, Christopher R. K.; Thomopoulos, Sophia I.; Jansen, Andreas; Kircher, Tilo; Krug, Axel; Nenadić, Igor; Stein, Frederike; Dannlowski, Udo; Grotegerd, Dominik; Lemke, Hannah; Meinert, Susanne; Winter, Alexandra; Erb, Michael; Kreifelts, Benjamin; Gong, Qiyong; Lui, Su; Zhu, Fei; Mwangi, Benson; Soares, Jair C.; Wu, Mon Ju; Bayram, Ali; Canli, Mesut; Tükel, Raşit; Westenberg, P. Michiel; Heeren, Alexandre; Cremers, Henk R.; Hofmann, David; Straube, Thomas; Doruyter, Alexander; Löchner, Christine; Peterburs, Jutta; Tol, Marie-José van; Gur, Raquel E.; Kaczkurkin, Antonia N.; Larsen, Bart; Satterthwaite, Theodore D.; Filippi, Courtney; Gold, Andrea L.; Harrewijn, Anita; Zugman, André; Bülow, Robin; Grabe, Hans J.; Völzke, Henry; Wittfeld, Katharina; Böhnlein, Joscha; Dohm, Katharina; Kugel, Harald; Schrammen, Elisabeth; Zwanzger, Peter; Leehr, Elisabeth J.; Sindermann, Lisa; Ball, Tali M.; Paulus, Martin P.; Simmons, Alan N.; Stein, Murray B.; Klumpp, Heide; Phan, K. Luan; Furmark, Tomas; Månsson, Kristoffer; Manzouri, Amirhossein; Avery, Suzanne N.; Blackford, Jennifer Urbano; Clauss, Jacqueline A.; Feola, Brandee; Harper, Jennifer C.; Lueken, Ulrike; Veltman, Dick J.; Winkler, Anderson M.; Jahanshad, Neda; Pine, Daniel S.; Thompson, Paul M.; Stein, Dan J.; Wee, Nic J.A. van der

doi:10.1038/s41380-022-01933-9

Cited by 11 publications

(7 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent mega-analytic study using 37 samples consisting of 1115 individuals with SAD and 2775 HCs was conducted by ENIGMA-Anxiety. This study found smaller amygdala volumes in SAD individuals with comorbid anxiety disorder and comorbid MDD 13 . Additionally, given that the amygdala and hippocampus consist of structurally heterogenous units of specialized subfields that can be identified by their cytoarchitecture, histochemistry and connectivity profile 14 , it is likely that investigating the volume of the amygdala and hippocampal as whole structures might not reveal subfield specific differences that may occur in SAD.…”

Section: Introductionsupporting

confidence: 45%

Specific amygdala and hippocampal subfield volumes in social anxiety disorder and their relation to clinical characteristics – an international mega-analysis

Ntwatwa,

Spreckelmeyer,

Bas-Hoogendam

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Social anxiety disorder (SAD) has been associated with alterations in amygdala and hippocampal volume but there is mixed evidence for the direction of volumetric alterations. Additionally, little is known about the involvement distinct subfields of these regions in the pathophysiology of SAD. Methods: T1-weighted MRI images from a large multi-centre sample of 107 adult patients with SAD and 140 healthy controls (HCs) were segmented using FreeSurfer to produce 9 amygdala and 12 hippocampal subfield volumes. Volumes were compared between groups using linear mixed-effects models adjusted for age, age-squared, sex, site and whole amygdala and hippocampal volumes. Subgroup analyses examined subfield volumes in relation to comorbid anxiety disorder, and comorbid major depressive disorder (MDD), psychotropic medication status, and symptom severity. Results: SAD was associated with smaller amygdala volumes in the basal (d=-0.32, pFDR=0.022), accessory basal (d=-0.42, pFDR=0.005) and corticoamygdaloid transition area (d=-0.37, pFDR=0.014), and larger hippocampal volume in the CA3 (d=0.34, pFDR=0.024), CA4 (d=0.44, pFDR=0.007), dentate gyrus (d=0.35, pFDR=0.022) and molecular layer (d=0.28, pFDR= 0.033), compared to HCs. Patients with SAD without comorbid anxiety, in addition, had smaller lateral amygdala (d=-0.30, pFDR=0.037) and hippocampal amygdala transition area (d=-0.33, pFDR=0.027) compared to HCs. In patients with SAD without comorbid MDD, only the smaller accessory basal amygdala remained significant (d=-0.41, pFDR=0.017). No association was found between subfield volume and medication status or symptom severity. Conclusions. We observed distinct patterns of volumetric differences across specific amygdala and hippocampal subfields, regions that are associated with sensory information processing, threat evaluation and fear generalization. These findings suggest a possible disruption in information flow between the amygdala and hippocampal formation for fear processing in SAD.

show abstract

Section: Introductionsupporting

confidence: 45%

Specific amygdala and hippocampal subfield volumes in social anxiety disorder and their relation to clinical characteristics – an international mega-analysis

Ntwatwa,

Spreckelmeyer,

Bas-Hoogendam

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Remarkably, reduced putamen grey matter volume was the only significant main effect of group (SAD vs. HC) in subcortical areas in a recent study with 1,115 SAD patients and 2,775 controls [77]. In one study, social anxiety severity was positively correlated with putamen volume [76], but this effect was later questioned [77]. Regarding functional activity, a number of studies have reported altered putamen activations in SAD patients in response to both socially positive and negative stimuli [4, 7, 19, 20].…”

Section: Discussionmentioning

confidence: 99%

“…Altered putamen structure and activity have been associated with the diagnosis of SAD in several previous studies. Structural studies revealed altered grey matter volumes in the putamen in SAD patients relative to HC [e.g., [76][77][78][79]]. Remarkably, reduced putamen grey matter volume was the only significant main effect of group (SAD vs. HC) in subcortical areas in a recent study with 1,115 SAD patients and 2,775 controls [77].…”

Section: Discussionmentioning

confidence: 99%

“…Structural studies revealed altered grey matter volumes in the putamen in SAD patients relative to HC [e.g., [76][77][78][79]]. Remarkably, reduced putamen grey matter volume was the only significant main effect of group (SAD vs. HC) in subcortical areas in a recent study with 1,115 SAD patients and 2,775 controls [77]. In one study, social anxiety severity was positively correlated with putamen volume [76], but this effect was later questioned [77].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Altered Putamen Activation for Social Comparison-Related Feedback in Social Anxiety Disorder: A Pilot Study

Lin,

Bruchmann,

Straube

2023

Neuropsychobiology

Self Cite

View full text Add to dashboard Cite

Introduction: Social anxiety disorder (SAD) is characterized by abnormal processing of performance-related social stimuli. Previous studies have shown altered emotional experiences and activations of different sub-regions of the striatum during processing of social stimuli in patients with SAD. However, whether and to what extent social comparisons affect behavioural and neural responses to feedback stimuli in patients with SAD is unknown. Materials and Methods: To address this issue, emotional ratings and functional magnetic resonance imaging (fMRI) responses were assessed while patients suffering from SAD and healthy controls (HC) were required to perform a choice task and received performance feedback (correct, incorrect, non-informative) that varied in relation to the performance of fictitious other participants (a few, half, or most of others had the same outcome). Results: Across all performance feedback conditions, fMRI analyses revealed reduced activations in bilateral putamen when feedback was assumed to be received by only a few compared to half of the other participants in patients with SAD. Nevertheless, analysis of rating data showed a similar modulation of valence and arousal ratings in patients with SAD and HC depending on social comparison-related feedback. Conclusions: This suggests altered neural processing of performance feedback depending on social comparisons in patients with SAD.

show abstract

“…These genetically informed findings are consistent with previous observational studies. For example, increased bilateral pallidum volumes were found to be associated with social anxiety disorder (SAD) in adults (44). Furthermore, negative covariation between salivary cortisol during public speaking and regional cerebral blood flow in Brodmann area 6 was reported in SAD patients (45).…”

Section: Discussionmentioning

confidence: 99%

Brain-Wide Mendelian Randomization Study of Anxiety Disorders and Symptoms

Zanoaga,

Friligkou,

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

BackgroundTo gain insights into the role of brain structure and function on anxiety (ANX), we conducted a genetically informed investigation leveraging information from ANX genome-wide association studies available from UK Biobank (UKB; N=380,379), FinnGen Program (N=290,361), and Million Veteran Program (MVP; N=199,611) together with UKB genome-wide data (N=33,224) related to 3,935 brain imaging-derived phenotypes (IDP).MethodsA genetic correlation analysis between ANX and brain IDPs was performed using linkage disequilibrium score regression. To investigate ANX–brain associations, a two-sample Mendelian randomization (MR) was performed considering multiple methods and sensitivity analyses. A subsequent multivariable MR (MVMR) was executed to distinguish between direct and indirect effects. Finally, a generalized linear model was used to explore the associations of brain IDPs with ANX symptoms.ResultsAfter false discovery rate correction (FDR q<0.05), we identified 41 brain IDPs genetically correlated with ANX without heterogeneity among the datasets investigated (i.e., UKB, FinnGen, and MVP). Six of these IDPs showed genetically inferred causal effects on ANX. In the subsequent MVMR analysis, reduced area of the right posterior middle-cingulate gyrus (rpMCG; beta=-0.09, P= 8.01×10-4) and reduced gray-matter volume of the right anterior superior temporal gyrus (raSTG; beta=-0.09, P=1.55×10-3) had direct effects on ANX. In the ANX symptom-level analysis, rpMCG was negatively associated with “tense sore oraching muscles during the worst period of anxiety” (beta=-0.13, P=8.26×10-6).ConclusionsThis study identified genetically inferred effects generalizable across large cohorts, contributing to understand how changes in brain structure and function can lead to ANX.

show abstract

Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group

Abstract: Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.

Cited by 11 publications

References 61 publications

Specific amygdala and hippocampal subfield volumes in social anxiety disorder and their relation to clinical characteristics – an international mega-analysis

Specific amygdala and hippocampal subfield volumes in social anxiety disorder and their relation to clinical characteristics – an international mega-analysis

Altered Putamen Activation for Social Comparison-Related Feedback in Social Anxiety Disorder: A Pilot Study

Brain-Wide Mendelian Randomization Study of Anxiety Disorders and Symptoms

Contact Info

Product

Resources

About