Hostname: page-component-8448b6f56d-xtgtn Total loading time: 0 Render date: 2024-04-18T12:08:13.945Z Has data issue: false hasContentIssue false
  • English
  • Français

Altered gray matter volume and structural co-variance in adolescents with social anxiety disorder: evidence for a delayed and unsynchronized development of the fronto-limbic system

Published online by Cambridge University Press:  17 March 2020

Zhen Liu Open the ORCID record for Zhen Liu [Opens in a new window] ,
Yang Hu ,
Yiwen Zhang ,
Wenjing Liu ,
Lei Zhang ,
Yunyi Wang ,
Hanshu Yang ,
Jingyi Wu ,
Wenhong Cheng  and
Zhi Yang Open the ORCID record for Zhi Yang [Opens in a new window]
Zhen Liu
Affiliation:
Department of Child and Adolescent Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yang Hu
Affiliation:
Laboratory of Psychological Health and Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yiwen Zhang
Affiliation:
Laboratory of Psychological Health and Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Wenjing Liu
Affiliation:
Department of Child and Adolescent Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Lei Zhang
Affiliation:
Laboratory of Psychological Health and Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yunyi Wang
Affiliation:
Department of Psychological Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Hanshu Yang
Affiliation:
Department of Child and Adolescent Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Jingyi Wu
Affiliation:
Department of Child and Adolescent Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Wenhong Cheng*
Affiliation:
Department of Child and Adolescent Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Psychological Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Zhi Yang*
Affiliation:
Laboratory of Psychological Health and Imaging, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China Institute of Psychological and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai, China Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China
*
Author for correspondence: Wenhong Cheng, E-mail: chengwhb@aliyun.com; Zhi Yang, E-mail: yangz@smhc.org.cn
Author for correspondence: Wenhong Cheng, E-mail: chengwhb@aliyun.com; Zhi Yang, E-mail: yangz@smhc.org.cn
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Social anxiety disorder (SAD) is a prevalent mental disorder diagnosed in childhood and adolescence. Theories regarding brain development and SAD suggest a close link between neurodevelopmental dysfunction at the adolescent juncture and SAD, but direct evidence is rare. This study aims to examine brain structural abnormalities in adolescents with SAD.

Methods

High-resolution T1-weighted images were obtained from 31 adolescents with SAD (15–17 years) and 42 matching healthy controls (HC). We evaluated symptom severity with the Social Anxiety Scale for Children (SASC) and the Screen for Child Anxiety Related Emotional Disorders (SCARED). We used voxel-based morphometry analysis to detect regional gray matter volume abnormalities and structural co-variance analysis to investigate inter-regional coordination patterns.

Results

We found significantly higher gray matter volume in the orbitofrontal cortex (OFC) and the insula in adolescents with SAD compared to HC. We also observed significant co-variance of the gray matter volume between the OFC and amygdala, and the OFC and insula in HC, but these co-variance relationships diminished in SAD.

Conclusions

These findings provide the first evidence that the brain structural deficits in adolescents with SAD are not only in the core regions of the fronto-limbic system, but also represented by the diminished coordination in the development of these regions. The delayed and unsynchronized development pattern of the fronto-limbic system supports SAD as an adolescent-sensitive developmental mental disorder.

Keywords

Adolescentsbrain developmentfronto-limbicgray matter volumesocial anxiety disorderstructural co-variance
Type
Original Article
Information
Psychological Medicine , Volume 51 , Issue 10 , July 2021 , pp. 1742 - 1751
Check for updates
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

†

These authors contributed equally to this work as joint first authors.

References

Alexander-Bloch, A., Giedd, J. N., & Bullmore, E. (2013). Imaging structural co-variance between human brain regions. Nature Reviews Neuroscience, 14(5), 322–336. doi:10.1038/nrn3465.CrossRefGoogle ScholarPubMed
American Psychiatric Association (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: American Psychiatric Press.Google Scholar
Ashburner, J. (2007). A fast diffeomorphic image registration algorithm. NeuroImage, 38(1), 95–113. doi:10.1016/j.neuroimage.2007.07.007.CrossRefGoogle ScholarPubMed
Beer, J. S., John, O. P., Scabini, D., & Knight, R. T. (2006). Orbitofrontal cortex and social behavior: Integrating self-monitoring and emotion-cognition interactions. Journal of Cognitive Neuroscience, 18(6), 871–879. doi:10.1162/jocn.2006.18.6.871.CrossRefGoogle ScholarPubMed
Beesdo-Baum, K., Knappe, S., Fehm, L., Höfler, M., Lieb, R., Hofmann, S. G., & Wittchen, H. U. (2012). The natural course of social anxiety disorder among adolescents and young adults. Acta Psychiatrica Scandinavica, 126(6), 411–425. doi:10.1111/j.1600-0447.2012.01886.x.CrossRefGoogle ScholarPubMed
Bell, H. C., Pellis, S. M., & Kolb, B. (2010). Juvenile peer play experience and the development of the orbitofrontal and medial prefrontal cortices. Behavioural Brain Research, 207(1), 7–13. doi:10.1016/j.bbr.2009.09.029.CrossRefGoogle ScholarPubMed
Birmaher, B., Khetarpal, S., Brent, D., Cully, M., Balach, L., Kaufman, J., & Neer, S. M. (1997). The Screen for Child Anxiety Related Emotional Disorders (SCARED): Scale construction and psychometric characteristics. Journal of the American Academy of Child & Adolescent Psychiatry, 36(4), 545–553. doi:10.1097/00004583-199704000-00018.CrossRefGoogle ScholarPubMed
Blackford, J. U., & Pine, D. S. (2012). Neural substrates of childhood anxiety disorders: A review of neuroimaging findings. Child and Adolescent Psychiatric Clinics, 21(3), 501–525. doi:10.1016/j.chc.2012.05.002.CrossRefGoogle ScholarPubMed
Blakemore, S. J. (2008). The social brain in adolescence. Nature Reviews Neuroscience, 9(4), 267–277. doi:10.1038/nrn2353.CrossRefGoogle ScholarPubMed
Boehme, S., Ritter, V., Tefikow, S., Stangier, U., Strauss, B., Miltner, W. H. R., & Straube, T. (2014). Brain activation during anticipatory anxiety in social anxiety disorder. Social Cognitive and Affective Neuroscience, 9(9), 1413–1418. doi:10.1093/scan/nst129.CrossRefGoogle ScholarPubMed
Brühl, A. B., Delsignore, A., Komossa, K., & Weidt, S. (2014). Neuroimaging in social anxiety disorder – A meta-analytic review resulting in a new neurofunctional model. Neuroscience & Biobehavioral Reviews, 47, 260–280. doi:10.1016/j.neubiorev.2014.08.003.CrossRefGoogle Scholar
Caouette, J. D., & Guyer, A. E. (2014). Gaining insight into adolescent vulnerability for social anxiety from developmental cognitive neuroscience. Developmental Cognitive Neuroscience, 8, 65–76. doi:10.1016/j.dcn.2013.10.003.CrossRefGoogle ScholarPubMed
Caruana, F., Jezzini, A., Sbriscia-Fioretti, B., Rizzolatti, G., & Gallese, V. (2011). Emotional and social behaviors elicited by electrical stimulation of the insula in the macaque monkey. Current Biology, 21(3), 195–199. doi:10.1016/j.cub.2010.12.042.CrossRefGoogle ScholarPubMed
Casey, B. J., Glatt, C. E., & Lee, F. S. (2015). Treating the developing versus developed brain: Translating preclinical mouse and human studies. Neuron, 86(6), 1358–1368. doi:10.1016/j.neuron.2015.05.020.CrossRefGoogle ScholarPubMed
Castro, D. C., & Berridge, K. C. (2017). Opioid and orexin hedonic hotspots in rat orbitofrontal cortex and insula. Proceedings of the National Academy of Sciences, 114(43), E9125–E9134. doi:10.1073/pnas.1705753114.CrossRefGoogle ScholarPubMed
Clark, D. M., & Wells, A.. (1995). A cognitive model of social phobia. In Heimberg, R. G., Liebowitz, M. R., Hope, D. A., & Schneier, F. R. (Eds.), Social phobia: Diagnosis, assessment and treatment (pp. 69–93). New York: Guilford Press.Google Scholar
Clarke, H. F., Horst, N. K., & Roberts, A. C. (2015). Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making. Proceedings of the National Academy of Sciences, 112(13), 4176–4181. doi: 10.1073/pnas.1422440112.CrossRefGoogle ScholarPubMed
Clos, M., Rottschy, C., Laird, A. R., Fox, P. T., & Eickhoff, S. B. (2014). Comparison of structural covariance with functional connectivity approaches exemplified by an investigation of the left anterior insula. NeuroImage, 99, 269–280. doi:10.1016/j.neuroimage.2014.05.030.CrossRefGoogle ScholarPubMed
Cloutman, L. L., Binney, R. J., Drakesmith, M., Parker, G. J. M., & Lambon Ralph, M. A. (2012). The variation of function across the human insula mirrors its patterns of structural connectivity: Evidence from in vivo probabilistic tractography. NeuroImage, 59(4), 3514–3521. doi:10.1016/j.neuroimage.2011.11.016.CrossRefGoogle ScholarPubMed
Core Team R. (2018). R: A language and environment for statistical computing. Vienna, Austria. Retrieved from http://www.R-project.org/.Google Scholar
Etkin, A., & Wager, T. D. (2007). Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry, 164(10), 1476–1488. doi:10.1176/appi.ajp.2007.07030504.CrossRefGoogle ScholarPubMed
Fair, D. A., Dosenbach, N. U. F., Church, J. A., Cohen, A. L., Brahmbhatt, S., Miezin, F. M., … Schlaggar, B. L. (2007). Development of distinct control networks through segregation and integration. Proceedings of the National Academy of Sciences, 104(33), 13507–13512. doi: org/10.1073/pnas.0705843104.CrossRefGoogle Scholar
Fuhrmann, D., Knoll, L. J., & Blakemore, S. J. (2015). Adolescence as a sensitive period of brain development. Trends in Cognitive Sciences, 19(10), 558–566. doi:10.1016/j.tics.2015.07.008.CrossRefGoogle ScholarPubMed
Gaser, C., & Dahnke, R. (2016). CAT-a computational anatomy toolbox for the analysis of structural MRI data. HBM, 336–348.Google Scholar
Gogtay, N., Giedd, J. N., Lusk, L., Hayashi, K. M., Greenstein, D., Vaituzis, A. C., … Thompson, P. M. (2004). Dynamic mapping of human cortical development during childhood through early adulthood. Proceedings of the National Academy of Sciences, 101(21), 8174–8179.10.1073/pnas.0402680101.CrossRefGoogle ScholarPubMed
Goldin, P. R., Manber, T., Hakimi, S., Canli, T., & Gross, J. J. (2009). Neural bases of social anxiety disorder: Emotional reactivity and cognitive regulation during social and physical threat. Archives of General Psychiatry, 66(2), 170. doi:10.1001/archgenpsychiatry.2008.525.CrossRefGoogle ScholarPubMed
Gong, G., He, Y., Chen, Z. J., & Evans, A. C. (2012). Convergence and divergence of thickness correlations with diffusion connections across the human cerebral cortex. NeuroImage, 59(2), 1239–1248. doi:10.1016/j.neuroimage.2011.08.017.CrossRefGoogle ScholarPubMed
Guyer, A. E., Lau, J. Y. F., McClure-Tone, E. B., Parrish, J., Shiffrin, N. D., Reynolds, R. C., … Nelson, E. E. (2008). Amygdala and ventrolateral prefrontal cortex function during anticipated peer evaluation in pediatric social anxiety. Archives of General Psychiatry, 65(11), 1303–1312. doi: org/10.1001/archpsyc.65.11.1303.CrossRefGoogle ScholarPubMed
Hahn, A., Stein, P., Windischberger, C., Weissenbacher, A., Spindelegger, C., Moser, E., … Lanzenberger, R. (2011). Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder. NeuroImage, 56(3), 881–889. doi:10.1016/j.neuroimage.2011.02.064.CrossRefGoogle ScholarPubMed
Haller, S. P. W., Cohen Kadosh, K., Scerif, G., & Lau, J. Y. F. (2015). Social anxiety disorder in adolescence: How developmental cognitive neuroscience findings may shape understanding and interventions for psychopathology. Developmental Cognitive Neuroscience, 13, 11–20. doi:10.1016/j.dcn.2015.02.002.CrossRefGoogle ScholarPubMed
Kawaguchi, A., Nemoto, K., Nakaaki, S., Kawaguchi, T., Kan, H., Arai, N., … Akechi, T. (2016). Insular volume reduction in patients with social anxiety disorder. Frontiers in Psychiatry, 7, 3. doi:10.3389/fpsyt.2016.00003.CrossRefGoogle ScholarPubMed
Kelly, C., Toro, R., Di Martino, A., Cox, C. L., Bellec, P., Castellanos, F. X., & Milham, M. P. (2012). A convergent functional architecture of the insula emerges across imaging modalities. NeuroImage, 61(4), 1129–1142. doi:10.1016/j.neuroimage.2012.03.021.CrossRefGoogle ScholarPubMed
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry, 62(6), 593–602. doi:10.1001/archpsyc.62.6.593.CrossRefGoogle ScholarPubMed
Khundrakpam, B. S., Reid, A., Brauer, J., Carbonell, F., Lewis, J., Ameis, S., … O'Neill, J. (2013). Developmental changes in organization of structural brain networks. Cerebral Cortex, 23(9), 2072–2085.10.1093/cercor/bhs187.CrossRefGoogle ScholarPubMed
Killgore, W. D. S., & Yurgelun-Todd, D. A. (2005). Social anxiety predicts amygdala activation in adolescents viewing fearful faces. NeuroReport, 16(15), 1671–1675. doi:10.1097/01.wnr.0000180143.99267.bd.CrossRefGoogle ScholarPubMed
Kim, M. J., Loucks, R. A., Palmer, A. L., Brown, A. C., Solomon, K. M., Marchante, A. N., & Whalen, P. J. (2011). The structural and functional connectivity of the amygdala: From normal emotion to pathological anxiety. Behavioural Brain Research, 223(2), 403–410. doi:10.1016/j.bbr.2011.04.025.CrossRefGoogle ScholarPubMed
La Greca, A. M., & Stone, W. L. (1993). Social anxiety scale for children-revised: Factor structure and concurrent validity. Journal of Clinical Child Psychology, 22(1), 17–27. doi:10.1207/s15374424jccp2201_2.CrossRefGoogle Scholar
Leigh, E., & Clark, D. M. (2018). Understanding social anxiety disorder in adolescents and improving treatment outcomes: Applying the cognitive model of Clark and Wells (1995). Clinical Child and Family Psychology Review, 21(3), 388–414. doi:10.1007/s10567-018-0258-5.CrossRefGoogle Scholar
Lenroot, R. K., & Giedd, J. N. (2006). Brain development in children and adolescents: Insights from anatomical magnetic resonance imaging. Neuroscience & Biobehavioral Reviews, 30(6), 718–729. doi:10.1016/j.neubiorev.2006.06.001.CrossRefGoogle ScholarPubMed
Li, X., Cao, Q., Pu, F., Li, D., Fan, Y., An, L., … Wang, Y. (2015). Abnormalities of structural covariance networks in drug-naïve boys with attention deficit hyperactivity disorder. Psychiatry Research: Neuroimaging, 231(3), 273–278. doi:10.1016/j.pscychresns.2015.01.006.CrossRefGoogle ScholarPubMed
Li, A., Jing, D., Dellarco, D. V., Hall, B. S., Yang, R., Heilberg, R. T., … Lee, F. S. (2019). Role of BDNF in the development of an OFC-amygdala circuit regulating sociability in mouse and human. Molecular Psychiatry. doi:10.1038/s41380-019-0422-4. [Epub ahead of print]Google ScholarPubMed
Liu, Y., Liu, J., & Wang, Y. (2010). Reliability and validity of Chinese version of the Mini International Neuropsychiatric Interview for Children and Adolescents (Parent Version). Chinese Mental Health Journal, 24, 921–925. doi:10.3969/j.issn.1000-6729.2010.12.009.Google Scholar
Liu, Y., Liu, J., & Wang, Y. (2011). Reliability and validity of Chinese version of the Mini International Neuropsychiatric Interview for Children and Adolescents (Child Version). Chinese Mental Health Journal, 25, 8–13. doi:10.3969/j.issn.1000-6729.2011.01.003.Google Scholar
Liu, H., Qin, W., Qi, H., Jiang, T., & Yu, C. (2015). Parcellation of the human orbitofrontal cortex based on gray matter volume covariance. Human Brain Mapping, 36(2), 538–548. doi:10.1002/hbm.22645.CrossRefGoogle ScholarPubMed
Malone, I. B., Leung, K. K., Clegg, S., Barnes, J., Whitwell, J. L., Ashburner, J., … Ridgway, G. R. (2015). Accurate automatic estimation of total intracranial volume: A nuisance variable with less nuisance. NeuroImage, 104, 366–372. doi:10.1016/j.neuroimage.2014.09.034.CrossRefGoogle ScholarPubMed
Månsson, K. N. T., Salami, A., Frick, A., Carlbring, P., Andersson, G., Furmark, T., & Boraxbekk, C. J. (2016). Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder. Translational Psychiatry, 6(2), e727. doi:10.1038/tp.2015.218.CrossRefGoogle ScholarPubMed
Meng, Y., Lui, S., Qiu, C., Qiu, L., Lama, S., Huang, X., … Zhang, W. (2013). Neuroanatomical deficits in drug-naïve adult patients with generalized social anxiety disorder: A voxel-based morphometry study. Psychiatry Research: Neuroimaging, 214(1), 9–15. doi:10.1016/j.pscychresns.2013.06.002.CrossRefGoogle ScholarPubMed
Merz, E. C., He, X., & Noble, K. G. (2018). Anxiety, depression, impulsivity, and brain structure in children and adolescents. NeuroImage: Clinical, 20, 243–251. doi:10.1016/j.nicl.2018.07.020.CrossRefGoogle ScholarPubMed
Mesulam, M.-M., & Mufson, E. J. (1982). Insula of the old world monkey. Architectonics in the insulo-orbito-temporal component of the paralimbic brain. The Journal of Comparative Neurology, 212(1), 1–22. doi:10.1002/cne.902120102.CrossRefGoogle ScholarPubMed
Miers, A. C., Blöte, A. W., Heyne, D. A., & Westenberg, P. M. (2014). Developmental pathways of social avoidance across adolescence: The role of social anxiety and negative cognition. Journal of Anxiety Disorders, 28(8), 787–794. doi:10.1016/j.janxdis.2014.09.008.CrossRefGoogle ScholarPubMed
Milad, M. R., & Rauch, S. L. (2007). The role of the orbitofrontal cortex in anxiety disorders. Annals of the New York Academy of Sciences, 1121(1), 546–561. doi:10.1196/annals.1401.006.CrossRefGoogle ScholarPubMed
Mills, K. L., Goddings, A. L., Clasen, L. S., Giedd, J. N., & Blakemore, S. J. (2014). The developmental mismatch in structural brain maturation during adolescence. Developmental Neuroscience, 36(3–4), 147–160. doi:10.1159/000362328.CrossRefGoogle ScholarPubMed
Miskovic, V., & Schmidt, L. A. (2012). Social fearfulness in the human brain. Neuroscience & Biobehavioral Reviews, 36(1), 459–478. doi:10.1016/j.neubiorev.2011.08.002.CrossRefGoogle ScholarPubMed
Noble, K. G., Houston, S. M., Brito, N. H., Bartsch, H., Kan, E., Kuperman, J. M., … Sowell, E. R. (2015). Family income, parental education and brain structure in children and adolescents. Nature Neuroscience, 18(5), 773–778. doi:10.1038/nn.3983.CrossRefGoogle ScholarPubMed
Otto, M. W., Pollack, M. H., Maki, K. M., Gould, R. A., Worthington, J. J., Smoller, J. W., & Rosenbaum, J. F. (2001). Childhood history of anxiety disorders among adults with social phobia: Rates, correlates, and comparisons with patients with panic disorder. Depression and Anxiety, 14(4), 209–213. doi:10.1002/da.1068.CrossRefGoogle ScholarPubMed
Phan, K. L., Orlichenko, A., Boyd, E., Angstadt, M., Coccaro, E. F., Liberzon, I., & Arfanakis, K. (2009). Preliminary evidence of white matter abnormality in the uncinate fasciculus in generalized social anxiety disorder. Biological Psychiatry, 66(7), 691–694. doi:10.1016/j.biopsych.2009.02.028.CrossRefGoogle ScholarPubMed
Qin, S., Young, C. B., Duan, X., Chen, T., Supekar, K., & Menon, V. (2014). Amygdala subregional structure and intrinsic functional connectivity predicts individual differences in anxiety during early childhood. Biological Psychiatry, 75(11), 892–900. doi:10.1016/j.biopsych.2013.10.006.CrossRefGoogle ScholarPubMed
Saleem, K. S., Kondo, H., & Price, J. L. (2008). Complementary circuits connecting the orbital and medial prefrontal networks with the temporal, insular, and opercular cortex in the macaque monkey. The Journal of Comparative Neurology, 506(4), 659–693. doi:10.1002/cne.21577.CrossRefGoogle ScholarPubMed
Shiba, Y., Oikonomidis, L., Sawiak, S., Fryer, T. D., Hong, Y. T., Cockcroft, G., … Roberts, A. C. (2017). Converging prefronto-insula-amygdala pathways in negative emotion regulation in marmoset monkeys. Biological Psychiatry, 82(12), 895–903. doi:10.1016/j.biopsych.2017.06.016.CrossRefGoogle ScholarPubMed
Sladky, R., Höflich, A., Küblböck, M., Kraus, C., Baldinger, P., Moser, E., … Windischberger, C. (2015). Disrupted effective connectivity between the amygdala and orbitofrontal cortex in social anxiety disorder during emotion discrimination revealed by dynamic causal modeling for fMRI. Cerebral Cortex, 25(4), 895–903. doi:10.1093/cercor/bht279.CrossRefGoogle ScholarPubMed
Smith, S., & Nichols, T. (2009). Threshold-free cluster enhancement: Addressing problems of smoothing, threshold dependence and localisation in cluster inference. NeuroImage, 44(1), 83–98. doi:10.1016/j.neuroimage.2008.03.061.CrossRefGoogle ScholarPubMed
Steiger, V. R., Brühl, A. B., Weidt, S., Delsignore, A., Rufer, M., Jäncke, L., … Hänggi, J. (2017). Pattern of structural brain changes in social anxiety disorder after cognitive behavioral group therapy: A longitudinal multimodal MRI study. Molecular Psychiatry, 22(8), 1164–1171. doi:10.1038/mp.2016.217.CrossRefGoogle ScholarPubMed
Strawn, J. R., Hamm, L., Fitzgerald, D. A., Fitzgerald, K. D., Monk, C. S., & Phan, K. L. (2015). Neurostructural abnormalities in pediatric anxiety disorders. Journal of Anxiety Disorders, 32, 81–88. doi:10.1016/j.janxdis.2015.03.004.CrossRefGoogle ScholarPubMed
Syal, S., Hattingh, C. J., Fouché, J.-P., Spottiswoode, B., Carey, P. D., Lochner, C., & Stein, D. J. (2012). Grey matter abnormalities in social anxiety disorder: A pilot study. Metabolic Brain Disease, 27(3), 299–309. doi:10.1007/s11011-012-9299-5.CrossRefGoogle ScholarPubMed
Talati, A., Pantazatos, S. P., Schneier, F. R., Weissman, M. M., & Hirsch, J. (2013). Gray matter abnormalities in social anxiety disorder: Primary, replication, and specificity studies. Biological Psychiatry, 73(1), 75–84. doi:10.1016/j.biopsych.2012.05.022.CrossRefGoogle ScholarPubMed
Terasawa, Y., Shibata, M., Moriguchi, Y., & Umeda, S. (2013). Anterior insular cortex mediates bodily sensibility and social anxiety. Social Cognitive and Affective Neuroscience, 8(3), 259–266. doi:10.1093/scan/nss108.CrossRefGoogle ScholarPubMed
Tzourio-Mazoyer, N., Landeau, B., Papathanassiou, D., Crivello, F., Etard, O., Delcroix, N., … Joliot, M. (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage, 15(1), 273–289. doi:10.1006/nimg.2001.0978CrossRefGoogle ScholarPubMed
Wang, X., Cheng, B., Luo, Q., Qiu, L., & Wang, S. (2018). Gray matter structural alterations in social anxiety disorder: A voxel-based meta-analysis. Frontiers in Psychiatry, 9, 449. doi:10.3389/fpsyt.2018.00449.CrossRefGoogle ScholarPubMed
Supplementary material: File

Liu et al. supplementary material

Liu et al. supplementary material

Download Liu et al. supplementary material(File)
File 20.6 KB