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      Impaired neural habituation to neutral faces in families genetically enriched for social anxiety disorder

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          Abstract

          Background

          Social anxiety disorder (SAD) is an incapacitating disorder running in families. Previous work associated social fearfulness with a failure to habituate, but the habituation response to neutral faces has, as of yet, not been investigated in patients with SAD and their family members concurrently. Here, we examined whether impaired habituation to neutral faces is a putative neurobiological endophenotype of SAD by using data from the multiplex and multigenerational Leiden Family Lab study on SAD.

          Methods

          Participants ( n = 110; age, 9.2 – 61.5 years) performed a habituation paradigm involving neutral faces, as these are strong social stimuli with an ambiguous meaning. We used functional magnetic resonance imaging data to investigate whether brain activation related to habituation was associated with the level of social anxiety within the families. Furthermore, the heritability of the neural habituation response was estimated.

          Results

          Our data revealed a relationship between impaired habituation to neutral faces and social anxiety in the right hippocampus and right amygdala. In addition, our data indicated that this habituation response displayed moderate ‐ to‐moderately high heritability in the right hippocampus.

          Conclusion

          The present results provide support for altered habituation as a candidate SAD endophenotype; impaired neural habitation cosegregrated with the disorder within families and was heritable. These findings shed light on the genetic susceptibility to SAD.

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          Most cited references61

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          Social anxiety disorder.

          Our understanding of social anxiety disorder (also known as social phobia) has moved from rudimentary awareness that it is not merely shyness to a much more sophisticated appreciation of its prevalence, its chronic and pernicious nature, and its neurobiological underpinnings. Social anxiety disorder is the most common anxiety disorder; it has an early age of onset--by age 11 years in about 50% and by age 20 years in about 80% of individuals--and it is a risk factor for subsequent depressive illness and substance abuse. Functional neuroimaging studies point to increased activity in amygdala and insula in patients with social anxiety disorder, and genetic studies are increasingly focusing on this and other (eg, personality trait neuroticism) core phenotypes to identify risk loci. A range of effective cognitive behavioural and pharmacological treatments for children and adults now exists; the challenges lie in optimum integration and dissemination of these treatments, and learning how to help the 30-40% of patients for whom treatment does not work.
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            Behavioral inhibition and risk for developing social anxiety disorder: a meta-analytic study.

            Behavioral inhibition (BI) has been associated with increased risk for developing social anxiety disorder (SAD); however, the degree of risk associated with BI has yet to be systematically examined and quantified. The goal of the present study was to quantify the association between childhood BI and risk for developing SAD. A comprehensive literature search was conducted to identify studies that assessed both BI and SAD. Meta-analyses were performed to estimate the odds ratio (OR) of the association between BI and SAD in children. Seven studies met inclusion criteria. BI was associated with a greater than sevenfold increase in risk for developing SAD (odds ratio = 7.59, p < .00002). This association remained significant even after considering study differences in temperament assessment, control group, parental risk, age at temperament assessment, and age at anxiety diagnosis. Identifying early developmental risk factors is critical for preventing psychiatric illness. Given that 15% of all children show extreme BI, and that almost half of these inhibited children will eventually develop SAD, we propose that BI is one of the largest single risk factors for developing SAD. Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
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              Social anxiety among adolescents: linkages with peer relations and friendships.

              This study examined the utility of modifying the Social Anxiety Scale for Children-Revised (SASC-R) for use with adolescents, and examined associations between adolescents' social anxiety (SA) and their peer relations, friendships, and social functioning. Boys (n = 101) and girls (n = 149) in the 10th through 12th grades completed the Social Anxiety Scale for Adolescents (SAS-A) and measures of social support, perceived competence, and number and quality of their best friendships. Factor analysis of the SAS-A confirmed a three-factor structure: Fear of Negative Evaluation, Social Avoidance and Distress in General, and Social Avoidance Specific to New Situations or Unfamiliar Peers. Girls reported more SA than boys, and SA was more strongly linked to girls' social functioning than boys'. Specifically, adolescents with higher levels of SA reported poorer social functioning (less support from classmates, less social acceptance), and girls with higher levels of SA reported fewer friendships, and less intimacy, companionship, and support in their close friendships. These findings extend work on the SASC-R to adolescents, and suggest the importance of SA for understanding the social functioning and close friendships of adolescents, especially girls.
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                Author and article information

                Contributors
                j.m.hoogendam@fsw.leidenuniv.nl
                Journal
                Depress Anxiety
                Depress Anxiety
                10.1002/(ISSN)1520-6394
                DA
                Depression and Anxiety
                John Wiley and Sons Inc. (Hoboken )
                1091-4269
                1520-6394
                10 October 2019
                December 2019
                : 36
                : 12 , FOCUS ON: DEPRESSION AND ANXIETY IN THE MIX ( doiID: 10.1002/da.v36.12 )
                : 1143-1153
                Affiliations
                [ 1 ] Developmental and Educational Psychology, Institute of Psychology Leiden University Leiden The Netherlands
                [ 2 ] Department of Psychiatry Leiden University Medical Center Leiden The Netherlands
                [ 3 ] Leiden Institute for Brain and Cognition Leiden The Netherlands
                [ 4 ] Cognitive Psychology Unit, Institute of Psychology University of Leiden Leiden The Netherlands
                [ 5 ] Department of Psychiatry and Behavioral Sciences Vanderbilt University Medical Center Nashville Tennessee
                [ 6 ] Department of Veterans Affairs Medical Center Research Service, Research and Development Nashville Tennessee
                Author notes
                [*] [* ] Correspondence Janna Marie Bas‐Hoogendam, Developmental and Educational Psychology, Institute of Psychology, Leiden University, Pieter de la Court Building, room 3.B47, Wassenaarseweg 52, 2333 AK Leiden, The Netherlands.

                Email: j.m.hoogendam@ 123456fsw.leidenuniv.nl

                Author information
                http://orcid.org/0000-0001-8982-1670
                Article
                DA22962
                10.1002/da.22962
                6916167
                31600020
                7a65918c-4c1b-429a-973d-9b29030cb0b7
                © 2019 The Authors. Depression and Anxiety Published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 30 April 2019
                : 22 August 2019
                : 24 August 2019
                Page count
                Figures: 1, Tables: 2, Pages: 11, Words: 8212
                Funding
                Funded by: Leiden University Research Profile ‘Health, Prevention and the Human Life Cycle’
                Funded by: Leiden University, Institute of Psychology
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                December 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.3 mode:remove_FC converted:17.12.2019

                Clinical Psychology & Psychiatry
                amygdala,endophenotypes,family research,fsl (rrid:scr_002823),functional neuroimaging,hippocampus,phobia,social

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