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      The Leiden Family Lab study on Social Anxiety Disorder: A multiplex, multigenerational family study on neurocognitive endophenotypes

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          abstract

          Objectives

          Social anxiety disorder (SAD) is a serious and prevalent psychiatric condition, with a heritable component. However, little is known about the characteristics that are associated with the genetic component of SAD, the so‐called “endophenotypes”. These endophenotypes could advance our insight in the genetic susceptibility to SAD, as they are on the pathway from genotype to phenotype. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) is the first multiplex, multigenerational study aimed to identify neurocognitive endophenotypes of social anxiety.

          Methods

          The LFLSAD is characterized by a multidisciplinary approach and encompasses a variety of measurements, including a clinical interview, functional and structural magnetic resonance imaging and an electroencephalography experiment. Participants are family members from 2 generations, from families genetically enriched for SAD.

          Results

          The sample ( n = 132 participants, from 9 families) was characterized by a high prevalence of SAD, in both generations (prevalence (sub)clinical SAD: 38.3%). Furthermore, (sub)clinical SAD was positively related to self‐reported social anxiety, fear of negative evaluation, trait anxiety, behavioral inhibition, negative affect, and the level of depressive symptoms.

          Conclusions

          By the multidimensional character of the measurements and thorough characterization of the sample, the LFLSAD offers unique opportunities to investigate candidate neurocognitive endophenotypes of SAD.

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          Most cited references82

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          Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States.

          Estimates of 12-month and lifetime prevalence and of lifetime morbid risk (LMR) of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) anxiety and mood disorders are presented based on US epidemiological surveys among people aged 13+. The presentation is designed for use in the upcoming DSM-5 manual to provide more coherent estimates than would otherwise be available. Prevalence estimates are presented for the age groups proposed by DSM-5 workgroups as the most useful to consider for policy planning purposes. The LMR/12-month prevalence estimates ranked by frequency are as follows: major depressive episode: 29.9%/8.6%; specific phobia: 18.4/12.1%; social phobia: 13.0/7.4%; post-traumatic stress disorder: 10.1/3.7%; generalized anxiety disorder: 9.0/2.0%; separation anxiety disorder: 8.7/1.2%; panic disorder: 6.8%/2.4%; bipolar disorder: 4.1/1.8%; agoraphobia: 3.7/1.7%; obsessive-compulsive disorder: 2.7/1.2. Four broad patterns of results are most noteworthy: first, that the most common (lifetime prevalence/morbid risk) lifetime anxiety-mood disorders in the United States are major depression (16.6/29.9%), specific phobia (15.6/18.4%), and social phobia (10.7/13.0%) and the least common are agoraphobia (2.5/3.7%) and obsessive-compulsive disorder (2.3/2.7%); second, that the anxiety-mood disorders with the earlier median ages-of-onset are phobias and separation anxiety disorder (ages 15-17) and those with the latest are panic disorder, major depression, and generalized anxiety disorder (ages 23-30); third, that LMR is considerably higher than lifetime prevalence for most anxiety-mood disorders, although the magnitude of this difference is much higher for disorders with later than earlier ages-of-onset; and fourth, that the ratio of 12-month to lifetime prevalence, roughly characterizing persistence, varies meaningfully in ways consistent with independent evidence about differential persistence of these disorders. Copyright © 2012 John Wiley & Sons, Ltd.
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            The positive and negative affect schedule (PANAS): construct validity, measurement properties and normative data in a large non-clinical sample.

            To evaluate the reliability and validity of the PANAS (Watson, Clark, & Tellegen, 1988b) and provide normative data. Cross-sectional and correlational. The PANAS was administered to a non-clinical sample, broadly representative of the general adult UK population (N = 1,003). Competing models of the latent structure of the PANAS were evaluated using confirmatory factor analysis. Regression and correlational analysis were used to determine the influence of demographic variables on PANAS scores as well as the relationship between the PANAS with measures of depression and anxiety (the HADS and the DASS). The best-fitting model (robust comparative fit index = .94) of the latent structure of the PANAS consisted of two correlated factors corresponding to the PA and NA scales, and permitted correlated error between items drawn from the same mood subcategories (Zevon & Tellegen, 1982). Demographic variables had only very modest influences on PANAS scores and the PANAS exhibited measurement invariance across demographic subgroups. The reliability of the PANAS was high, and the pattern of relationships between the PANAS and the DASS and HADS were consistent with tripartite theory. The PANAS is a reliable and valid measure of the constructs it was intended to assess, although the hypothesis of complete independence between PA and NA must be rejected. The utility of this measure is enhanced by the provision of large-scale normative data. Copyright 2004 The British Psychological Society
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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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                Author and article information

                Contributors
                j.m.hoogendam@fsw.leidenuniv.nl , j.m.hoogendam@gmail.com
                Journal
                Int J Methods Psychiatr Res
                Int J Methods Psychiatr Res
                10.1002/(ISSN)1557-0657
                MPR
                International Journal of Methods in Psychiatric Research
                John Wiley and Sons Inc. (Hoboken )
                1049-8931
                1557-0657
                26 April 2018
                June 2018
                : 27
                : 2 ( doiID: 10.1002/mpr.v27.2 )
                : e1616
                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 Leiden University Leiden The Netherlands
                [ 5 ] Curium Leiden University Medical Center Leiden The Netherlands
                [ 6 ] Department of Statistics University of Leeds Leeds UK
                [ 7 ] Section of Molecular Epidemiology, Department of Medical Statistics and Bioinformatics Leiden University Medical Center Leiden The Netherlands
                Author notes
                [*] [* ] Correspondence

                Janna Marie Bas‐Hoogendam, Developmental and Educational Psychology, Institute of Psychology, Leiden University, Pieter de la Court Building, room 3.B43, Wassenaarseweg 52, 2333 AK Leiden, The Netherlands.

                Email: j.m.hoogendam@ 123456fsw.leidenuniv.nl ; j.m.hoogendam@ 123456gmail.com

                Author information
                http://orcid.org/0000-0001-8982-1670
                Article
                MPR1616 IJMPR-Dec-2017-0129.R1
                10.1002/mpr.1616
                6001802
                29700902
                a7a41eb0-b36c-4f7e-a809-85b6e7cab2dc
                © 2018 The Authors International Journal of Methods in Psychiatric Research Published by John Wiley & Sons Ltd

                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
                : 14 December 2017
                : 13 March 2018
                : 19 March 2018
                Page count
                Figures: 3, Tables: 6, Pages: 15, Words: 5752
                Funding
                Funded by: Institute of Psychology of Leiden University
                Funded by: Leiden University Research Profile “Health, Prevention and the Human Life Cycle”
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                mpr1616
                June 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.1.1 mode:remove_FC converted:14.06.2018

                Clinical Psychology & Psychiatry
                eeg,endophenotypes,family study,mri,social anxiety disorder
                Clinical Psychology & Psychiatry
                eeg, endophenotypes, family study, mri, social anxiety disorder

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