Intergenerational Transmission of Social Anxiety Disorder · 2014-06-30 · Intergenerational Transmission of Social Anxiety (Disorder) Endophenotype: 1. Associated with the phenotype

Intergenerational Transmission Intergenerational Transmission of of Social Anxiety DisorderSocial Anxiety Disorder

Irene van Vliet, on behalf of the research team Leiden Social Anxiety Family Study

• Social Anxiety Disorder (DSM-IV-R)

• Extreme and irrational fear or shame

• Being scrutinized by others

• In social and performance type

situations

• Somatic symptoms (trembling,

blushing, sweating, palpitations)

• Avoidance or endurance with intense

anxiety and distress

Health, Prevention and the Human life cycle 18-4-20132

Health, Prevention and the Human life cycle

Social Anxiety Disorder / ‘Social Phobia’

� High prevalence (life-time: 7-13% Western countries (Furmark 2002); 4.8% the Netherlands (NEMESIS 1997, 2011); subclinical: 25%

� Early age of onset: childhood, adolescence (Schneier 1992; Rapee 2004)

� Chronic course, life-long disease

� High rate of co-morbidity (other anxiety disorders, depression, substance abuse)

� Unnoticed; ‘normal shyness’

�High burden on functioning: less relationships and marriage, lower level of education, early leave of school, risk of being unemployed, engagement in jobs below level of qualification (Dingemanse 2001; Wittchen 1999; Lampe 2003)

� Higher costs: SAD €12,000/year; sub-threshold SAD €5,000/year; other psychological problems €3,000/year (Acaturk 2009)

�Subclinical social anxiety grows to social anxiety disorder

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Age at onset of social anxiety disorder

0

5

1 0

1 5

2 0

2 5

0 to 5 1 6 to 2 0 3 1 to 3 5 4 6 to 5 0 6 1 to 6 5

n o . o f s u b je c ts

Schneier 1992Health, Prevention and the Human life cycle 18-4-20134

• Need for preventive interventions

• Indicated prevention, focussing on subjects with increased social anxiety or subclinical SAD

• Need for insight in risks and protective factors

• For development and maintenance of SAD



Intergenerational Transmission Intergenerational Transmission of Social Anxiety (Disorder)of Social Anxiety (Disorder)

SAD both heriditary and environmentalSAD both heriditary and environmentalbut but ‘‘genegene--environment relationsenvironment relations’’ not clearnot clear

•• SAD runs in families; 10x risk in first degree relatives; 1 pareSAD runs in families; 10x risk in first degree relatives; 1 parent nt with SAD=> 9.6% child with SAD (vs 2.1% no parent with SAD) with SAD=> 9.6% child with SAD (vs 2.1% no parent with SAD) (Lieb (Lieb 2000)2000)

•• Twin studies: heritability estimated 30% Twin studies: heritability estimated 30% -- 50% 50% (Kendler 1992; (Kendler 1992; Middeldorp 2005; Distel 2008)Middeldorp 2005; Distel 2008)

•• GWAS: SADGWAS: SAD--specific genetic background, which genes??specific genetic background, which genes??•• Relationship temperament and personalityRelationship temperament and personality•• Influence environmental factors (raising style, teased by peersInfluence environmental factors (raising style, teased by peers, , emotional maltreatment)emotional maltreatment)

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Step 1: identification endophenotypes (specific trait, genetic,Step 1: identification endophenotypes (specific trait, genetic, , , familiair, yes/no social anxiety disorder)familiair, yes/no social anxiety disorder)

Step 2: identification genotype (Gene Mapping with Linkage Step 2: identification genotype (Gene Mapping with Linkage Approach)Approach)

Step 3: identification geneStep 3: identification gene--environment relations => phenotypeenvironment relations => phenotype

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Step 1: Profiling endophenotypes in social anxiety disorder:

A neurocognitive approach (P12.061)

14 families (± 150 persons)

ProceduresPsychiatric interview

en questionnaires

Neurobiological paradigm’s (fMRI, EEG)

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Endophenotype:1. Associated with the phenotype (diagnosis)2. Independent of clinical state3. Highly heritable4. Impairment is co-segregated with the illness within a family, with non-

affected family members showing impairment relative to the general population (Glahn 2007)

=> Are the psychophysiological and neurocognitive abnormalities found in SAD heritable, and also found in family members?

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Paradigms: 1. Attention and 2. Social Cognition ( Clark & McManus 2002; Rapee & Spence 2004; Stein & Stein 2008)

Expected: biased attentional orienting response and impaired inhibition of attention to social threatening information and impaired inhibition of negative social cognitions, or rumination.

⇒ EEG : Dot probe, direction of attention to social threat; approach-avoidance response to emotional faces; social evaluation, sensitivity to social rejection.

⇒ fMRI : neural responses to familiar versus novel faces, amygdala reactivity, connectivity patterns; neural activity on social embarrassing versus neutral situations.




• Blair (2010): SAD ptn higher brain activity vs controles in non-intentional

shamefull situations.

• Interactions of group-by-transgression. BOLD responses within (a) left MPFC (-7, 59, 13), and (b) right MPFC (5, 58, 38) to behaviors involving

intentional, unintentional and no social transgressions for the two groups

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Where are we standing now?

• Protocol 12.061 accepted by the METC

• Developing and testing EEG

• Developing and testing fMRI

• Searching for families (NESDA, LUMC, Curium/LUMC, Rivierduinen,

Parnassia, ADF-Stichting, NedKAD)

• Pilotting

• Application Research Talent NWO

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Leiden Social Anxiety Family StudyWORK in PROGRESS by:

StaffPsychology/FSW:Prof. dr. P.M. WestenbergProf. dr. P.H. Spinhovendr. M.J.W. van der Molen (post-doc/UD)dr. C.L. Bokhorst (UD)

Ondersteunende medewerkersS. Fincan, MSc (coordination)dr. I. van Soelen (general coordination family lab)dr. J. Hoogendam, BMSc, MCognNSc (fMRI)G. Corton en M. Van Hoorn (research nurses

Netherlands Study of Depression and Anxiety) A. Harrewijn, BSc (Research Master student)S. van Luenen, BSc (Research Master student)C. van Hartingsveldt, BSc (Master student)E. Poppelaars (Honours Research Bachelor

Student)

Psychiatry/LUMC:Prof. dr. A.M. van Hemertdr. I. M. van Vliet (UHD)dr. N. van der Wee (UHD)dr. C. Reichart (UHD)

Methodological ondersteuningProf. dr. J. J. Houwing-Duistermaat (LUMC-

Dept of Medical Statistics and Bioinformatics)

Dr. M. de Rooij (UHD; Psychology/FSW)

Cooperation/ConsultantsProf. dr. E. Crone (FSW), Prof dr. S.

Rombouts (FSW/LIBC), Prof. dr. E. Slagboom (LUMC), Prof. S. Bögels (UvA), Prof. dr. K. Roelofs (RUN)

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Intergenerational Transmission of Social Anxiety Disorder · 2014-06-30 · Intergenerational Transmission of Social Anxiety (Disorder) Endophenotype: 1. Associated with the phenotype