Comprehensive Summaries of Uppsala Dissertations from the Faculty of Social Sciences 104 _____________________________ _____________________________ Social Phobia The Family and the Brain BY MARIA TILLFORS ACTA UNIVERSITATIS UPSALIENSIS UPPSALA 2001 Dissertation for the Degree of Doctor of Philosophy in Psychology presented at Uppsala University in 2001 ABSTRACT Tillfors, M. 2001. Social Phobia. The Family and the Brain. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Social Sciences 104. 72 pp. Uppsala. ISBN 91-554-5096-2. The present thesis investigated family history and neurobiology of social phobia. Social phobia is a disabling disorder characterized by a marked fear of scrutiny in a variety of social situations. By using a validated questionnaire, study I related family history of excessive social anxiety to social phobia and avoidant personality disorder in epidemiologically identified probands in the Swedish general population. A two- to threefold increased relative risk of social anxiety was observed for both diagnostic groups. Thus, having an affected family member is associated with approximately a doubled risk for both social phobia and avoidant personality disorder. The neurobiological studies explored situational and anticipatory elicited anxiety by means of positron emission tomography and 15O-water. Study II examined the functional neuroanatomy of social anxiety provocation in social phobics and a healthy comparison group during a public speaking task. Social phobia symptomatology was associated with higher neural activity in the amygdaloid complex, i.e. “the alarm system” of the brain, and lower activity in the prefrontal cortex. Study III examined the neural correlates of anxiety elicited by the anticipation of public speaking in individuals with social phobia. Anticipatory anxiety was accompanied by enhanced regional cerebral blood flow in the dorsolateral prefrontal and inferior temporal cortices as well as in the amygdaloid-hippocampal region. Brain blood flow was lower in the temporal pole and in the cerebellum. These results suggest that social phobia has a neuroanatomical basis in a highly sensitive fear network centered in the amygdaloid-hippocampal region and encompassing the prefrontal cortex. Key words: Anticipation, anxiety, avoidant personality disorder, family history, fear, neuroimaging, positron emission tomography, regional cerebral blood flow, social phobia, symptom provocation. Maria Tillfors, Department of Psychology, Uppsala University, Box 1225, SE-751 42 Uppsala, Sweden Maria Tillfors 2001 ISSN 0282-7492 ISBN 91-554-5096-2 Printed in Sweden by Uppsala University, Tryck & Medier, Uppsala 2001 The present thesis is based on the following papers referred to by their Roman numerals: Paper I. Tillfors, M., Furmark T., Ekselius L. & Fredrikson M. (2001). Social phobia and avoidant personality disorder as related to parental history of social anxiety: A general population study. Behaviour Research and Therapy, 39, 289-298. Paper II. Tillfors, M., Furmark T., Marteinsdottir, I., Fischer, H., Pissiota, A., Långström, B. & Fredrikson, M. (2001). Cerebral blood flow in subjects with social phobia during stressful speaking tasks: A PET-study. American Journal of Psychiatry, 158, 1220-1226. Paper III. Tillfors, M., Furmark, T., Marteinsdottir, I. & Fredrikson, M. (2001). Functional neuroanatomy of anticipatory anxiety: A PET study of social phobia. (Submitted). Reprints of Paper I and Paper II were made with permission of the publisher. “The brain is my second favorite organ” Woody Allen 5 TABLE OF CONTENTS ABBREVIATIONS USED IN TEXT ............................................................................6 INTRODUCTION................................................................................................................7 The present thesis....................................................................................................................7 Social phobia – What is it?......................................................................................................7 DIAGNOSTIC ISSUES ...................................................................................................10 Development of DSM criteria................................................................................................10 Prevalence and caseness ........................................................................................................11 Sociodemographic findings...................................................................................................11 Subtypes of social phobia......................................................................................................12 Comorbidity with avoidant personality disorder ....................................................................13 Shyness.................................................................................................................................14 ETIOLOGY .........................................................................................................................14 Genetics and family aggregation............................................................................................14 Behavioral inhibition..............................................................................................................16 Personality traits....................................................................................................................18 Family environment...............................................................................................................18 Cognitive factors....................................................................................................................19 Associative learning accounts ................................................................................................20 Neurobiological influences....................................................................................................21 THEORIES OF EMOTION ..........................................................................................24 NEURONAL UNDERPINNINGS OF FEAR AND ANXIETY........................24 Neuroimaging: Studies of social phobia................................................................................30 THE EMPIRICAL STUDIES........................................................................................32 Study I...................................................................................................................................32 Study II .................................................................................................................................35 Study III................................................................................................................................40 Discussion of the individual studies ......................................................................................44 The family study................................................................................................................44 The brain imaging studies..................................................................................................45 General discussion ................................................................................................................48 CONCLUDING REMARKS .........................................................................................50 REFERENCES ...................................................................................................................52 ACKNOWLEDGEMENTS............................................................................................73 6 ABBREVIATIONS USED IN TEXT ANOVA Analysis of variance APA American Psychiatric Association APD Avoidant personality disorder BAS the Behavioral activation system BIS the Behavioral inhibition system DAT1 the Dopamine transporter gene D4DR the Dopamine 4 receptor gene DIP-Q the DSM-IV and ICD-10 Personality Disorder Questionnaire DSM-I the Diagnostic and Statistical Manual of Mental Disorders, 1st edition DSM-II the Diagnostic and Statistical Manual of Mental Disorders, 2nd edition DSM-III the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition DSM-III-R the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition revised DSM-IV the Diagnostic and Statistical Manual of Mental Disorders, 4th edition fMRI Functional magnetic resonance imaging 5-HT 5-hydroxotryptamine (serotonin) 5-HTP 5-hydroxotryptofan 5-HTT 5-HT transporter gene NCS the National Comorbidity Survey PET Positron emission tomography rCBF Regional cerebral blood flow SSRI Selective serotonin reuptake inhibitor STAI-S Spielberger’s State Anxiety Inventory 7 INTRODUCTION The present thesis The expression of fear and anxiety are perfectly normal reactions in the appropriate context. But what makes some individuals and not others to go beyond this level of adaptive fear and anxiety to develop pathological anxiety? The present thesis is about social phobia, also known as social anxiety disorder, which at least in Western countries is considered to be the most common anxiety disorder (Jefferys, 1997), characterized by a marked fear of scrutiny in a variety of social situations. The thesis is based on three studies, where the first study examines family history in social phobics, that is if social phobia runs in families in a more systematic way than what could be expected by chance.