Physiological parameters within three paradigms and perceived symptoms in social phobia

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Universität Konstanz Mathematisch-Naturwissenschaftliche Sektion Fachbereich Psychologie

Physiological parameters within three paradigms and perceived symptoms in social phobia

Dissertation

zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften

eingereicht von Dipl.-Psych. Elisabeth Kley

Erstgutachter: Herr Prof. Dr. T. Elbert

Zweitgutachter: Herr Prof. Dr. J. Vila Castellar

Tag der mündlichen Prüfung: 17.11.2004

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This research was supported by a grant from the

“Landesgraduiertenförderung Baden-Württemberg”.

My special thanks in Germany goes to… My special thanks in Spain goes to…

…Professor Elbert for his willingness in granting me a “long-distance”- accompaniment without which this study would not have been possible. I also thank him for the numerous suggestions, advice and expert counsel and the speedy e-mail communication at all times.

…Dr. Nagl for his advice concerning methods and his help with the application of statistical procedures.

…Katalin Mikustyak for proof-reading and for her qualified guidance through the English jungle of grammar, spelling and punctuation.

…my mother for her support everyday in every way, especially during the last phase of this project.

My special thanks in the USA goes to…

…Professor Lang, Dr. Bradley and their team for the kind welcome they gave me, for their expert advice and for the opportunity to learn so much about the methodology and procedure of the

“anxiety protocol” during my research stay.

…Professor Vila Castellar who accompanied me through all phases of the work, for the warm reception into his team, the patience he showed especially in regard to communication and linguistic difficulties, the numerous suggestions and expert advice concerning the collection of data and his support with regard to the analysis without which it would have been impossible to complete this work.

…all members of the research group for their heartfelt welcome and integration into their team, their feedback and support with the collection of the data.

…Sonia Rodríguez Ruiz for her help with the recruitment of the participants- the adventurous motorcycle tour during to the screening process remains unforgettable.

…José-Luis Mata Martín and Miguel Muñoz García for their support with regard to all my questions concerning software programs, their installation and trouble-shooting.

…Cynthia Vico Fuillerat “la reina de la grabación” for her unbeatable talent to spontaneously record scenes of exactly 12-second duration under any circumstances at any time of the day.

…Pedro Guerra Muñoz for his patience and support in every respect, from broken cables, over language-related concerns to his assistance in emotionally troubling phases of the dissertation.

…my friends who encouraged and supported me in so many ways throughout this project.

…the students of the University of Granada, who volunteered to participate and shared information about themselves in questionnaire-based and physiological recording.

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TABLES OF CONTENTS

Page

1. INTRODUCTION...1

2. THEORY ...3

2.1 Fear and anxiety as emotions ...3

2.2 Social phobia ...5

2.2.1 Diagnostical features of social phobia ...5

2.2.2 Subtypes ...5

2.2.1.1 Specific versus generalized social phobia...6

2.2.1.2 Social phobia without versus with avoidant personality disorder...7

2.2.3 Epidemiology ...8

2.2.3.1 Prevalence ...8

2.2.3.2 Incidence ...10

2.2.3.3 Age of onset ...11

2.2.3.4 Course of social phobia ...11

2.2.3.5 Comorbidity ...12

2.2.3.6 Psychosocial impairment...13

2.2.3.7 Risk factors...13

2.2.4 Social phobia under an evolutionary perspective...14

2.2.5 Social phobia under a biological perspective...15

2.2.5.1 Genetics...15

2.2.5.2 Substance induced symptom provocation ...16

2.2.5.3 Transmitter systems...17

2.2.5.4 Autonomic nervous system ...20

2.3 The network model and social phobia ...22

2.3.1 Characteristics of the network...22

2.3.2 Neuronal structures involved in the activation of the fear network...23

2.3.3 The activation of the fear network ...25

2.3.3.1 Behavioral approaches ...27

2.3.3.2 Behavioral cognitive approaches...28

2.4 Measurement of the three response systems ...32

2.4.1 Affective report ...32

2.4.2 Physiological responses...33

2.4.2.1 Heart rate and heart rate variability...34

2.4.2.2 Blood pressure...35

2.4.2.3 Pulse ...36

2.4.2.4 Respiration ...37

2.4.2.5 Electrodermal activity ...38

2.4.2.6 Electromyography, startle reflex and emotional priming ...39

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2.4.3 The defense cascade ...42

2.4.4 Physiological reactivity within the picture paradigm...43

2.4.5 Physiological reactivity within the imagery paradigm...44

2.4.5.1 General characteristics ...44

2.4.5.2 Physiological reaction in social phobics within the imagery paradigm...46

2.5 Hypotheses...51

3. METHODS ...57

3.1 Participants ...57

3.2 Materials...57

3.2.1 Questionnaires...57

3.2.2 Pictures ...65

3.2.3 Imagery scenes ...66

3.2.4 Acoustic stimuli...66

3.2.5 Apparatus ...66

3.3 Design...67

3.3.1 Defense paradigm ...67

3.3.2 Picture paradigm ...67

3.3.3 Imagery paradigm ...68

3.4 Physiological response measurement...71

3.5 Procedure ...73

3.6 Data reduction...75

3.6.1 Defense paradigm ...76

3.6.2 Picture paradigm ...77

3.6.3 Imagery paradigm ...78

3.7 Data analysis ...79

4. RESULTS ...83

4.1 Results concerning questionnaire-based data...83

4.1.1 Questionnaires used for the screening ...83

4.1.2 Questionnaires used before physiological recording...85

4.2 Results concerning the defense paradigm ...88

4.2.1 Heart rate...88

4.2.2 Systolic blood pressure ...90

4.2.3 Diastolic blood pressure...91

4.2.4 Pulse amplitude...93

4.2.5 Respiration amplitude...94

4.2.6 Respiration rate ...96

4.2.7 Skin conductance ...98

4.2.8 Startle reflex...99

4.2.9 Heart rate variability ...100

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4.3 Results concerning the picture paradigm...101

4.3.1 Affective rating due to pictures: Self-assessment manikin ...101

4.3.1.1 Valence rating of pictures ...101

4.3.1.2 Arousal rating of pictures...103

4.3.1.3 Dominance rating of pictures ...104

4.3.2 Results concerning physiological measurements due to pictures 106 4.3.2.1 Heart rate ...106

4.3.2.2 Systolic blood pressure...107

4.3.2.3 Diastolic blood pressure ...109

4.3.2.4 Pulse amplitude ...110

4.3.2.5 Skin conductance...111

4.3.2.6 Startle reflex ...112

4.4 Results concerning the imagery paradigm...115

4.4.1 Affective rating due to scenes: Self-assessment manikin ...116

4.4.1.1 Valence rating of scenes...116

4.4.1.2 Arousal rating of scenes ...119

4.4.1.3 Dominance rating of scenes ...121

4.4.2 Results concerning physiological measurements due to scenes...123

4.4.2.1 Heart rate ...123

4.4.2.5 Respiration amplitude ...141

4.4.2.6 Respiration rate ...144

5. DISCUSSION ...155

5.1 Discussion concerning questionnaire-based data ...155

5.1.1 Questionnaires used for the screening...155

5.1.2 Questionnaires used before physiological recording ....155

5.2 Discussion concerning the defense paradigm...157

5.2.1 Heart rate ...157

5.2.2 Systolic blood pressure...158

5.2.3 Diastolic blood pressure ...158

5.2.4 Pulse amplitude ...159

5.2.5 Respiration amplitude ...160

5.2.6 Respiration rate ...160

5.2.7 Skin conductance...161

5.2.8 Startle reflex ...162

5.2.9 Heart rate variability...162

5.2.10 Summary of the discussion concerning the defense paradigm...163

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5.3 Discussion concerning the picture paradigm ...165

5.3.1 Affective rating due to pictures...165

5.3.1.1 Valence...165

5.3.1.2 Arousal ...165

5.3.1.3 Dominance ...166

5.3.2 Physiological responses due to pictures ...167

5.3.2.1 Heart rate ...167

5.3.3 Summary of the discussion concerning the picture paradigm...170

5.4 Discussion concerning the imagery paradigm ...173

5.4.1 Affective rating due to scenes ...173

5.4.1.1 Valence...173

5.4.1.2 Arousal ...174

5.4.1.3 Dominance ...175

5.4.2 Physiological responses due to scenes ...176

5.4.2.1 Heart rate ...176

5.4.2.5 Respiration amplitude ...183

5.4.2.6 Respiration rate ...184

5.4.3 Summary of the discussion concerning the imagery paradigm....189

5.5 Summary of discussion...195

5.6 Conclusions...197

6. SUMMARY ...199

7. ZUSAMMENFASSUNG ...203

LIST OF REFERENCES...208 APPENDIX

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LIST OF TABLES

Page Table 1a... 69 Overview of trials and stimulus material presented within the picture paradigm

Table 1b ... 70 Overview of trials and stimulus material presented within the imagery paradigm

Table 2a... 84 Internal consistencies, means and standard deviations for questionnaires used

for the screening

Table 2b ... 86 Internal consistencies, means and standard deviations for questionnaires used

before physiological recording

Table 3... 89 Means and standard deviations of the medians of each interval within defense

for heart rate

Table 4a... 91 Means and standard deviations of the medians of each interval within defense

for systolic blood pressure

Table 4b ... 92 Means and standard deviations of the medians of each interval within defense

for diastolic blood pressure

for pulse amplitude

Table 6a... 95 Means and standard deviations of the medians of each interval within defense

for respiration amplitude

Table 6b ... 97 Means and standard deviations of the medians of each interval within defense

for respiration rate

for skin conductance

for startle reflex

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Table 9... 100 Heart rate variability during defense

Table 10a... 102 Means and standard deviations for the SAM-rating pertaining to the dimension of valence Table 10b ... 103 Means and standard deviations for the SAM-rating pertaining to the dimension of arousal Table 10c... 105 Means and standard deviations for the SAM-rating pertaining to the dimension of

dominance

Table 11... 107 Means and standard deviations for picture valence for heart rate

Table 12a... 108 Means and standard deviations for picture valence for systolic blood pressure

Table 12b ... 109 Means and standard deviations for picture valence for diastolic blood pressure

Table 13... 111 Means and standard deviations for picture valence for pulse amplitude

Table 14... 112 Means and standard deviations for picture valence for skin conductance

Table 15... 113 Means and standard deviations for picture valence for the startle reflex

Table 16a... 117 Means and standard deviations for the SAM-rating pertaining to the dimension of valence Table 16b ... 120 Means and standard deviations for the SAM-rating pertaining to the dimension of arousal Table 16c... 122 Means and standard deviations for the SAM-rating pertaining to the dimension of

dominance

Table 17... 126 Means and standard deviations for valence of scenes by period for heart rate

Table 18... 130 Means and standard deviations for valence of scenes by period for systolic blood pressure Table 19... 135 Means and standard deviations for valence of scenes by period for diastolic blood pressure

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Table 20... 140 Means and standard deviations for valence of scenes by period for pulse amplitude

Table 21... 143 Means and standard deviations for valence of scenes by period for respiration amplitude Table 22... 147 Means and standard deviations for valence of scenes by period for respiration rate

Table 23... 151 Means and standard deviations for valence of scenes by period for skin conductance

Table 24... 153 Means and standard deviations for valence of scenes by period for the startle reflex

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LIST OF GRAPHICS AND FIGURES

Page Graphic 1a ... 68 Overview of the procedure of the defense and picture paradigm

Graphic 1b... 70 Overview of the procedure of the imagery paradigm

Figure 1a ... 85 Means for the total scores of the questionnaires used for the screening

Figure 1b... 87 Means for the total scores of anxiety, depression and worry-related measurements

Figure 1c ... 87 Means for the total scores of questionnaires related to control for imagery-related

abilities

Figure 2 ... 89 Heart rate during defense

Figure 3a ... 90 Systolic blood pressure during defense

Figure 3b... 92 Diastolic blood pressure during defense

Figure 4 ... 94 Pulse amplitude during defense

Figure 5a ... 95 Respiration amplitude during defense

Figure 5b... 96 Respiration rate during defense

Figure 6 ... 99 Skin conductance during defense

Figure 7 ... 99 Startle reflex during defense

Figure 8a ... 102 SAM valence rating of pictures by group

Figure 8b ... 104 SAM arousal rating of pictures by group

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Figure 8c ... 105 SAM dominance rating of pictures by group

Figure 9 ... 106 Heart rate during picture presentation

Figure 10a ... 108 Systolic blood pressure during picture presentation

Figure 10b... 109 Diastolic blood pressure during picture presentation

Figure 11 ... 110 Pulse amplitude during picture presentation

Figure 12 ... 112 Skin conductance during picture presentation

Figure 13 ... 113 Startle reflex during during picture presentation

Figure 14a ... 118 SAM valence rating for scenes by group

Figure 14b... 118 SAM valence rating for type of scene by group

Figure 14c ... 119 SAM arousal rating for scenes by group

Figure 14d... 121 SAM dominance rating for scenes by group

Figure 15a ... 123 Heart rate in half-second change scores during presentation, imagery and post-

interval for social phobic participants

Figure 15b... 123 Heart rate in half-second change scores during presentation, imagery and post-

interval for control participants

Figure 15c ... 124 Heart rate in average change scores during presentation

Figure 15d... 124 Heart rate in average change scores during imagery

Figure 15e ... 124 Heart rate in average change scores during post-interval

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Figure 15f... 125 Heart rate in average change scores across all three periods

Figure 15g ... 125 Heart rate for fear-related scenes during imagery

Figure 16a ... 127 Systolic blood pressure in second change scores during presentation, imagery and

post-interval for social phobic participants

Figure 16b... 127 Systolic blood pressure in second change scores during presentation, imagery and

post-interval for control participants

Figure 16c ... 128 Systolic blood pressure in average change scores during presentation

Figure 16d... 128 Systolic blood pressure in average change scores during imagery

Figure 16e ... 128 Systolic blood pressure in average change scores during post-interval

Figure 16f... 129 Systolic blood pressure in average change scores across all three periods

Figure 16g ... 131 Systolic blood pressure for fear-related scenes during imagery

Figure 17a ... 131 Diastolic blood pressure in second change scores during presentation, imagery and

Figure 17b... 132 Diastolic blood pressure in second change scores during presentation, imagery and

Figure 17c ... 132 Diastolic blood pressure in average change scores during presentation

Figure 17d... 133 Diastolic blood pressure in average change scores during imagery

Figure 17e ... 133 Diastolic blood pressure in average change scores during post-interval

Figure 17f... 133 Diastolic blood pressure in average change scores across all three periods

Figure 17g ... 134 Diastolic blood pressure for fear-related scenes during imagery

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Figure 18a ... 136 Pulse amplitude in second change scores during presentation, imagery and post-

interval for social phobic participants

Figure 18b... 137 Pulse amplitude in second change scores during presentation, imagery and post-

interval for control participants

Figure 18c ... 137 Pulse amplitude in average change scores during presentation

Figure 18d... 138 Pulse amplitude in average change scores during imagery

Figure 18e ... 138 Pulse amplitude in average change scores during post-interval

Figure 18f... 138 Pulse amplitude in average change scores across all three periods

Figure 18g ... 139 Pulse amplitude for fear-related scenes during imagery

Figure 19a ... 141 Respiration amplitude in percentage average change scores during imagery

Figure 19b... 141 Respiration amplitude in percentage average change scores during post-interval

Figure 19c ... 142 Respiration amplitude in percentage average change scores across two periods

Figure 19d... 142 Respiration amplitude for fear-related scenes during imagery

Figure 20a ... 144 Respiration rate in percentage average change scores during imagery

Figure 20b... 145 Respiration rate in percentage average change scores during post-interval

Figure 20c ... 145 Respiration rate in percentage average change scores across two periods

Figure 20d... 145 Respiration rate for fear-related scenes during imagery

Figure 21a ... 148 Skin conductance in half-second change scores during presentation, imagery and

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Figure 21b ... 148 Skin conductance in half-second change scores during presentation, imagery and

Figure 21c ... 149 Skin conductance in average change scores during presentation

Figure 21d... 149 Skin conductance in average change scores during imagery

Figure 21e ... 149 Skin conductance in average change scores during post-interval

Figure 21f... 150 Skin conductance in average change scores across all three periods

Figure 21g ... 150 Skin conductance for fear-related scenes during imagery

Figure 22a ... 152 Startle reflex during imagery

Figure 22b... 154 Startle reflex for fear-related scenes during imagery

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1. INTRODUCTION

Pertaining to the bio-informational model of Lang (1978, 1994), social anxiety can be conceptualized as the activation of an emotional network structure in memory, that is closely connected to evolutionary older regions of the brain. The activation of this network due to social phobia relevant stimuli leads to defensive reactions, like freezing or avoidance behavior. Under certain conditions, these for anxiety and fear typical reactions have protective functions in order to ensure the survival of the organism, whereas in social phobia as a clinical phenomena it is clearly maladaptive. In order to understand better the underlying structure of the assumed network as well as possible incoherencies between subjective perception of symptoms and physiological reactivity, this study compares social phobic participants with control participants within a Spanish sample, regarding questionnaire-based data on social anxiety, physiological reactivity and subjective report towards stimuli within the so-called defense, picture and imagery paradigm.

In chapter 2.1 an overview is given conceptualizing fear and anxiety as underlying basic aspects of social phobia within the bio-informational network model of emotion. Then, the concept of fear and anxiety and its adaptive versus maladaptive function is presented, before in chapter 2.2 social phobia as clinical phenomena with regard to diagnostical features (see paragraph 2.2.1), possibilities of subtyping the disorder (see paragraph 2.2.2), epidemiological data and information concerning psychosocial impairment and risk factors is explained (see paragraph 2.2.3). Further, social phobia will be introduced under an evolutionary (see paragraph 2.2.4) and a biological perspective, with the latter including genetic components, substance induced symptom provocation and controversially discussed abnormalities in several transmitter systems and the autonomous system (see paragraph 2.2.5).

This is followed by an integration of social phobia in the network model in chapter 2.3 with regard to the different types of information the network contains (see paragraph 2.3.1).

Further, neuronal structures that are closely linked to the activation of the fear network in general and with special focus on social phobia will be explained (see paragraph 2.3.2). Then the conditions under which the network can be activated will be introduced with emphasis on unconscious as well as higher cognitive processes, including the presentation of sensoric information, like within the picture paradigm or the imagination of emotional relevant material. Finally, the integration of behavioral-cognitive approaches and related empirical findings towards social phobia in the network model is undertaken (see paragraph 2.3.3).

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Chapter 2.4 presents the measurement of the response systems of the activated network, with special emphasis on affective report (see paragraph 2.4.1) and physiological responses (see paragraph 2.4.2), where the measurement of electrodermal activity, heart rate, heart rate variability, blood pressure, pulse, respiration, electromyography and startle reflex are explained, including its disadvantages and advantages concerning measurement (see paragraphs 2.4.2.1 to 2.4.2.7). Two factors underlying emotion, namely valence and arousal, defined by the pleasantness of stimuli and the physiological activation these stimuli produce, are introduced. Then the concept of the so-called defense cascade, a reaction pattern towards an aversive stimulus will be explained (see paragraph 2.4.3), as well as physiological reactivity within the picture paradigm (see paragraph 2.4.4).

In paragraph 2.4.5 the imagery paradigm will be presented in more detail with focus on social phobic subjects, their physiological reactivity in terms of the above mentioned parameters and therefore possible differentiations of subgroups. This is followed by interpretations of these results with regard to special characteristics the network in social phobia might have, before the hypothesis of this study will be formulated (see chapter 2.5).

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2. THEORY

2.1 Fear and anxiety as emotions

Emotions in the context of scientific study can be seen as a process that includes attention, information processing, arousal, mobilization and finally action; the latter does not necessarily occur in each context, because action might be suppressed (Davis & Lang, 2001). Lang (1995) conceptualizes emotion threefold, as they consist mainly of three components: language, in terms of reported affect¹ and expressive language, physiology and behavior. Influenced by Fridja’s concept, he assumes that these three components are represented in the form of memory structures in the brain, which can be characterized as an associative network. Emotional networks differ from other knowledge structures (see Anderson & Bower, 1974; Kintsch, 1974), in that they include connections to the primitive cortex, the sub-cortex and the mid-brain, which form the so-called primary motivational system that is crucial to ensure survival in terms of an evolutionary perspective. This system has a biphasic structure and can be differentiated in an appetitive and defensive system. The first mentioned is activated by pleasant stimuli that provoke approach-behavior, again under an evolutionary perspective these stimuli are mainly related to sexual and nuturant behavior, which enhance or maintain individuals or the species. The second one is activated by unpleasant stimuli that provoke defensive behavior like fight-flight reactions or withdrawal and these stimuli are related to any type of potential danger or harm they can produce (Bradley & Lang, 2000; Davis & Lang, 2001; Lang, Davis & Öhman, 2000). Each system can vary in terms of arousal, which reflects the intensity concerning metabolic and neural activation (see also Cacioppo & Bernston, 1994). This defense versus approach behavior can already be observed in simple organisms (Schneirla, 1959), but in human beings there exist many forms of emotion and patterns of response can vary within subjects and between contexts of stimulation, which are shaped by genetics and learning (Lacey, 1958; Lacey &

Lacey, 1970; Lang, Bradley & Cuthbert, 1990). So, for example, the activation of the defense system by an actual threat can lead to an anger reaction, as well as to a flight reaction (Lang, Bradley & Cuthbert, 1990). Therefore, human emotions are complex and show a great variety. But their fundamental organization remains motivational and they can

1 In this context emotions should be differentiated from “feelings” and “affect”, which can be interpreted as subjective inner states, and therefore as important components of emotions, but not as emotions per se (for an overview see Lang, 1994).

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be primarily described within a hypothetical two-dimensional space in terms of affective valence, namely appetitive versus aversive, and arousal as intensity of activation. In this sense, emotion can be viewed as biological phenomena that reflect evolutionary inheritance (Bradley & Lang, 2000) and can be defined as “action dispositions” (Fridja, 1986; Bradley

& Lang, 2000).

In fear and anxiety as negative emotions, it is assumed that the defensive motivational system is activated in order to serve as an adaptive function and to protect the organism of potential threat, which leads to an autonomic and somatic output. This output can be further differentiated into two types of behavior tendencies, one which is called defensive freezing, that includes vigilance and immobility and one that is called defensive action, that includes fight and flight reactions. In the following, differences between fear and anxiety, as well as their differentiation in adaptive versus maladaptive phenomena will be explained: As fear and anxiety are both characterized by tension, autonomic hyperactivity, apprehensive expectation and vigilance, there exist several approaches to distinguish between these two phenomena: Fear results as an emotion due to an external source of threat, whereas anxiety is defined as tension or apprehension due to the anticipation of danger in the absence of a recognizable external source of threat (see also APA, 1987). Epstein (1972) criticizes this view and mentions that external stimuli are not sufficient to distinguish between fear and anxiety. He relates fear to escape and avoidance behavior. If this behavior is blocked, fear turns into anxiety. Therefore, anxiety is seen as unresolved fear and a state of undirected arousal following the perception of threat. As mentioned above, fear and anxiety responses themselves are not malfunctional, but the fact that they can be triggered in a malfunctional context as in phobias or that there exist dysfunctionally low thresholds to activate them as in panic disorder, leads to pathological forms of fear and anxiety (Nesse, 1987; Öhman, Dimberg, Öst, 1985; Öhman, 1993). The difference between “normal” in the sense of adaptive and “clinical” in the sense of maladaptive with regard to fear and anxiety, are mainly the following. Clinical fear and anxiety are more recurrent and persistent. Their intensity is not reasonable in terms of danger or threat and tend to paralyze individuals and produce helplessness which in turn prevent them from coping well with the given context and lead to impaired psychosocial or physiological functioning (Marks & Lader, 1973;

Öhman, 1993). For a differentiation between the types of anxiety disorders see DSM-IV-TR (American Psychiatric Association, 2000).

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In the following, social phobia and its associated symptoms in terms of a maladaptive reaction towards social situations is presented. A differentiation into subtypes is given, which is followed by epidemiological, social demographical and etiological information under an evolutionary and biological perspective concerning the disorder, before social phobia will be integrated in more detail into the concept of Lang’s (1978, 1979, 1984, 1985, 1987, 1994) fear network model.

2.2 Social phobia

2.2.1 Diagnostical features of social phobia

According to the “Diagnostical and S tatistical Manual of Mental Disorders” (DSM -IV-TR, 2000), social phobia belongs to the diagnostical category of the anxiety disorders and is characterized by an intense and persistent fear of social and/or performance situations in which the person is confronted with unknown people and is worried that he/she will behave in a way that could be embarrassing or humiliating. The fear is recognized as exaggerated or unfounded and is avoided if possible. This response may take the form of a situationally bound or situationally predisposed panic attack. If avoidance is not possible, anxious anticipation and intense fear and distress is experienced. The person’s every day life, her normal routine and occupational functioning, as well as social activities and relationships are impaired or there is a marked distress about having the phobia. The diagnosis is not appropriate if the fear or avoidance is due to the effect of a substance or of a general medical condition or is better accounted for by another mental disorder, as well as if it is not limited to concern about its social impact. Associated descriptive features are hypersensitivity to criticism, negative evaluation or rejection, as well as difficulty being assertive, low-self esteem, or feelings of inferiority and often the manifestation of poor social skills.

Differential diagnosis with agoraphobia with and without panic attacks is not always clear, but the main difference is that social phobics experience panic attacks only in social contexts and their avoidance involves fear of evaluation and scrutiny (DSM-IV-TR, 2000).

2.2.2 Subtypes

The differentiation of social phobia in various subtypes is discussed controversially (Gerlach, 2002; Heimberg, Hope, Dodge & Becker, 1990; Manuzza, Schneier, Chapman, Liebowitz, Klein & Fyer, 1995). Wittchen and Fehm (2001) give an overview of different possibilities for subtyping social phobia: Performance versus interactional fear, speaking

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versus non-speaking fears, and social fears with and without deficits in social competence are mentioned. The most common differentiation refers to circumscribed or specific social phobia versus generalized social phobia.

2.2.2.1 Specific versus generalized social phobia

According to DSM-IV, social phobia can be specified as generalized if the fear includes most social situations, usually both public performance situations and social interaction situations, whereas the circumscribed or specific subtype refers to more specific social situations, mostly to public performance or speaking, when scrutiny is inevitable.

Approximately one third of the subjects with lifetime social phobia report experiencing fear of speaking, and two thirds report at least one additional fear (Kessler, Stein & Berglund, 1998). Further, individuals with generalized social phobia may be more likely to manifest deficits in social skills and to have severe social and work impairment (DSM-IV-TR, 2000;

Brunnello et al., 2000; Stemberger, Turner, Beidel & Calhoun, 1995; Turner, Beidel &

Townsley, 1992). Compared to subjects with specific social phobia, patients with generalized social phobia are younger, report an earlier age of onset, are less educated, less likely to be employed, and less likely to be married. They show higher measures of social anxiety, avoidance, general anxiety, and concerns about negative evaluation, as well as depression, more additional comorbid diagnosis and a more severe impairment. There are no differences in gender or anxiety during behavioral tests of observed social skills. (see Brown, Heimberg & Juster, 1995; Heimberg et al., 1993; Kessler, Stang, Wittchen, Ustan, Roy- Byrne & Walters, 1998). Although there exist only a few empirical studies (see for example Heimberg et al., 1990; Stein, Walker & Forde, 1996), Heimberg and colleagues differentiate between a generalized subtype, similar to the above mentioned authors, but in addition differentiate a non-generalized from a circumscribed subtype, which shows normal functioning in at least one broad social domain, whereas the circumscribed subtype experiences anxiety in one or two discrete situations (Heimberg, Holt, Schneier, Spitzer &

Liebowitz, 1993). Recent studies suggest that a schema including four different domains of situations in which social phobics may typically experience symptoms, namely, formal speaking and interaction, informal speaking and interaction, assertive interaction, and observation by others, can be useful for subtyping individuals with social phobia (Hofmann, Albano, Heimberg, Tracey, Chorpita & Barlow, 1999; Hofmann & Roth, 1996; Holt, Heimberg & Hope, 1992). Eng and colleagues (2000) criticize that attempts to determine subgroups have relied on clinical descriptions or a priori theoretical speculation, and propose

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therefore a model of subtyping that can be seen as a result of a cluster analysis on subscales which represent social interactions, public speaking, observation by others, and eating or drinking in public (Eng, Heimberg, Coles, Schneier & Liebowitz, 2000). Following Heimberg and colleagues’ classification, they found three gro ups that can be differentiated in terms of age, age of onset of social phobia, measures of social anxiety, general anxiety and depressive symptomatology and named them “pervasive social anxiety”, “moderate social interaction anxiety” and “dominant public s peaking anxiety”. Pervasive social anxiety resembles generalized social phobia, whereas moderate social interaction anxiety resembles specific social phobia, referring to social interaction and speaking situations. Dominant public speaking anxiety resembles specific social phobia pertaining only to public speaking fears. So, the latter two clusters represent a further differentiation within specific social phobia, but in general, the results of this analysis is very similar to the differentiation between specific versus generalized social phobia and Eng and colleagues themselves emphasize that future research is needed to examine whether these three groups assure clinical utility and how they are represented in a non-clinical population (Eng et al., 2000;

Heimberg, Holt, Schneier, Spitzer & Liebowitz, 1993).

2.2.2.2 Social phobia without versus with avoidant personality disorder

Further, social phobia can be differentiated in with and without comorbid avoidant personality disorder on axis II of DSM (for details see DSM-IV-TR, 2000). There is a continuum of increasing severity, from specific to generalized social phobia without and with avoidant personality disorder. Avoidant personality disorder may be a more severe variant of generalized social phobia, as the majority of the criteria for avoidant personality disorder include a social interaction component (Hofmann & Barlow, 2002). In addition, both diagnoses are associated with a high level of social anxiety, poor overall psychosocial functioning, greater psychopathology, high trait anxiety and depression (see for example Boone et al., 1999; Brown et al., 1995; Tran & Chambless, 1995). Scores on measures of social anxiety, of interpersonal sensitivity and general symptomatology, as well as measures of depression, are higher for subjects with generalized social phobia and avoidant personality disorder compared to subjects with specific social phobia and avoidant personality disorder.

With one exception according to trait anxiety (see Herbert, Hope & Bellack, 1992), there are no differences on measures of state and performance anxiety, neither on cognitive and somatic expressions of anxiety, nor on fear of negative evaluation or observer ratings of social skills, nor on demographic aspects, except that subjects with generalized social phobia

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and comorbid avoidant personality disorder seem to be less likely to be married (see Brown et al., 1995; Tran & Chambless, 1994). However, there are differences concerning the subtypes in cognitive processing (Hofmann, Gerlach, Wender & Roth, 1997; McNeil et al., 1995) and psychophysiological responses reported (Boone et al., 1999; Heimberg et al., 1990; Hofmann, Newman, Ehlers & Roth, 1995; Levin et al., 1993, see also chapter 2.5), as well as the presence of a higher percentage of traumatic conditioning experiences for the specific subtype (Stemberger et al., 1995).

In conclusion, although quantitative differences between social phobia and avoidant personality disorder are important (Boone et al., 1999; Tran & Chambless, 1995), there is a high overlap between these two diagnoses (Heimberg, 1996; Schneier, Spitzer, Gibbon, Fyer

& Liebowitz, 1991), so that some authors doubt whether this form of subtyping really differentiates these two disorders usefully (Brown et al., 1995; Herbert, Hope & Bellack, 1992; McNeil, 2001).

2.2.3 Epidemiology

2.2.3.1 Prevalence

In general, there exists a wide variety according to the lifetime prevalence and the prevalence for a defined period within social phobia. Lifetime prevalence can be estimated within the general population between 0.4% and 18.7% (Hwu, Yeh & Chang, 1989; Kessler, Stein & Berglund, 1998; Lee et al., 1990; Wacker, Müllejans, Klein, Battegay, 1992;

Wittchen, Nelson & Lachner, 1998), a 6 month prevalence between 1.1% and 1.5% (Canino et al., 1987; Robins & Regier, 1991) and a 12-month prevalence between 2.0% and 7.9%

(Kessler et al., 1994; see Lieb & Müller, 2002 for an overview; Wittchen, Pfister, Schmidtkunz, Winter & Müller, 2000). For example in the “National Comorbidity Survey”

conducted between 1990 and 1992 in the United States where 8098 subjects from the age of 15 to 54 were interviewed by the “Composite International Diagnostic Interview”, lifetime prevalence of 13.3% and a 12-month prevalence of 8% was found (Kessler et al., 1994). The most recent studies according to the prevalence of social phobia including DSM-IV criteria and using standardized interviews, were carried out in Australia, Germany and Italy.

Faravelli and colleagues reported in their study that 3.2% from a community sample of 2500 subjects being interviewed by use of the “Florence Psychiatric Interview”, which is reliable and valid against the “Composite International Diagnostic Interview”, suffered from social phobia during their lifetime (Faravelli et al., 2000). This could even be corrected to 4%, if

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age as a variable was considered. They found that women with a lifetime prevalence of 4%

showed twice the lifetime rate than men with 1.9%. Also, Kessler and colleagues found a female-to-male ratio for social phobia of 3:2 (Kessler et al., 1994), although with regard to treatment, both sexes are represented equally or the majority of patients treated for social phobia is male (DSM-IV-TR, 2000). Wittchen and colleagues (1999) found in their study

“Münchner Early Develop ment Stages of Psychopathology”, that from a sample of 3021 adolescents and young adults, aged 18 to 24 being interviewed from 1995 to 1999 by the

“Münchner -Composite International Diagnostic Interview”, lifetime prevalence for social phobia came to 8.7% and 12-month prevalence to 6.2%, whereas in a further sample of the

“Bundesweiten Gesundheitssurvey” from 1997 to 1998, 12 -month prevalence came to 2.0%

for a sample of 7124 subjects from the age of 16 to 65 (Wittchen, Stein & Kessler, 1999).

Andrews and colleagues reported a lifetime prevalence of 2.7% for an Australian sample of 10600 subjects aged 18 years and older, who were interviewed as well by the “Composite - International Diagnostic Interview” (Andrews, Hall, Teesson & Henderson, 1999). Becker and his group reported a lifetime prevalence of 12.0% in a sample of 1538 female adolescents who were between 18 and 25 years old using the “Diagnostisches Interview bei psychischen Störungen-Forschungsversion” (Becker, Türke, Neumer, Soeder, Krause &

Margraf, 2000). For a prevalence rate of social phobia in the Spanish population, there seem to be no actual data available. However, López (2001) found a lifetime prevalence of 8.9%

and a 12-month prevalence of 4.6% in a sample of 237 Spanish women.

Concerning subtypes of social phobia within community samples, specific social phobia can be estimated between 55% and 79% of social phobia (see Kessler et al., 1998; Lieb &

Müller, 2002; Robins & Regier, 1991), and is less frequent than generalized social phobia, whereas the generalized subtype is more frequent in clinical samples (for details see Amies, Gelder & Shaw, 1983; Holt, Heimberg & Hope, 1992; Turner, Beidel & Larkin, 1986).

Faravelli and colleagues reported that 42.9% of their subjects suffering from social phobia also have an additional diagnosis of avoidant personality disorder (Faravelli et al., 2000).

The comorbidity rates for generalized social phobia with avoidant personality disorder can be estimated between 25% and 89%, and is therefore higher than for specific social phobia with avoidant personality disorder, which can be estimated between 0% and 44% (for an overview see Brown et al., 1995).

In sum, prevalence for social phobia can be estimated as relatively high, although there exists a high variety according to prevalence relevant data. This variety can be explained by

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various aspects and has to be seen in the context that epidemiological studies suffer from heterogeneity. First, the composition of the sample can contribute to this diversity:

representative samples of the general population provide a fuller description of a disorder and its prevalence than do clinical samples, because the last mentioned already are influenced by the bias of self-selection. Samples with a higher proportion of younger adults report higher prevalence rates, because onset is also early. So studies including older subjects could correct prevalence rates and could consider an increasing number of partial remissions. Another aspect is cultural characteristics. In Asia, for example, social phobia has the lowest lifetime prevalence (see Hwu et al., 1989; Lee et al., 1990), which might be due to different constructs and mental representations of this condition and what might be regarded as shyness. In this context it is important to mention that diagnostic criteria and diagnostic instruments should be examined whether they are cross-culturally valid (Wittchen & Fehm, 2001). Second, diagnostic criteria lead to variance: between DSM-III and DSM-IV, for example, the coverage of qualifying situations for social phobia, the formulation of symptoms and the impairment and exclusion criteria have changed. But also within DSM-IV criteria, there remains the problem of a diagnostic threshold. According to distress and impairment, there is no clear cut-off criterion when social anxiety becomes pathologic, and it remains unclear how to distinguish social phobia from normal shyness (Brunnello et al., 2000; Wittchen & Fehm, 2001; Heiser, Turner & Beidel, 2003). The use of different interviews make the problem even more complex. So the frequently used “Composite International Diagnostic Interview” puts higher thresholds for severity than other interviews do (Brunnello et al, 2000). In addition, it is necessary to overcome the differences in evaluation methodology over different periods of time, as well as the lack of sufficient long term studies in order to reduce this diversity (Lieb & Müller, 2002).

2.2.3.2 Incidence

Within the general population, the Epidemiologic Catchment Area Program found a 1-year- incidence rate of 0.5% for social phobia, defined by the DSM-IV criteria (see Neufeld, Swartz, Bienvenu, Eaton & Cai, 1999) and also the “Münchner Follow -up Studie” found a 7 - year incidence rate of 0.3% (see Wittchen, 1993). Younger cohorts in general show a higher incidence rate: the “Münchner Early Development Stages of Psychopathology” showed an incidence rate of 2.8% for 4 years for the 14 to 24 year olds, which was even higher for the 14 to 17 year olds with 3.4% compared to the 18 to 24 year olds, if groups were split (Wittchen et al., 1999).

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2.2.3.3 Age of onset

The period when social phobia is manifested for the first time is typically early to late adolescence. Average age and high risk period is between 10 and 17, and the risk for beginning symptoms after the age of 25 is less likely and rather an exception. The generalized subtype seems to manifest earlier than the specific one (Brown et al., 1995;

Davidson, Hughes, George, Blazer, 1993; Degonda & Angst, 1993; DeWit, Ogborne, Offord, MacDonald, 1999; Faravelli et al., 2000; Lieb & Müller, 2002; Mannuzza, et al., 1995; Müller, 2002; Schneier, Johnson, Hornig, Liebowitz, Weissman, 1992; Stemberger, Turner, Beidel &Calhoun, 1995). The prevalence of social phobia in younger cohorts seems to augment, as they also show higher life-incidence rates, which was analyzed retrospectively by Magee and colleagues on the basis of the data of the “National Comorbidity Survey”. In this context, it should be mentioned that these results could be influenced by memory effects in older cohorts, which again shows the necessity of prospective longitudinal studies (Magee, Eaton, Wittchen, McGonagle & Kessler, 1996).

2.2.3.4 Course of social phobia

In retrospective studies, the clinical course of social phobia seems to be chronic (Amies et al., 1983; Marks, 1970; Öst, 1987) and often goes untreated with a significant impairment (Magee et al., 1996). The average duration in a clinical sample was reported between ages 10 to 21 (Lelliot, 1991; Lieb & Müller, 2002; Perugi, Simmonini, Savino, Mengali, Cassano

& Akiskal, 1990; Rapee, Sanderson & Barlow, 1988). In a community sample, it was reported between ages 19 to 29 (Davidson et al., 1993; DeWit et al., 1999; Lieb & Müller, 2002; Kessler et al., 1998). More valid than retrospective studies, are prospective longitudinal studies. The Zürich-Studie showed no stability in terms of a repeated fulfillment of all diagnostic criteria over a 10-year period, where subjects were interviewed four times.

14.7% received the diagnosis two times, but in a later additional study 41% reported still having fear or avoidance behavior (Degonda & Angst, 1993). In the “Münchner Early Development Stages of Psychopathology“, 11% of the subjects aged 14 to 24, showed a stable diagnosis for social phobia (Müller, 2002), and paralleling the findings of the “Zürich - Studie”, where 36.4% of the subjects still showed symptoms of anxiety in social situations.

Higher stability was found in the study of the “Epidemiologic Catchment Area Program”, showing that the beginning of social phobia before the age of 11 is related to a reduced probability of remission (Davidson et al., 1993; Lieb & Müller, 2002).

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2.2.3.5 Comorbidity

Comorbidity with other psychiatric disorders is estimated between 46% and 81% within the general population, as well as in clinical samples (see Brown, Campbell, Lehman, Grisham

& Mancill, 2001; Magee et al., 1996; Schneier, Johnson, Hornig, Liebowitz & Weissman 1992). Comorbidity rates for other anxiety disorders, major depression and dysthymia, as well as substance-, drug-, and nicotine abuse according to DSM-III, DSM-III-R and DSM- IV, from the Epidemiologic Catchment Area Program, the National Comorbidity Survey, the Zürich-, as well as the Münchner Early Development Stages of Psychopathology are the following: Within the anxiety disorders, specific phobia has the highest comorbidity rate with social phobia and lies between 37.6% and 59.0%, followed by agoraphobia with 8.8%

to 44.9%, posttraumatic stress disorder with 5.9% to 15.8%, generalized anxiety disorder with 2.3% to 13.3%, obsessive compulsive disorder with 2.3% to 11.1% and panic disorder with 4.7% to 10.9%, (see Lieb & Müller, 2002). Besides agoraphobia and specific phobia, social phobia is the most frequent anxiety disorder (DSM-IV-TR, 2000). The Münchner Early Development Stages of Psychopathology shows a comorbidity rate between social phobia and major depression and/ or dysthymic disorder of 43.9%, whereas the other above mentioned studies show a comorbidity rate between 16.6% and 25.5% for major depression and 10.9% to 14.6% for dysthymic disorder. Alcohol abuse and dependency range between 10.9 and 19.4%, drug abuse and dependency range between 5.3% and 14.8%, and nicotine dependency around 31.9%. Comorbidity rates with anorexia or bulimia nervosa are as well high with up to 60% (see Godart et al., 2000). Brown and colleagues found similar rates for a clinical sample, where 45% of the social phobics met criteria for either an anxiety or mood disorder, 28% for an anxiety disorder alone, and 29% for a mood disorder alone. Concerning comorbidity over a lifetime span, mood disorders range about 44% as comorbid disorder in social phobia (Brown et al., 2001). Merikangas and Angst (1995) conclude that social phobia normally precedes the comorbid disorder, except for specific phobia that seems to be manifested before the onset of social phobia (see Öst, 1987; Wittchen, Lieb, Schuster &

Oldehinekl, 1999).

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2.2.3.6 Psychosocial impairment

Wittchen and colleagues (2000) for example showed in a non-clinical case study, that subjects with social phobia without any further comorbid disorder feel clearly impaired with regard to their job or school education as well as their work productivity and intimate relationships. For social phobia with comorbidity the impairment was more severe. The study “Münchner Early Development Stages of Psychopathology” (Wittchen, Stein &

Kessler, 1999) showed high percentages of impairment within the areas of school, work, household, leisure time, social contacts and relationships for all subjects. The generalized subtype showed higher percentage rates due to impairment than the non-generalized subtype.

Anderson and Harvey (1988) found that over half of the social phobics in their study reported high levels of low sociability and loneliness.

2.2.3.7 Risk factors

In epidemiological and community-based studies, women seem to have a 1.5 to 2 times higher risk for social phobia (DSM-IV-TR, 2000; Lieb & Müller, 2002), which is lower compared to other anxiety disorders. In many clinical samples women and men are equally represented or the majority is male (DSM-IV-TR, 2000; Faravelli et al., 2000). Subjects with social phobia are less likely to be married and more likely to live separated. Separation can also lead to the outbreak of social phobia. Social status is lower compared to healthy controls, whereas this factor must be considered as well as a possible consequence of social phobia. Temperamental factors like behavioral inhibition and physiological aspects like a higher heart rate frequency and higher levels of cortisol, as well as cognitive, perceptional and attention related factors can be seen as risk or related factors to social phobia (see Lieb

& Müller, 2002). Concerning familiar risk factors there is a higher occurrence within families, and twin studies support a genetic component as well as a high influence due to environmental factors (see paragraph 2.2.5).

Below, an overview of social phobia under an evolutionary as well as under a biological perspective is given, with the latter including aspects pertaining not only to genetics, but also substance induced symptom provocation, transmitter systems and the autonomous nervous system with possible deviations regarding social phobia being discussed.

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2.2.4 Social phobia under an evolutionary perspective

Nesse (1998), Tooby and Cosmides (1990) argue that fear and anxiety evolve because they are adaptive in terms of genetic fitness, referring to Darwin’s principle of the survival of the fittest, because they help in anticipating danger and facilitating avoidance and escape.

Gilbert and colleagues combine this evolutionary perspective with social phobia. They assume that humans like other species, compete with one another for resources and seek or appear attractive to conspecifics, sexually or otherwise (Gilbert & McGuire, 1998; Gilbert &

Trower, 1990). According to Chance (1988), they differentiate two forms of group living in the service of reproductive success, an agonic, or threat based mode, which is characterized by dominance hierarchies and the hedonic, or affiliation based mode, which is characterized by mutual dependence and reciprocal relationships. Anxiety depends on the activation of the appraisal of stimuli as threat or loss that might endanger the position or status of an individual within its social group. In this sense, anxiety serves as a useful function because it helps to regulate social life while minimizing the risks of aggression or a breakdown in the group’s activity. It also serves the function of providing the indi vidual with self-knowledge, enhancing awareness of standards of behavior and encouraging processes of self-regulation.

It then becomes dysfunctional when anxiety is perceived in any type of social interaction. In this context, the defense system might be activated inappropriately, which may result as a consequence of a lack of an activation of the so-called safety-system or from the fear of appearing unattractive to others (Crozier & Alden, 2001; Gilbert & McGuire, 1998; Gilbert

& Trower, 1990).

Öhman (1986, 1993) sees social conflicts as a consequence of the above mentioned dominance hierarchies. He also argues that within an evolutionary perspective humans form dominance-submissive-systems that have adaptive functions in order to promote social order by means of facilitating the establishment of dominance-hierarchies with advantages of being nearer to the top than the bottom. Even individuals occupying lower parts of the hierarchy have advantages of remaining in the group, but are forced at the same time to interact with others higher in the hierarchy. Referring to social anxiety this means that individuals have to confront these interactions despite their anxiousness. As competing dominance involves threat and fear, this is portrayed by corresponding facial expressions.

This means that for an angry facial expression as a conditioned stimuli the conditioning process might be facilitated in terms of a biological preparedness. Mogg and Bradley (2002) showed a vigilance effect for masked threat faces in socially anxious subjects. Some

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empirical evidence also exists, that aversive conditioning processes on angry facial expressions compared to happy or neutral facial expressions have a higher resistance to extinction, but not a faster acquisition of the conditioned reaction, so that the concept of preparedness referring to social phobia in this context remains to be proven (Dimberg, 1986;

Hermann, 2002; Öhman, 1986; Öhman, Dimberg & Öst; 1985).

Bond and Siddle (1996) draw several predictions from Öhman’s theory. As Öhman (1985) points out, dominance hierarchies begin during adolescence, which could serve as an explanation as to why the onset of social phobia is often in adolescence. In general, there might be readiness in any individual to associate an angry facial expression with an aversive outcome. There might however be individual differences, so social phobics could be especially sensitive for instance. These differences should be especially noticeable in interactions with strangers, where dominance relationships are still unknown. Due to the need to stay within the social group, it is not always possible to avoid these situations even if a dominance encounter is lost. So, in this case, individuals have to signal that loss and make the best of it. This reaction is more subtle than, for example, an active avoidance behavior.

Therefore, there might be less reflexive sympathetic activation shown, as for example within animal phobias. In addition, the need to appraise the situation and to choose from several possible responses means that there will be a greater reliance on controlled processing (Bond

& Siddle, 1996; Shiffrin & Schneider, 1977).

2.2.5 Social phobia under a biological perspective

According to Hermann (2002) there exists relatively little knowledge according to neurobiological correlates of social phobia compared to other anxiety disorders. She distinguishes between two approaches, one oriented towards neurosciences, classical conditioning, as well as neuroplastic changes and a second one oriented towards biological- psychiatric aspects which includes genetic predispositions, abnormalities in neurotransmitter systems and endocrinology, which the latter approach being presented below.

2.2.5.1 Genetics

According to genetic aspects, family studies show a higher frequency for social phobia, but this does not allow any statement about heritability. If a case-control-design is used as a method where relatives of social phobics, the so-called “cases” are compared with control subjects, social phobia is found with a frequency three times higher in relatives than in

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control subjects (Fyer, Mannuzza, Chapman, Liebowitz & Klein, 1993; Merikangas, Risch

& Weissman, 1994; Reich & Yates, 1988). These studies have the assumption in common that social phobia is a homogenous clinical disorder. But it is not clear if the genetic component varies in its significance according to different subtypes of social phobia. Stein and colleagues (1998) found a ten times higher risk for the generalized subtype in families of social phobics, whereas for fear of performance, and non-generalized social anxiety no differences were found (Mannuzza et al., 1995; Stein et al., 1998). The familiar frequency for social phobia seemed to be specific, because there were no differences in frequency found between relatives of social phobics and controls regarding other anxiety disorders like specific phobias and panic disorder, and the frequency of social phobia was higher in families of social phobics compared to families of specific phobia or panic disorder (Fyer et al., 1993).

There are no data on adoption studies available concerning social phobia (Hermann, 2002;

Margraf & Schneider, 2003). Twin studies, which included either exclusively or mainly women as subjects, showed a concordance rate for social phobia between 24% and 47% for monozygot and 15% for heterozygot twins (Hermann, 2002; Kendler, Neale, Kessler, Heath

& Eaves, 1992; Skre, Onstad, Torgersen, Lygren & Kringlen, 2000). As in anxiety disorders in general, the heredity for a predisposition for social phobia can be estimated between 30%

and 50%, which means, that environmental influences are also crucial (Hettema, Neale &

Kendler, 2001; Kendler, Heath, Martin & Eaves, 1987; Reiss, Plomin & Hetherington, 1991). Studies concerning the heredity of subtypes of social phobia are missing. To date, there are no genetic abnormalities or genes identified that could be seen in relation with social phobia, so the genetic disposition to develop social phobia may be nonspecific (Hofmann, 2002). However, twin studies point towards a specific genetic vulnerability (Kendler et al., 1992), especially for the generalized subtype (Hermann, 2002).

2.2.5.2 Substance induced symptom provocation

Substance induced symptom provocation methods try to provoke anxiety reactions by inhaling or administrating various substances, like caffeine, lactate, or carbon dioxide. If such a response can be provoked, this can be interpreted as a hypersensitivity of central chemoreceptors, that could be discussed as a genetic predisposition, as for example in panic disorder (Hermann, 2002; Klein, 1993; Papp, Klein & Gorman, 1993; Perna, Bertani, Caldirola & Bellodi, 1996; Perna, Cocchi, Bertani, Arancio & Bellodi, 1995). Compared to controls, social phobics show a higher rate of panic attacks after inhaling a mixture of highly

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concentrated carbon dioxide. However, the frequency of occurring attacks was lower compared to patients with a panic disorder (Gorman et al., 1990; Papp et al., 1993). So social phobics failed to show the specific and sensitive anxiety reaction that panic patients develop when inhaling a 5% mixture of carbon dioxide (Caldirola, Perna, Arancio, Bertani &

Bellodi, 1997; Gorman et al., 1990; Holt & Andrews, 1989; Papp et al., 1993; Pine et al., 2000; Rapee, Brown, Antony & Barlow, 1992). Neither hyperventilation nor infusions of lactate led to a higher rate of panic attacks (Holt & Andrews, 1989; Liebowitz et al., 1985;

Rapee et al., 1992). Caffeine led to higher rates of panic attacks in social phobics compared to controls. However, social phobics reported the induced feelings of anxiety as less typical compared to the feelings of anxiety they experience in social situations (Tancer, Mailman, Stein, Mason, Carson & Golden, 1994). The administration of pentagastrin led to panic attacks with equal frequency in social phobics than in panic patients, but only in the context of a social interaction task, which might have in turn influenced the results (McCann, Slate, Geraci, Roscow-Terrill & Uhde, 1997). Taking into account the few studies that exist, it is only partially possible to draw conclusions concerning the importance of a chemical hypersensitivity in social phobia, which is less profound compared to panic patients, but more pronounced compared to controls (Hermann, 2002).

2.2.5.3 Transmitter systems

According to direct measurements in transmitter systems, the concentration of transmitters or their metabolites in the blood or the cerebrospinal liquid, the density of receptors for a specific transmitter, the affinity and the bonding capacity of receptors that regulate the reuptake of a transmitter and are located at the presynaptical side, are common measurements.

As indirect methods, the measurement of a target parameter, for example the distribution of hormones that are controlled by a specific transmitter is applied, and deviations of the expected effect as a consequence of the stimulation by means of an agonist or antagonist, allow conclusions pertaining to changes in the functionality of the transmitter system.

Results concerning the investigation of abnormalities in the transmitter system in social phobics are inconsistent or not demonstrable, for one reason because the studies are hardly comparable due to different registration of functional aspects of transmitter systems, different measurements and heterogeneous samples (Hermann, 2002), and often they do not control for effects of the experimenter or performance demands in the laboratory setting (Craske, 1999). A brief overview of research due to related results to neuroendocrinology and several transmitter systems referring to social phobia is given below.

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Neuroendocrinology

There are no empirical studies that could support the hypothesis of a dysfunction of the hypothalamus-hypophysis-adrenal-suprarenal-axis or the hypothalamus-hypophysis-thyroid- axis in social phobics. There were no heightened levels of cortisol found and reaction on the dexamethason-suppression test was normal (for details see Hermann, 2002; Potts, Davidson, Krishnan, Doraiswamy & Ritchie, 1991; Tancer, Stein, Gelernter & Uhde, 1990; Uhde, Tancer, Gelernter & Vittone, 1994).

GABA

There are very few clues which indicate a reduced activity of the central GABA system (Bell, Malizia & Nutt, 1999; Coupland, Bell, Potokar, Dorkins & Nutt, 2000). There might be a reduction of the density of peripheral benzodiazepin receptors, which might rather reflect the distress experienced by social phobics through repeated confrontation with social, and therefore anxiety and fear provoking situations and might be less specific for social phobia itself (Hermann, 2002; Johnson et al., 1998; Weizman et al., 1994).

Noradrenalin

Several measurements of adrenerg functioning like the administration of adrenerg agonists, for instance, clonidine (Craske, 1999; Hermann, 2002; Nicholas & Tancer, 1995; Tancer, Stein & Uhde, 1993; Tancer, Stein & Uhde, 1994), the infusion of epinephrine (see Papp, Gormann, Liebowitz, Fyer, Cohen & Klein, 1988) and the measurement of receptor activity in peripheral tissue, which reflects the central receptor activity (Stein, Huzel & Delaney, 1993) show contradictory results and do not give clear hints of a central, noradrenergic hyperactivity.

Serotonin

Concerning serotonin, in studies regarding density, as well as affinity of serotonerg receptors there were no differences found between social phobics and controls (Chatterjee, Sunitha, Velayudhan & Khanna, 1997; Stein, Delaney, Chartier, Kroft & Hazan, 1995). Hollander and colleagues, as well as Tancer and his group, could show a normal serotonerg mediated release of prolactin but a heightened release of cortisol, which was interpreted as a specific hypersensitivity of postsynaptical receptors of the serotonerg system (Hollander et al., 1998;

Tancer, Mailman et al., 1994). So, although the given effectivity of pharmacological

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treatment with selective serotonin reuptake inhibitors of social phobia, like paroxetine (Gorman & Kent, 1999; Stein et al., 1998), fluvoxamine (vanVliet, den Boer & Westenberg, 1994), sertraline (Katzelnick et al, 1995), and fluoxetine (Black, Uhde & Tancer, 1992;

Schneier, Chin, Hollander & Liebowitz, 1992; Sternbach, 1990; vanAmeringen, Mancini &

Streiner, 1993), there remain inconsistent results regarding the functionality of the serotonerg system (Hermann, 2002).

Dopamin

Concerning the dopaminerg system, structural abnormalities in social phobias were postulated because of the specific effectiveness of the MAO-inhibitor Phenelzin, an antidepressant, (Gelernter et al., 1991; Liebowitz, Campeas & Hollander, 1987; Liebowitz et al., 1992; Versiani, Nardi, Mundim, Alves, Liebowitz & Amrein, 1992), as well as through results by other pharmacological stimulation (Mikkelsen, Detlor & Cohen, 1981; Stein, Heuser, Juncos & Uhde, 1990; vanVliet, denBoer, Westenberg, 1992). Slaap and colleagues found that social phobics reacted positively towards fluvoxamine or brofaromine, a MAO- inhibitor. Non-responders were characterized by higher heart rate and blood pressure as well as higher scores on several psychometric scales (Slaap, vanVliet, Westenberg & denBoer, 1996). Potts and Davidson (1992), as well as Tiihonen and colleagues, who included controls in their study found via single-photon-emission-computed-tomography, a diminished density of receptors (Potts & Davidson, 1992; Tiihonen, Kuikka, Bergström, Leopola, Koponen & Leinonen, 1997). Schneier and colleagues found a reduced dopamine bonding (Schneier, Liebowitz, Abi-Dargham, Zea-Ponce, Lin & Laruelle, 2000). Johnson and colleagues could show a lower level of the primary dopamine metabolite, homovanillin (Johnson, Lydiard, Zealberg, Fossey & Ballanger, 1994). Diminished activity of the dopaminerg system can be seen best of all as a biological marker and specific for social phobia, as this could not be found in other anxiety disorders, except to some extent in specific phobia. However, alternatively this could also be seen as a correlate of comorbid depression, as in many studies it remains unclear if they controlled for dysthimic disorder or subclinical depression (Hermann, 2002; Kestler, Malhotra, Finch, Adler & Breier, 2000;

Parsey et al., 2001). Recently, the activity of the dopaminerg system as a neurobiological correlate of so called extraverted behavior that can be characterized by active search for interpersonal contact, little shyness, and a tendency towards dominant behavior and the seeking for new stimuli in general, is discussed (Cloninger, 1994; Depue & Collins, 1999;

Hermann, 2002).