ANHEDONIA AND DEFICITS IN POSITIVE EMOTIONAL EXPERIENCE IN INDIVIDUALS WITH GENETIC LIABILITY FOR SCHIZOPHRENIA A Dissertation Presented to The Faculty of the Graduate School At the University of Missouri In Partial Fulfillment Of the Requirements for the Degree Doctor of Philosophy By Anna R. Docherty Dr. John G. Kerns, Dissertation Supervisor MAY 2013 The undersigned, appointed by the dean of the Graduate School, have examined the dissertation entitled ANHEDONIA AND DEFICITS IN POSITIVE EMOTIONAL EXPERIENCE IN INDIVIDUALS WITH GENETIC LIABILITY FOR SCHIZOPHRENIA Presented by Anna Docherty A candidate for the degree of Doctor of Philosophy of Psychology And hereby certify that, in their opinion, it is worthy of acceptance. Professor John Kerns Professor Denis McCarthy Professor Bruce Bartholow Professor Judith Miles ACKNOWLEDGEMENTS I would like to express my deepest gratitude to John Kerns, my advisor, mentor, and dissertation committee chair. He has provided excellent guidance and support during my doctoral training. I am also grateful to my dissertation committee members, Drs. Denis McCarthy, Bruce Bartholow, and Judith Miles. Each member has provided strong mentorship and support throughout the development of this program of research, and their expertise has greatly enhanced this dissertation. Drs. Scott Sponheim, Phil Wood, Deborah Levy, and Daniel Weinberger have provided exceptional mentorship, resources, and technical support during the process of research design, data collection, and data analysis. I am grateful to the participants, and to the graduate and undergraduate research assistants at the Minneapolis Veterans Affairs Medical Center and at the University of Minnesota, without whom the project would have not been possible. ii TABLE OF CONTENTS ACKNOWLEDGEMENTS .......................................................................................ii LIST OF TABLES .....................................................................................................iv LIST OF ILLUSTRATIONS .....................................................................................vi CHAPTER 1: INTRODUCTION ..............................................................................1 OVERVIEW .........................................................................................................1 BACKGROUND AND SIGNIFICANCE ............................................................4 RESEARCH AIMS ...............................................................................................15 CHAPTER 2: METHODS .........................................................................................18 CHAPTER 3: RESULTS ...........................................................................................34 PRELIMINARY ANALYSES .............................................................................34 HYPOTHESES 1-4: Individuals with Schizophrenia...........................................38 HYPOTHESES 5-9: First-Degree Relatives and Controls ...................................43 SUPPLEMENTAL ANALYSES..........................................................................46 CHAPTER 4: DISCUSSION .....................................................................................55 REFERENCES ..........................................................................................................66 TABLES ....................................................................................................................86 APPENDIX ................................................................................................................101 DNA COLLECTION METHODS ......................................................................101 OLFACTORY HEDONIC RATING FORM ......................................................106 CURRENT AFFECT RATING LIST .................................................................107 VITA ..........................................................................................................................108 iii LIST OF TABLES Table 1 ........................................................................................................................86 Demographic Characteristics: Schizophrenia Probands, First-Degree Relatives, and Controls Table 2 ........................................................................................................................87 Spearman Correlations among Self-Report and Interview Measures of Negative Symptoms: Participants with Schizophrenia Table 3 ........................................................................................................................88 Divergent Validity of Anhedonia Measures with Other Measures of Negative Symptoms and Personality: Participants with Schizophrenia Table 4 ........................................................................................................................89 Spearman Correlations among Affect Measures: Participants with Schizophrenia Table 5 ........................................................................................................................90 Spearman Correlations among Affect Measures: First-Degree Relatives Table 6 ........................................................................................................................91 Spearman Correlations among Affect Measures: Controls Table 7 ........................................................................................................................92 Associations between Interview Ratings of Negative Symptoms and Hedonic Liking and Wanting Measures in the Schizophrenia Probands Table 8 ........................................................................................................................93 Associations between Self-Reported Symptoms, Personality and Hedonic Liking and Wanting Measures in the Schizophrenia Probands Table 9 ........................................................................................................................94 Correlations of Hedonic Liking and Wanting Measures with Self-Reported Schizotypal Traits in First-Degree Relatives iv Table 10 ......................................................................................................................95 Comparisons of Emotion Variable Means Table 11 ......................................................................................................................96 Intensity of Positive Affect (PA) and Negative Affect (NA) by Arousal Level and by Measure Across Groups Table 12 ......................................................................................................................97 Comparisons of Self-Reported Interpersonal Traits in Probands and Relatives Table 13 ......................................................................................................................98 Comparisons of Self-Reported Interpersonal Traits in Relatives and Controls Table 14 ......................................................................................................................99 Associations between Ambivalence in Hedonic Behavioral & Self-Report Measures and Affect in Schizophrenia Probands v LIST OF ILLUSTRATIONS Figure 1 ......................................................................................................................100 Comparison of Ambivalence across Groups vi 1. INTRODUCTION Overview There is growing evidence that anhedonia--the extent to which an individual reports pleasure or interest in social and physical stimuli--is important to the pathophysiology of schizophrenia. Anhedonia has been associated with genetic liability to schizophrenia in several studies (Clementz, 1992; Kendler, 1996; Docherty & Sponheim, 2008) and has predicted the future development of schizophrenia-spectrum disorders (Kwapil, 1998, Gooding, 2006). At the same time, in patients with schizophrenia, anhedonia has been associated with poor long-term outcome (Fenton & McGlashan, 1991). Despite the importance of anhedonia as an endophenotype of schizophrenia, there are unanswered questions about what anhedonia is , and how anhedonia relates to the pathogenesis of the disorder. It has long been thought that the symptom might reflect emotion deficits (Burbridge & Barch, 2007). In multiple studies using standardized stimuli, we found that anhedonia in nonclinical individuals is associated with decreased self-reported positive affect (PA) intensity (Kerns, Docherty & Martin, 2008). However, the association of anhedonia with decreased PA intensity has not yet been examined in people with schizophrenia or their biological relatives. At the same time, some research has suggested that there are different facets of positive affect experience, such as liking vs. wanting (Berridge & Robinson, 1998). Previous research has not directly examined the relationship between anhedonia and task measures of liking and wanting. 1 In addition to decreased PA intensity, other research has found evidence that anhedonia is associated with specific risk alleles. In particular, in one prior study we found that relatives with a high-activity polymorphism of the Val158Met COMT gene (rs4680) responsible for dopamine regulation have higher levels of anhedonia (Docherty & Sponheim, 2008). Importantly, previous research has consistently found evidence for an involvement of dopamine in the experience of PA (DePue, 1999). This suggests that decreased PA intensity in anhedonia might be related to COMT alleles. However, previous research has not examined the relationship