The Neural Basis of Social Cognition and Its Relationship to Social Functioning in Young People at Risk for Schizophrenia The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Lincoln, Sarah Hope. 2015. The Neural Basis of Social Cognition and Its Relationship to Social Functioning in Young People at Risk for Schizophrenia. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845421 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA The neural basis of social cognition and its relationship to social functioning in young people at risk for schizophrenia A dissertation presented by Sarah Hope Lincoln to The Department of Psychology in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the subject of Psychology Harvard University Cambridge, Massachusetts May 2015 © 2015 Sarah Hope Lincoln All rights reserved. Dissertation Advisor: Professor Christine I. Hooker Sarah Hope Lincoln The neural basis of social cognition and its relationship to social functioning in young people at risk for schizophrenia Abstract These three studies seek to contribute to the neurological characterization of the development of schizophrenia as well as begin to branch into understanding how neuroanatomical structure and function may relate to specific deficits in social cognition and social functioning within in this population. Paper #1 investigates the relationship between brain structure in young adults at clinical high risk for schizophrenia and social functioning. Paper #2 expands upon the findings of paper #1 by looking at brain structure, social cognition, and social functioning in children and risk for psychosis. Finally, paper #3 focuses on brain function for theory of mind in typically developing children and its relationship to social cognition and social functioning. Investigating the neural mechanisms underlying social cognitive deficits and social functioning impairment in young adults and children at risk for schizophrenia will contribute to the field’s understanding of the development of this disorder. iii Table of Contents Abstract ......................................................................................................................................... iii Acknowledgements ....................................................................................................................... v Background and Introduction ........................................................................................................ 1 Social Dysfunction in Schizophrenia Spectrum Disorders………................................................. 1 Social Cognition and Social Functioning in the At-Risk Population............................................. 2 Neurobiology of Social Cognition.................................................................................................. 5 Neurobiology in Clinical At-Risk .................................................................................................. 6 Research Questions ........................................................................................................................ 7 Paper #1: Neural structure and social dysfunction in individuals at clinical high risk for psychosis....................................................................................................................................... 10 Paper #2: Neural structure in children at clinical high risk for schizophrenia.............................. 28 Paper #3: The neural basis of social cognition in typically developing children and the relationship to social functioning.................................................................................................. 51 Discussion and Conclusion .......................................................................................................... 72 Summary of Findings ................................................................................................................... 72 Implications .................................................................................................................................. 74 Limitations ................................................................................................................................... 77 Conclusion ................................................................................................................................... 78 iv Acknowledgements I would like to thank my advisor, Dr. Christine I. Hooker, for her teaching, mentorship, and unfailing belief in these projects and in me. I would also like to thank the members of my committee, Dr. Larry J. Seidman, Dr. Matthew Nock, and Dr. Eugene D’Angelo, for their thoughtful comments and support throughout this endeavor. To my colleagues and friends, Laura Tully, Laura Germine, and David Dodell-Feder, I am incredibly grateful for your wisdom, generosity, and friendship-you make the impossible seem reasonable. I am indebted to Natalie Kleeman for her undeniable enthusiasm and commitment to this work. Additional thanks to the SNAP Lab, including a team of amazing research assistants, Alexandra Arnold, Lindsey Rosen, Ariel Suazo-Maler, and Katherine Frost, who made this project possible. I am incredibly privileged to work with an amazing team of researchers in our lab; you all have been invaluable resources. To my graduate school cohort, Don Robinaugh and Alex Millner, your unending support and knowledge have made me a better scientist. Special thanks must be given to the Wellesley community, including my mentors, Dr. Tracy Gleason, Dr. Julie Norem, and Dr. Sally Theran, who first introduced me to the idea and the excitement of being a woman in science. Thank you to my best friends Amita Parashar and Jennifer Sohn, who found innumerable ways to empower and entertain. Finally, to my family, in particular mom, dad, and Andrew, who taught me that compassion and love, go hand in hand with scientific adventures, and whose faith in me never ceases, I am grateful. This work was generously funding by the Sackler Scholars in Psychobiology, the Richmond Fellowship from the Center on the Developing Child, and the Advanced Multimodal Neuroimaging Grant. v ! Background and Introduction A complex brain disorder, theories on the etiology of schizophrenia have argued for a disorder of neurodevelopment (Rapoport et al., 2005; Seidman, 1990), others a neurodegenerative disorder that begins in early development (Lieberman, 1999), or perhaps a combination of the two (Ashe et al., 2001). Though there is an extensive body of literature on schizophrenia, its symptoms, treatments, risk factors, and progression from behavioral and biological perspectives, what remains unclear are the questions of what and when in regard to the disruption of the neurobiology. The factors that set the stage for the development of this disorder, likely a combination of biological and environmental variables, are at this time unknown. This dissertation addresses specific aspects of the etiology of the disorder, by focusing on at-risk populations, in different age groups, to make connections between neurobiology, behavior, and symptoms, in order to better understand factors throughout development that may relate to the onset of the disorder. Specifically, we focus on one of the core symptoms of schizophrenia, social impairment, given that this symptoms is seen before the onset of the disorder (Addington et al., 2008b), is predictive of symptom severity (Addington et al., 2003a), and is often unchanged by typical psychopharmacological treatment (Bond et al., 2004; Hamilton et al., 2000). Below I present a targeted review of the relevant literature, and then a statement outlining the specific research questions addressed by this dissertation. What follows are three papers addressing these research questions, and then a summary of the implications of this work. Social Dysfunction in Schizophrenia Spectrum Disorders Social dysfunction in schizophrenia is a particularly debilitating symptom, negatively affecting individuals’ self-care, interpersonal relationships, and family and occupational functioning. Research has shown that social dysfunction is an early predictor of schizophrenia. ! 1! ! Clinical studies with individuals at risk for schizophrenia have suggested that deficits in social functioning may be one of the earliest key predictive markers for the future onset of psychosis (Addington et al., 2008b). More specifically, global deficits in social functioning are apparent in individuals at a clinical high risk for schizophrenia relative to healthy controls (Addington et al., 2008b) (Ballon et al., 2007). Social functioning deficits before the onset of psychosis are predictive of overall symptom severity, cognitive deficits, and general functioning (Addington et al., 2003b). Additionally, premorbid social functioning is predictive of clinical high risk (CHR) individuals who transition to a psychotic disorder versus those who do not (Tarbox et al., 2013). The goal with this research is to elucidate the underlying factors that contribute to social dysfunction in individuals at risk for schizophrenia. Social Cognition and Social Functioning