Harm avoidance and incompleteness as dimensional endophenotypes in anxiety and OC spectrum disorders

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PROJECT SUMMARY Obsessive Compulsive (OC) spectrum and anxiety disorders are the most prevalent psychiatric conditions in the United States. The economic costs of these disorders to society are enormous, accounting for 31% of total mental health costs. In spite of the development of effective cognitive behavioral and pharmacologic treatments, a substantial portion of patients remain ill. The limitations of symptom and diagnosis based approaches in understanding the underlying pathobiology of anxiety and OC spectrum disorders, coupled with the need for better treatments, strongly suggest the importance of looking beyond symptoms and diagnoses toward latent dimensional endophenotypes. The overall goal of this study is to link key aspects of OC spectrum and anxiety psychopathology with a circuit-based model of disease. We propose to test the validity of a novel conceptual model of two core constructs, harm avoidance (HA) and incompleteness (INC) postulated to be underlying motivational drives leading to OC and anxiety symptoms, and posited to be differentially associated with specific neural circuits and cognitive affective tasks. In order to take the initial steps in this process, we conceptualize these two core constructs (INC and HA) as specific RDoC domains and assess them using cognitive affective paradigms associated with specific frontostriatal circuitry. We will then test whether there are different patterns of resting state functional connectivity and diffusion imaging parameters associated with these core constructs. This study has significant implications for the development of a reconceptualization of the heterogeneity of the OC spectrum and anxiety disorders. Broadening the scope of target circuits can pave the way for novel advances in our understanding of mechanisms of etiology, as well as the development of novel psychosocial and biological interventions.