Central and Peripheral Nervous System Correlates of Difficulty Discarding in Hoarding Disorder

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There is a critical gap in our understanding of the underlying neurobiological mechanisms of difficulty discarding, the core behavioral feature of hoarding disorder (HD). This gap represents an important problem because, until it is filled, the field will not be able to precisely identify mechanistic targets for new treatment development in HD. The long-term goal of the proposed research is to identify biomarkers of difficulty discarding in HD and to develop treatments that engage those biomarkers. This is important because current treatments for HD are only modestly effective, with only a 35% response rate across studies. The short-term goal here is to determine the peripheral (PNS) and central nervous system (CNS) correlates of difficulty discarding behavior in HD and to distinguish these correlates from related psychopathology. The rationale for this goal is that by assessing PNS and CNS responses and the degree to which they are unique to HD and specifically to difficulty discarding, we will identify meaningful biomarker-based intervention targets. We will recruit 40 patients with primary HD, 40 clinical controls with anxiety disorders but not HD, and 40 healthy controls without psychiatric disorders. We will assess electrodermal, cardiac, and neural (EEG) activity during a series of discarding-relevant and emotionally neutral (discarding-irrelevant) tasks. Our central hypothesis is that patients with HD will demonstrate greater psychophysiological arousal and error related negativity during the discarding-relevant task than will anxious and healthy control participants. The proposed study will pursue the following specific aims: 1) determine the PNS and CNS correlates of difficulty discarding by comparing PNS and CNS activity during the discarding and neutral tasks; 2) determine the causal relationship between PNS and CNS activity and discarding behavior; and 3) determine whether PNS and CNS correlates of difficulty discarding are present to a greater degree in HD relative to other psychopathology. Our approach is innovative because it uses multilevel analysis and will examine, for the first time, the immediate CNS effects of discarding decisions in clinical HD participants. Our focus on the neurobiological mechanisms of HD is significant, as HD is a common and poorly treated condition and the proposed study will have direct implications for biomarker- informed novel treatment development.