Identifying Intermediate Phenotypes for Compulsive Hoarding

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DESCRIPTION (provided by applicant): The aim of this application is to conduct a pilot study of work to examine frontally-mediated neurocognitive function in severe compulsive hoarding (SCH), a maladaptive social behavior that is related to obsessive compulsive disorder (OCD) and like OCD, has a complex genetic etiology, with the ultimate goal of identifying intermediate phenotypes that will be useful for genetic studies(1-11). SCH is defined as the excessive acquisition of and inability to discard seemingly useless items, resulting in living and/or work spaces that are unusable for their intended purposes, and affects 2% of the population(1, 5-11, 16, 17, 20, 26-29, 32-34). For such behavioral syndromes with variable phenotypic expression and complex genetic etiologies, the use of intermediate phenotypes can be a useful aid to genetic studies(25). Although there are studies examining potential intermediate phenotypes for OCD, very little work has been done for SCH, despite evidence of both shared and independent genetic contributions(2, 12-24). Individuals with SCH exhibit indecisiveness, perfectionism, difficulty with categorization, disorganization, procrastination, slowness in completing tasks, actual or perceived alterations in memory, and difficulty with concentration and attention(6, 22, 46-51). Decision-making, categorization ability, attention, and speed of information processing are collectively referred to as the "executive functions" of the brain. Electrophysiological measures associated with performance monitoring and error detection have been shown to be abnormal among individuals with OCD, most prominently the error-related negativity or ERN, which is thought to reflect the mismatch of actual and intended responses on error trials(61). Our data suggest that individuals with SCH also have impairments or abnormalities in neuropsychological measures of executive function and in the ERN. Although studies have suggested that apparently unaffected family members of individuals with OCD have impaired cognitive flexibility, motor inhibition, decision making, planning, and spatial working memory, no studies have yet been conducted examining these functions in family members of individuals with SCH(12-15). In addition to being abnormal in individuals with SCH, these neurocognitive functions are heritable, making them of particular interest as potential intermediate phenotypes(77-84). We propose to conduct pilot studies aimed at identifying potentially useful intermediate neurocognitive phenotypes by 1) determining the feasibility of recruiting and assessing 25 individuals with SCH and their family members and 25 individuals with non-hoarding OCD (NH- OCD and their family members, 2) assessing the variety of family structures available for study, and 3) assessing the neurocognitive profiles of SCH, NH-OCD, and their family members compared to healthy matched controls (HMC) using neuropsychological and electrophysiological measures, including the ERN and neuropsychological measures of categorization, speed of information processing, and decision-making. PUBLIC HEALTH RELEVANCE: Severe compulsive hoarding (SCH) is an under-recognized and under-treated disorder that is highly comorbid with obsessive-compulsive disorder (OCD), and like OCD, carries a substantial public health burden, including increased morbidity and mortality. This proposal will pilot a protocol aimed at identifying specific neurocognitive profiles uniquely associated with SCH and those associated with both SCH and OCD. The identification of SCH-specific neurocognitive profiles will be very useful, both to identify and follow at-risk individuals who would benefit from interventions to minimize the impact of SCH, and for etiological investigations such as genetic studies.