Project 5 - Several studies have demonstrated an association between low cholesterol and both violent death (including suicide) and psychiatric disorders such as antisocial disorder, affective disorders, personality disorders and conduct disorder. Based on this observation, we hypothesized that carriers of mutations associated with cholesterol synthesis might also have a higher risk for behavioral problems.
The aim of this study is to characterize the behavioral phenotype in carriers of disorders of sterol metabolism associated with low cholesterol, including Smith-Lemli Opitz syndrome, CK syndrome, SC4MOL deficiency, CHILD syndrome and chondrodysplasia punctata 2. A total of 144 individuals (75 subjects and 69 controls) will be recruited from the 5 sites (UBC, OHSU, UNMC, CCHMC, and UPMC) as part of the STAIR consortium. Our study will be done in 2 parts. Firstly, well validated personality disorder questionnaires (Dimensional Assessment of Personality Pathology-Basic Questionnaire [DAPP-BQ], the Schedule for Nonadaptive and Adaptive Personality-2 [SNAP-2]) will be administered to all subjects and 30 controls to identify aberrant behavioral traits. Secondly, to clarify the functional brain changes associated with these behaviors, the hemodynamic responses to working memory tasks will be examined using fMRI. Fifty one subjects (chosen randomly from the above stated 75 subjects) and 39 controls will undergo this part of the study. Behavioral and fMRI Data will be analyzed at UBC with the help of the the STAIR statistical core. Based on our preliminary data, we anticipate finding significant changes in behavior amonst carriers of sterol biosynthesis disorders compared to controls. In addition, we predict that the neuron activation seen in carriers of sterol metabolism disorders will be significantly lower then controls. The long term goal of this study is through the use of the proposed tools, find new markers that could potentially lead to improved behavioral therapies not only for disorders of cholesterol synthesis but also for individuals in the general population that suffer from similar behaviors.

Public Health Relevance

This study will provide further insight into the association between low cholesterol and abnormal behaviors. Our increased understanding of these behaviors will help in the development of new and improved therapeutic interventions for these individuals as well as the broader general population.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZTR1-CI-8 (01))
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Krotoski, Danuta
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University of Nebraska Medical Center
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