The NIMH Research Domain Criteria (RDoC) Project provides a framework for the integration of basic and translational research, by defining basic dimensions of function that cut across disorders. Circadian and sleep disturbances, observed in several highly incapacitating and debilitating mental disorders, represent the key constructs within the Arousal and Regulatory system RDoC Domain. The study of circadian and sleep disturbances in psychiatric populations is difficult and contradictory results between numerous small scale studies may be due to a high degree of genetic and phenotypic heterogeneity. Our long-term aim is to evaluate the feasibility of applying actigraphy for large-scale genetic studies across traditional diagnostic categories. To facilitate these studies, we need to evaluate novel methods for large scale, longitudinal profiling of activity patterns.
Our Aims are:
Aim 1. To identify actigraphy devices and establish protocols suitable for concurrent and longitudinal ascertainment of activity and sleep: wake patterns and mood symptoms in 100 subjects recruited from an outpatient mood disorders treatment program;
and Aim 2. To test heritability of an array of quantitative parameters collected using actigraphy devices (including activity levels, timing of activity and rest onsets, amplitude, organization of activity-rest cycles) and self- reported mood symptoms in a set of 250 twin pairs from the Pennsylvania Twin Registry. The comparison of individual difference measures and heritability of parameters related to mood, sleep: wake or rest: activity patterns in subjects presenting at the mood clinic and in a set of twins represents will provide important preliminary insights into parameter selection for large scale genetic studies across several disorders. Finally, the RDoC initiative is new and will require an integration of approaches across fields. This proposal will provide an opportunity for the interdisciplinary team (geneticists, clinical psychologists, psychiatrists and statisticians) t initiate RDoC-based phenotyping relevant to sleep and circadian disturbances.

Public Health Relevance

Sleep abnormalities are seen in virtually all psychiatric disorders. Given the important need for effective basic and translational RDoC-based research across these complex and common diseases, we believe that application of novel rest: activity monitoring methods combined with genomic characterization and diagnostic measures make the timing ideal for this pilot project.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21MH103963-01A1
Application #
8828845
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Senthil, Geetha
Project Start
2014-11-10
Project End
2016-10-31
Budget Start
2014-11-10
Budget End
2015-10-31
Support Year
1
Fiscal Year
2015
Total Cost
$240,000
Indirect Cost
$90,000
Name
University of Pennsylvania
Department
Genetics
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Bu?an, Maja (2016) Expanding the phenotype half of the genotype-phenotype space. Proc Natl Acad Sci U S A 113:1477-9
Perlis, Michael L; Grandner, Michael A; Brown, Gregory K et al. (2016) Nocturnal Wakefulness as a Previously Unrecognized Risk Factor for Suicide. J Clin Psychiatry 77:e726-33