Project Summary

Colleen Ann McClung, Ph.D. (Young Investigator 2005) of the University of Texas Southwestern Medical Center at Dallas, plans to use animal models to study how a gene involved in circadian rhythms might lead to the development of affective disorders. For some time, researchers have speculated that the circadian clock, which controls the sleep/wake cycles and daily hormonal and temperature rhythms, may be disrupted in people with mood disorders, such as anxiety, seasonal affective disorder and bipolar disorder. Indeed, polymorphisms in individual circadian clock genes in humans have been correlated with susceptibility to these disorders. However, nothing is known about the genes’ function in the development or treatment of mood disorders. Dr. McClung plans to examine the role of one such gene, NPAS2, in animal models of mood disorders. Dr. McClung has found that stress induces NPAS2 in the brain and that mice lacking a functional NPAS2 gene have less anxiety in three behavioral assays. Also, NPAS2 knock-out mice are resistant to the anxiolytic drug, diazepam, suggesting that NPAS2 regulates the pathways that respond to anxiolytic drugs. Dr. McClung plans to continue behavioral tests on these mice and on mice that overexpress NPAS2. These studies should help elucidate how a gene involved in circadian rhythms, NPAS2, functions in the development and treatment of depression and anxiety disorders.

Program Area: MULTIPLE FOCUS AREAS\Anxiety Disorders/Unipolar Depression

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