Serotonin Transporter Dysregulation in Depression

Robert Y. Moore

University of Pittsburgh, Pittsburgh, PA

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

January 1996, for 4 years

Funding Amount:

$100,000

Investigator Biographies

Robert Y. Moore

Professor of Neurology, Psychiatry and Neuroscience, University of Pittsburgh

Hypothesis

Hypothesis:
The pathophysiology of depression is characterized by alterations in the function of the serotonin transporter, which can be elucidated using positron emission tomography (PET).

Goals:
To validate the use of a new PET ligand for the serotonin transporter and apply it to a preliminary study of transporter binding in untreated, newly-diagnosed patients with unipolar depression in comparison to controls.

Methods:
The PET imaging was performed using a Siemens/CTI ECAT HR+ tomograph in the 3D mode using the serotonin transporter ligand, [11C]McN5652, with a region of interest analysis that included the raphe nuclei and multiple cortical areas. Results: There is a reduction of binding to the serotonin transporter in all areas analyzed, including the cell body area of the raphe and terminal areas in the cerebral cortex.

Follow-on Funding:

NIH MH-61566 Sleep-Guided PET Studies in Depression 2/1/01-1/31/05 $1,000,000

Pittsburgh Foundation PET Studies of Depression in Parkinson's Disease 1/1/99-6/30/02 $150,000

Selected Publications

Meltzer C.C., Smith G., DeKosky S.T., Pollock B.G., Mathis C.A., Moore R.Y., Kupfer D.J., and Reynolds C.F. III. Serotonin in aging, late-life depression and Alzheimer’s disease: the emerging role of functional imaging. Neuropsychopharmacology. 1998 Jun;18(6):407-30 .

Nofzinger E.A., Nichols T.E., Meltzer C.C., Price J., Steppe D.A., Miewald J.M., Kupfer D.J., Moore R.Y. Changes in forebrain function from waking to REM sleep in depression: preliminary analysis of [18F] DG PET studies. Psychiatry Res. 1999 Aug 31;91(2):59-78.