Area of Research

Models of Psychiatric Disorders

Specialization

Understanding the molecular and structural neurobiology of mood disorders using animal models, brain imaging, and clinical assessment.

RESEARCH THEME

Our laboratory is focused on the development and enhancement of brain imaging tools and the application of these tools to further our understanding of mood disorders.  Our major tools are positron emission tomography (PET) and magnetic resonance imaging (MRI). Because most medications used to treat mood disorders act on the serotonergic system, it has been a major focus of our research. We have demonstrated that never medicated unipolar depressed subjects show increased serotonin 1A (5-HT1A) receptors compared to healthy volunteers. Further these same subjects have lower serotonin transporter (5-HTT) than healthy volunteers. Both of these measures appear not only to be hallmarks of the illness but also may be predictive in determining whether individual patients may respond to a certain class of medications. We are also expanding our horizons and examining the role of the opiod and glutamatergic systems in mood disorders.


In addition to our work in mood disorders we collaborate with Dr. Dev Devanand in developing and optimizing imaging technologies for the detection of amyloid plaque deposition both in subjects with mild cognitive impairment and also those with Alzheimer’s disease. We are determining the sensitivity and specificity of the measure for diagnosis and treatment monitoring.



As our understanding of these disorders increases, we realize the need to increase novel methods and tools as well. Our large chemistry program is involved in the creation and evaluation of novel chemical compounds designed specifically for the imaging of a variety of brain proteins. We work with several other groups on extending MRI capabilities, specifically in the area of diffusion tensor imaging, functional MRI, and MR spectroscopy. The group is multidisciplinary with psychiatrists, psychologists, statisticians, chemists, biomedical engineers, physicists, and electrical engineers. We mathematically evaluate new radioligands and develop novel methods for quantification of binding of the radioligands. Also we have several ongoing projects associated with the detection and correction of motion during the scans, correction of partial volume effects, and methods for deriving the input function from the brain scans without the use of an arterial line. With the statistician in our group, Dr. R. Todd Ogden, we address several issues in data modeling, error estimation and propagation, curve fitting, and tests for highly correlated multivariate comparisons and correction for multiple comparisons.

SELECTED PUBLICATIONS

Kumar JS,Prabhakaran J, Majo VJ, Milak M, Hsiun S, Tamir H., Simpson NR, VanHeertum RL, Mann JJ, Parsey RV (2007). Synthesis and in vivo evaluationof a novel 5-HT1A receptor agonist radioligand[O-Methyl-11C]2-(4-(2-methoxyphenyl)pipe-razi-n-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione in nonhumanprimates. Eur. J. of Nuc. Med. And Mol. Imag., Jan. 13: [Epub]

Parsey RV, Oquendo MA, Ogden RT, Olvet DM, Simpson N,Huang Y, Van Heertum RL, Arango V, Mann JJ (2006). Altered Serotonin 1ABinding in Major Depression: A [carbonyl-C-11]WAY100635 PositronEmission Tomography Study. Biol. Psych., 59: 106-113.

Parsey RV, Hastings RS, Oquendo MA, HuangY, Simpson N, Arcement J, Huang Y, Ogden RT, Van Heertum RL, Arango VA,and Mann JJ (2006). Lower serotonin transporter binding potential inthe human brain during major depressive episodes. Am. J. Psych., 163:52-58.

Parsey RV, Hastings RS, Oquendo MA, HuX, Goldman D, Huang Y, Simpson N, Arcement J, Huang Y, Ogden RT, VanHeertum RL, Arango VA, and Mann JJ (2006). Effect of a triallelicfunctional polymorphism of the serotonin-transporter-linked promoterregion on expression of serotonin transporter in the human brain. Am.J. Psych., 163: 48-51

Parsey RV, Slifstein M, Hwang DR, Abi-Dargham A, Simpson N, Mawlawi O,Guo N, Van Heertum R, Mann JJ, Laruelle M (2000). Validation andreproducibility of measurement of 5-HT1A receptor parameters with[carbonyl-11C]WAY-100635 in humans: comparison of arterial andreference tissue input functions. J. Cerebral Blood Blood Flow &Metab., 20: 1111-1133 .