The primary goal of the Laboratory of Neuropsychopharmacology is to understand the cellular and molecular basis and treatment of complex psychiatric diseases including depression, anxiety disorders and schizophrenia. To address these issues, we use a variety of molecular, cellular, pharmacological and behavioral techniques and laboratory animals and humans.

Our laboratory has been particularly interested in the neurobiology of depression and anxiety disorders. We were one of the first to identify elevated levels of corticotropin-releasing factor (CRF) in depressed patients. Since then, our lab, among others, has been one of the driving forces in understanding the role CRF may play in the pathophysiology and treatment of mood and anxiety disorders. We have demonstrated that chronic administration of a number of antidepressants, benzodiazepines, as well as mood stabilizers, all interact with the CRF system. We are currently investigating the behavioral, endocrine, and pharmacological effects associated with acute and chronic treatment of CRF1 receptor antagonists in rodents. These compounds show great potential as novel antidepressants, anxiolytics, and/or neuroimaging agents. We are also currently exploring the use of gene arrays to identify novel behaviorally-relevant genes.

We also use analogous methodologies to explore the mechanism of action of antipsychotic drugs and the pathogenesis of schizophrenia. Currently, antipsychotic drugs are not completely effective and their ultimate mechanisms of action are obscure. Since 1980, many have hypothesized a role of neurotensin (NT) as an endogenous antipsychotic. Strong evidence (anatomical, biochemical, pharmacological, and behavioral) has been gathered, in our laboratory and others, suggesting that mesolimbic NT transmission is involved in both phenomena. Currently, the lines of research in the laboratory include manipulation of the mesolimbic NT system (via knock out mice and viral vector technologies), exploration of the interaction between the estrous cycle, schizophrenia and the NT system; and the study of protein-protein interaction between NT and dopamine receptors in vitro and in vivo. In collaboration with Dr. Arnold Mandell and Dr. Karen Selz (Cielo Institute) we have also been investigating how hydrophobic interactions between protein motifs, as identified via mathematical analysis of the primary amino acid sequence, can be used to generate novel biologically active peptides.

The techniques currently used in our laboratory range from theoretical design of novel peptides, molecular biology, cellular biology, genetics, and behavioral pharmacology. Our lab also studies the pharmacokinetics and pharmacodynamics of psychotherapeutics. One of the most relevant applications of this has been studies from our lab investigating the effects of fetal and infant exposure to antidepressants and antipsychotics. We are currently assessing the effects of in utero drug exposure on the development of serotonergic and noradrenergic brain systems. Also, in collaboration with Dr. Zachary Stowe, M.D.(Womens Mental Health Program) , and Dr. James Ritchie, Ph.D., we are able to directly measure drug exposure in infants of breast-feeding mothers which allows us to directly determine mother-infant transmission rates. In addition, we have recently been developing methodologies to assess ex vivo receptor occupancy of antidepressant medications in clinical populations. This may lead to relatively simple methods to correlate pharmacokinetic parameters with treatment response and also help identify patients who are non-responders due to inadequate dosing. We have also initiated studies to correlate in vivo receptor occupancy as measured via PET imaging with our new ex vivo methodology.

List of Current Grants:

“Psychobiology of Corticotropin-Releasing Factor”

“Neurotensin, and Endogenous Neuroleptic-Like Peptide”

“Project 1 – CRF & Urocortin Systems”

“Project 2 – Sertonergic Systems”

“HPA axis regulation and ectopetidase action”

“Role of CRF 2A receptors in stress and anxiety”

“Project 3 – Rodent Modeling of Drug Exposure in PRegnacy and Lactation”

“Adminstrative Core”

“The Role of Inhibition of the Dopamine Transporter”

“Sertraline Occupancy of the Dopamine Transporter”

“Norepinephrine Transporter Occupancy by Paroxetine and Venlafaxine”

Pending: "Paxil vs Duloxetine: Effects on Heart Rate Variability and Autonomic Cardiovascular Control”

Click here to see samples of our published research