Stanley J. Watson, M.D., Ph.D.

The emotional regulation of complex behaviors such as reinforcement, feeding and stress are central to the proper functioning of both animals and humans. The Watson laboratory focuses on the central nervous system (CNS) circuits and cellular systems that participate and regulate these states in the brains of individuals with severe mental illness.

As the following projects illustrate, using a variety of molecular, anatomical, behavioral and pharmacological approaches, it is possible to focus on key circuits and molecules of interests.:

1. Depression, bipolar disease and schizophrenia are all studied in postmortem human brains using microarrays across several regions of the CNS. Families of genes have been found to be dysregulated in these three major illnesses and are being further evaluated in animal studies. Most recently Watson’s team and other members of the Pritzker Neuropsychiatric Disease Research Consortium have shown significant changes in fibroblast growth factor, mitochondria and immune gene families in major depression, bipolar disease, and schizophrenia respectively. The next step is for broad-based genetic studies to be undertaken in large-sized patient sets.

2. Stress and substance abuse responsive systems have been mapped in rodent CNS using in situ hybridization of mRNA and intronic RNA for a large number of candidate molecules. By combining in situ regulatory studies with track tracing and other anatomical tools, the Watson lab has described how the brain responds to stress. Mixing these basic strategies with genetically altered mice has provided rich perspectives on the roles of the glucocorticoid receptor in mice. Similar analyses in high versus low responder rats have proven powerful tools to reveal propensity to use drugs of abuse, and for understanding some aspects of maternal and risk-taking behaviors. The regulation of important neural circuits is clearly altered in such animals.