Identifying the Molecular Substrates of OCD Using Human Post-mortem Brain and Optogenetics in Mice

2017 Seed Grant
Susanne Ahmari, M.D., Ph.D.
University of Pittsburgh

Obsessive compulsive disorder (OCD) is a chronic, severe mental illness that affects 2-3% of people worldwide, and is a leading cause of illness-related disability according to the World Health Organization. Brain imaging studies in OCD patients have consistently shown abnormal activity in regions of the brain involved in decision-making (orbitofrontal cortex) and selection of actions (striatum). However, we have no knowledge regarding the molecular changes in these brain regions that contribute to abnormal function in people who suffer from OCD. In this project, we will therefore conduct RNA-sequencing on post-mortem brain tissue from people with OCD and matched unaffected controls to identify OCD-related gene expression changes in the orbitofrontal cortex and striatum. This unbiased approach will allow us to uncover the biological gene networks most affected in OCD patients. In a complementary experiment, we will then determine if expression of these genes is altered in homologous brain regions in a mouse model of OCD, paving the way for future studies to directly determine how changes in gene expression lead to abnormal compulsive behaviors. Together, these experiments will allow us to identify the molecular changes underlying OCD in OCD-relevant brain regions for the first time, with the goal of ultimately developing new treatments.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The Role of Microglial Lysosomes in Selective Neuronal Vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the Nervous System Constructs Internal Models of the External World
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the Orchestra of Movement—Functional Role of Striatal Astrocytes in Health and Disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…