Our work aims to define the mechanisms underlying resistance to antidepressant treatment through a variety of approaches. Depression and anxiety are polygenic and highly complex neuropsychiatric disorders that are a major burden on society. Large-scale clinical studies have demonstrated that commonly used medications from several classes of antidepressants only provide relief for a subset of patients. The reasons why some individuals respond to treatment while others do not are poorly understood. To address this question, we study depression and anxiety in mouse models that offer an appropriate framework to assess treatment resistance with face, construct, and predictive validity. For example, we group mice engineered to display features of depression and anxiety by their behavioral response to treatment interventions. Gene expression profiles in selected brain regions that we define as critical for mediating an antidepressant response, such as the dentate gyrus, are then compared between responders and non-responders to treatment through either traditional microarrays or more modern techniques such as RNA sequencing. This line of investigation has yielded candidate signaling pathways that fail to be activated or suppressed in non-responders. The results of these screens form the basis for more advanced molecular, cellular, genetic, and behavioral studies. In addition, our long-term plans are to tailor this approach to define the neural circuitry that mediates response and resistance to various treatments. These lines of research will help identify the molecular mechanisms and neural circuitry underlying treatment response and resistance, and ultimately may be useful for human genetics through identification of novel treatments, determining whether patients will respond to treatments, and developing personalized treatment strategies.
Clinical or Educational Responsibilities
I teach undergraduate and graduate level courses at Rutgers through my primary appointment in the Department of Psychology. Classes I’ve taught include Neuropsychopharmacology, Physiological Psychology, Nervous System & Behavior, and Neural Circuitry of Mood Disorders. I’ve also given guest lectures in Behavioral and Neural Genetics (a course in the Genetics Department) and in Advanced Neurobiology (a course in Cell Biology and Neuroscience).