Jamie Maguire , Ph.D.

Research in the Maguire lab takes a systems physiology approach to studying the mechanisms contributing to neurological and neuropsychiatric diseases, with a focus on epilepsy and mood disorders. Our research has explored the impact of the neuroendocrine system on the comorbidity of epilepsy and depression as well as the role in postpartum depression. Working from the vantage point of synaptic changes, such as GABAergic dysregulation, to circuit dysfunction between the prefrontal cortex and the amygdala, to in vivo changes in excitability and behavior, we have explored many mechanistic levels contributing to neurological and neuropsychiatric diseases. We have incorporated cutting edge tools into our research program, where appropriate, to study the contribution of specific cell types and circuits in mediating physiological and pathological processes. Based on our discovery of neurosteroid-mediated alterations in GABAA receptor subunit expression during pregnancy and the postpartum period and our theory for a potential role in postpartum depression, a company designing neurosteroid-based treatment approaches embarked on a series of successful clinical trials for the treatment of postpartum depression. Our discoveries have also generated two useful mouse models of postpartum depression, leading to a collaboration with SAGE Therapeutics to perform preclinical studies on the underlying mechanisms and treatment options for postpartum depression. Our basic research program is also actively investigating the mechanisms of hypothalamic-pituitary-adrenal (HPA) axis regulation during the peripartum period and the contribution of dysregulation of the HPA axis in abnormal postpartum behaviors. Our research has also discovered a novel mechanism contributing to epilepsy progression and associated comorbidities, involving dysfunction in the regulation of the HPA axis. This work has carved out a niche in the field, establishing our lab as experts in this area. This work also earned two competitive research grants (RO1s) from the National Institutes of Health to fund this work. Our lab is presenting investigating the pathological consequences of seizure-induced activation of the HPA axis, focusing on the role of hypercortisolism in seizure susceptibility and associated comorbidities.