Mohamed Sherif, MD, MSc, who will join the Yale Department of Psychiatry as an instructor, has been awarded the VA New England Healthcare system career development award for two years.
Sherif will study EEG biomarkers for the antidepressant effect of ketamine following a "course" of six intravenous (IV) ketamine infusions.
Sherif is a former research fellow in the Special VA Psychopharmacology Research fellowship. His work involved studying psychopharmacological interventions, including ketamine, in humans, under the supervision of Deepak Cyril D'Souza, MD, Professor of Psychiatry and Director of the Schizophrenia Neuropharmacology Research Group at Yale (SNRGY).
Sherif also uses computer (in silico) modeling techniques to investigate the mechanisms of action of these interventions at cellular and microcircuit levels, mentored by Dr. William Lytton, Professor of Neurology, and of Physiology and Pharmacology at SUNY Downstate Medical Center, and Dr. Gordon Shepherd, professor of Neuroscience at Yale.
Depression and suicide are disabling mental health problems, especially in veterans. The discovery of ketamine’s rapid onset antidepressant action in patients who had previously not responded to standard antidepressant treatments is a major breakthrough that may revolutionize how depression is treated.
Sherif’s grant aims to investigate EEG biomarkers that would correlate with the anti-depressant effect following a "typical" IV ketamine course of six infusions. Such EEG biomarkers have the potential to aid with monitoring treatment, as well as potentially identifying patients who would benefit from ketamine treatment.
“After identifying EEG changes that take place following six treatments of ketamine infusion, in silico modeling can aid in identifying the underlying cellular and microcircuit-level mechanisms of the EEG changes,” Sherif said. “This can help in identifying ways to maintain the anti-depressant effect of ketamine.”
Forty-five to 70 percent of patients with treatment-resistant depression show improvement in their depressive symptoms for a few weeks following six ketamine infusions. Sherif said It will be valuable to identify the patients who have a high probability of responding to ketamine to limit the exposure to them, given the possibility of cognitive impairment and risk of dependence associated with ketamine.
During his grant, Sherif will be mentored by Patrick Skosnik, PhD, Assistant Professor of Psychiatry and head of the Psychophysiology Research Unit at SNRGY, and Mohini Ranganathan, MBBS, Associate Professor of Psychiatry and Director of the Treatment-Resistant Depression Clinic at the West Haven campus of the VA Connecticut Healthcare System.
He will also be mentored by Gerard Sanacora, MD, PhD, Professor of Psychiatry, Director of the Yale Depression Research Program, and an expert in the use of ketamine for the treatment of treatment-resistant depression.