The Niciu Lab is broadly interested in the pathophysiology and experimental therapeutics of major mood disorders, particularly glutamate and subanesthetic-dose ketamine in treatment-resistant major depression. Another major aim is the identification, replication and dissemination of antidepressant response biomarkers. As an example, our group and others have observed that treatment-resistant depressed subjects with a family history of an alcohol use disorder in a first-degree relative have a greater and more sustained antidepressant response to ketamine. We are currently studying potential alcohol-sensitive multimodal, e.g. psychological, neurophysiological and neuroimaging, biomarkers to predict antidepressant response with greater sensitivity and specificity than family history alone. On the translational front, we use human-induced pluripotent stem cell (hiPSC)-based models, i.e. cortical-like spheroids, to study genetic, molecular and cellular mechanisms of disease and pharmacological response to racemic ketamine, bioactive ketamine metabolites and other compounds in the future.