The Niciu Lab is broadly interested in the pathophysiology and experimental therapeutics of major mood disorders, especially treatment-resistant major depressive disorder (MDD) and bipolar disorder. One major aim to date has been the identification, replication and dissemination of treatment response biomarkers to glutamate-based therapies. As an example, our group has identified 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. Based on this observation, 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. We are also a lead research group in the University of Iowa’s Interventional Psychiatry Service Patient Registry, which is comparing and contrasting treatment response to interventional treatment modalities for major depression, e.g. electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), intravenous ketamine infusion, and intranasal esketamine insufflation. Finally, our translational laboratory uses human pluripotent stem cell (hPSC)-based models, i.e. cortical-like spheroids/cerebral organoids, to study genetic, molecular and cellular mechanisms of disease and pharmacological response.

The relevance of our research program to intellectual and development disabilities (IDD) is several-fold. IDD may be comorbid with major mood disorders, and this comorbidity is associated with treatment-resistance. Our understanding of the pathophysiology of comorbid mood disorders and IDD is inadequate, which could be investigated in collaboration with the core divisions offered by the IDDRC, e.g. the Neurocircuitry and Behavior Core. Next, to improve treatment alternatives, there is a critical need to develop novel therapeutic targets for mood disorders with IDD comorbidity; this may occur in collaboration with the Clinical Translational Core. Finally, as mentioned above, our laboratory creates human cortical spheroids (hCS), closely following the experimental methodologies pioneered by Sergiu Pasca Ph.D.’s laboratory at Stanford University. hCSs have been successfully employed as a model system to study typical neurodevelopment as well as neurodevelopmental disorders, i.e. autism spectrum disorder (ASD). Our laboratory has also used this model system to study gene expression difference over time/neurodevelopment, e.g. recently mature spheroids in relation to spheroids >1 year old, and in response to antidepressant treatment, e.g. low-dose racemic ketamine.