Jordan Karp, MD, is professor of Psychiatry, Anesthesiology, and Clinical and Translational Science at the University of Pittsburgh and UPMC Western Psychiatric Hospital. Late-life depression may be brain “toxic.” This episode discusses geriatric depression and ongoing multi-site PCORI/NIH geriatric research about a treatment-resistant depression (OPTIMUM/OPTIMUM-Neuro) trial. This comparative effectiveness research includes patients’ cognition and brain imaging.