Linda L. Carpenter - US grants

DESCRIPTION (provided by applicant): Major depressive disorder is a significant public health problem, disproportionately affecting women. Approximately 70% of patients do not respond or only partially respond to standard SSRI treatment despite adequate dosing. In our open-label pilot data, two-thirds of women with major depressive disorder who were resistant or partially resistant to antidepressants achieved a response to very low-dose, physiologic transdermal testosterone administration; one-third of women treated achieved remission after 8 weeks of therapy, with no hyperandrogenic side effects. We propose a collaborative, randomized, placebo-controlled trial to determine whether larger, multi-center trials are indicated to investigate whether low-dose testosterone is an efficacious and well-tolerated augmentation strategy in women with major depressive disorder and SSRI partial/nonresponse. We propose a collaborative, multidisciplinary study from two academic medical centers in order to increase sample size, accelerate recruitment and increase sample diversity.

Project Summary The research projects proposed in the COBRE Center for Neuromodulation involve a broad range of neuroimaging and neuromodulatory methods, and often involving clinical participants or those with neuropsychiatric pathology. Neuroimaging methods include task- and resting state MRI, and stimulation methods include single pulse and repetitive transcranial magnetic stimulation or transcranial direct stimulation. These techniques are, by their nature, highly complex and require significant technical mastery to successful deploy them in clinical populations. This problem is significantly prominent for relatively junior investigators or those new to these fields. The function of this COBRE Neuroimaging and Neuromodulation Core (NNC) is to provide ongoing expert support, training, assistance and advice to the COBRE project leaders in the wide-range of practical aspects of implementation, data collection, and management related to these methods. Therefore, the Specific Aims of the NNC are to (1) provide support, training and assistance to COBRE Project Leaders (PLs) to promote and facilitate the acquisition of high quality neuroimaging data; (2) provide support, training and assistance to COBRE PLs to facilitate the application of high quality neuromodulation; and (3) to establish core resources with a trajectory toward self- sustaining and enduring status that will serve the larger neuromodulation research community in Rhode Island. To meet these aims, the NNC of this COBRE Center will provide highly specialized expertise, hands-on training, educational forums, and assistance in numerous aspects of protocol implementation, data acquisition and resources as required to meet the aims in each COBRE project and the unique needs of neuromodulation investigators. It will offer critical laboratory space, equipment, infrastructure, and medical supervision needed by investigators working with clinical samples. By meeting these goals, the NNC will (a) accelerate the pace of high-quality mechanism-oriented COBRE research; (b) facilitate the use of safe and scientifically rigorous stimulation protocols; (3) ensure the availability and accessibility of high quality research infrastructure over time for COBRE investigators and the broader Rhode Island research community.