This proposed Mentored Patient-Oriented Research Career Development Award (K-23) research project will provide me the support and training to become a successful independent researcher. The research plan studies participants with Major Depressive Disorder (MOD), a common and devastating mental illness. Specifically, the research probes the functioning of the primary reward system in depression as it can shed light on the core symptom of anhedonia that can provide important future therapeutic target for more effective interventions. Taste stimuli in the form of fruit juice (pleasant) and quinine (aversive) will be delivered during event-related fMRI to characterize the reward circuitry and it's functioning in un-medicated depressed patients by contrasting it with normal controls. Also, possible differential response to taste reward versus monetary reward will be investigated in the exploratory aim. We will recruit 40 participants with MOD and 40 matched controls to test our hypothesis. We hypothesize that compared to controls, during the anticipation of the pleasant taste; depressed patients will have decreased activation in the ventral striatum with relatively preserved or minimal dysfunction in the activation in the orbitofrontal cortex (OFC) to the receipt of the pleasant taste (specific aim 1). Furthermore, depressed patients will have greater activation to the anticipation of the aversive stimuli (quinine) in the amygdala with minimally increased or preserved representaion of receipt in the anterior cingulate cortex and the OFC (more lateral to the reward activations) [specific aim 2]. We will then use a dual reward paradigm with both taste and monitory reward in the same experiment simultaneously. We hypothesize that the anticipation of monetary reward will elicit a larger activation in the ventral striatum and the representation of the receipt of monetary reward will be more anteriorly situated in the OFC when compared to primary taste reward. (Exploratory aim) In patients with depression, the anticipatory component of primary reward will be more compromised than the anticipation of money whereas in the receipt component, the response to juice will be preserved while the receipt of money will be compromised. This mentored career development award will provide me the essential time; education and mentoring to develop my research skills by conducting the translational research detailed in the award thus accomplish my goal of becoming an independent scientist. ? ? ? ?
