Stress and Inflammation in MDD
Brief Description Of Study
Depression (MDD) is a cause of disability worldwide, but the etiology of MDDremains unclear. An emerging concept is that inflammation may have relevance. We have data supporting increased inflammatory cytokines in MDD compared with controls that are associated with decreased hippocampus and amygdala volumes. MDD also had impairment in neuropsychological function in episodic memory, executive function, decreased hippocampus and amygdala resting state functional connectivity. Antidepressant treatment improved IL-6 levels, neuropsychological testing and resting state connectivity. We will recruit patients with MDD (n = 100) and controls (n = 50) to characterize immune function, brain structure and connectivity and neuropsychological function. Further, we will randomize participants with LLD to SSRI treatment (n=50) or no treatment (n=50) and then re-randomize to SSRI plus placebo (n=50) or SSRI + celecoxib (n=50) and assess participants preand post-treatment with peripheral and central cytokine levels, neuropsychological tests and brain resting state functional connectivity. Participants initially randomized to placebo will remain in Phase 1 for 8 weeks to be treated with escitalopram before moving to Phase 2. Hypothesis 1: a) Compared with matched controls, MDD will have abnormalities in peripheral and CSF inflammatory cytokines, neuropsychological function, hippocampal, amygdala and prefrontal cortex (PFC) structure and functional connectivity; b) Peripheral/central inflammatory cytokine levels will be associated with volume loss in hippocampus and amygdala; and c) Cumulative duration of depression will correlate with volume loss in hippocampus, amygdala, and PFC. Hypothesis 2: a) Subjects randomized to treatment will have greater normalization of IL-6 and IL-10, greater improvements in memory, executive function, and in resting state functional connectivity compared with those randomized to no treatment; b) Improvement in clinical depressive scores will correlate with normalization of inflammatory cytokines.
Additional Information About The Study
This study will last for 8 weeks. It is a randomized treatment study, which means you will be given either an anti-depressant (we use a drug called escitalopram, also known as lexapro) or a sugar pill. We won't know which you are getting until the end of the 8 weeks. If it turns out you were on the sugar pill we will treat you with 8 weeks of escitalopram. If you pass a phone screening we will ask you to come in for an hour in-person screen that involves meeting with the study team and having an EKG. If you decide to enroll in the study we will ask you to come in for longer beginning and end of study visits, and every other week in between to get more medication.