Clinical Trials

Depression is the predominant prevailing pole in bipolar disorder and it is associated with substantial morbidity and mortality. However, in comparison to acute mania, bipolar depression is understudied both from the standpoint of its pathophysiology as well as clinical trials and FDA-approved treatments. With little guidance, clinicians and patients are limited as to what evidence-based treatment is available for bipolar depression. Proton magnetic resonance spectroscopy (1H-MRS) is a valuable, non-invasive method to study in-vivo brain biochemistry. Of the novel imaging paradigms, MRS is uniquely positioned to investigate biochemical mechanism of drug action that is objectively measurable and clinically relevant. As there is increasing interest in glutamatergic dysregulation in mood disorders, this project will utilize 1H-MRS at 3T to study glutamate and glutamine levels in brain regions implicated in bipolar disorder [anterior cingulate (Brodmann's areas 24a/b and 32) and dorsolateral prefrontal cortex (Brodmann's 9/46)]. The goal of this project is to evaluate whether anterior cingulate and prefrontal cortex glutamine, quantified as a CSF-corrected absolute concentration percent change from baseline, is associated with clinical remission (MADRS=12) to the anti-glutamatergic mood stabilizer lamotrigine. This is a 5-year single-site study (RO1 MH079261) of bipolar depression utilizing 1H-MR spectroscopy at 3T before and after treatment with lamotrigine.. At baseline bipolar depressed subjects and age-matched controls will undergo a 1H-MRS on a GE 3T Signa MRI scanner at Mayo Clinic Rochester. The bipolar depressed subjects will then be placed on 12-week, open evaluation of lamotrigine monotherapy. After 12 weeks, the bipolar subjects will undergo a second 1H-MRS scan.