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Research Studies
Up one levelBelow you will find descriptions of the studies currently being conducted at our laboratory.
Brain Mechanisms and Targeting Insomnia in Major Depression
Primary Investigator: Ian A. Cook, MD - Preliminary studies suggest that the response to antidepressant medication can be accelerated by targeting insomnia with adjunctive use of eszopiclone. It is not yet known what mechanism(s) support this acceleration in response, though preliminary findings support the hypothesis that early restoration of sleep may facilitate BDNF-based effects of antidepressant medications. The optimal duration of co-treatment is also unknown. This study will test specific hypotheses about brain mechanisms and evaluate the effects of continued eszopiclone beyond the time window when response acceleration should be observed.
Biomarkers of Antidepressant Treatment in Adoloescents with Major Depression
Primary Investigator: Ian A. Cook, M.D. - Major depressive disorder (MDD) is one of the most common, disabling, and costly conditions, and when it arises during childhood or adolescence, the impact on cognitive and emotional development can have long-lasting consequences. Many adolescents with MDD do not respond to an initial trial of and SSRI antidepressant, and the difference between placebo and medication response rates in this age group is often smaller than in trials for adults with MDD. Some adolescents exposed to antidepressant medication experience treatment-emergent suicidal ideation, so the balance of risks and benefits of antidepressants for adolescents may be different than for adults. A biomarker that could help identify which individuals would benefit from pharmacotherapy could aid in the management of MDD in this age group. Since the 1990s, our laboratory has worked to discover and refine physiologic biomarkers based on EEG changes arising in the first week of treatment. Work with our cordance biomarker has been independently replicated by other investigators. As a further refinement, the BRITE-MD trial (Biomarkers for Rapid Identification of Treatment Effectiveness in Major Depression) found that data from a 15 minute office-based EEG could predict 7 week remission with 74% accuracy, superior to clinical and genetic markers. All these trials have excluded individuals under the age of 18, so accuracy of any of our EEG biomarkers in adolescents and children is unknown. We propose a pilot study of 26 adolescents with MDD, age 14-18, to evaluate the performance of two biomarkers, early changes in prefrontal cordance, and the Antidepressant Treatment Response index (ATR) as used in the BRITE-MD trial. Subjects will receive 12 8 weeks of double-blinded treatment with fluoxetine (FLX) or placebo, with EEG data recorded prior to and serially during treatment. Outcome measures will be symptomatic and functional improvement. We will evaluate the relationship between these physiologic biomarkers and treatment outcome in this new patient population. This project will integrate research efforts now on-going in several components of the Integrative Study Center on Mood Disorders: the Unipolar Depression Research Program, the Laboratory of Brain, Behavior, and Pharmacology, and the Division of Child and Adolescent Psychiatry.
Biomarkers for Outcomes In Late-life Depression (BOLD)
Primary Investigator: Ian A. Cook, MD - Grant #: 1RC1MH088438 Major depressive disorder (MDD) is a common psychiatric illness with high cost to society and individual patients. One reason for the high cost is that most patients endure lengthy and ultimately unsuccessful empiric antidepressant trials before a successful medication is identified by trial-and-error. Care would be improved if a biomarker could determine, early in the course of treatment, whether a particular antidepressant would likely lead to response, remission, or treatment failure. Physicians could rapidly change treatments to an antidepressant which the biomarker indicated would be likely to help the patient. We have identified quantitative electroencephalographic (QEEG) changes that emerge early in the course of treatment with selective serotonin reuptake inhibitors (SSRIs) that appear to predict later response and remission in a general adult patient population. Demographic trends in the United States suggest that improved care for MDD will be essential for a growing number of elderly with late-life depression. While the consequences of prolonged trial-and-error periods to find a successful treatment are particularly inauspicious for elders with late-life depression, this patient group has not been included in the past studies which demonstrated the use of this biomarker approach in a general adult population. We propose a 12-week treatment trial to evaluate a practical biomarker for predicting outcome based on data from the first week of antidepressant treatment, with a focus only on depression in late life (age ≥65).
Neurophysiologic Predictors of Outcome with rTMS Treatment of Major Depressive Disorder
Primary Investigator: Ian A. Cook, MD - Transcranial magnetic stimulation (TMS) therapy has proven to lead to symptom improvement in many individuals with major depressive disorder (MDD), yet there is heterogeneity in outcome, with some patients showing robust remission and other showing minimal symptom change. Identifying which individuals are likely to benefit from TMS therapy early in the course of treatment would support continued treatment for those predicted to do well, and consideration of alternative treatments for others individuals. This study will test specific hypotheses about the relationships between early neurophysiologic changes and later clinical outcome with TMS treatment.
