Objectives
depressive, depressed
Although considerable evidence supports the clinical effectiveness of psychoanalytic therapies, we do not yet understand the mechanisms through which they improve symptoms and reduce functional impairments – knowledge that can further enhance treatment effectiveness, especially in the highest risk and most complex clinical populations. This mechanistic clinical trial will identify the mediators of psychoanalytic therapy treatment response in depressed patients. These neurobiological as well as clinical mediators, once identified, will allow their targeting in the development of new therapies and in improving existing ones. Using these mediators as surrogate endpoints will facilitate smaller and more cost-effective future clinical trials of psychoanalysis than those that have only clinical measures as endpoints [In addition to identifying mediators of treatment response, this mechanistic clinical trial will identify baseline predictors of psychoanalytic treatment response in chronic, severely depressed patients. In future studies, we will be able to use the predictors we discover here to determine, for example, whether we can screen depressed patients for these predictive biomarkers and thereby significantly improve treatment response rates. Identifying these markers will provide a framework for developing personalized care in depressed patients.The prototypical study design in modern medicine for inferring causation is the Randomized Controlled Trial (RCT), which assesses the effects of an experimentally manipulated intervention on the dependent (outcome) variable, usually illness severity. RCTs studying the efficacy and effectiveness of psychotherapy traditionally use clinical measures of symptom change as their primary outcome measure. Many cognitive, behavioral, and neural systems influence symptom severity, however, making these outcome measures very noisy, which in turn reduces the statistical power to detect real change that the therapies produce. Low statistical power in turn necessitates large numbers of participants to detect significant effects of the intervention, thereby increasing the size, duration, and cost of RCTs. Instead of employing change in symptom severity as the usual clinical outcome measure, MODE will use the change in brain imaging measures from the study baseline to study endpoint as the primary study outcome, providing strong causal inference that the treatment causes the changes in brain measures and depressive symptoms observed [