Research suggests that deficits in general emotion regulation skills (GEMS; e.g., the abilities to be aware of, understand, accept, tolerate and modify negative emotions) help maintain symptoms in depression, as well as in other mental disorders often co-occurring with depression. Therefore, systematically targeting these deficits can be hypothesized to enhance efficacy and efficiency of current treatments for this severe and highly prevalent disorder. However, at this point there is a lack of prospective studies that investigate the causal effects of a broad range of potentially relevant GEMS on depression, evaluate the effects of systematically enhancing these skills with specific interventions, and investigate whether the level of comorbid symptom load moderates the importance of GEMS in depression. Therefore, we assess GEMS, depressive symptom severity (DSS) and comorbid symptom load in 150 individuals seeking treatment for major depressive disorder (MDD) across multiple assessment points, and clarify causal pathways between GEMS and DSS. Nested within the longitudinal design, prior to individual cognitive behavioral therapy for depression (iCBT-D) participants will be randomly assigned either to (a) a group-based training of GEMS (ART = affect regulation training; Berking, 2010), (b) an active treatment condition designed to control for unspecific effects of psychotherapeutic interventions (i.e., common-factor-based-treatment control condition, CFT-C), or (c) a wait-list-control condition (WLC). Potential effects of systematically enhancing GEMS on DSS will be assessed during an 8-week pre-iCBT-D interval (stand-alone effects) and during the first four months of subsequent iCBT-D (augmentation effects). Assessment will include retrospective self-ratings, observer-based ratings, and ecological momentary assessment (EMA). Thus, in addition to providing important information on the relevance of GEMS for the maintenance of depression, the study will help evaluate different methodological approaches of identifying deficits in GEMS.