Adolescent major depressive disorder (MDD) is common and debilitating. Presently, gold-standard treatments are only effective for approximately half of patients, underscoring the need to develop novel interventions, particularly to target core underlying mechanisms and more effectively treat this recurrent disorder.~Rumination, the tendency to perseverate about depressive symptoms, contributes to MDD onset and predicts treatment non-response and relapse. At the neural level, rumination is characterized by elevated functional connectivity within the default mode network (DMN), and similarly, prior research has consistently demonstrated patterns of DMN hyper-connectivity in MDD. Interestingly, mindfulness meditation, which trains attentional focus to the present moment, reduces perseverative thinking, ruminative tendencies, and depression symptoms. Further, our research and others have shown that adolescents can apply mindfulness practices to decrease perceived stress, increase sustained attention, and suppress DMN activity. Although mindfulness has profound mental health benefits, for some, mindfulness alone may not be sufficient to mitigate ruminative tendencies during a depressive episode. That is, MDD symptoms, including reduced motivation, inattention, and lack of self-efficacy, may impede a patient's progress in successfully acquiring and utilizing mindfulness strategies necessary to change perceptions about one's environment and relationships. To directly address this challenge, this project will use real-time fMRI neurofeedback to enhance the acquisition and utilization of mindfulness skills to better target DMN hyper-connectivity, rumination, and depressive symptoms.~Specifically, a novel, mindfulness-based, real-time neurofeedback (mbNF) paradigm will be used whereby people observe a visual display of their brain activity and practice mindfulness to volitionally reduce DMN activation. 90 adolescents (ages 13-18) diagnosed with MDD will complete a 45-minute mindfulness training outside the scanner. To test target engagement of reducing DMN hyper-connectivity and optimal dosing, adolescents will then be randomized to receive either a 15- or a 30-minute mbNF session (n=45/dose group). Clinician-administered instruments, self-reports, and ecological momentary assessment will be used test whether mbNF contributes to a greater reduction in clinician assessed depression symptoms (primary outcome) as well as decreased rumination (secondary outcome) across the post-treatment and 1-month post-treatment. As a whole, mbNF is directly in line with precision medicine initiatives, and if successful, could revolutionize clinical care for depressed adolescents.
In the United States, adolescents experience alarmingly high rates of major depression, and gold-standard treatments are only effective for approximately half of patients. Rumination may be a promising treatment target, as it is well-characterized at the neural level and contributes to depression onset, maintenance, and recurrence as well as predicts treatment non-response. Accordingly, the proposed research will investigate whether an innovative mindfulness-based real-time functional magnetic resonance imaging (fMRI) neurofeedback intervention successfully elicits change in the brain circuit underlying rumination to improve clinical outcomes among depressed adolescents.