Targeting adolescent depression symptoms using network-based real-time fMRI neurofeedback and mindfulness meditation

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PROJECT SUMMARY 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 prior research also has consistently demonstrated patterns of DMN hyperconnectivity 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, we propose using real-time fMRI neurofeedback to enhance the acquisition and utilization of mindfulness skills to better target DMN hyperconnectivity, rumination, and depressive symptoms. We developed a novel, 15-minute mindfulness-based, real-time neurofeedback (mbNF) paradigm whereby people observe a visual display of their brain activity and practice mindfulness to volitionally reduce DMN activation. In the R61 phase, 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 hyperconnectivity and optimal dosing, adolescents will then be randomized to receive either a 15- or a 30-minute mbNF session (n=45/dose group). If we meet our Go criterion (i.e., significantly reducing DMN hyperconnectivity), we will then proceed to the R33 phase to investigate whether mindfulness with mbNF outperforms mindfulness only. Thus, a new sample of 120 depressed adolescents (ages 13-18) will participate in a double-blind randomized clinical trial and receive mindfulness with the optimal mbNF dose (i.e., per the R61) or mindfulness only (n=60/group). We will test–using clinician-administered instruments, self-reports, and ecological momentary assessment– whether compared to mindfulness only, mindfulness with mbNF contributes to a greater reduction in clinician assessed depression symptoms (primary outcome) as well as decreased rumination (secondary outcome) across the post-treatment, 1-month, and 3-month assessments. As a whole, mbNF is directly in line with precision medicine initiatives, and if successful, could revolutionize clinical care for depressed adolescents.