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.
