Neurobehavioral Targets of Mindfulness in Youth At Risk for Mood Disorders

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Mood lability, defined as frequent and exaggerated changes in mood, is an important transdiagnostic symptom that causes significant impairment and increases suicide risk. This symptom is a common precursor to mood disorder onset, particularly in youth at familial risk. Since adolescence is a peak period for mood disorder onset and an important window of neural plasticity, it may be an optimal time for an intervention to decrease mood lability. Meta-analyses in youth have found that mindfulness-based interventions (MBIs) decrease mood symptoms and improve emotion/behavioral dysregulation, constructs closely related to mood lability; however, neural/behavioral mechanisms of these effects are unknown. It is essential to understand how and for whom MBIs work, to design interventions that more efficiently engage appropriate targets and deliver treatment to those most likely to benefit. In adults, MBIs have been shown to increase resting-state functional connectivity (rsFC) between the posterior cingulate (PCC) and the frontoparietal control network (FPCN), neural circuitry which may subserve awareness of mind-wandering. A behavioral indicator of unintentional mind-wandering, errors on the Sustained Attention to Response Task (SART), has also been found to decrease following MBIs. Since unintentional mind-wandering amplifies negative affect, awareness of mind-wandering may facilitate the adaptive use of emotion regulation strategies, leading to improved stress response and decreased mood lability. Indeed, previous studies have linked increased PCC-FPCN rsFC to downstream effects of decreased anxiety and depression; and our recent pilot study in youth found that MBI-related increases in PCC-FPCN rsFC predicted later decreases in mood lability. Given these promising pilot data, the next step is to conduct a randomized controlled trial to assess MBI-specific effects on mind-wandering related targets and mood lability. In a sample of 100 adolescents (11-13 years old) with mood lability and a parent with a major mood disorder, we propose to test whether: (1) an 8-week MBI (vs. control) modifies mind-wandering-related targets (PCC-FPCN rsFC, SART performance); (2) changes in mind-wandering measures lead to less mood lability; and (3) intake mind- wandering measures predict differential MBI benefit. Participants will be randomized – stratified on non-mood DSM-5 diagnosis and sex-by-pubertal status – to an 8-week MBI or control. We will scan youth before, 4 weeks into, immediately after, and 3 months after intervention to assess longitudinal relationships amongst changes in PCC-FPCN rsFC and behavioral/clinical measures. Behavioral/clinical outcomes will also be assessed at 9 months post-intervention. We will assess mood lability via self-report and ecological momentary assessment, focusing on variability in negative affect and ability to sustain positive mood. This design will allow us to assess, with temporal precision and across levels of analysis, the impact of decreasing unintentional mind-wandering on subsequent mood lability, focusing on a crucial developmental period in at-risk youth; and will also allow us to assess who will benefit most from MBIs, moving toward a personalized medicine approach.