Early life abuse (ELA) impacts neurobiological systems that regulate stress, arousal and emotion. As such, ELA represents an environmental event altering fundamental mechanisms that cut across a variety of psychopathologies. Menstrually related mood disorders (MRMDs), including premenstrual dysphoric disorder (PMDD), are defined by the cyclic recurrence of affective and somatic/pain symptoms and impairment during the luteal phase of the menstrual cycle. MRMDs are associated with high rates of ELA and represent a model of psychopathology whose pathophysiologic underpinnings are linked to ELA. The primary objective of this application is to test predictors and biobehavioral mechanisms of efficacy of a behavioral intervention for MRMDs. Mindfulness based stress reduction (MBSR) is a promising intervention with evidence for beneficial modulation of stress, arousal and emotion. We hypothesize, based on the evidence that MRMD women with ELA have more severe symptoms, dysregulation in stress reactivity, and greater pain sensitivity than MRMD women without ELA, that MBSR will be efficacious in reducing symptoms, functional impairment and pain sensitivity in women with MRMD, especially in those with ELA. Our secondary objective is to examine biopsychosocial mediators of efficacy, thus advancing our understanding of pathophysiological mechanisms in MRMD and other disorders with high rates of ELA and aiding in the identifying therapeutic targets. 120-130 women meeting prospective criteria for a MRMD will be randomized (stratified on ELA and baseline premenstrual depression severity) to either the 8-week MBSR program or to an 8-week Health Education Program (HEP) Control Group. Primary outcome measures are: 1) premenstrual depression symptomatology assessed prospectively throughout the intervention;2) functional impairment;and 3) sensitivity to cold pressor pain. If hypotheses for primary outcomes are supported, secondary outcome measures involving premenstrual anxiety, irritability and total symptom severity as well as sensitivity to the temporal summation of heat pain procedure (indexing central pain processing) will be examined. In the laboratory (before and after the intervention), predicted biological mediators of MBSR efficacy will be assessed at rest and in response to mental stress: 1) sympathetic nervous system (blood pressure, heart rate, plasma norepinephrine and epinephrine);2) hypothalamic-pituitary-adrenal (plasma ACTH and cortisol);3) inflammatory (plasma IL-6);and 4) cardiac autonomic control (baroreceptor reflex sensitivity). Predicted psychological mediators of treatment efficacy are: 1) trait mindfulness;2) acceptance;and 3) rumination, assessed before, at the mid-point, and after the intervention. Following the 8 week intervention, women will be followed for 6 months to assess sustainability of beneficial outcomes. Outcomes will be as for the intervention phase: daily symptom ratings, function and pain sensitivity (tested at months 3 and 6), as well as adherence.

Public Health Relevance

Early life abuse (ELA) is associated with a cascade of molecular and neurobiological effects that contribute to long-term disruption in the physiologic regulation of stress, arousal and emotion. Women with menstrually related mood disorders (MRMD), a disorder characterized by the cyclic recurrence of mood and somatic/pain symptoms during the second half of the menstrual cycle with significant functional impairment, experience high rates of ELA (e 60%), more severe premenstrual symptoms, and alterations in physiologic stress reactivity. This project seeks to determine whether a mindfulness-based stress reduction intervention (involving moment- to-moment non-judgmental awareness and acceptance, meditative practices, etc.) will be effective in treating MRMD, and to determine predictors and mediators of treatment-related benefit. Since mindfulness training has been shown to modulate stress, arousal and emotion, it is predicted that a mindfulness intervention will be especially beneficial for MRMD women with a history of ELA.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Interventions Committee for Adult Disorders (ITVA)
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Muehrer, Peter R
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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