Prolonged Grief Disorder (PGD) was recently introduced in the WHO International Classification of Diseases, and the DSM-5TR. A core symptom of PGD is the heightened reactivity to reminders of the death. This stress response, if exaggerated and persisting, is associated with increased risk for physical and mental health problems including suicide. To date, no efficacious intervention for reducing a bereavement-related stress response exist to prevent the negative health outcomes o PGD. Mindfulness Training has shown efficacy to decrease the general stress reactivity, as was shown in healthy individuals and in anxiety disorders. Therefore, it has the potential to successfully target bereavement-related stress-reactivity in individuals with PGD, as supported by our pilot data. Furthermore, little is known about the neurobiological changes that underlie the decrease in stress reactivity that results from mindfulness training.

The present proposal is the first ever efficacy trial of Mindfulness Training to decrease the psychiatric and somatic symptoms of PGD. It will also be the first ever examination of changes in peripheral and neuroimaging biomarkers of bereavement-related stress reactivity associated with Mindfulness Training. As PGD is a newly recognized psychiatric condition, there are very limited data available about its pathophysiology and neurobiology, and in particular how treatments can intervene on it. Although we have shown that mind-body interventions such as Mindfulness Training are efficacious for stress-related conditions (e.g., Hoge et al., J Clin Psychiatry., 2013), limited data are available about their mechanisms of actions.

The CALM-NIPS study aims: to examine the effects of an 8-week standardized mindfulness training program on PGD symptom severity, and on stress reactivity; and to elucidate the neural mechanism of these effects. The specific are :

• to examine the efficacy of Mindfulness Training compared to a waitlist control group, to decrease
  PGD symptom severity (primary outcome)
• to examine the efficacy of Mindfulness Training compared to a waitlist control group on peripheral
  and neuroimaging biomarkers of stress reactivity
• to examine potential mechanisms of treatment change of Mindfulness Training.

This study will include N=30 adult subjects with PGD, randomly assign to receiving immediately an 8-week Mindfulness Training program, adapted from the Stress Management and Resiliency Training (SMART) vs. after an 8-week waitlist. At baseline, midpoint, endpoint, and at one-month follow-up, subjects will be assessed for psychiatric and somatic symptoms. They will also be assessed for peripheral (physiological responses) and functional neuroimaging biomarkers of bereavement-related and general stress reactivity at the baseline, and endpoint.