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Mechanisms and Biomarkers of Mind and Body Approaches

Introduction and Explanation of Need

Complementary and integrative health approaches include a broad range of practices and interventions that may have originated outside of conventional medicine and are gradually being integrated into mainstream health care. These approaches can be classified by their primary therapeutic input, which may be nutritional, psychological, and/or physical. Psychological and/or physical approaches encompass what have been commonly considered mind and body approaches. Commonly used psychological approaches include meditation and cognitive behavioral therapy, while physical approaches include acupuncture, other manual therapies (soft tissue manipulation, massage, spinal and joint manipulation, and related devices), and physical exercise. Some approaches, such as yoga and tai chi, comprise both psychological and physical components. Psychological and/or physical approaches have been generally used by the public to treat or manage disorders and symptoms such as pain, sleep disturbance, stress, and anxiety, as well as to support general health.

The majority of the mechanistic studies of psychological and physical approaches focus on the neural system (human adult) and psychological and social systems, while other physiological systems, organs, and tissues (e.g., immune, microbial, cardiovascular, musculoskeletal, endocrine, respiratory, metabolic, digestive, reproductive) remain understudied. Similarly, mechanistic studies involving combined multicomponent approaches (e.g., yoga, massage) are scarce compared to studies evaluating single interventions. Fundamental animal and human research on mechanisms impacting multiple domains (biological, behavioral, social, environmental) that underly psychological and physical interventions, as well as research on potential biomarkers to predict intervention efficacy or treatment responses, are critical for developing strategies to optimize the beneficial effects of these interventions. Such studies are scientifically challenging due to individual heterogeneity (e.g., variability in genetic and epigenetic makeup or psychosocial and environmental factors) and the current lack of optimal tools and technologies to evaluate mechanistic and clinical effects. Nevertheless, recent advances in genomics, neuroscience, stem cells, systems biology, neuroimaging, and predictive computational modeling offer promising technological and conceptual resources and opportunities for innovative and impactful mechanistic studies of physical and psychological approaches.

What Does Success Look Like?

Successful mechanistic studies of psychological and physical approaches include two separate but interoperable accomplishments in model systems/organisms and/or human/clinical populations across the lifespan:

  • Identification of predictive markers or biomarkers that can differentiate responders from nonresponders to psychological and physical approaches.
  • Identification of novel mechanisms of action underlying psychological and physical approaches that may shed new insights into the fundamental science of these approaches or be used to optimize the beneficial effects of these approaches alone or in combination with other therapies.


  • Develop or use innovative (1) humanized cellular or organ systems or (2) transgenic or preclinical animal models to investigate the mechanisms relevant to psychological and physical approaches.
  • Elucidate the mechanisms underlying multisystem effects (e.g., physical and psychological) or the effects of combined multicomponent interventions (e.g., yoga and massage) in humans.
  • Elucidate the mechanistic effects of psychological and physical interventions combined with conventional medical approaches (pharmacologic and surgical interventions).
  • Identify and validate potential biomarkers that predict the therapeutic response to or efficacy of psychological and physical interventions.
  • Elucidate the innovative mechanisms of psychological and physical interventions for symptom management (e.g., stress, anxiety, sleep disorders, pain) and health promotion, restoration, and disease prevention across the lifespan (e.g., children, older adults) or in underrepresented populations (e.g., women, underserved, veterans).
  • Assess multisystem mechanisms and their interactions underlying psychological and physical interventions (e.g., musculoskeletal-immune, cardiovascular-endocrine, genetic-social, brain-gut).
  • Ascertain the interactions of physiological systems (e.g., neural, musculoskeletal, immune) and psychosocial factors in response to force-based interventions (e.g., acupuncture, massage therapy, spinal and/or joint manipulation) in animal models or human subjects.
  • Investigate the mechanisms of relatively less studied psychological and physical interventions, such as exercise-based (e.g., stretching, yoga, tai chi, qi gong), stimulatory (nerve stimulation, transcranial magnetic stimulation, neuromodulation), and art-based (music therapy, dance, visual art) interventions.
  • Investigate the mechanisms by which psychological contextual factors and social/environmental interactions (e.g., at the family or community level) modulate psychological and physical interventions.
  • Develop and validate tools and technologies for mechanistic studies of psychological and physical approaches.