The Biology of Resilience

Condition(s) targeted: Stress Response

Intervention: intranasal oxytocin (Drug); Placebo (Drug); Social support (Behavioral); No Social Support (Behavioral); Female gender (Other); Male Gender (Other)

Phase: N/A

Status: Recruiting

Sponsored by: Harvard School of Public Health

Official(s) and/or principal investigator(s):
Laura D Kubzansky, PhD, Principal Investigator, Affiliation: Harvard School of Public Health

Overall contact:
Laura D Kubzansky, PhD, Phone: 617-432-3589, Email: lkubzans@hsph.harvard.edu

Positive social relationships have consistently been associated with better health, although the neurobiological underpinnings of these observed effects remain largely unknown. The overall goal of the proposed work is to explore novel biological pathways that may explain how social relationships influence health. Recent theorizing suggests that the oxytocin system may underlie some of the observed beneficial effects. Four hypotheses will be examined:

1. Oxytocin ameliorates the deleterious neuroendocrine, cardiovascular, and subjective effects of stress.

2. Oxytocin and social support have similar and additive stress-buffering effects.

3. Effects of oxytocin are evident among younger and older adults.

4. Effects of oxytocin are stronger in women vs men.

Official title: The Biology of Resilience: Oxytocin, Social Relationships and Health

Study design: Allocation: Randomized, Control: Placebo Control, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Primary outcome: stress response measured by autonomic, neuroendocrine, and affective responses

Detailed description: Positive social relationships have consistently been associated with better health, although the neurobiological underpinnings of these observed effects are not well understood. Valuable insight may be gained by a life course perspective as it is becoming increasingly apparent that early life social experiences are crucially related to later life functioning and well-being. The overall goal of the proposed work is to explore novel biological pathways that help to explain how social relationships influence health. Recent theorizing on the biology relating positive social and emotional factors to health and patterns of resilience suggest that the oxytocin system may underlie some of the observed beneficial effects. Historically, most work on the oxytocin system in humans has been tied to reproductive outcomes (e. g., lactation), with more limited work on children and young adults. A growing body of experimental research with animals suggests that early in life, oxytocin not only creates powerful social bonds between a mother and child but may also stimulate growth and restorative processes as well as buffer deleterious stress-related neuroendocrine activation throughout the life course. Moreover, the animal literature has suggested that oxytocin is more potent in the presence of higher estrogen levels, leading investigators to hypothesize that effects of oxytocin are stronger in women than men, but few studies have tested this hypothesis in humans. A better understanding of the inter-relationships between oxytocin, social relationships, stress, and health will be gained by examining these factors in a controlled laboratory setting. The immediate goal of this research is to determine whether oxytocin plays a critical role in determining neuroendocrine, cardiovascular, and subjective responses to stress across age and gender, and to examine the effects of oxytocin in relation to those of social support. To achieve these goals, experimental research is proposed to examine the effects of exogenously administered (intranasal) oxytocin on psychological and physiological outcomes, under conditions of stress. The specific aims of this exploratory project are to test the following hypotheses:

1. Oxytocin ameliorates the deleterious neuroendocrine, cardiovascular, and subjective effects of stress.

2. Oxytocin and social support have similar and additive stress-buffering effects.

3. Effects of oxytocin are stronger in women versus men.

4. Effects of oxytocin are similar across a range of younger and older adult ages.

Hypotheses will be tested via a placebo-controlled double blind study using a sample of healthy men and women recruited from the community (overall n = 320). The proposed experimental study will consider oxytocin effects on a range of outcomes. These include autonomic reactivity as measured by blood pressure responses and high frequency heart rate variability (measure of vagal tone). Stress-related cardiovascular phenotypes as characterized by the patterning of ventricle contractility, vascular resistance, and cardiac output will also be assessed. Other outcomes include measures of neuroendocrine effects as measured by levels of cortisol and DHEA hormone, subjective distress and positive affect. Participants will be randomly assigned to receive either exogenous oxytocin or placebo. They will undergo a social stress manipulation with or without social support (randomly assigned), and outcome measures will be obtained at multiple times during the experimental procedure. The experiment will test whether effects of oxytocin and social support are similar and additive, and will also compare effects of oxytocin and social support across men and women of varying ages. This multidisciplinary study uses a biobehavioral framework to examine interactions between psychological, social, and biological levels of functioning, and is informed by theories of how key early life exposures may impact health over the life course. The provision of an R21 award for this work will facilitate novel research that could have a major impact on our understanding of whether and how oxytocin influences responses to stress in humans. The proposed exploratory research will lay the groundwork for the submission of an R01 grant proposal that will have greater resources for addressing both the questions that cannot be addressed with this more limited mechanism as well as new questions that will undoubtedly arise. Ultimately we expect this project will provide a solid platform from which to launch a larger program of research aimed at identifying how positive social and emotional experiences influence adult health and longevity. A neurobiological understanding of resilience can inform efforts for both prevention and intervention of diseases or problems common in later life.

Minimum age: 22 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- age 22-65, BMI < 30, healthy, English-speaking, 9th grade reading level.

Exclusion Criteria:

- any known medical condition (including mental disorders) or on any type of medication

- high levels of social anxiety

- smokers

- high rates of alcohol or drug use

- pregnant or suspected pregnant

- breastfeeding

- blood pressures > 140/90 mm Hg

- subject does not have a close friend available to participate in the study with

him/her

Laura D Kubzansky, PhD, Phone: 617-432-3589, Email: lkubzans@hsph.harvard.edu

Harvard School of Public Health, Boston, Massachusetts 02115, United States; Recruiting
Laura D Kubzansky, PhD, Phone: 617-432-3589, Email: lkubzans@hsph.harvard.edu
Gail K Adler, Md, PhD, Sub-Investigator
Wendy B Mendes, PhD, Sub-Investigator

Starting date: February 2009
Last updated: May 4, 2010