The Biology of Resilience

Not Applicable

Completed

Conditions: Oxytocin
Placebo

Interventions: Drug: Placebo
Drug: intranasal oxytocin
Behavioral: Social support
Behavioral: No Social Support

Registration Number: NCT01011465

Lead Sponsor: Harvard School of Public Health (HSPH)

Brief Summary: 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.

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 dehydroepiandrosterone (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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 270

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Oxytocin	Social support	One primary experimental manipulation is the receipt of intranasal oxytocin vs placebo spray prior to participation in a psychosocial stress protocol
Oxytocin	No Social Support	One primary experimental manipulation is the receipt of intranasal oxytocin vs placebo spray prior to participation in a psychosocial stress protocol
Placebo	Placebo	The comparison condition for receipt of oxytocin is receipt of a saline intranasal spray
Placebo	Social support	The comparison condition for receipt of oxytocin is receipt of a saline intranasal spray
Placebo	No Social Support	The comparison condition for receipt of oxytocin is receipt of a saline intranasal spray
Social Support	Placebo	Participants bring a friend to the laboratory who sits with them while they engage in the stress protocol tasks
Social Support	Social support	Participants bring a friend to the laboratory who sits with them while they engage in the stress protocol tasks
No Social Support	intranasal oxytocin	Individuals in this condition do not have a friend present while they are engaging in the laboratory protocol.
No Social Support	Placebo	Individuals in this condition do not have a friend present while they are engaging in the laboratory protocol.
No Social Support	No Social Support	Individuals in this condition do not have a friend present while they are engaging in the laboratory protocol.
Female Gender	intranasal oxytocin	Effects of oxytocin and social support are examined among women versus men
Female Gender	Placebo	Effects of oxytocin and social support are examined among women versus men
Female Gender	Social support	Effects of oxytocin and social support are examined among women versus men
Female Gender	No Social Support	Effects of oxytocin and social support are examined among women versus men
Male Gender	Placebo	Consider effects of oxytocin and social support in men versus women
Male Gender	Social support	Consider effects of oxytocin and social support in men versus women
Male Gender	No Social Support	Consider effects of oxytocin and social support in men versus women
Oxytocin	intranasal oxytocin	One primary experimental manipulation is the receipt of intranasal oxytocin vs placebo spray prior to participation in a psychosocial stress protocol
Social Support	intranasal oxytocin	Participants bring a friend to the laboratory who sits with them while they engage in the stress protocol tasks
Male Gender	intranasal oxytocin	Consider effects of oxytocin and social support in men versus women

Primary Outcome Measures

Name	Time	Method
Systolic Blood Pressure Change From Baseline to Second Stress Task Experience - Autonomic Stress Response Measure	within 2 hours of treatment	Systolic blood pressure (SBP)is connected with reaction to exposure to stress. Systolic blood pressure is collected at baseline and after nasal spray administration/directly before stress tasks; it represents anticipatory stress reaction. This measure represents the difference between baseline and pre-task systolic blood pressure values. A greater difference score represents an increase from baseline in systolic blood pressure during the pre-task, and so a larger difference score represents higher reactivity. A lower difference score, or negative difference score, indicates a lower increase, or even decrease, from baseline in systolic blood pressure during the pre-task and reflects less reactivity. Reactivity is associated with increased risk of developing hypertension. Range of baseline/pre-count differences in SBP: -11 to 37.7
Difference of Pre-count and Baseline Self-reported Negative Affect (Using Negative Sub-scale of Positive and Negative Affect Schedule (PANAS) Measure).	2 hours	Based on 20-item Positive and Negative Affect Schedule (PANAS) which comprises two mood scales, positive affect and negative affect. Each item is rated on a 5-point scale ranging from (1 = very slightly or not at all) to (5 = extremely) to indicate how the respondent felt at the moment the question was asked. Here, we've used the negative affect sub-scale which consists of the sum of the 10 negative affect items, with a possible range of 10 (least negative affect) to 50 (most negative affect). This score was measured at baseline (study range: 10 to 29) and directly before stress exposure (study range: 10 to 37), and the reported value is the difference between these two scores (range of differences: -13 to 26). It estimates negative affect due to anticipatory stress. The value is the difference between the pre-stress measure and baseline measure, therefore a larger number for the difference means a bigger increase in negative affect due to anticipatory stress, and is a worse outcome.
Speech Threat and Challenge	2 hours	Measure of threat and challenge calculated from observation of non-verbal behavioral cues during stress exposure. Threat (negative reaction) results when an individual does not feel that he or she has sufficient resources to complete a task or manage a difficult situation. Its reverse, challenge (positive reaction), occurs when an individual perceives that he or she has sufficient resources. Independent observers used videotapes of behavior during the stress tasks and rated participants on 7 point scales for 11 challenge-related behaviors (comfortable, confident, enthusiastic, clear, alert, high level of eye contact, etc), and for 8 threat-related behaviors (agitation, rigid posture, speech disfluency, etc). Challenge scores were averaged, and threat scores averaged then reverse-scored. The mean of challenge and reversed threat scores comprise the score used here. Range: 1.1 to 6.1, with higher scores representing more challenge orientation and reflecting a better outcome.