Oxytocin Activity is Linked to Attachment, Trust and Stress in

Women and Men

Kathleen LightDepartment of Anesthesiology

University of Utah

Supported by NIH grant R01 HL084222

Oxytocin Activity is Linked to Attachment, Trust and Stress in

Women and Men

Kathleen LightDepartment of Anesthesiology

University of Utah

Supported by NIH grant R01 HL084222

Oxytocin and Blood Pressure

Mammalian hypothalamic neuropeptide OT sometimes called “the bonding hormone”.

OT administration, maternal licking or substitute stroking to enhance natural OT activity leads to prolonged blood pressure (BP) decreases in both normotensive and SHR rats (Petersson & Uvnas-Moberg, Neurosci Letters 2008).

Greater OT activity induced by closeness to mate or sib has also been linked to faster wound healing, decreased atherosclerotic changes, and reduced behavioral anxiety in new environments and reduced sensitivity to painful stimuli in animal models.

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OTDecrease

Minimal OTChange

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Baby Day No Baby Day

Light et al, Health Psychol 2000 Based on only 2 blood samples per test day

Hold Feed Post Feed No Hold Sleep

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Awake DBP by OT Group

OT Increase OT Decrease

Comparison of Cocaine-exposed vs. Non-exposed Mother-Infant Dyads

Mothers who used cocaine when pregnant tended to hold their babies less often at home, and had higher BP at home.

In the lab, they had higher blood pressure EXCEPT after holding their babies.

Emotional mismatch during interactions; cocaine exposed mothers laughed more while their babies cried more.

In a small pilot study, they reported less stress when separated from their babies in the lab, and had lower OT levels to all stimuli related to maternal behavior.

(Light et al., Addictive Behaviors 2004 and new pilot data)

Interaction Separation Replay Recov0.00

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Adjusted for Feeding Group, Between Subjects Effect of Cocaine: F=6.98, p=.0298

Salivary Oxytocin has Advantages as a Biomarker over Plasma Oxytocin, if It is Feasible to Assay and Valid

Validation study in 20 mothers of infants (Grewen, Davenport, Light, Psychophysiology 2010 )

Used standard Assay Designs antibody kit but with essential extraction step to concentrate sample 3.2 times

Compared breast feeders vs. bottle feeders across 7 plasma and 5 saliva sampling points

Breast feeders always had both higher plasma OT and higher salivary OT

7

Base Interact ion Post -I nx Speech Replay Recov Feed2 .0 0

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Recovery Plasma and Salivary Oxytocin

r = +0.59, p = 0.025

Grewen & Light (2010, in prep)

In another study of 28 mothers of infants aged 3-5 months, we found:

1) Plasma oxytocin increases during emotional stress (talking about recent stressful life event involving family) and during forehead ice application.

2) Mothers with higher average oxytocin levels (Area Under the Curve from 9 sampling times) show less vasoconstriction during both speech and ice stressors.

IV Speech1Speech2 Replay1 Replay2 Ice1 Ice2 Recov1 Recov20.50

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moms DBP

IV Speech1Speech2 Replay1 Replay2 Ice1 Ice2 Recov1 Recov20.50

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p = 0.017

OT_AUCT2 * DICE1VRI2; N=28

Summary of Mother-Infant StudiesIn mothers, higher OT after warm contact is

linked to lower BP levels at home as well as before, during and after lab stress.

Prenatal cocaine users have lower OT; cocaine may “hijack” the OT-dopamine reward pathway normally activated in new mothers.

Salivary OT generally tracks changes in plasma OT, although the correlation is stronger during “stable” conditions vs. conditions when plasma OT is increasing or decreasing.

Lower vascular reactivity is associated with lower overall levels of plasma OT when sampled 9 times over a 90 minute period including 2 stressors and 2 rests.

Oxytocin is linked to trust, generosity, empathy and recognition of positive facial expressions in young adults

Work by Zak and colleagues using games involving money that can be given either reciprocally or as simple sharing has linked higher plasma OT to trust and trustworthiness (reciprocation), and to greater equity in sharing $40 after empathy is enhanced by films. Zak PJ, Kurzban R, Matzner WT. Horm Behav. 2005; Barraza JA, Zak PJ. Ann N Y Acad Sci. 2009

Baumgartner et al in Neuron 2008 report that fMRIs of subjects given intranasal OT vs. placebo show less activation in “fear” regions (amygdala, midbrain) when trust is violated by no reciprocation, and the OT recipients continue to trust /give more $.

Marsh et al Psychopharmacol 2010 report that intranasal OT vs. placebo improves ability of both men and women to detect happy facial expression without altering responses to negative emotions.

Zak, Stanton, Ahmadi PLoS One 2007 Generosity is 80% larger in the intranasal OT group vs. the placebo group (p = 0.005, N = 68).

Zak, Kurzban, Ahmadi et al PLoS One 2009 Men given androgen vs. placebo had a 27% reduction in giving (p = .035)

Couple Contact-Oxytocin Non-stress Study

N= 38 men and 38 women spouses/live-in partners Protocol: Rest Alone, then Warm Contact, then Rest Alone Are there gender differences in OT response? Is OT linked to lower BP and sympathetic activity

(norepinephrine)? Is OT linked to partner relationship quality/ low ambivalence based

on the Social Relationship Index (comparing High vs. Low SRI subjects) ?

(Grewen, Girdler, Amico & Light, Psychosom Med 2005)

If Even One Spouse Reports High Partner Support, Oxytocin Levels of Both Spouses are Higher During

Anticipation of Warm Contact with Spouse Grewen, Girdler, Amico & Light Psychosom Med 2005

0.00 1.20 2.40 3.60 4.80 6.00

plasma oxytocin (pg/ml)

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Base- 0.45 *

Min 4- 0.33

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Min 9- 0.40 *r =

Based on 4 blood samples taken before (Base) and at 4,7 and 10 min after warm contact with husband, wives’ oxytocin and

norepinephrine levels are consistently inversely correlated.

Couple Contact-Oxytocin Stress Study

N= 59 premenopausal women tested with partners Protocol: Rest Alone, then Warm Contact, then Speech Prep and

Speech Alone Grouping subjects by low, moderate and high Baseline OT, is

higher OT linked to lower stress BP level or BP reactivity (change from baseline)?

Do women reporting more frequent partner hugs on the Physical Affection Scale have higher OT and lower BP?

(Light, Grewen & Amico, Biol Psychol 2005)

1. Base 2. Prep 3. Speech 4. Recover

Adjusted for age differences

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All three factors (Hugs, OT and BP Levels) are correlated with each other at Baseline and Speech Prep (r’s = .32 -.42).

Partialing for OT reduces the relationships between Hugs and BP.Thus, OT may be a partial mediator of effect of Hugs on BP.

Oxytocin

Base & Speech Prep

Blood Pressure

Partner Hugs

Oxytocin can alter BP both directly and indirectly

It can lead to decreases in total vascular resistance through direct effects on oxytocin receptors in vessels.

It can decrease overall sympathetic activity, which can lower BP by decreasing both cardiac contractile force and cardiac output, and can also decrease vascular resistance.

Can we show that increases in caring and support by loved ones leads to increases in oxytocin and decreases in BP and sympathetic activity?

BYU Married Couple Intervention Study:Increasing Expression of Caring Support Through One Month’s

Practice of 2 Types of Warm Touch(Holt-Lunstad, Birmingham & Light, Psychosom Med, 2008)

N= 34 married couples with less than perfect “couple hugs” scores.

Intervention: 2 training sessions (Rosen Listening Touch & Head/Neck/Shoulder Massage), then 4 weeks of home practice for 20 min 3x/week.

Protocol: Randomized to Intervention vs. Monitoring Only Groups (20/14). Diary of phys. affection/mood.

Measures: 24 hour Ambulatory BP, Salivary Cortisol & Alpha Amylase (5 samples over 24 hrs) Pre- and Post- Treatment

Evening Salivary Oxytocin 2x/week Weeks 1 & 4

Week 1 Week 42

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Intervention Control

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Intervention Control

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low depression high depression

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Pre-Intervention plasma OT according to Gender and Level of Depression

Summary of Intervention Study Findings Training and frequent home practice in expressing

support and affection through warm touch led to increased oxytocin and decreased sympathetic activity (indexed by salivary alpha amylase) in both husbands and wives. Once we control for depression scores , both plasma and salivary OT increases are significant.

24-hour Systolic BP levels were also decreased in men but not women in the Intervention group, with the decrease in BP correlating significantly with the decrease in alpha-amylase. No cortisol effects seen.

Future research with couples at risk for adverse cardiovascular and/or marital outcomes is promising.

Work in progress on oxytocin-related biomarkers

100 mothers of infants aged approx. 3 months Examine saliva OT in mother & infants, plus

plasma and urine OT in mothers only, in 2 hr. protocol involving baby feeding and play, and maternal stress (speech and ice).

First look at leukocyte gene expression: OT, OT receptor, adrenergic receptors, 5HT receptor, dopamine receptor

“Dream no small dreams…” Goethe

…because we have barely scratched the surface of what we can discover with the new biomarker methods that we now have or soon will have.

Thanks to my colleagues Karen Grewen and Julianne Holt-Lunstad and many student helpers.

Strengths and weaknesses of measures of oxytocin from plasma, saliva and urine

Plasma Reflects both quantities of OT from hypothalamus and from

peripheral vascular sources If interested in direct effect on short-term cardiovascular responses,

may be the best measure Due to short half life, intermittent sampling may miss peak

responses or may over- or under-estimate mean levels Difficult to obtain in home environment, and single stick samples

may reflect the stress/anxiety associated with needle insertion

More pluses and minuses…

Saliva Easy to obtain in home environment and with minimal stress/anxiety, even from

infants & children May likewise have a short half life, and may not accurately mirror peak responses Must be concentrated by extraction or “dry down” to use commercial antibody

EIA assay.

Urine OT levels seem very stable. It may be very useful to assess chronic or mean OT

activity.

Less useful for acute or short-term responses, to detect peak responses.