Karen M. Grewen

Effects of partner support on resting oxytocin, cortisol, norepinephrine, and blood pressure before and after warm partner contact

Objective: We examined whether the magnitude of plasma oxytocin (OT), norepinephrine (NE), cortisol, and blood pressure (BP) responses before and after a brief episode of warm contact (WC) with the spouse/partner may be related to the strength of perceived partner support. Methods: Subjects were 38 cohabiting couples (38 men, 38 women) aged 20 to 49 years. All underwent 10 minutes of resting baseline alone, 10 minutes of WC together with their partner, and 10 minutes of postcontact rest alone. Results: Greater partner support (based on self-report) was related to higher plasma oxytocin in men and women across the protocol before and after WC. In women, higher partner support was correlated with lower systolic blood pressure (SBP) during solitary rest after WC but not before. Also, higher OT in women was linked to lower BP at baseline and to lower NE at all 4 measurements. Conclusion: Greater partner support is linked to higher OT for both men and women; however, the importance of OT and its potentially cardioprotective effects on sympathetic activity and BP may be greater for women. ABP = ambulatory blood pressure; BMI = body mass index; BP = blood pressure; CVD = cardiovascular disease; DBP = diastolic blood pressure; HPA = hypothalamic–pituitary–adrenal; HR = heart rate; IV = intravenous; MI = myocardial infarction; NE = norepinephrine; OT = oxytocin; SBP = systolic blood pressure; SNS = sympathetic nervous system; SRI = Social Relationships Index; WC = warm contact.

More frequent partner hugs and higher oxytocin levels are linked to lower blood pressure and heart rate in premenopausal women

In animals, ventral stroking for >5 days increases oxytocin (OT) activity and decreases blood pressure (BP), but related human studies are few. Thus, relationships between self-reported frequency of partner hugs, plasma OT and BP levels were examined in 59 premenopausal women before and after warm contact with their husbands/partners ending with hugs. Higher baseline OT before partner contact was associated with lower BP and heart rate, and met criteria to be a partial mediator of the lower resting BP shown by women reporting more frequent hugs (P<0.05). OT levels during post-contact stress were unrelated to hugs or BP. Menstrual cycle phase did not influence any OT measure. Thus, frequent hugs between spouses/partners are associated with lower BP and higher OT levels in premenopausal women; OT-mediated reduction in central adrenergic activity and peripheral effects of OT on the heart and vasculature are pathways to examine in future research.

A functional genomic perspective on human well-being

To identify molecular mechanisms underlying the prospective health advantages associated with psychological well-being, we analyzed leukocyte basal gene expression profiles in 80 healthy adults who were assessed for hedonic and eudaimonic well-being, as well as potentially confounded negative psychological and behavioral factors. Hedonic and eudaimonic well-being showed similar affective correlates but highly divergent transcriptome profiles. Peripheral blood mononuclear cells from people with high levels of hedonic well-being showed up-regulated expression of a stress-related conserved transcriptional response to adversity (CTRA) involving increased expression of proinflammatory genes and decreased expression of genes involved in antibody synthesis and type I IFN response. In contrast, high levels of eudaimonic well-being were associated with CTRA down-regulation. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity in structuring the observed differences in gene expression associated with eudaimonic well-being (reduced NF-κB and AP-1 signaling and increased IRF and STAT signaling). Transcript origin analysis identified monocytes, plasmacytoid dendritic cells, and B lymphocytes as primary cellular mediators of these dynamics. The finding that hedonic and eudaimonic well-being engage distinct gene regulatory programs despite their similar effects on total well-being and depressive symptoms implies that the human genome may be more sensitive to qualitative variations in well-being than are our conscious affective experiences.

Adrenergic Dysregulation and Pain With and Without Acute Beta-blockade in Women with Fibromyalgia and Temporomandibular Disorder

UNLABELLED In patients with fibromyalgia syndrome (FMS) and temporomandibular disorder (TMD), stress and pain may chronically enhance sympathetic activity, altering cardiovascular responses and worsening pain. This study examined cardiovascular, epinephrine (EPI), norepinephrine (NE), cortisol and clinical pain responses in 54 female patients with these disorders and 34 controls. In a subsample of 10 FMS, 10 TMD patients and 16 controls, using a counterbalanced, double-blind, crossover design, the same responses were assessed after intravenous administration of low dose propranolol vs placebo. Testing included baseline, postural, speech and ischemic pain stressors. FMS patients showed lesser heart rate (HR) increases to posture challenge but greater blood pressure (BP) increases to postural and speech tasks than controls, as well as higher overall BP and greater total vascular resistance (TVR) than TMDs or controls. TMDs showed higher overall cardiac output and lower TVR than controls. Both FMS and TMD groups showed lower baseline NE than controls, and TMDs showed lower overall EPI and NE levels. Group differences in HR, EPI and NE were abolished after propranolol although BP, CO and TVR differences persisted. In both FMS and TMD, the number of painful body sites and ratings of total clinical pain obtained 4 times during each session were significantly lower after beta-blockade vs placebo. PERSPECTIVE These findings support the hypothesis that both FMS and TMD may frequently involve dysregulation of beta-adrenergic activity that contributes to altered cardiovascular and catecholamine responses and to severity of clinical pain. Acute treatment with low-dose propranolol led to short-term improvement in all these domains.

Warm partner contact is related to lower cardiovascular reactivity.

Abstract The authors investigated the relationship between brief warm social and physical contact among cohabitating couples and blood pressure (BP) reactivity to stress in a sample of healthy adults (66 African American, 117 Caucasian; 74 women, 109 men). Prior to stress, the warm contact group underwent a 10-minute period of handholding while viewing a romantic video, followed by a 20-second hug with their partner, while the no contact group rested quietly for 10 minutes and 20 seconds. In response to a public speaking task, individuals receiving prestress partner contact demonstrated lower systolic BP, diastolic BP, and heart rate increases compared with the no contact group. The effects of warm contact were comparable for men and women and were greater for African Americans compared with Caucasians. These findings suggest that affectionate relationships with a supportive partner may contribute to lower reactivity to stressful life events and may partially mediate the benefit of marital support on better cardiovascular health.

Elevated Salivary Levels of Oxytocin Persist More than 7 h after Intranasal Administration.

We addressed the question how long salivary oxytocin levels remain elevated after intranasal administration, and whether it makes a difference when 16 or 24 IU of oxytocin administration is used. Oxytocin levels were measured in saliva samples collected from 46 female participants right before intranasal administration (at 9:30 a.m.) of 16 IU (n = 18) or 24 IU (n = 10) of oxytocin, or a placebo (n = 18), and each hour after administration, for 7 h in total. Oxytocin levels did not differ among conditions before use of the nasal spray. Salivary oxytocin levels in the placebo group showed high stability across the day. After oxytocin administration oxytocin levels markedly increased, they peaked around 1 h after administration, and were still significantly elevated 7 h after administration. The amount of oxytocin (16 or 24 IU) did not make a difference for oxytocin levels. The increase of oxytocin levels for at least 7 h shows how effective intranasal administration of oxytocin is. Our findings may raise ethical questions about potentially persisting behavioral effects after participants have left the lab setting. More research into the long-term neurological and behavioral effects of sniffs of oxytocin is urgently needed.

Association Between Maternal Mood and Oxytocin Response to Breastfeeding

BACKGROUND Postpartum depression is associated with reduced breastfeeding duration. We previously hypothesized that shared neuroendocrine mechanisms underlie this association. We sought to measure the association between maternal mood and neuroendocrine response to breastfeeding. METHODS We conducted a longitudinal cohort study of women recruited during pregnancy who intended to breastfeed. Baseline depression and anxiety history were assessed with a structured clinical interview. We measured mood symptoms using validated psychometric instruments, and we quantified affect and neuroendocrine responses to breastfeeding during laboratory visits at 2 and 8 weeks postpartum. RESULTS We recruited 52 women who intended to breastfeed, among whom 47 completed 8-week follow-up. Duration and intensity of breastfeeding through 8 weeks were similar among mothers with lower versus higher anxiety and depression scores. In the third trimester, oxytocin was inversely correlated with Edinburgh Postnatal Depression Scale (EPDS) score (p=0.03). We did not find differences in neuroendocrine profile during breastfeeding at 2 weeks postpartum. Among the 39 women who breastfed at 8 weeks postpartum, oxytocin area under the curve during breastfeeding was inversely correlated with maternal EPDS and STAI-State and STAI-Trait anxiety scores (all p≤0.01). Higher anxiety and depression scores was further associated with lower oxytocin (group p<0.05) during feeding. During feeding at both visits, higher anxiety and depression scores were also associated with more negative affect: mothers reported feeling less happy and more depressed, overwhelmed, and stressed during feeding than women with lower scores. CONCLUSION Symptoms of depression and anxiety were associated with differences in oxytocin response and affect during breastfeeding.

An investigation of plasma and salivary oxytocin responses in breast‐ and formula‐feeding mothers of infants

Oxytocin (OT) is a peptide increasingly studied in relation to human social interactions, affiliation, and clinical disorders. Studies are constrained by use of invasive blood draws and would benefit from a reliable salivary OT assay. Our goals were to examine feasibility of salivary OT measurement, compare salivary to plasma OT responses in 12 breast- and 8 formula-feeding mothers, and assess the degree of correlation between plasma and salivary OT. Using a commercial EIA kit, we measured OT in 5 saliva and 7 plasma samples in a protocol designed to elicit changes in OT (Rest, Infant Interaction, Stress, Feeding). Breast-feeders had higher OT levels than formula-feeders across all conditions in plasma (+36%) and saliva (+23%). OT levels and ranges were similar in saliva and plasma, with slightly greater variance in saliva. Concurrently sampled plasma and salivary OT were correlated at end of Baseline Rest (r=+.59, p=.022) and Post-Stress Recovery (r=+.59, p=.025). These data suggest that salivary OT assay is feasible, and will be of value where plasma samples are not possible. Validation with larger samples is needed.

Hormone replacement improves hemodynamic profile and left ventricular geometry in hypertensive and normotensive postmenopausal women.

Background Postmenopausal estrogen replacement, with or without progestins, has been related to lower cardiovascular risks. Objective We investigated whether the actions of estrogen on vascular resistance contribute to this cardioprotective effect. Design and methods In a 6-month double-blind study, pre- and post-treatment blood pressure, cardiac index, total vascular resistance index and plasma catecholamine responses during baseline and mental stressors were compared in 69 women (including 19 with mild hypertension but no history of heart disease). Women were randomized to receive either conjugated estrogens alone, estrogens plus medroxyprogesterone, or placebo. Results Both groups on active hormone replacement showed similar decreases in vascular resistance and modest blood pressure reductions, which differed from the unchanged responses of those on placebo (P < 0.05) after 3 and 6 months of treatment. Hypertensive women showed greater reductions in vascular resistance than normotensives (P < 0.05) and their blood pressure reductions tended to be larger. Women receiving hormone replacement showed increased stroke volume and cardiac index at 6 months, particularly among hypertensives and those receiving medroxyprogesterone (P < 0.05). Hormone replacement was also related to decreases in plasma norepinephrine. Finally, in 33 women receiving hormone replacement, significant 5 and 3% decreases in echocardiographic measures of left ventricular mass index and relative wall thickness were evident at 6 months (P < 0.05), while 20 placebo-treated women showed no reliable echocardiographic improvements (P = NS). Conclusions These findings suggest that estrogen-mediated reductions in hemodynamic load on the heart may contribute to the reduced risk of cardiovascular events in relatively healthy postmenopausal women who use hormone replacement.

Failed Lactation and Perinatal Depression: Common Problems with Shared Neuroendocrine Mechanisms?

In the early postpartum period, mother and infant navigate a critical neuroendocrine transition from pregnancy to lactation. Two major clinical problems that occur during this transition are failed lactation and perinatal mood disorders. These disorders often overlap in clinical settings. Failed lactation is common. Although all major medical organizations recommend 6 months of exclusive breastfeeding, only 13% of women in the United States achieve this recommendation. Perinatal mood disorders affect 10% of mothers, with substantial morbidity for mother and child. We hypothesize that shared neuroendocrine mechanisms contribute to both failed lactation and perinatal mood disorders. In this hypothesis article, we discuss data from both animal models and clinical studies that suggest neuroendocrine mechanisms that may underlie these two disorders. Research to elucidate the role of these underlying mechanisms may identify treatment strategies both to relieve perinatal depression and to enable women to achieve their infant feeding goals.