Janet A. Amico

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.

Deficiency in Mouse Oxytocin Prevents Milk Ejection,but not Fertility or Parturition

Oxytocin is a nonapeptide hormone that participates in the regulation of parturition and lactation. It has also been implicated in various behaviors, such as mating and maternal, and memory. To investigate whether or not oxytocin (OT) is essential for any of these functions, we eliminated, by homologous recombination, most of the first intron and the last two exons of the OT gene in mice. Those exons encode the neurophysin portion of the oxytocin preprohormone which is hypothesized to help in the packaging and transport of OT. The homozygous mutant mice have no detectable neurophysin or processed oxytocin in the paraventricular nucleus, supraoptic nucleus or posterior pituitary. Interestingly, homozygous mutant males and females are fertile and the homozygous mutant females are able to deliver their litters. However, the pups do not successfully suckle and die within 24 h without milk in their stomachs. OT injection into the dams restores the milk ejection in response to suckling. These results indicate an absolute requirement for oxytocin for successful milk ejection, but not for mating, parturition and milk production, in mice.

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.

Anxiety and Stress Responses in Female Oxytocin Deficient Mice

Oxytocin is believed to attenuate the response of the hypothalamic‐pituitary‐adrenal axis to stress and to be anxiolytic. Stressors with a psychological component evoke both central and peripheral secretion of oxytocin in laboratory rodents. Oxytocin gene deletion mice provide a novel way to understand the role of oxytocin in stress and anxiety‐related behaviours. We present our experience with female oxytocin deficient mice that were tested in an elevated plus maze (EPM), a behavioural test of anxiety, or exposed to psychogenic stressors (platform shaker or novel environment). Oxytocin‐deficient mice not only displayed more anxiety‐related behaviour, but also released more corticosterone after a psychogenic stressor and manifested greater stress‐induced hyperthermia compared to wild‐type mice. The diurnal variation of corticosterone and the response of corticosterone to corticotropin‐releasing factor were not significantly different between genotypes. We also measured Fos‐immunoreactive protein, an index of neuronal activation, in the medial amygdala of female mice after EPM testing. The medial amygdala is important for processing of psychogenic stress and anxiety and also contains oxytocin pathways and oxytocin receptors. The expression of Fos in the medial amygdala of mice not exposed to the EPM was not different between genotypes. Following EPM exposure, Fos expression was greater in oxytocin null compared to wild‐type mice. Our findings support the hypothesis that central oxytocin is anxiolytic, and attenuates the stress response to psychogenic provocation in female mice.

Bilateral Massive Adrenal Hemorrhage: Early Recognition and Treatment

PURPOSE To develop a clinical perspective on bilateral massive adrenal hemorrhage and an algorithm for its diagnosis and treatment. DATA IDENTIFICATION Case reports were identified through a computer search using MEDLIN (1976 to 1987), and from bibliographies in review articles (up to 1978). STUDY SELECTION Twelve reports published since 1978 were found. DATA EXTRACTION Data from 20 recently reported cases and 5 cases from personal records were compared with data from 142 previously reported, autopsy-proven cases summarized in a 1978 review article. RESULTS OF DATA ANALYSIS Thromboembolic disease, coagulopathy, and the postoperative state were the three major risk factors. Except for abdominal pain and remittent fever, clinical features were not helpful in diagnosis. A fall in hemoglobin, and progressive biochemical hypoadrenalism were important clues. Diagnosis was confirmed by computed tomography and an absent cortisol response to intravenous corticotropin. Long-term follow-up showed complete atrophy and functional failure of the adrenal gland. CONCLUSIONS Death from bilateral massive adrenal hemorrhage can be prevented by pre-emptive steroid therapy in high-risk patients who have certain clinical and laboratory features.

Evidence of dysregulated peripheral oxytocin release among depressed women.

Objective: Oxytocin is a hypothalamic neuropeptide that plays a key role in mammalian female reproductive function. Animal research indicates that central oxytocin facilitates adaptive social attachments and modulates stress and anxiety responses. Major depression is prevalent among postpubertal females, and is associated with perturbations in social attachments, dysregulation of the hypothalamic-pituitary-adrenal stress axis, and elevated levels of anxiety. Thus, depressed women may be at risk to display oxytocin dysregulation. The current study was developed to compare patterns of peripheral oxytocin release exhibited by depressed and nondepressed women. Methods: Currently depressed (N = 17) and never-depressed (N = 17) women participated in a laboratory protocol designed to stimulate, measure, and compare peripheral oxytocin release in response to two tasks: an affiliation-focused Guided Imagery task and a Speech Stress task. Intermittent blood samples were drawn over the course of two, 1-hour sessions including 20-minute baseline, 10-minute task, and 30-minute recovery periods. Results: The 10-minute laboratory tasks did not induce identifiable, acute changes in peripheral oxytocin. However, as compared with nondepressed controls, depressed women displayed greater variability in pulsatile oxytocin release over the course of both 1-hour sessions, and greater oxytocin concentrations during the 1-hour affiliation-focused imagery session. Oxytocin concentrations obtained during the imagery session were also associated with greater symptoms of depression, anxiety, and interpersonal dysfunction. Conclusions: Depressed women are more likely than controls to display a dysregulated pattern of peripheral oxytocin release. Further research is warranted to elucidate the clinical significance of peripheral oxytocin release in both depressed and nondepressed women. HPA = hypothalamic-pituitary-adrenal; MDD = major depressive disorder; SCID-IV = Structured Clinical Interview for Axis I DSM-IV disorders; HRSD-17 = 17-item Hamilton Rating Scale for Depression; BDI = Beck Depression Inventory; BAI = Beck Anxiety Inventory; IIP = Inventory of Interpersonal Problems; AUC = area under the curve; pg/ml = picograms per milliliter; CSF = cerebrospinal fluid; PVN = paraventricular nucleus; SON = supraoptic nucleus.

Oxytocin Responsivity in Mothers of Infants: A Preliminary Study of Relationships With Blood Pressure During Laboratory Stress and Normal Ambulatory Activity

The neuropeptide oxytocin (OT) enhances maternal behavior and decreases blood pressure (BP) and stress responses in animals. Thus, the relationship of OT responsivity to BP in 14 breast- and 11 bottle-feeding mothers of infants was examined. Laboratory BP was assessed during baseline, speech preparation, active speech, and recovery on 2 days, 1 in which baseline and speech were separated by 10 min of baby holding and the other by no baby contact. Systolic BP reactivity to speech was lower after baby contact. Plasma OT change from baseline to speech after baby contact defined OT increase, minimal OT change, and OT decrease groups. OT increase mothers were primarily breast-feeders, and they had lower BP throughout both stress sessions and after baby feeding at home than OT decrease mothers, who also had greater BP reactivity to preparation and recovery. These results suggest that oxytocin has antistress and BP-lowering effects in humans.

Salivary cortisol is associated with diagnosis and severity of late-life generalized anxiety disorder

Age-associated alterations in hypothalamic-pituitary-adrenal (HPA) axis functioning may make individuals more susceptible to HPA dysregulation in the context of mood and anxiety disorders. Little to no research has been done to examine HPA axis function in generalized anxiety disorder (GAD), particularly in late-life GAD, the most prevalent anxiety disorder in the elderly. The study sample consisted of 71 GAD subjects and 40 nonanxious comparison subjects over 60 years of age. We examined the hypotheses that elderly individuals with GAD will have elevated salivary cortisol levels compared to nonanxious subjects, and that elevated cortisol levels in GAD will be associated with measures of symptom severity. We report that late-life GAD is characterized by elevated basal salivary cortisol levels, with higher peak cortisol levels and larger areas under the curve, compared to nonanxious subjects. Additionally, severity of GAD as measured by the GAD Severity Scale and the Penn State Worry Questionnaire are positively correlated with cortisol levels. These data demonstrate HPA axis dysfunction in late-life GAD and suggest the need for additional research on the influence of aging on HPA axis function in mood and anxiety disorders.

CONCENTRATIONS OF LEPTIN IN THE SERUM OF PREGNANT, LACTATING, AND CYCLING RATS AND OF LEPTIN MESSENGER RIBONUCLEIC ACID IN RAT PLACENTAL TISSUE

Leptin concentrations were measured in the serum of cycling, pregnant, and lactating Sprague-Dawley rats. Serum leptin concentrations did not vary significantly during the estrous cycle. In contrast, as gestation advanced, serum leptin concentrations increased significantly, p < 0.0001. Following delivery, leptin concentrations declined and remained stable during lactation. Leptin messenger ribonucleic acid (mRNA) was identified in the visceral adipose tissue and placenta of rats sacrificed on days 14 and 21 of pregnancy. The relative abundance of placental leptin mRNA increased approximately 4 to 5 fold from day 14 to 21 of gestation. The pattern of elevated leptin concentrations in the serum of late pregnant rats is similar to that reported in pregnant women, therefore the rat may be a useful model for the study of leptin during pregnancy. The increase in leptin in the serum of late pregnant rats, as well as an increase in placental mRNA, raises the possibility that leptin may serve a physiological role for the late parturient rat and/or its young.

Suckling-Induced Attenuation of Plasma Cortisol Concentrations in Postpartum Lactating Women

The effect of suckling on serum cortisol concentrations was assessed in postpartum lactating women studied during serial breast feeding sessions 1-24 weeks postpartum. The mean +/- SD serum cortisol concentration at 15 min after the start of nursing, 9.8 +/- 3.89 micrograms/dl, was significantly lower, P = 0.001, than prior to the start of nursing, 13.2 +/- 5.92 micrograms/dl. The decline in the serum cortisol concentrations in the breast feeding women was not due entirely to the normal metabolism of the hormone or the normal circadian variation in cortisol secretion. These studies complement and expand upon a recent report [3] of a significant decrease in plasma adrenocorticotrophic hormone in breast feeding women studied one week postpartum. The neuroendocrine mechanisms responsible for this effect in women have yet to be defined.