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Biomedical subjects

Susan S Girdler

Publications and source records attributed to Susan S Girdler.

At least 19 recordsLinked to original sources

Associations of histories of depression and PMDD diagnosis with allopregnanolone concentrations following the oral administration of micronized progesterone.

Twenty-three women with premenstrual dysphoric disorder (PMDD) and 29 non-PMDD controls were compared for plasma progesterone (P) and its neuroactive steroid metabolite allopregnanolone (ALLO), as well as the ALLO/P ratio following the double-blind, placebo controlled administration of 300 mg oral micronized progesterone. Approximately half of each group had prior depression (DEP) (13 PMDD, 12 non-PMDD), though all were free of current depression. Progesterone and ALLO were sampled 160, 190, 225, and 255 min after progesterone administration. Changes over time in plasma concentrations and the ALLO/P ratio were assessed using area under the curve analyses. Women with prior DEP had lower ALLO levels (p=0.05) and marginally lower P levels (p<0.07) following progesterone administration compared to never depressed women, and this was especially evident in the non-PMDD women (p<0.01). PMDD women with no prior DEP had higher pre-progesterone ALLO/P ratios than all other groups (Ps<0.05) and higher ratios than the never depressed, non-PMDD women following oral progesterone (p<0.05). Results could not be accounted for by group differences in steroid hormone binding protein concentrations. For all women, progesterone administration was associated with increased confusion, fatigue, and with reduced confidence (Ps<0.01), even after controlling for placebo-associated mood change. These results suggest a persistent effect of prior DEP on P and ALLO concentrations following oral progesterone and that PMDD women, especially those with no prior DEP, may have alterations in the metabolic pathways underlying the conversion of P to ALLO.

Administration, Oral↗

Mood and thyroid immunity assessed by ultrasonographic imaging in a primary health care.

BACKGROUND: Psychiatric morbidity is highly prevalent in the primary health care settings and it may be related to autoimmune thyroid disease (AITD). The aim of this study was to evaluate the impact of thyroid immunity, evident by hypo-echoic thyroid ultrasound pattern, on prevalence of depression and anxiety in a primary care setting. METHODS: In a cross-sectional design, 504 consecutive primary care patients were invited to the study and 474 patients completed the study. They were screened for depression and anxiety using the Hospital Anxiety and Depression Scale (HADS), were interviewed for affective disorders using the Mini International Neuropsychiatric Interview, and were evaluated by ultrasonographic imagining of the thyroid gland. RESULTS: Among patients with hypo-echoic thyroid (n=122) prevailed women and those patients were older than patients with normo-echoic thyroid (n=352). Women, but not men, with hypo-echoic thyroid compared to those with normo-echoic thyroid had higher scores on the anxiety subscale of the HADS (p=0.03). Among women with hypo-echoic thyroid, only those pre-menopause, but not those post-menopause, had greater prevalence of high scores on the depression subscale of the HADS (p=0.02) and a greater likelihood of using psychiatric medications (p=0.001). LIMITATIONS: Lack of cytological evaluation of the thyroid gland; lack of serum thyroid antibodies concentrations; and lack of thyroid hormone concentrations. CONCLUSIONS: Thyroid immunity is related to mood symptoms in primary care patients. These effects are gender specific and in women, they are most evident before menopause.

Adolescent↗

Depression and thyroid axis function in coronary artery disease: impact of cardiac impairment and gender.

BACKGROUND: Increased rates of depression are reported in coronary artery disease (CAD). In heart disease, depression increases disability, reduces quality of life, and increases mortality. HYPOTHESIS: The study was undertaken to examine the relationship between depression and thyroid axis function in patients with CAD. METHODS: In all, 73 patients with CAD, consecutively admitted to a cardiac rehabilitation hospital, were assessed for depression using the Hospital Anxiety and Depression scale (HADS). Blood was drawn for assessment of thyroid axis hormones and the N-amino terminal fragment of the pro-B-type natriuretic peptide (NT-pro BNP). RESULTS: The patients with CAD with depressive symptoms had a higher prevalence of cardiac failure (p = 0.04), higher NT-pro BNP concentrations (p = 0.02), and lower free triiodothyronine (T3) concentrations (p = 0.04) than patients with CAD but without depressive symptoms. They also showed a strong trend (p = 0.058) toward a higher incidence of the low T3 syndrome. Higher NT-pro BNP concentrations were related to lower total T3 concentrations (r = -0.294, p = 0.011) and to higher reverse T3 concentrations (r = 0.353, p = 0.002). In men, higher scores of depression were related to lower total T3 concentration (r = -0.289, p = 0.034) and to higher NT-pro BNP concentration (r = 0.380, p = 0.005). CONCLUSION: These findings suggest that symptoms of depression in patients with CAD are associated with changes in thyroid axis function and with cardiac impairment, especially in men.

Coronary Artery Disease↗

Ethnic differences in allopregnanolone concentrations in women during rest and following mental stress.

The neuroactive steroid allopregnanolone (ALLO) is stress sensitive, negatively modulates the HPA axis, and has been implicated in mood disorders. We examined ethnic differences in plasma ALLO at rest and following mental stress in African American (AA) men (n = 21) and women (n = 24) and non-Hispanic White men (n = 24) and women (n = 25). Overall, AA women had lower ALLO concentrations than non-Hispanic White women (p < .05), especially following mental stress (p < .01). Only 20% of AA women showed the expected stress-induced increase in ALLO compared with 59% of non-Hispanic White women (p < .01). No ethnic differences were seen in men. For both ethnic groups, poststress ALLO was negatively correlated with poststress cortisol (p < .05). Results are interpreted to reflect dysregulation in ALLO mechanisms in AA women and may have implications for ethnic differences in mood disorders.

Adolescent↗

Histories of depression, allopregnanolone responses to stress, and premenstrual symptoms in women.

Twenty-six women meeting DSM criteria for premenstrual dysphoric disorder (PMDD) and 39 non-PMDD controls were tested for allopregnanolone (ALLO) responses to mental stress. Approximately half of each group had a history of depression (DEP) (14 PMDD, 17 non-PMDD), though all were free of current psychiatric illness. ALLO was sampled in response to venipuncture stress, after an extended baseline, and again 30 and 60 min following the onset of mental stressors. All women with prior DEP, regardless of PMDD status, showed a blunted ALLO stress response at 30 and 60 min (p < 0.05), and also failed to show the expected decrease from venipuncture to baseline rest (p = 0.08) compared to women with no prior DEP. Women with prior DEP did not show the expected correlation between progesterone and ALLO (r = 0.16) that was seen in those with no prior DEP (r = 0.37, p < 0.05). ALLO levels at extended baseline and blunted ALLO reactivity predicted more severe premenstrual symptoms, but only in PMDD women with prior DEP (p values <0.05). These results suggest that a history of DEP is associated with a failure of ALLO to be appropriately responsive to challenge, with alterations in the conversion of progesterone to ALLO, and confirm prior reports linking ALLO to symptoms in PMDD, but only in PMDD women with histories of DEP.

Adult↗

Lack of beneficial effects of clonidine in the treatment of premenstrual dysphoric disorder: results of a double-blind, randomized study.

OBJECTIVES: To test the effects of clonidine in comparison with active placebo on premenstrual symptoms, mood scores and norepinephrine (NE) concentration, in women with premenstrual dysphoric disorder (PMDD). METHODS: Twelve women with prospectively confirmed PMDD were randomly assigned to oral 0.3 mg/day clonidine, as an active treatment, or 10 mg/day loratadine, as an active placebo, for 2 months each using a double-blind, cross-over design. NE concentration, premenstrual symptom ratings and mood scales were measured on three occasions: at pretreatment, after clonidine treatment and after placebo treatment. All patients were free of current psychiatric co-morbidity and medication use. RESULTS: There were no significant differences between clonidine and placebo for mood scales or premenstrual symptom ratings, though clonidine significantly suppressed NE concentration and produced more side effects in comparison with placebo. CONCLUSION: Compared with an active placebo clonidine demonstrated no beneficial changes in mood and premenstrual symptoms in women with PMDD.

Administration, Oral↗

Histories of sexual abuse are associated with differential effects of clonidine on autonomic function in women with premenstrual dysphoric disorder.

In women meeting strict criteria for premenstrual dysphoric disorder (PMDD), we examined whether clonidine, an alpha2-adrenergic receptor (AR) agonist, would have different effects on sexually abused versus non-abused PMDD women for measures of autonomic nervous system function. Twelve women meeting prospective, DSM-IV criteria for PMDD, five of whom had a history of sexual abuse, participated in a randomized, placebo-controlled, double-blind, cross-over design study, comparing 2 months of on oral clonidine (0.3 mg/day) with 2 months on active placebo. During the luteal phase that preceded randomization and following each two-month challenge, women were tested for cardiovascular measures at rest and in response to mental stress, and for resting plasma norepinephrine (NE) concentrations as well as beta1 and beta2-AR responsivity using the isoproterenol sensitivity test. Results revealed that in comparison to placebo, clonidine significantly reduced plasma norepinephrine concentrations, increased both beta1- and beta2-AR responsivity, and reduced resting and stress heart rate (HR) and blood pressure (BP) (p < 0.05) in all PMDD women. With clonidine, sexually abused PMDD women exhibited greater decreases in resting and stress-induced HR (p < 0.01) and stress-induced systolic BP (p < 0.05), while non-abused PMDD women exhibited greater reductions in plasma NE concentration (p = 0.07), and greater increases in beta2-AR responsivity (p < 0.05) than abused PMDD women. These results suggest PMDD women with and without a history of sexual abuse respond differently to a clonidine challenge in measures reflecting autonomic nervous system functioning, indicating that abuse may modify presynaptic alpha2-AR function in PMDD.

Administration, Oral↗

Cigarette smoking, stress-induced analgesia and pain perception in men and women.

This study examined gender differences in smoking-related analgesia and stress-induced analgesia (SIA), as a function of pain modality. Forty men (20 smokers, 20 nonsmokers) and 37 women (17 smokers) were tested twice for pain sensitivity to tourniquet ischemia, thermal heat, and cold pressor tests; once following mental stress and once following rest control, counterbalancing order. Cardiovascular and neuroendocrine responses to mental stress were also examined. While expected gender differences in pain sensitivity were observed, women smokers had greater threshold and tolerance times to ischemic pain than women nonsmokers (P<0.05) when pain testing followed rest. Male smokers had greater threshold and tolerance to cold pressor pain than male nonsmokers (P<0.05) after both rest and stress. Only women showed evidence for SIA, since women nonsmokers demonstrated greater ischemic pain threshold and tolerance following mental stress versus rest (P<0.05), and all women reported lower thermal heat pain unpleasantness after stress versus rest (P=0.05). Only nonsmokers showed expected inverse relationships between sympathetic and hypothalamic-pituitary-adrenal (HPA) axis reactivity measures and sensitivity to pain. Smokers showed evidence for blunted HPA-axis function at rest and stress. These results indicate that analgesia related to both being a smoker and stress is influenced by gender and pain modality. The reduced pain perception in smokers and absence of relationships between endogenous pain regulatory mechanisms and pain sensitivity may reflect a maladaptive response to chronic smoking.

Adrenocorticotropic Hormone↗

Oxytocinergic activity is linked to lower blood pressure and vascular resistance during stress in postmenopausal women on estrogen replacement.

Estrogen administration results in increased release of the oxytocin (OT) prohormone reflected by increases in oxytocin intermediate peptide (OT Int) in both animal models and humans, and sequential treatment of ovariectomized rats with estrogen/progesterone then progesterone withdrawal leads to increased hypothalamic OT mRNA. Blood pressure (BP) reductions have been related to increased exogenous and endogenous OT in rats and to higher endogenous OT activity in premenopausal women, but not previously in postmenopausal women. Thus, we used plasma obtained at rest and during a speech stressor from 54 postmenopausal women who participated in a 6-month randomized trial of oral conjugated estrogens vs. placebo to examine effects of estrogen replacement therapy (ERT) on plasma OT and OT Int levels and their relationships to changes in BP during the trial. ERT alone and with progesterone (but not placebo) led to significant increases in plasma levels of OT Int, but no change in plasma OT levels. Women showing greater increases in OT Int during treatment showed greater decreases in BP and total vascular resistance during a series of behavioral stressors compared to women with moderate or no increases in OT Int, even after controlling for effects related to treatment condition or to changes in plasma estradiol. The findings suggest that enhanced oxytocinergic activity may contribute to BP decreases associated with ERT in more responsive postmenopausal women.

Adult↗

Relationship quality: effects on ambulatory blood pressure and negative affect in a biracial sample of men and women.

BACKGROUND: Prospective studies link marriage to better cardiovascular health, but marital dissatisfaction and discord predict increased rates of hypertension, higher blood pressure (BP), greater reactivity to stress, and left ventricular mass. OBJECTIVE: To determine and compare effects of partner status and relationship quality on 24-h BP, urinary norepinephrine and cortisol, and self-reported stress and negative affect. METHODS: Ambulatory BP (ABP) and 24-h urine collections were obtained during a typical work day in 325 adults, including 139 African Americans (AAs). Participants cohabiting with a spouse or partner were classified into high, intermediate and low relationship quality (RQ) groups and compared to those without partners (Alone). RESULTS: Mean ABP was nearly identical in participants with versus without partners (125.7/76.9 versus 125.9/76.7 mmHg). High RQ subjects had lower mean waking ABP than intermediate/low RQ and Alone groups [systolic blood pressure (SBP), F=3.45; diastolic blood pressure (DBP), F=3.38, P-values <0.05]. High RQ was related to lower SBP and DBP in African Americans, and to lower SBP in Whites. High RQ was also linked to lower SBP and DBP in men, and to lower SBP in women. High RQ subjects reported less negative affect and stress than all other groups (P<0.05). Norepinephrine was lower in partnered versus Alone women regardless of RQ status. CONCLUSIONS: Relationship quality is a better predictor of daily BP, affect and stress than partner status. High RQ is linked to lower ABP across race and gender. This reduced ABP may be due, in part, to the stress buffering effects of better RQ and/or the stress enhancing effects of poor RQ.

Adolescent↗

Cardiovascular effects of 6 months of hormone replacement therapy versus placebo: differences associated with years since menopause.

OBJECTIVE: In response to post-Women's Health Initiative dialog regarding individualized hormone replacement therapy (HRT), this study evaluates cardiovascular and neuroendocrine effects of HRT versus placebo in postmenopausal women grouped according to time since menopause. STUDY DESIGN: Resting and stress blood pressure (BP), hemodynamic, plasma catecholamine, and cholesterol levels were obtained in 69 women randomly assigned to placebo or active HRT in a 6-month double-blind study. Analyses evaluated if treatment effects differed among those postmenopausal less than 5 years versus 5 years or more. RESULTS: Compared with the placebo-treated and HRT > or =5 groups, the HRT < 5 group showed reduced BP (P<.0007) and trends toward reduced vascular resistance and norepinephrine (P<.07). HRT > or =5 group generally did not differ from placebo. CONCLUSION: Reduced BP and sympathetic tone are evident in some HRT users, with diminishing benefit after the initial postmenopausal years. Time since menopause may be an important consideration in making individualized patient treatment decisions.

Adult↗

Relationship of ethnicity, gender, and ambulatory blood pressure to pain sensitivity: effects of individualized pain rating scales.

UNLABELLED: A growing literature has reported significant reductions in pain sensitivity associated with increasing levels of blood pressure. However, most of this research has been limited to casual blood pressure assessments in white men. The present study examined associations between pain reports and ambulatory blood pressure in a sample of African American and white men and women. Possible response bias during pain assessment due to ethnicity and gender was evaluated with individualized pain rating scales. One hundred thirty-five (72 African American and 63 white) men and women underwent 24-hour blood pressure monitoring and arm ischemia pain sensitivity evaluation with both standard verbal rating scales and individually ordered verbal rating scales of intensity and unpleasantness. Lower individualized pain intensity and unpleasantness ratings were associated with higher levels of ambulatory blood pressure. African Americans and women reported higher levels of pain intensity when using the standard verbal rating scale but not when using the individually ordered rating scale. Collectively, these results support previous research relating reduced pain sensitivity with increased blood pressure among men and women. Furthermore, reported differences in pain sensitivity between ethnic groups and genders might in part be associated with variations in response styles to standard pain assessment tools. PERSPECTIVE: The findings of the present study suggest that, in some instances, different ethnic groups and genders may use the same descriptors to report different levels of pain. In the context of clinical pain assessment, it may be important to consider the possibility that descriptions of painful sensations reflect, in part, demographic characteristics.

Adult↗

Bupropion and paroxetine differentially influence cardiovascular and neuroendocrine responses to stress in depressed patients.

BACKGROUND: There exists a need to identify safe and effective treatments for depression in patients with coronary heart disease (CHD). METHODS: Using a cross-sectional design, 17 depressed patients being treated with bupropion (200-450 mg/day) were compared with 17 depressed patients being treated with paroxetine (10-50 mg/day) and with a group of 15 unmedicated, non-depressed controls for cardiovascular, neuroendocrine and heart rate variability (HRV) measures at rest and in response to mental and physical stressors. RESULTS: Regardless of treatment, both treated groups exhibited blunted plasma cortisol, plasma epinephrine, systolic blood pressure, cardiac output, and pre-ejection period responses to mental stressors relative to controls. Bupropion treated individuals exhibited greater total peripheral resistance (TPR) increases than either the paroxetine or control groups, and greater plasma norepinephrine (NE) increases to mental stressors than the paroxetine group. The bupropion group also displayed reduced HRV at rest relative to the controls and during orthostatic challenge relative to both the control and paroxetine groups. LIMITATIONS: Despite the fact that the treated groups were well matched for depression and other psychiatric histories, lack of randomization into treatment arms may be associated with a selection bias in the two treated groups. CONCLUSIONS: Although both pharmacological treatments were associated with a blunting of some cardiovascular and neuroendocrine responses to stress relative to controls, which may be reflective of their therapeutic mechanisms of action, the results of our study also suggest that bupropion is associated with a more detrimental autonomic profile than paroxetine, as reflected in increased TPR and NE, and reduced HRV. The results of this study may have implications for the pharmacological treatment of depression in CHD patients.

Adult↗

Transdermal versus oral estrogen therapy in postmenopausal smokers: hemodynamic and endothelial effects.

OBJECTIVE: To test the hypothesis that, in postmenopausal smokers, transdermal estrogen would be more effective than oral estrogen in reducing blood pressure (BP) and vascular and norepinephrine responses to stress and in increasing endothelial function and vascular beta2-adrenoceptor responsivity. METHODS: By using a randomized, double-blind, placebo-controlled design, 82 healthy postmenopausal smokers were tested before and after 6 months of therapy with transdermal estrogen (0.05 mg/d) plus a progestin (2.5 mg/d; n = 31), oral conjugated equine estrogen (0.625 mg/d) plus a progestin (2.5 mg/d; n = 30), or placebo (n = 21). Dependent measures included resting and stress-induced increases in BP, total peripheral resistance, and plasma norepinephrine, as well as endothelial function and beta-adrenoceptor responsivity. RESULTS: When compared with placebo, the transdermal estrogen group showed more consistent reductions in total peripheral resistance at rest and in response to mental stress than the oral estrogen group. Only the transdermal group showed treatment-related reductions in behavioral stress norepinephrine, baseline rest, and behavioral stress BP levels, and increases in vascular beta2-adrenoceptor responsivity and endothelium-dependent vasodilation. Posttreatment concentrations of serum estradiol and estrone were lower and the serum estradiol/estrone ratio closer to pre-menopausal values in the group receiving transdermal estrogen compared with oral estrogen. CONCLUSION: Six months of transdermal estrogen therapy is associated with greater reductions in measures reflecting vascular sympathetic tone than oral estrogen therapy in healthy postmenopausal smokers. Thus, transdermal estrogen may be associated with a more favorable risk/ benefit ratio in postmenopausal smokers, a group at high risk of osteoporosis and cardiovascular disease.

Administration, Cutaneous↗

Warm partner contact is related to lower cardiovascular reactivity.

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.

Adult↗

Sympathoadrenergic mechanisms in reduced hemodynamic stress responses after exercise.

PURPOSE: This study examines the acute effects of moderate aerobic exercise on 1) hemodynamic and sympathetic activity during behavioral stress and 2) beta-adrenergic receptor responsivity in a biracial sample of 24 sedentary adults. METHODS: Before and after exercise, blood pressure (BP), impedance-derived cardiovascular measures, and plasma norepinephrine (NE) and epinephrine (EPI) were assessed during mental arithmetic and active speech tasks, and beta-adrenergic receptor responsivity was assessed using a standard isoproterenol challenge procedure. RESULTS: After exercise, BP, NE, and EPI responses to stress were reduced (0.0001 < P < 0.08), preejection period (PEP) was elongated (P < 0.0001), and beta(1)- and beta(2)-receptor responsivity (P < 0.02) was enhanced. Approximately 65% of the prepost exercise mean arterial pressure response difference could be accounted for by changes in sympathetic factors, with change in NE and PEP being the single best predictors. CONCLUSIONS: Reduced BP responses to stress after acute exercise are strongly linked to a decrease in sympathetic drive, as evidenced by reduced NE responses and elongation of the PEP. Coincident with this overall dampening of the hemodynamic response to stress, increases in cardiac and vascular beta-adrenergic receptor responsivity occur. These findings may have important implications for future translational studies that seek to articulate the mechanisms through which regular aerobic exercise reduces the risks of hypertensive and coronary heart disease.

Adult↗

Changes in hemodynamics and left ventricular structure after menopause.

To evaluate the cardiovascular changes associated with menopause, we studied hemodynamics at rest, ambulatory blood pressure, and left ventricular structure in a biracial cohort of pre- and postmenopausal women of similar age, race, weight, and blood pressure. Despite similar levels of blood pressure, postmenopausal women had a higher indexed peripheral resistance (2,722 +/- 757 vs 2,262 +/- 661 dynes.s.m(2)/cm(5), p <0.01) and a lower cardiac index (2.64 +/- 0.73 vs 3.10 +/- 0.71 L/min.m(2), p <0.01) than premenopausal women. Postmenopausal women also had less nocturnal decreases in both systolic (15 +/- 8 vs 19 +/- 8 mm Hg, p <0.01) and diastolic (12 +/- 6 vs 15 +/- 6 mm Hg, p = 0.05) pressures during ambulatory monitoring and higher levels of hematocrit (40 +/- 2% vs 38 +/- 3%, p <0.01). In association with this greater hemodynamic load, postmenopausal women had evidence of early concentric left ventricular remodeling, manifested by a greater relative wall thickness (0.38 +/- 0.06 vs 0.35 +/- 0.06, p <0.01) than that observed in premenopausal women. Differences between pre- and postmenopausal women in hemodynamics, diurnal blood pressure variation, and left ventricular structure were observed in white and African-American subjects. These results suggest that menopause is associated with hemodynamic changes and left ventricular remodeling, which may contribute to the enhanced cardiovascular risk observed in postmenopausal women.

Black or African American↗