Biomedical subjects

Kathleen C Light

Publications and source records attributed to Kathleen C Light.

At least 19 recordsLinked to original sources

PubMed2006

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↗

PubMed2006

Patterns of salivary cortisol secretion in pregnancy and implications for assessment protocols.

Cortisol is used in research as a biomarker of psychological stress. Logistical considerations argue for collecting as few samples as possible, balanced against diurnal rhythms and intra-individual variations. 100 pregnant women gave five saliva samples a day for 3 days, at waking, 30 min after waking, and 11:00 a.m., 5:00 p.m., and 9:00 p.m. Timing of collection was confirmed by monitors. Another sample was taken during a clinic visit. Using the 15 measures as the gold standard, correlations and mean area under the curve (AUC) were compared with subsets and the single clinic sample to evaluate alternate collection protocols. Five samples in 1 day, or protocols involving morning and night samples, had the highest correlations with mean AUC (correlation coefficient ranging from 0.82 to 0.88). Standardizing the clinic measurement to a single time of day did not substantially improve correlations with mean AUC. Correlations with measures of reported stress were also not strong.

Adult↗

PubMed2006

Orthostatic hypotension predicts mortality in middle-aged adults: the Atherosclerosis Risk In Communities (ARIC) Study.

BACKGROUND: An association between orthostatic hypotension (OH) and mortality has been reported, but studies are limited to older adults or high-risk populations. METHODS AND RESULTS: We investigated the association between OH (a decrease of 20 mm Hg in systolic blood pressure or a decrease of 10 mm Hg in diastolic blood pressure on standing) and 13-year mortality among middle-aged black and white men and women from the Atherosclerosis Risk in Communities Study (1987-1989). At baseline, 674 participants (5%) had OH. All-cause mortality was higher among those with (13.7%) than without (4.2%) OH. After we controlled for ethnicity, gender, and age, the hazard ratio (HR) for OH for all-cause mortality was 2.4 (95% confidence interval [CI], 2.1 to 2.8). Adjustment for risk factors for cardiovascular disease and mortality and selected health conditions at baseline attenuated but did not completely explain this association (HR = 1.7; 95% CI, 1.4 to 2.0). This association persisted among subsets that (1) excluded those who died within the first 2 years of follow-up and (2) were limited to those without coronary heart disease, cancer, stroke, diabetes, hypertension, or fair/poor perceived health status at baseline. In analyses by causes of death, a significant increased hazard of death among those with versus without OH persisted after adjustment for risk factors for cardiovascular disease (HR = 2.0; 95% CI, 1.6 to 2.7) and other deaths (HR = 2.1; 95% CI, 1.6 to 2.8) but not for cancer (odds ratio = 1.1; 95% CI, 0.8 to 1.6). CONCLUSIONS: OH predicts mortality in middle-aged adults. This association is only partly explained by traditional risk factors for cardiovascular disease and overall mortality.

Age Factors↗

PubMed2006

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↗

PubMed2006

Social correlates of the chronic stress of perceived racism among Black women.

OBJECTIVES: This study describes the perceptions of racism, passive and active responses to this psychosocial stressor, and it examines socioeconomic correlates of perceived racism in an economically diverse population of Black women. METHODS: The Telephone-Administered Perceived Racism Scale was administered to 476 Black women, aged 36 to 53 years, who were randomly selected from a large health plan. RESULTS: The percentage of respondents who reported personally experiencing racism in the past five years ranged from 66% to 93%, depending on the specific item asked. When respondents were asked about racism toward Blacks as a group, perceptions of racism were even higher. For example, 68% "agreed" or "strongly agreed" that they had personally experienced being followed or watched while shopping because of their race, and 93% reported that Blacks in general experience this form of discrimination. Strong emotional responses to racism were often reported, and though more respondents (41%) reported experiencing very strong active emotions including anger, a substantial group (16%) reported experiencing very strong passive emotions such as powerlessness. Higher education was associated with higher perceived racism, while growing up in a middle-income or well-off family was associated with lower perceived racism and reduced likelihood of passive responses to racism. CONCLUSIONS: The high prevalence of perceived racism in this study population warrants further examination of this stressor as a potential determinant of racial health disparities. Higher education and income do not appear to protect women from experiencing racism and feeling hopeless or powerless in response.

Adult↗

PubMed2006

Dietary sodium restriction alters postprandial ghrelin: implications for race differences in obesity.

OBJECTIVES: To examine the effect of sodium restriction on the appetite-stimulating hormone, ghrelin, as a function of race, salt sensitivity, and obesity. DESIGN: PARTICIPANTS completed two 4-day outpatient dietary interventions (moderate vs low sodium), and blood samples were drawn two hours after a controlled test meal under both conditions. SETTING: A university research laboratory and affiliated General Clinical Research Center. PARTICIPANTS: 37 women (18 Black, 19 White) and 18 men (9 Black, 9 White), aged 36-63 years. MEASURES: Cardiovascular function (blood pressure, heart rate, impedance-derived indices of cardiac output and peripheral resistance) was measured after a 20-minute rest before each test meal. Blood was drawn by intravenous forearm catheter two hours after each test meal and later assayed for ghrelin, leptin, and norepinephrine. RESULTS: After four days of sodium restriction, postprandial ghrelin increased in White men and women and Black men but decreased in Black women. Salt sensitivity, but not obesity, was also related to ghrelin response during sodium restriction; postprandial ghrelin tended to increase among salt-sensitive subjects during salt restriction but decrease among salt-resistant subjects during salt restriction. CONCLUSIONS: Satiety hormone dysregulation may play a role in: 1) the heightened obesity-related morbidity among Black women, in particular; 2) adherence to sodium-restricted diets; and 3) race differences in behavioral weight-loss interventions that include sodium restriction.

Adult↗

PubMed2005

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↗

PubMed2005

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↗

PubMed2005

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↗

PubMed2005

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↗

PubMed2005

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↗

PubMed2005

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↗

PubMed2005

Hostility, conflict and cardiovascular responses in married couples: a focus on the dyad.

This study examined the relations of one's own total trait hostility and one's spouse's hostility as influences on cardiovascular (CV) responses to couple interactions (including conflict discussions) in 45 married couples aged 24-50. Systolic blood pressure and cardiac index (CI) reactivity to conflict discussion and recovery after conflict was greater in low hostile males if they were interacting with high hostile wives (p < .02). Vascular resistance index (VRI) reactivity to interactions was greater in high hostile husbands with high hostile wives (p < .05). Women showed no adverse CV effects of having a hostile spouse when their own hostility was low. Instead, seeming to anticipate the subsequent couple interactions, wives from duos in which both partners were high in hostility had higher baseline VRI levels and lower baseline CI compared to wives from duos in which both were low in hostility (ps < .05), and they simply maintained these group differences with no greater CV reactivity during the interactions. Findings suggest that CV responses before, during, and after marital discussions, particularly those characterized by conflict, may be influenced not only by one's own hostility but by the hostility of one's partner as well.

Adult↗

PubMed2004

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.

Adult↗

PubMed2004

Deficits in plasma oxytocin responses and increased negative affect, stress, and blood pressure in mothers with cocaine exposure during pregnancy.

In animals, oxytocin enhances maternal behavior and lowers blood pressure (BP) and negative affect, while parturitional cocaine disrupts oxytocin activity and increases maternal neglect and aggression. Thus, we compared oxytocin, BP, maternal behavior, and affect in mothers of infants who used cocaine (cocaine, n = 10) or did not (no drug, n = 25) during pregnancy. Laboratory BP and circulating oxytocin, catecholamines, and cortisol were examined before and during a speech stressor on 2 days, with vs. without prestress baby holding. Ambulatory monitoring assessed BP, urinary norepinephrine, and cortisol for 24 h at home. The cocaine group had lower oxytocin levels, greater hostility and depressed mood, less support from others and mastery over life events, higher BP during all events of testing without the baby, and higher ambulatory BP and urinary norepinephrine at home, while cortisol and epinephrine responses were blunted. Although they tended to hold their babies less often at home, baby holding in the laboratory led to decreased BP in cocaine mothers who then did not differ from no-drug mothers in BP or observed affect.

Adult↗

PubMed2004

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↗

PubMed2004

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↗

PubMed2004

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↗