Endogenous oestradiol and progesterone as predictors of oncogenic human papillomavirus (HPV) persistence.

BACKGROUND: High-risk human papillomavirus (HR-HPV) is the main aetiological factor for the development of cervical cancer. While nearly 70% of HR-HPV infections are cleared within 12 months, in the remainder of women they persist and can progress into cervical cancer. Oestradiol and progesterone have been shown to be involved in the development and progression of cervical cancer. The objective of this study was to investigate, for the first time, whether diurnal oestradiol and progesterone are also involved in HR-HPV persistence - before cervical cancer develops. METHODS: A total of N = 39 women between 18 and 31 years of age were investigated. All were nulliparous and regular users of combined oral contraceptives. Presence of HR-HPV was determined by cervical swabs. Salivary oestradiol and progesterone were measured upon awakening and at 11 am, 2 pm, and 5 pm. All HR-HPV positive women were re-tested in terms of HR-HPV status 12 months later. RESULTS: HR-HPV positive women had significantly higher morning (p = .007, partial eta2 = .221) and daily oestradiol levels (p < .001, partial eta2 = .442) when compared to HR-HPV negative women. In addition, those with persistent HR-HPV 12 months later had significantly elevated morning (p = .005, partial eta2 = .534) and daily (p = .027, partial eta2 = .346) oestradiol. Progesterone was found to be unrelated to HR-HPV. CONCLUSIONS: Oestradiol was positively linked to HR-HPV presence and persistence. Provided that these findings are replicated, regular monitoring of oestradiol levels may prove useful in identifying women who are at risk of developing cervical cancer.

Covariation of psychobiological stress regulation with valence and quantity of social interactions in everyday life: disentangling intra- and interindividual sources of variation.

While the overall effects of social relationships on stress and health have extensively been described, it remains unclear how the experience of social interactions covaries with the activity of psychobiological stress in everyday life. We hypothesized that the valence as well as quantitative characteristics of social interactions in everyday life would attenuate psychobiological stress. Sixty healthy participants provided data for the analyses. Using an ecological momentary assessment design, participants received 6 prompts on their smartphone for 4 days. At each prompt, they reported on social interactions since the last prompt (any occurrence, frequency, duration, quality, and perceived social support), current subjective stress, and provided one saliva sample for the analyses of cortisol (sCort) and alpha-amylase (sAA). Experiencing any contact within days as well as higher daily levels of contact quality and perceived social support were associated with reduced levels of sCort. Furthermore, on a daily level, experiencing at least one contact in-between prompts more often as well as having more contacts on average attenuated the sAA output. Perceived social support and contact quality as well as higher daily contact durations were associated with lower subjective stress. For sCort, daily levels of stress moderated the effects of experiencing any contact within days while daily perceived social support moderated the effects of subjective stress. For sAA, experiencing at least one contact in-between prompts more often on a daily level moderated the effects of subjective stress. There were no between-person effects throughout all analyses. The results show ecologically valid evidence for direct attenuating effects of social interactions on psychobiological stress as well as for the stress-buffering hypothesis in everyday life. Increasing the quantity and improving the valence of social interactions on an intrapersonal level can possibly reduce psychobiological stress and prevent its consequences.

Is stress related to the presence and persistence of oncogenic human papillomavirus infection in young women?

BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) is the most important risk factor for the development of cervical cancer, but factors contributing to HR-HPV persistence are incompletely understood. The objective of this study was to test for associations of chronic stress and two aspects of diurnal cortisol secretion (i.e., the cortisol awakening response [CAR] and total cortisol output over the day [AUCgday]) with HR-HPV status at baseline and 12 months later (follow-up). METHODS: We evaluated 188 women (25 ± 3 years) at baseline. Follow-up investigation was restricted to HR-HPV infected women at baseline. Of the initial 48 HR-HPV positive participants, 42 completed the follow-up (16 HR-HPV positive and 26 HR-HPV negative). At baseline and follow-up, we determined HR-HPV status in cervical smears, assessed chronic stress, and repeatedly measured salivary cortisol over the day. At baseline, we analyzed salivary cortisol only in a subgroup of 90 participants (45 HR-HPV negative and 45 HR-HPV positive). RESULTS: At baseline, higher chronic stress (excessive demands at work: p = .022, chronic worrying: p = .032), and a higher CAR (p = .014) were related to baseline HR-HPV positivity. At follow-up, there was a statistical trend for a positive association between the CAR and HR-HPV positivity (p = .062). Neither the CAR nor the AUCgday mediated the associations between chronic stress and HR-HPV status. CONCLUSIONS: Our findings suggest that both chronic stress and diurnal cortisol are related to the presence of HR-HPV infection and may thus play a role in HPV-associated cervical carcinogenesis.

Attributional styles and stress-related atherogenic plasma lipid reactivity in essential hypertension.

OBJECTIVE: Hypertension and an atherogenic lipid profile are known risk factors for coronary heart disease (CHD). Hypertensives show greater changes in atherogenic plasma lipids to acute stress than normotensives. In this study, we investigated whether attribution of failure is associated with lipid stress reactivity in hypertensive compared with normotensive men. METHODS: 18 normotensive and 17 hypertensive men (mean±SEM; 45±2.2 years) underwent an acute standardized psychosocial stress task that can be viewed as a situation of experimentally induced failure. We assessed external-stable (ES), external-variable (EV), internal-stable (IS), and internal-variable (IV) attribution of failure and psychological control variables (i.e. extent of depression and neuroticism). Moreover, total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), and norepinephrine were measured immediately before and several times after stress. RESULTS: ES moderated TC- and LDL-C-stress reactivity in hypertensives as compared to normotensives (interaction mean arterial pressure [MAP]-by-ES for TC: F=3.71, p=.015; for LDL-C: F=3.61, p=.016). TC and LDL-C levels were highest in hypertensives with low ES immediately after stress (p≤.039). In contrast, hypertensives with high ES did not differ from normotensives in TC and LDL-C immediately after stress (p's>.28). Controlling for norepinephrine, depression, and neuroticism in addition to age and BMI did not significantly change results. There were no significant associations between lipid baseline levels or aggregated lipid secretion and IS, IV, or EV (p's>.23). CONCLUSION: Our data suggest that ES may independently protect from elevated lipid stress reactivity in hypertensive individuals. ES thus might be a protective factor against CHD in hypertension.

Efficacy of Coming Out Proud to reduce stigma's impact among people with mental illness: pilot randomised controlled trial.

BACKGROUND: Facing frequent stigma and discrimination, many people with mental illness have to choose between secrecy and disclosure in different settings. Coming Out Proud (COP), a 3-week peer-led group intervention, offers support in this domain in order to reduce stigma's negative impact. AIMS: To examine COP's efficacy to reduce negative stigma-related outcomes and to promote adaptive coping styles (Current Controlled Trials number: ISRCTN43516734). METHOD: In a pilot randomised controlled trial, 100 participants with mental illness were assigned to COP or a treatment-as-usual control condition. Outcomes included self-stigma, empowerment, stigma stress, secrecy and perceived benefits of disclosure. RESULTS: Intention-to-treat analyses found no effect of COP on self-stigma or empowerment, but positive effects on stigma stress, disclosure-related distress, secrecy and perceived benefits of disclosure. Some effects diminished during the 3-week follow-up period. CONCLUSIONS: Coming Out Proud has immediate positive effects on disclosure- and stigma stress-related variables and may thus alleviate stigma's negative impact.

Functional polymorphism in the neuropeptide Y gene promoter (rs16147) is associated with serum leptin levels and waist-hip ratio in women.

OBJECTIVE: The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution. METHOD: We genotyped and measured the serum leptin levels of the NP-Y rs16147 polymorphism in 1,097 Caucasian subjects in the context of a population-based, case-control multicenter study. We measured weight, height and waist circumference, from which we then calculated BMI and waist-to-hip ratio (WHR). RESULTS: We found the CT-genotype of the SNP rs16147 to be significantly associated with lower WHRs and higher serum leptin levels in women, compared to homozygote gene carriers. No association between rs16147, WHR and serum leptin levels was found in men. CONCLUSION: Our results provide evidence that the functionally relevant SNP in the NP-Y promoter gene affects body fat distribution and serum leptin levels in women, pointing towards possible behavioral effects of NPY in obesity.

Lack of association of a functional catechol-O-methyltransferase gene polymorphism with risk of tobacco smoking: results from a multicenter case-control study.

BACKGROUND: The catechol-O-methyltransferase (COMT) modulates dopaminergic neurotransmission in the prefrontal cortex as well as in the mesolimbic reward system. Since the reward system mediates addictive behavior, the COMT gene is a strong candidate gene regarding the pathophysiology of tobacco dependence and smoking behavior. Because of rather conflicting results in previous studies, the purpose of the present study was to test for association between a functional genetic variant in the COMT gene (single nucleotide polymorphism [SNP] rs4680) and tobacco smoking behavior. METHODS: In a population-based case-control multicenter study designed for tobacco addiction research, a total of 551 current smokers of European ancestry and 548 age-matched healthy volunteers (never-smokers) were genotyped for SNP rs4680 and extensively characterized concerning their smoking behavior. RESULTS: We found no association between smoking status and SNP rs4680 genotype nor did we find a significant association to the degree of tobacco dependence. CONCLUSIONS: Although prefrontal cortical and ventral striatal activity are highly relevant for addictive behavior, and under partial control of COMT rs4680 genotype, no association between COMT and smoking behavior was observed. Other genetic variants may account for the high heritability of behavioral smoking phenotypes.

Genetic variation in the neuropeptide Y gene promoter is associated with increased risk of tobacco smoking.

BACKGROUND: Neuropeptide Y (NPY) is a strong candidate gene regarding the pathophysiology of tobacco dependence. It has been associated with various addictive and psychiatric disorders, and closely interacts with the brain reward system. The aim of the present study was to test for association between a functional genetic variant in the NP-Y promoter gene (SNP rs16147) and tobacco smoking. METHODS: In a population-based case-control multicenter study designed for tobacco addiction research, a total of 550 Caucasian current smokers, and 544 never-smokers were genotyped for SNP rs16147 and behaviorally characterized with the State-Trait Anxiety Inventory (STAI). RESULTS: Subjects with TT genotype of the SNP rs16147 were significantly more frequently smokers than never-smokers (p = 0.046). In addition, TT genotype exhibited increased state anxiety scores compared to carriers of the C allele (p = 0.037). CONCLUSIONS: Our results provide evidence for an involvement of the functionally relevant SNP rs16147 in the pathophysiology of tobacco dependence. Further studies are needed to confirm our findings.

Increased psychological and attenuated cortisol and alpha-amylase responses to acute psychosocial stress in female patients with borderline personality disorder.

OBJECTIVE: Borderline personality disorder (BPD) is characterized by increased self-reported stress and emotional responding. Knowledge about the psychological and physiological mechanisms that underlie these experiences in BPD patients is scarce. The objective was to assess both psychological and endocrinological responses to a standardized psychosocial stressor in female BPD patients and healthy controls. METHODS: A total of 15 female BPD patients and 17 healthy control subjects were included in a case-control study. All subjects were free of any medication, had a regular menstrual cycle, and were investigated during the luteal phase of their menstrual cycle. Co-occurring current major depression, current substance abuse/dependence, and lifetime schizophrenia or bipolar I disorder were excluded. Psychological measures of stress, salivary cortisol, salivary alpha-amylase, plasma ACTH, plasma norepinephrine and epinephrine concentrations were measured before, during, and after exposure to a standardized psychosocial stress protocol. RESULTS: BPD patients displayed maladaptive cognitive appraisal processes regarding the upcoming stressor as well as significantly higher subjective stress, coupled with a substantial cortisol and alpha-amylase hyporeactivity to the stressor in comparison to the controls. No significant differences for ACTH and catecholaminergic responses were observed, while the ACTH:cortisol ratio was higher in BPD patients than in controls. CONCLUSIONS: Attenuated cortisol responsiveness in BPD patients might in part be explained by decreased adrenal responsiveness to endogenous ACTH and altered central noradrenergic activation as reflected by alpha-amylase.

Sex differences in emotional and psychophysiological responses to musical stimuli.

Although it is known that men and women differ in their music preferences and emotional reactions to music, little is known about sex differences in physiological reactions to music. In our study, we therefore set out to examine the differential reactivity to two musical stimuli that elicit distinct psychological and physiological reaction patterns. Fifty-three healthy subjects (mean age: 26.13, SD: 3.97; 26 males, 27 females) were examined. Heart rate, electrodermal activity, skin temperature, salivary cortisol, salivary alpha-amylase, and psychological variables were assessed during the course of the whole study. Following baseline assessment, two musical stimuli, which were carefully selected and rated in a pre-study as relaxing and pleasant (renaissance music) and arousing and unpleasant (heavy metal), respectively, were introduced. They were presented on two different days in a randomized order. Whereas psychological variables did not differ between men and women, results of electrophysiological measures indicate significantly different reactivity patterns between men and women. Women displayed elevated response curves to the arousing and unpleasant stimulus, whereas men did not. However, no differences were found with regards to endocrine measures in saliva. Our results demonstrate sex differences in reactivity patterns to musical stimuli in psychophysiological measures. In our study, we were able to show that women tend to show hypersensitivity to aversive musical stimuli. This finding is in accordance with previous literature on sex differences in emotion research. Furthermore, our study indicates that the confounding effects of sex differences have to be considered when using musical stimuli for emotion induction.

Early versus delayed carotid endarterectomy after a nondisabling ischemic stroke: a prospective randomized study.

BACKGROUND: Although many retrospective and a few prospective studies have analyzed the outcome of early and delayed carotid endarterectomy (CEA) after a recent minor or nondisabling stroke (ie, a minimal and stabilized focal neurologic deficit of acute onset persisting for more than 24 hours and not leading to a handicap or to a significant impairment of daily living activities), the optimal timing of surgery remains uncertain. The purpose of this study was to prospectively compare the perioperative death and stroke rates of CEA performed within 30 days (early group) or more than 30 days (delayed group) after a nondisabling ischemic stroke in patients with carotid bifurcation disease. METHODS: During a 4-year period, of 86 patients experiencing a minor stroke, 45 were randomized to undergo early CEA and 41 to undergo delayed CEA. All patients underwent preoperative cerebral computed tomography, duplex ultrasonographic scanning and angiography of the supra-aortic trunks. All CEAs were carotid eversion endarterectomies and were performed by the same surgeon, using deep general anesthesia, with continuous electroencephalographic monitoring for the selective shunting. The perioperative death and stroke rates were compared between the 2 groups. RESULTS: No perioperative deaths occurred in either group. No recurrent strokes occurred during the waiting period in the delayed group. The incidence of perioperative stroke was comparable in the 2 groups (1 of 45, 2% vs 1 of 41, 2%). The mean follow-up was 23 months (range, 6 to 50 months). Survival rates after 1, 2, and 3 years were similar in the 2 groups. CONCLUSIONS: Early CEA after a nondisabling ischemic stroke can be performed safely with perioperative mortality and stroke rates comparable with those of delayed CEA. The timing of surgery does not seem to influence the benefit of the CEA.