Effects of chronic khat use on cardiovascular, adrenocortical, and psychological responses to stress in men and women.

BACKGROUND: Khat is a psychostimulant plant widely used in Africa and its use has been growing rapidly in Europe and North America. OBJECTIVES: We investigated effects of chronic khat (Catha edulis) use on cardiovascular, adrenocortical, and psychological responses to acute stress. METHODS: Chronic khat users and nonusers were compared on physiological measures and mood reports in a cross-sectional, mixed design. Measurements were conducted during 24-hour ambulatory monitoring and during a laboratory session. A total of 152 participants (58 women) were recruited by flyers posted around Sana'a University campus and the surrounding community in Sana'a, Yemen. Salivary cortisol and self-report measures were collected during a 24-hour ambulatory period prior to a lab testing session. In addition, blood pressures (BP), salivary cortisol, and mood measures were assessed during rest and in response to acute mental stress. RESULTS: Khat users exhibited enhanced evening and attenuated morning cortisol levels, reflecting a blunted diurnal pattern of adrenocortical activity compared to nonusers. Khat users reported greater negative affect during the ambulatory period and during the laboratory session. In addition, they exhibited attenuated BP responses to stress. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: These novel results demonstrate altered adrenocortical activity and increased dysphoric mood among khat users. The extent to which these associations are due to effects of chronic khat use per se or instead reflect predisposing risk factors for khat use is yet to be determined.

Psychophysiological responses to stress following alcohol intake in social drinkers who are at risk of hazardous drinking.

We examined whether social drinkers whose drinking behavior poses a risk for harmful consequences exhibit altered psychobiological responses to stress following moderate alcohol intake. At risk (n=17) and low risk drinkers (n=27), as identified by the Alcohol Use Disorders Identification Test, completed two laboratory stress sessions, one in which they consumed a drink with alcohol and one without alcohol. Subjective and physiological measures were obtained throughout the study. Reported stimulation following alcohol consumption and sedation post-stress on alcohol day were greater than the no alcohol day in at risk drinkers (ps<.05). Low risk drinkers exhibited stress dampening effects on cortisol levels (p<.05). This was not the case among the high risk drinkers. These results indicate that acute alcohol intake may be associated with enhanced subjective and altered hormonal responses to stress in individuals who are at risk for becoming problem drinkers.

Circulating leptin levels are associated with increased craving to smoke in abstinent smokers.

The adipocyte hormone leptin regulates satiety and energy expenditure. Recent evidence suggests that leptin is associated with increased craving for alcohol and with shorter length of abstinence during alcohol treatment. This study examined leptin's associations with craving for cigarettes and smoking relapse among smokers interested in cessation. Participants (32 smokers; 14 women) attended a laboratory session 24h following their designated quit day where circulating leptin levels and craving for smoking were assessed. Other measures of withdrawal symptoms, affect, physical symptoms, as well as neuroendocrine and cardiovascular measures were collected before and after performing two stress tasks (public speaking and cognitive tasks). High circulating leptin levels were associated with increased craving, withdrawal symptoms, negative affect, physical symptoms, and reduced positive affect. Circulating leptin levels were not related to cardiovascular and neuroendocrine measures, responses to acute stressors, or to smoking relapse. These results indicate that circulating leptin is a promising biological marker of craving for smoking and warrant further investigation of the links between appetite regulation and nicotine dependence.

Soft tissue preservation system: Applications.

The soft tissue preservation system (STPS) is emerging as a method of expressing the degree of soft tissue present on an ancient human body (mummy). In this system the intact body is divided into five anatomic segments (head, thorax, pelvis, arms and legs). Each of these segments is assigned a maximal potential number of five "points." In use, the examiner views the external surface of the disrobed mummy and estimates the degree to which soft tissue covers the underlying bone in each of the five segments. The values for each segment are added, and the total sum represents the "STP" score for that mummy. When large numbers of mummies are excavated, a subgroup is commonly assigned for complete autopsy dissection including examination of the internal organs. While such autopsies provide the most information if the internal organs are preserved, currently we have no method to predict soft tissue presence prior to dissection. This study was designed to determine whether the STP score correlates with the degree of visceral organ preservation. We reviewed the detailed autopsy records and photos of 282 spontaneously desiccated mummies from northern Chile's Atacama Desert. We found that their STP scores were predictive of internal organ preservation.

Blunted opiate modulation of hypothalamic-pituitary-adrenocortical activity in men and women who smoke.

OBJECTIVE: To examine the extent to which nicotine dependence alters endogenous opioid regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis functions. Endogenous opiates play an important role in regulating mood, pain, and drug reward. They also regulate the HPA functions. Previous work has demonstrated an abnormal HPA response to psychological stress among dependent smokers. METHODS: Smokers and nonsmokers (total n = 48 participants) completed two sessions during which a placebo or 50 mg of naltrexone was administered, using a double-blind design. Blood and saliva samples, cardiovascular and mood measures were obtained during a resting absorption period, after exposure to two noxious stimuli, and during an extended recovery period. Thermal pain threshold and tolerance were assessed in both sessions. Participants also rated pain during a 90-second cold pressor test. RESULTS: Opioid blockade increased adrenocorticotropin, plasma cortisol, and salivary cortisol levels; these increases were enhanced by exposure to the noxious stimuli. These responses were blunted in smokers relative to nonsmokers. Smokers tended to report less pain than nonsmokers, and women reported more pain during both pain procedures, although sex differences in pain were significant only among nonsmokers. CONCLUSIONS: We conclude that nicotine dependence is associated with attenuated opioid modulation of the HPA. This dysregulation may play a role in the previously observed blunted responses to stress among dependent smokers.

Nociceptive flexion reflex and pain rating responses during endogenous opiate blockade with naltrexone in healthy young adults.

The effect of opioid blockade on nociceptive flexion reflex (NFR) activity and subjective pain ratings was examined in 151 healthy young men and women. Using a within-subjects design, NFR threshold was assessed on 2 days after administration of either placebo or a 50mg dose of naltrexone. Electrocutaneous pain threshold and tolerance levels were measured after NFR threshold assessment on each day. Results indicated that administration of naltrexone was consistently associated with hypoalgesic responding. Specifically, participants exhibited lower levels of NFR activity and reported lower pain ratings for electrocutaneous stimulation delivered at pain threshold and tolerance levels following administration of naltrexone as compared to placebo. These findings indicate that opiate blockade using the current standard dose may elicit hypoalgesia. A potential moderating effect of dose of opiate-blockade medication and level of endogenous opioid activation should be carefully examined in future research.

Adrenocortical and nociceptive responses to opioid blockade in hypertension-prone men and women.

OBJECTIVE: Attenuated pain sensitivity and exaggerated adrenocortical stress reactivity have been documented in individuals at high risk for hypertension. The endogenous opioid system may play a role in these response alterations. We compared adrenocortical and nociceptive responses to opioid blockade using naltrexone in hypertension-prone men and women. METHODS: Ninety-nine participants completed two sessions during which a placebo or 50 mg naltrexone was administered using a double-blind, counterbalanced design. Participants rated their pain and completed the McGill Pain Questionnaire (MPQ) after three assessments of the nociceptive flexion reflex and after assessment of nociceptive pain threshold and tolerance. Saliva samples were obtained throughout the sessions. RESULTS: Salivary cortisol levels increased after pain assessment after the ingestion of naltrexone, but not after placebo, with the low-risk group exhibiting an earlier peak of cortisol response. Participants reported greater pain ratings and higher MPQ scores in the naltrexone versus placebo condition, and these effects were more pronounced in women. Pain threshold and tolerance were higher among high-risk men relative to low-risk men. CONCLUSIONS: The results are consistent with the inhibitory effects of the endogenous opioids on cortisol response and suggest an altered response timeline among hypertension-prone individuals. The results demonstrate that hypoalgesia may be a marker of hypertension risk in men but not in women.

Assessment of opiate modulation of pain and nociceptive responding in young adults with a parental history of hypertension.

This double blind, placebo-controlled study examined the effects of an opiate antagonist, naltrexone, on nociceptive flexion reflex (NFR) thresholds and subjective pain in individuals with and without a parental history of hypertension. Using a repeated measures design, NFR threshold was repeatedly assessed on two testing days after administration of either placebo or naltrexone. Immediately after NFR threshold was determined, participants rated the level of pain experienced during the preceding NFR assessment, and at the end of each session participants' electrocutaneous pain threshold was assessed. Two primary findings were obtained. First, individuals with a parental history of hypertension exhibited attenuated pain sensitivity. Second, endogenous opioid blockade was associated with increased pain ratings in women but with increased pain threshold in men. In sum, the present study did not support a direct involvement of the endogenous opioid system in the attenuated pain sensitivity observed in individuals at increased risk for hypertension.

Nociception and baroreceptor stimulation in hypertension-prone men and women.

We examined the effects of baroreceptor stimulation on nociceptive responding in men and women with a positive or negative parental history of hypertension. The effects of three baroreceptor conditions (stimulation, inhibition, and control) on subjective pain and nociceptive responding were evaluated during electrocutaneous sural nerve stimulation. Pain ratings were lower in men with positive parental history relative to men with negative parental history, but this difference was not found in women. Both stimulatory and inhibitory baroreceptor conditions were associated with reduced pain reports compared to the control condition. There were no significant differences in nociceptive responding as a function of parental history of hypertension. Although this study confirms a link between hypoalgesia and risk for hypertension in men, it does not support the hypothesis that this attenuated pain perception is due to enhanced baroreceptor activity.

Sex differences in pain and hypothalamic-pituitary-adrenocortical responses to opioid blockade.

OBJECTIVE: Sex differences in pain sensitivity and stress reactivity have been well documented. Little is known about the role of the endogenous opioid system in these differences. This study was conducted to compare adrenocortical, pain sensitivity, and blood pressure responses to opioid blockade using naltrexone in men and women. METHODS: Twenty-six participants completed 2 sessions during which placebo or 50 mg of naltrexone was administered, using a double-blind, counterbalanced design. Thermal pain threshold and heat tolerance were assessed. Participants also rated pain during a 90-second cold pressor test (CPT) and completed the McGill Pain Questionnaire (MPQ) after each pain challenge. Blood and saliva samples and cardiovascular and mood measures were obtained throughout the sessions. RESULTS: Plasma cortisol, adrenocorticotropin, beta endorphin, prolactin, and salivary cortisol levels increased similarly in men and women after naltrexone administration compared with placebo. Women reported more pain during both pain procedures and had lower thermal pain tolerance. In response to naltrexone, women exhibited reduced blood pressure responses and reduced MPQ pain ratings after CPT. No effects of naltrexone on these measures were found in men. CONCLUSIONS: Although men and women exhibited similar hormonal responses to opioid receptor blockade, women reported less pain and showed smaller blood pressure responses during CPT. Results suggest differential effects of the endogenous opioid system on pain perception and blood pressure in men and women.

Prospective examination of effects of smoking abstinence on cortisol and withdrawal symptoms as predictors of early smoking relapse.

This study addressed the hypothesis that exaggerated mood and cortisol changes during the first 24h of smoking abstinence are associated with early relapse. Salivary cortisol levels and mood reports were measured during 24-h ad libitum smoking and the first 24-h abstinence period of a quit attempt. Seventy-two habitual smokers (34 women and 38 men) who were interested in smoking cessation participated. Cotinine concentrations in saliva and expired carbon monoxide were measured before and after abstinence and 1 week after the quit date to verify smoking status. Abstinence produced significant withdrawal symptoms in all participants and reduced cotinine and carbon monoxide levels. While participants showed the expected diurnal changes in cortisol levels, those who relapsed within the first week post quitting exhibited a greater drop in morning cortisol concentrations during abstinence relative to their ad libitum smoking levels. Participants who relapsed reported greater withdrawal symptoms, craving for cigarettes, and distress, and they also reported greater reduction in positive affect during the first 24-h period of abstinence than those who maintained abstinence. These results support the hypothesis that early relapse is associated with exaggerated mood and adrenocortical perturbations observed during the first day of abstinence.

A 9,000-year record of Chagas' disease.

Tissue specimens from 283 principally spontaneously (naturally) desiccated human mummies from coastal and low valley sites in northern Chile and southern Peru were tested with a DNA probe directed at a kinetoplast DNA segment of Trypanosoma cruzi. The time interval spanned by the eleven major cultural groups represented in the sample ranged from approximately 9,000 years B.P. (7050 B.C.) to approximately the time of the Spanish conquest, approximately 450 B.P. ( approximately 1500 A.D.). Forty-one percent of the tissue extracts, amplified by the PCR reacted positively (i.e., hybridized) with the probe. Prevalence patterns demonstrated no statistically significant differences among the individual cultural groups, nor among subgroups compared on the basis of age, sex, or weight of specimen tested. These results suggest that the sylvatic (animal-infected) cycle of Chagas' disease was probably well established at the time that the earliest humans (members of the Chinchorro culture) first peopled this segment of the Andean coast and inadvertently joined the many other mammal species acting as hosts for this parasite.

Enhanced adrenocortical responses to stress in hypertension-prone men and women.

Hypertension risk may be associated with increased adrenocortical activity, but the extent to which this enhanced activation differs between men and women at rest and in response to psychological stress is not known. This study examined gender differences in adrenocortical responses to an extended public-speaking stressor in persons at high (resting systolic blood pressure > median; n = 21) or low risk (negative parental history and < or = median systolic blood pressure; n = 26). Salivary cortisol levels were assessed at rest and in response to public speaking in a repeated measure design on two test sessions held on separate days. Heart rate, systolic blood pressure, and diastolic blood pressure were obtained at 3-min intervals before, during, and after the task. High-risk participants showed greater cortisol, blood pressures, and heart rate responses to the public-speaking stressor than the low-risk group (ps < .01). Men showed greater cortisol concentrations than women (p < .05), independent of hypertension risk status. Cardiovascular measures during the acute stressor predicted subsequent cortisol production, but only in the high-risk group. Results suggest that hypertension risk is associated with enhanced physiological reactivity across sympathetic and adrenocortical systems, supporting the possibility that this exaggerated reactivity may represent a marker of risk in hypertension-prone men and women.

Attenuated adrenocortical and blood pressure responses to psychological stress in ad libitum and abstinent smokers.

Chronic smoking may alter physiological systems involved in the stress response. This study was designed to examine the effects of ad libitum smoking and abstinence on adrenocortical and cardiovascular responses to acute psychological stress in dependent cigarette smokers. We evaluated differences among abstinent smokers, smokers who continued to smoke at their normal rate, and nonsmokers in salivary cortisol concentrations, systolic and diastolic blood pressure (BP), heart rate (HR), and mood reports. Measurements were obtained during rest and in response to acute psychological stress (public speaking) in one session (stress session) and during continuous rest in a control session. Thirty-eight smokers (21 women) and 32 nonsmokers (18 women) participated. Smokers were assigned to either abstain from smoking the night prior to and the day of each session, or to continue smoking at their normal rate before each session. All groups showed significant stress-induced changes in BP and HR. Smokers, regardless of their assigned condition, showed attenuated systolic BP responses to the public-speaking stressor when compared to nonsmokers. While resting cortisol levels were greater among smokers than nonsmokers, no cortisol response to the acute stressor was demonstrated in either ad libitum or abstinent smokers. These results indicate that chronic smoking diminishes adrenocortical and cardiovascular responses to stress, and that short-term abstinence does not correct these alterations.

Archaeological contributions of skeletal lead analysis.

We developed a chemical method to quantitate lead in small skeletal specimens and used it to establish lead distribution and quantitation in modern skeletons for all age groups to standardize sampling sites. Application of the method to excavated ancient skeletal collections enabled prediction of socioeconomic status among Colonial Americans, as well as identification of lead poisoning in ancient Rome as related to lead production and in an 18th century Caribbean epidemic as related to distillation of rum. Depending upon the conditions of burial, bones may be contaminated by surrounding material. This can be a limiting factor for interpretation of lead levels, but multielement analysis and procedural modifications can permit continuing application of bone lead analysis to appropriately selected archaeological skeletal collections.

Psychophysiological effects of nicotine abstinence and behavioral challenges in habitual smokers.

We tested the hypothesis that psychophysiological responses to behavioral challenges are enhanced by short-term abstinence from smoking. Blood pressure (BP), salivary cortisol levels, and withdrawal symptoms were measured after a period of smoking abstinence (18 h) or ad libitum smoking, during rest, and in response to acute behavioral challenges. Thirty habitual smokers (15 women and 15 men) participated in two laboratory sessions conducted on two separate days (after abstinence or ad libitum smoking). Cotinine concentrations in saliva and expired carbon monoxide were measured in both conditions. Abstinence produced significant withdrawal symptoms in all participants, with women reporting greater desire to smoke than men. Participants showed greater systolic BP responses to the behavioral challenges in the abstinence condition than the control condition. They also showed worse cognitive performance on the challenges in the abstinence than in the ad libitum condition. Men had greater salivary cortisol levels than women, and both men and women showed the expected decline in cortisol levels across time, but showed no difference between the abstinence and ad libitum smoking conditions in the laboratory or during ambulatory measurements. These results indicate that abstinence alters mood, performance, and BP responses to acute challenges but not adrenocortical responses. It is possible that these changes mediate stress-related vulnerability to smoking relapse.

Adrenocortical and hemodynamic predictors of pain perception in men and women.

Research has demonstrated that women report more pain than men, and clinical observations suggest that attenuated adrenocortical activity is associated with high pain sensitivity. The extent to which cortisol concentrations and hemodynamics contribute to gender differences in pain sensitivity has not been investigated. Thirty-four women and 31 men performed the hand cold pressor test (CPT). Participants rated their pain every 15 s during a 90-s CPT and a 90-s post-CPT recovery period and reported pain using the McGill Pain Questionnaire (MPQ). Salivary cortisol samples and cardiovascular measures were collected prior to, during, and after the CPT. Women reported greater pain than men during and after the CPT and on the MPQ (Ps<0.01). CPT disrupted the expected diurnal decline in cortisol, as shown by a significant increase in cortisol concentration post-CPT (P<0.01) in men and women. Regression analyses revealed that pre-CPT cortisol concentrations predicted lower pain reports during and after CPT in men only (P<0.01). Systolic blood pressure (BP) and stroke volume correlated negatively with pain reports only in women (Ps<0.05). Controlling for potential confounding variables did not alter these relationships. The negative association between pre-CPT cortisol and pain perception in men and the association between BP and pain in women demonstrate different physiological predictors of pain perception in men and women.

Blood pressure but not parental history for hypertension predicts pain perception in women.

Previous work has suggested an attenuated sensitivity to painful stimulation in hypertensive men. We recently reported that, compared with persons with negative parental history, men, but not women, with a positive history for hypertension showed attenuated pain perception. This study specifically addressed factors that predict pain perception in women, including blood pressure, parental history and mood states. Fifty-four normotensive women with positive (PH+; n = 20) or negative parental history (PH-; n = 34) for hypertension and high or low casual systolic blood pressure (BP) performed the cold pressor (CP) test. Participants rated their pain every 15 s during a 90-s hand CP (0-4 degrees C) and a 90-s post-CP rest period. Detailed mood ratings were obtained immediately before the CP test. Data were evaluated using multivariate repeated measure analyses of variance and regression analyses. PH+ and PH- women did not differ in age, height, weight, education, resting BP, or heart rate. PH+ and PH- women did not differ in pain ratings during or after the CP, or pain ratings using the McGill Pain Questionnaire (MPQ), and they did not differ in their cardiovascular responses to the CP, confirming our earlier study in a separate sample. Women with high casual systolic BP reported significantly less pain, especially after the CP (P < 0.01). MPQ total scores confirmed this finding with high BP women reporting less pain than low BP women (P < 0.05). Regression analyses confirmed these effects. Controlling for potential confounding variables did not alter these relationships. These findings suggest that in women, phenotype systolic BP may be a better predictor of hypoalgesia than parental history of hypertension.