Prenatal cocaine exposure differentially affects stress responses in girls and boys: associations with future substance use.

Prenatal cocaine exposure may affect developing stress response systems in youth, potentially creating risk for substance use in adolescence. Further, pathways from prenatal risk to future substance use may differ for girls versus boys. The present longitudinal study examined multiple biobehavioral measures, including heart rate, blood pressure, emotion, and salivary cortisol and salivary alpha amylase (sAA), in response to a stressor in 193 low-income 14- to 17-year-olds, half of whom were prenatally cocaine exposed (PCE). Youth's lifetime substance use was assessed with self-report, interview, and urine toxicology/breathalyzer at Time 1 and at Time 2 (6-12 months later). PCE × Gender interactions were found predicting anxiety, anger, and sadness responses to the stressor, with PCE girls showing heightened responses as compared to PCE boys on these indicators. Stress Response × Gender interactions were found predicting Time 2 substance use in youth (controlling for Time 1 use) for sAA and sadness; for girls, heightened sadness responses predicted substance use, but for boys, dampened sAA responses predicted substance use. Findings suggest distinct biobehavioral stress response risk profiles for boys and girls, with heightened arousal for girls and blunted arousal for boys associated with prenatal risk and future substance use outcomes.

Daily stressors and adult day service use by family caregivers: effects on depressive symptoms, positive mood, and dehydroepiandrosterone-sulfate.

OBJECTIVE: This study examines effects of daily use of adult day service (ADS) programs by caregivers of individuals with dementia (IWD) on a salivary biomarker of stress reactivity, dehydroepiandrosterone-sulfate (DHEA-S), and whether these effects on DHEA-S are associated with daily variability in positive mood and depressive symptoms. METHODS: We used a daily diary design of 8 consecutive days with alternation of intervention (ADS) and nonintervention days to evaluate within- and between-person effects of the intervention. Family caregivers (N = 151) of IWD who were using ADS were interviewed daily by telephone at home. Saliva samples were collected from caregivers five times a day for 8 consecutive days and were assayed for DHEA-S. Daily telephone interviews assessed daily stressors and mood. RESULTS: DHEA-S levels were significantly higher on days after ADS use. Daily DHEA-S levels covaried significantly with daily positive mood but not with depressive symptoms. CONCLUSION: These results demonstrate an association of ADS use by family caregivers and higher DHEA-S levels on the next day. Prior research has found that higher DHEA-S levels are protective against the physiologic damaging effects of stressor exposure and may reduce risks of illness. Regular use of ADS may help reduce depletion of DHEA-S and allow the body to mount a protective and restorative response to the physiologic demands of caregiving. To our knowledge, this is the first study to examine DHEA-S levels across the day in connection with an intervention that affected daily exposure to stressors.

Effectiveness of the gluten-free, casein-free diet for children diagnosed with autism spectrum disorder: based on parental report.

OBJECTIVES: Studies on the gluten-free and/or casein-free (GFCF) dietary intervention for children with autism spectrum disorders (ASDs) suggest that some children may positively respond to implementation of the dietary intervention. Other research suggests that children diagnosed with ASD can be classified into subpopulations based on various factors, including gastrointestinal (GI) abnormalities and immune function. METHODS: This study analyzes parental report data collected using a 90-item online questionnaire from 387 parents or primary caregivers of children diagnosed with ASD on the efficacy of the GFCF diet. Parents reported on their child's GI symptoms, food allergy diagnoses, and suspected food sensitivities, as well as the degree and length of their diet implementation. RESULTS: Overall, diet efficacy among children whose parents reported the presence of GI symptoms, food allergy diagnoses, and suspected food sensitivities included greater improvement in ASD behaviors, physiological symptoms, and social behaviors compared with children whose parents reported none of these symptoms, diagnoses, or sensitivities (P < 0.05). Parental report of strict diet implementation, indicated by complete gluten/casein elimination and infrequent diet errors during and outside of parental care, also corresponded to improvement in ASD behaviors, physiological symptoms, and social behaviors (P < 0.05). DISCUSSION: These findings suggest that various intricacies related to diet implementation and GI and immune factors may play a role in differentiating diet responders from diet non-responders and substantiate the importance of further investigations into the various, nuanced factors that influence efficacy of the intervention among children with ASDs.

Effects of diets high in walnuts and flax oil on hemodynamic responses to stress and vascular endothelial function.

BACKGROUND: Polyunsaturated fatty acids (PUFA) have beneficial effects on cardiovascular risk, although the mechanisms are incompletely understood. In a previous article, we showed significant reductions in low-density lipoprotein cholesterol and several markers of inflammation with increasing intake of alpha-linolenic acid (ALA) from walnuts and flax. OBJECTIVE: To examine effects of ALA on cardiovascular responses to acute stress, flow-mediated dilation (FMD) of the brachial artery, and blood concentrations of endothelin-1 and arginine-vasopressin (AVP). DESIGN: Using a randomized, crossover study design, cardiovascular responses to acute stress were assessed in 20 hypercholesterolemic subjects, a subset of whom also underwent FMD testing (n  =  12). Participants were fed an average American diet (AAD) and 2 experimental diets that varied in the amount of ALA and linoleic acid (LA) that they contained. The AAD provided 8.7% energy from PUFA (7.7% LA, 0.8% ALA). On the LA diet, saturated fat was reduced, and PUFA from walnuts and walnut oil provided 16.4% of energy (12.6% LA, 3.6% ALA). On the ALA diet, walnuts, walnut oil, and flax oil provided 17% energy from PUFA (10.5% LA, 6.5% ALA). RESULTS: The ALA and LA diets significantly reduced diastolic blood pressure (-2 to -3 mm Hg) and total peripheral resistance (-4%), and this effect was evident at rest and during stress (main effect of diet, p < 0.02). FMD increased (+34%) on the diet containing additional ALA. AVP also increased by 20%, and endothelin-1 was unchanged. CONCLUSIONS: These results suggest novel mechanisms for the cardioprotective effects of walnuts and flax, and further work is needed to identify the bioactives responsible for these effects.

Female temperament, tumor development and life span: relation to glucocorticoid and tumor necrosis factor alpha levels in rats.

Behavioral characteristics closely associated with specific physiological profiles present an important area of research in understanding health disparities. In particular, glucocorticoid overproduction may be an important factor moderating disease progression; natural variance in production of this steroid has been proposed as one mechanism underlying individual differences in health and disease. In the current paper, we examined immune parameters in female rats of two different behavioral types previously shown to have differential glucocorticoid production and life spans. We categorized young female rats according to their behavioral response to novelty (high- or low-locomotion), and compared their glucocorticoid production, adrenal size, thymus size, tumor necrosis factor-alpha (TNF-alpha) production, tumor development and life span. As expected, high-locomotion females produced more glucocorticoids and had larger adrenal glands during young adulthood than did low-locomotion females. High-locomotion females had significantly smaller thymuses and reduced TNF-alpha levels compared to low-locomotion, suggesting altered immune function in young adulthood. Finally, high-locomotion females had shorter life spans than did low-locomotion females, and this was particularly true in females that developed pituitary tumors, but not in those that developed mammary tumors. These results, along with other published findings, suggest that high-locomotion rodent females experience life-long elevations in glucocorticoid responses to novelty, and that these elevated levels may be comparable to chronic stress. This naturally occurring endocrine profile may influence immune responses which in turn could affect disease susceptibility. Variance in immune function across personality types may be partially moderated by natural variance in glucocorticoid production.

Smoking is associated with worse mood on stressful days: results from a national diary study.

BACKGROUND: Many smokers report smoking because it helps them modulate their negative affect (NA). The stress induction model of smoking suggests, however, that smoking causes stress and concomitant NA. Empirical support for the stress induction model has primarily derived from retrospective reports and experimental manipulations with non-representative samples of smokers. Moreover, prior studies have typically not considered contextual factors (e.g., daily stressors) that may impact the smoking-NA relationship. PURPOSE: The aim of this study was to assess the stress induction model of smoking using a prospective design in a nationally representative sample of smokers while simultaneously examining the impact of daily stressors on the relationship between smoking and NA. We hypothesized that smoking and NA would be positively related, and this relationship would be intensified by exposure to daily stressors. METHODS: A national sample of middle-aged smokers (N = 256) were called on eight consecutive evenings to assess stressor exposure and intensity. Participants also reported on their daily NA and indicated the number of cigarettes they smoked. Analyses were conducted using hierarchical linear modeling to determine the relationship between daily smoking, NA, and stress. RESULTS: Smoking more than usual was associated with increased NA on days when respondents were exposed to any stressors. Smoking more than usual had no effect on NA on days when no stressors were encountered. Moreover, the moderating effect of stressor exposure remained significant even after controlling for the number and intensity of daily stressors reported. CONCLUSIONS: While smokers report that smoking alleviates their NA, our study suggests that the exact opposite may occur, particularly on stressful days. When smokers smoke more than usual on days when the encounter stress, they are likely to feel emotionally worse off.

Disruption in Th1/Th2 immune response in young adult smokers.

Interferon (IFN)-gamma and IL-10 cytokines, measures of Th1 and Th2 immunity, were examined in 20 healthy nonsmokers (12 males, 8 females) and 19 smokers (11 males, 8 females), aged 19-41 years (23.46+/-0.82 years). Nonsmokers came to the laboratory once; smokers came to the laboratory after ad lib smoking and following 24-h smoking abstinence. Salivary cotinine and expired CO confirmed smoking status. Plasma was collected at the end of each lab session and assayed for peripheral IFN-gamma and IL-10 levels. Among smokers, peripheral IFN-gamma, IL-10, or IFN-gamma/IL-10 ratio levels did not change in response to 24-h smoking abstinence. IFN-gamma levels and IFN-gamma/IL-10 ratios were higher among female smokers while smoking and following 24-h abstinence compared to male smokers in both conditions and compared to male and female nonsmokers. There was no sex or smoking status difference in IL-10 levels. Results suggest that cigarette smoking may have at least short-term damaging effects on the body's normal immune balance, particularly for women.

Relation of oxytocin to psychological stress responses and hypothalamic-pituitary-adrenocortical axis activity in older women.

OBJECTIVE: Animal research suggests that oxytocin (OT) plays a role in stress responses and that in females, this role is modulated by estrogen. Yet little is known about the relation of OT to human stress responses. This study was conducted to examine the relations between estrogen activity and OT, identify stressors distinctively associated with elevations in OT, and investigate whether OT is related to cardiovascular and hypothalamic-pituitary-adrenocortical (HPA) activity in a laboratory challenge paradigm. METHODS: Seventy-three postmenopausal women who were on hormone therapy (HT) or not completed questionnaires assessing psychological distress and social relationships and then participated in a laboratory stress challenge (Trier Social Stress Task), during which OT, cortisol, and blood pressure were assessed. RESULTS: HT was significantly associated with higher plasma OT. Controlling for HT, elevated plasma OT was significantly associated with gaps in social relationships, with less positive relationships with a primary partner, and with elevated cortisol levels. OT was not associated with stress reactivity or recovery. CONCLUSION: In women, plasma OT signals relationship stress and is associated with elevated cortisol; it does not appear to significantly affect cortisol or blood pressure responses to acute stress.

'Return to home cage' as a reward for maze learning in young and old genetically heterogeneous mice.

Recent studies have shown that 'return to home cage' can serve as a reward for maze learning in adult male mice. The present study examined whether the same reward is an effective motivator of learning in young and old mice and included females in the study design. We tested 25- and 65-d-old HS mice and 85- and 800-d-old B6D2F2 mice in a Lashley III maze. Return to home cage motivated maze acquisition in all groups. Compared with 65-d-old HS mice, 25-d-olds acquired the maze more slowly, took longer to achieve the test criterion, and showed increased latency to reach the goal box. There was no difference between 85- and 800-d-old B6D2F2 mice in rate of acquisition. This reward procedure may reduce the potentially confounding effects of deprivation or aversive stimuli on maze performance and may be suitable as a motivational procedure for a wide range of subject groups.

Risk indicators of metabolic syndrome in young adults: a preliminary investigation on the influence of tobacco smoke exposure and gender.

BACKGROUND: Metabolic syndrome is characterized by hypertension, dyslipidemia, insulin resistance, and obesity. Limited investigations have studied early indicators of metabolic syndrome in healthy young adults before diagnosis of disease. PURPOSE: The purpose of this investigation is to identify shifts in cardiovascular (CV), metabolic, and immune variables consistent with metabolic syndrome but occurring before development of the disorder, and to determine whether these variables are influenced by gender or cigarette smoking. METHODS: A pilot study of 41 subjects ages 18 to 39 years, with 20 smokers and 21 nonsmokers, was undertaken. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured to evaluate CV status; cholesterol, body mass index, leptin, percent glycated albumin, and homocysteine were measured to evaluate metabolic status; C-reactive protein, interleukin-1beta, and interleukin-10 were measured to evaluate immunologic status. Risk scores were assigned to each indicator, and total risk score was computed. RESULTS: Men had higher SBP (P<.001), DBP (P=.046), and body mass index (P=.01), whereas women had higher leptin (P=.002). Total risk scores in men were greater (P=.02). There was no effect of smoking on risk score, related to the increase in two risks for smokers (SBP, P=.04, DBP; P=.027) reciprocated by a decrease in another (percentage of glycated albumin; P=.02). CONCLUSION: Risk factors contributing to metabolic syndrome are present and highest in young men compared with women, whereas the effects of cigarette smoking on the syndrome are mixed. Early intervention to reduce modifiable risks may prevent full expression of disease.

Exposure to nicotine increases nicotinic acetylcholine receptor density in the reward pathway and binge ethanol consumption in C57BL/6J adolescent female mice.

Nearly 80% of adult smokers begin smoking during adolescence. Binge alcohol consumption is also common during adolescence. Past studies report that nicotine and ethanol activate dopamine neurons in the reward pathway and may increase synaptic levels of dopamine in the nucleus accumbens through nicotinic acetylcholine receptor (nAChR) stimulation. Activation of the reward pathway during adolescence through drug use may produce neural alterations affecting subsequent drug consumption. Consequently, the effect of nicotine exposure on binge alcohol consumption was examined along with an assessment of the neurobiological underpinnings that drive adolescent use of these drugs. Adolescent C57BL/6J mice (postnatal days 35-44) were exposed to either water or nicotine (200µg/ml) for ten days. On the final four days, ethanol intake was examined using the drinking-in-the-dark paradigm. Nicotine-exposed mice consumed significantly more ethanol and displayed higher blood ethanol concentrations than did control mice. Autoradiographic analysis of nAChR density revealed higher epibatidine binding in frontal cortical regions in mice exposed to nicotine and ethanol compared to mice exposed to ethanol only. These data show that nicotine exposure during adolescence increases subsequent binge ethanol consumption, and may affect the number of nAChRs in regions of the brain reward pathway, specifically the frontal cortex.

Sleep duration and the cortisol awakening response in dementia caregivers utilizing adult day services.

OBJECTIVE: Sleep complaints are common among caregivers and are associated with detriments in mental and physical health. Cortisol, a biomarker of the stress process, may link sleep with subsequent health changes in caregivers. The current study examines whether sleep duration is directly associated with the cortisol awakening response (CAR), or whether it is moderated by Adult Day Services (ADS) use, an intervention found previously to influence daily CAR by reducing stressor exposure. METHOD: Associations were examined in caregivers (N = 158) of individuals with dementia (IWD) on days when IWDs attended ADS and days when IWDs did not attend ADS. Data were gathered over 8 consecutive days. Caregivers were primarily female (87.3%) with a mean age of 61.59. A multilevel growth curve model tested the association of an interaction of today's ADS use and last night's sleep duration with today's CAR as the outcome. RESULTS: The interaction between ADS use and within-person sleep duration was significant such that when an individual sleeps longer than their average but does not use ADS, they have a smaller or blunted CAR. On the other hand when an individual sleeps longer than their average and uses ADS, they have a higher but nonsignificant CAR. Sleeping shorter than usual was associated with a dynamic rise regardless of ADS use. CONCLUSIONS: Findings indicate that ADS use moderates the association between sleep duration and CAR such that longer than average sleep is associated with blunted, dysregulated cortisol patterns only on non-ADS days.

Anticipating an Easier Day: Effects of Adult Day Services on Daily Cortisol and Stress.

PURPOSE OF THE STUDY: Family caregivers experience high levels of stress that place them at risk for poor health outcomes. We explore whether an intervention which lowers caregivers' daily exposure to stressors, adult day services (ADS), leads to improved regulation of the stress hormone, cortisol, which has implications for health and well-being. DESIGN AND METHODS: Participants (N = 158) were family caregivers of individuals with dementia (IWD) who were using ADS. Eligibility included: the IWD had a dementia diagnosis, IWD used ADS at least twice a week, and IWD and caregiver lived in the same household. A within-subject treatment design was used to compare caregivers' diurnal cortisol responses on days they received the intervention (ADS use by the IWD) and days they did not. Participants completed daily interviews over eight consecutive days and provided five saliva samples on each of those days. Primary outcomes were salivary cortisol awakening response (CAR) and cortisol area under the curve with respect to ground (AUC-G). RESULTS: Caregivers with a "burned-out" or flattened CAR, and associated low AUC-G on non-ADS days displayed a more normative CAR and AUC-G response on ADS days. Restored cortisol regulation was also observed on ADS days among caregivers with the highest CAR and AUC-G levels on non-ADS days. IMPLICATIONS: Results indicate that ADS use improves caregivers' cortisol regulation, which could enhance long-term health outcomes. Effects may be due to caregivers' anticipation of an easier day when the IWD attends ADS.

The Effects of a Cluster Randomized Controlled Workplace Intervention on Sleep and Work-Family Conflict Outcomes in an Extended Care Setting.

OBJECTIVES: To evaluate the effects of a workplace-based intervention on actigraphic and self-reported sleep outcomes in an extended care setting. DESIGN: Cluster randomized trial. SETTING: Extended-care (nursing) facilities. PARTICIPANTS: US employees and managers at nursing homes. Nursing homes were randomly selected to intervention or control settings. INTERVENTION: The Work, Family and Health Study developed an intervention aimed at reducing work-family conflict within a 4-month work-family organizational change process. Employees participated in interactive sessions with facilitated discussions, role-playing, and games designed to increase control over work processes and work time. Managers completed training in family-supportive supervision. MEASUREMENTS: Primary actigraphic outcomes included: total sleep duration, wake after sleep onset, nighttime sleep, variation in nighttime sleep, nap duration, and number of naps. Secondary survey outcomes included work-to-family conflict, sleep insufficiency, insomnia symptoms and sleep quality. Measures were obtained at baseline, 6-months and 12-months post-intervention. RESULTS: A total of 1,522 employees and 184 managers provided survey data at baseline. Managers and employees in the intervention arm showed no significant difference in sleep outcomes over time compared to control participants. Sleep outcomes were not moderated by work-to-family conflict or presence of children in the household for managers or employees. Age significantly moderated an intervention effect on nighttime sleep among employees (p=0.040), where younger employees benefited more from the intervention. CONCLUSION: In the context of an extended-care nursing home workplace, the intervention did not significantly alter sleep outcomes in either managers or employees. Moderating effects of age were identified where younger employees' sleep outcomes benefited more from the intervention.

Depressive Mood, Anger, and Daily Cortisol of Caregivers on High- and Low-Stress Days.

OBJECTIVES: This study examines the association of daily cortisol with depressive mood and anger. METHOD: Depressive mood, anger and 2 markers of cortisol, area under the curve (AUC), and cortisol awakening response (CAR) were examined for caregivers (N = 164) of individuals with dementia (IWDs) across 8 days, some of which IWDs attended an adult day service (ADS) program. Caregivers were primarily female (86.7%) with a mean age of 61.99. First, multilevel models were run with CAR and AUC each as separate covariates of anger and depressive mood. A second set of models examined contextual factors of caregivers (i.e., care-related stressors and amount of ADS use) were added to the models for anger and depressive mood (Model 2). RESULTS: On days where caregivers had AUCs below their average they expressed higher anger scores. However in Model 2, anger was associated with more care-related stressors, but not ADS use or daily cortisol. Caregivers who on average had smaller CARs were more likely to be depressed. In Model 2, depressed mood was associated with more care-related stressors and a low average CAR. DISCUSSION: We found that hypocortisol patterns, reflective of chronic stress experienced by caregivers, are associated with negative mood.

A workplace intervention improves sleep: results from the randomized controlled Work, Family, and Health Study.

STUDY OBJECTIVES: The Work, Family, and Health Network Study tested the hypothesis that a workplace intervention designed to increase family-supportive supervision and employee control over work time improves actigraphic measures of sleep quantity and quality. DESIGN: Cluster-randomized trial. SETTING: A global information technology firm. PARTICIPANTS: US employees at an information technology firm. INTERVENTIONS: Randomly selected clusters of managers and employees participated in a 3-month, social, and organizational change process intended to reduce work-family conflict. The intervention included interactive sessions with facilitated discussions, role playing, and games. Managers completed training in family-supportive supervision. MEASUREMENTS AND RESULTS: Primary outcomes of total sleep time (sleep duration) and wake after sleep onset (sleep quality) were collected from week-long actigraphy recordings at baseline and 12 months. Secondary outcomes included self-reported sleep insufficiency and insomnia symptoms. Twelve-month interviews were completed by 701 (93% retention), of whom 595 (85%) completed actigraphy. Restricting analyses to participants with e3 valid days of actigraphy yielded a sample of 473-474 for intervention effectiveness analyses. Actigraphy-measured sleep duration was 8 min/d greater among intervention employees relative to controls (P < .05). Sleep insufficiency was reduced among intervention employees (P = .002). Wake after sleep onset and insomnia symptoms were not different between groups. Path models indicated that increased control over work hours and subsequent reductions in work-family conflict mediated the improvement in sleep sufficiency. CONCLUSIONS: The workplace intervention did not overtly address sleep, yet intervention employees slept 8 min/d more and reported greater sleep sufficiency. Interventions should address environmental and psychosocial causes of sleep deficiency, including workplace factors.

Work-family conflict, cardiometabolic risk, and sleep duration in nursing employees.

We investigated associations of work-family conflict and work and family conditions with objectively measured cardiometabolic risk and sleep. Multilevel analyses assessed cross-sectional associations between employee and job characteristics and health in analyses of 1,524 employees in 30 extended-care facilities in a single company. We examined work and family conditions in relation to: (a) validated, cardiometabolic risk score based on measured blood pressure, cholesterol, glycosylated hemoglobin, body mass index, and self-reported tobacco consumption and (b) wrist actigraphy-based sleep duration. In fully adjusted multilevel models, work-to-family conflict but not family-to-work conflict was positively associated with cardiometabolic risk. Having a lower level occupation (nursing assistant vs. nurse) was associated with increased cardiometabolic risk, whereas being married and having younger children at home was protective. A significant Age × Work-to-Family Conflict interaction revealed that higher work-to-family conflict was more strongly associated with increased cardiometabolic risk in younger employees. High family-to-work conflict was significantly associated with shorter sleep duration. Working long hours and having children at home were both independently associated with shorter sleep duration. High work-to-family conflict was associated with longer sleep duration. These results indicate that different dimensions of work-family conflict may pose threats to cardiometabolic health and sleep duration for employees. This study contributes to the research on work-family conflict, suggesting that work-to-family and family-to-work conflict are associated with specific health outcomes. Translating theory and findings to preventive interventions entails recognition of the dimensionality of work and family dynamics and the need to target specific work and family conditions.

The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor.

The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood.

Sex differences in voluntary oral nicotine consumption by adolescent mice: a dose-response experiment.

Recent studies with adolescent rodents offer valuable information regarding the neurochemical and behavioral effects of adolescent nicotine exposure. One hundred twenty-one male and 125 female adolescent (35 days of age) C57BL/6J mice were tested for voluntary nicotine consumption by providing 24-h access to both saccharin-only (SAC) and one of six nicotine-containing solutions [10, 25, 50, 75, 100, 200 ug (-)-freebase nicotine/ml in 2% SAC] in the home cage for 7 days. Although males and females drank similar volumes (ml) of nicotine, the female mice consumed more nicotine adjusted for body weight (mg/kg) and as a percentage of total fluid intake than did the male mice. In contrast, there was no sex difference in overall serum cotinine levels (adjusted for liver weight). For all mice, nicotine consumption and serum cotinine levels increased in a dose-dependent manner, and the volume of nicotine intake (ml), percent nicotine intake, and nicotine dosage (mg/kg) on the last day of the experiment were positively correlated with cotinine levels. Cotinine levels were inversely related to body weight only for females. Sex differences in nicotine consumption, but not in cotinine levels, suggest sex differences in pharmacokinetic processes that may contribute to oral nicotine consumption behavior during periadolescence.

Predictors of fatigue in healthy young adults: moderating effects of cigarette smoking and gender.

Fatigue is a common complaint of patients seen in primary care. Factors that contribute to fatigue in a patient population include poor health status, psychological stress, poor nutrition, and pregnancy. Less well understood are factors that contribute to fatigue among healthy, nonpregnant individuals. Within the framework of the theory of unpleasant symptoms, 40 healthy young smoking and nonsmoking adults between the ages of 18 and 35 were evaluated to determine self-report level of fatigue and contributing physiological, psychological, and situational factors. Results indicate that while self-report of fatigue did not vary in this population based on gender, subjects who were moderate to heavy cigarette smokers were significantly more fatigued than were nonsmokers (F = 10.24, df = 1, 38, P < 0.01), with the effect being specific to male smokers. Self-report of fatigue did not correlate with body mass index, baseline inflammatory or immune status, or blood pressure. Positive psychological and situational predictors of fatigue included depression (r = 0.556, P < 0.001), state anxiety (r = 0.569, P < 0.001), sleep quality (r = -0.399, P < 0.05), and sleep quantity (r = -0.411, P < 0.05). These results suggest that psychological and situational factors are key contributors to fatigue in young adults and that smoking is a risk factor for fatigue in men.