Background Can stressful events in early life alter the response characteristics of the human stress axis? Individual differences in stress reactivity are considered potentially important in long-term health and disease, however little is known about the sources of these individual differences. We present evidence that adverse experience in childhood and adolescence can alter core components of the stress axis, including cortisol and heart rate reactivity. Methods We exposed 354 healthy young adults (196 women) to public speaking and mental arithmetic stressors in the laboratory. Stress responses were indexed by self-report, heart rate, and cortisol levels relative to measures on a nonstress control day. Subjects were grouped into those who had experienced 0, 1, or 2 or more significant adverse life events including Physical or Sexual Adversity (mugged, threatened with a weapon, experienced a break-in or robbery; or raped or sexually assaulted by a relative or nonrelative) or Emotional Adversity (separation from biological mother or father for at least 6 months prior to age 15). Results Experience of adversity predicted smaller heart rate and cortisol responses to the stressors in a dose-dependent fashion (0 > 1 > 2 or more events; (Fs = 5.79 and 8.11, ps < .004) for both men and women. This was not explained by differences in socioeconomic status, the underlying cortisol diurnal cycle, or subjective experience during the stress procedure. Conclusion The results indicate a long-term impact of stressful life experience on the reactivity of the human stress axis.

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Caffeine elevates cortisol secretion, and caffeine is often consumed in conjunction with exercise or mental stress. The interactions of caffeine and stress on cortisol secretion have not been explored adequately in women. We measured cortisol levels at eight times on days when healthy men and women consumed caffeine (250 mg × 3) and underwent either mental stress or dynamic exercise protocols, followed by a midday meal, in a double blind, placebo-controlled, crossover design. Men and women had similar cortisol levels at the predrug baselines, but they responded differently to mental stress and exercise. The cortisol response to mental stress was smaller in women than in men (p=.003). Caffeine acted in concert with mental stress to further increase cortisol levels (p=.011), the effect was similar in men and women. Exercise alone did not increase cortisol, but caffeine taken before exercise elevated cortisol in both men and women (ps<.05). After a postexercise meal, the women had a larger cortisol response than the men, and this effect was greater after caffeine (p<.01). Cortisol release in response to stress and caffeine therefore appears to be a function of the type of stressor and the sex of the subject. However, repeated caffeine doses increased cortisol levels across the test day without regard to the sex of the subject or type of stressor employed (p<.00001). Caffeine may elevate cortisol by stimulating the central nervous system in men but may interact with peripheral metabolic mechanisms in women.

Background Stressful early life experience may have adverse consequences in adulthood and may contribute to behavioral characteristics that increase vulnerability to alcoholism. We examined early life adverse experience in relation to cognitive deficits and impulsive behaviors with a reference to risk factors for alcoholism. Methods We tested 386 healthy young adults (18 – 30 years of age; 224 women; 171 family history positive for alcoholism) using a composite measure of adverse life experience (low socioeconomic status plus personally experienced adverse events including physical and sexual abuse and separation from parents) as a predictor of performance on the Shipley Institute of Living scale, the Stroop color-word task, and a delay-discounting task assessing preference for smaller immediate rewards in favor of larger delayed rewards. Body mass index was examined as an early indicator of altered health behavior. Results Greater levels of adversity predicted higher Stroop interference scores (F = 3.07, p = .048), faster discounting of delayed rewards (F = 3.79, p = .024), lower Shipley mental age scores (F = 4.01, p = .019), and higher body mass indexes in those with a family history of alcoholism (F = 3.40, p = .035). These effects were not explained by age, sex, race, education, or depression. Conclusion The results indicate a long-term impact of stressful life experience on cognitive function, impulsive behaviors, and early health indicators that may contribute to risk in persons with a family history of alcoholism.

A disinhibited temperament may underlie a behavioral impulsivity that contributes to elevated risk for future alcoholism, especially among FH+ males.

Summary. Background: Coated-platelets are a subset of platelets with procoagulant potential observed upon dual agonist stimulation with collagen and thrombin. Objective:The goal was to investigate if coated-platelet production differs between patients with lacunar ischemic stroke and non-lacunar (cortical) ischemic stroke as compared with controls. Patients and methods: Blood samples from 60 patients with ischemic stroke (20 lacunar and 40 cortical) and 70 controls were analyzed for coated-platelet production. Results: Coated-platelet production was significantly lower in patients with lacunar stroke (21.8 ± 11.4%, mean ± 1 SD) as compared with either controls (31.6 ± 13.2%, P = 0.008) or patients with cortical stroke (39.4 ± 12.7%, P < 0.001). The increase in coatedplatelets for patients with cortical stroke as compared with controls was also significant (P = 0.008). Conclusions: Our results indicate a marked difference in coated-platelet synthesis in lacunar vs. non-lacunar stroke, thereby providing additional support for the existence of distinct pathological processes underlying these two subtypes of ischemic stroke. Further investigation of the role of coated-platelets in stroke, taking into account these preliminary findings, is warranted.

Objective-Caffeine increases cortisol secretion in people at rest or undergoing mental stress. It is not known whether tolerance develops in this response with daily intake of caffeine in the diet. We therefore tested the cortisol response to caffeine challenge after controlled levels of caffeine intake.Methods-Men (N = 48) and women (N = 48) completed a double-blind, crossover trial conducted over 4 weeks. On each week, subjects abstained for 5 days from dietary caffeine and instead took capsules totaling 0 mg, 300 mg, and 600 mg/day in 3 divided doses. On day 6, they took capsules with either 0 mg or

Abstinent alcoholics show a blunted stress cortisol response that may be a consequence of drinking or a preexisting risk marker. We tested cortisol responses to psychological stress in 186 18-30 year-old, healthy social drinkers having no personal history of alcohol or drug dependence, 91 of whom had one or two alcoholic parents (FH+) and 95 having no family alcoholism for two generations (FH-). We predicted that, similar to alcoholic patients, the FH+ would have reduced stress cortisol responses that would be partially determined by their temperament characteristics, specifically antisocial tendencies as measured by the California Psychological Inventory. On a stress day, subjects performed continuous simulated public speaking and mental arithmetic tasks for 45 min, and on a control day they sat and rested for the same time period. The FH+ who were low in sociability had smaller cortisol responses than FH-, high-sociability persons (t=2.27, p=.02). These two groups were not different in diurnal cortisol secretion patterns or affective responses to the stressors. Persons with a familial risk for alcoholism who have more antisocial tendencies may have altered central nervous system responses to emotionally relevant social challenges. Disrupted cortisol stress responses may serve as a risk marker for the development of substance use disorders.