To understand the underlying genetic and environmental sources of individual variation in basal cortisol levels, we collected salivary cortisol at awakening and at six fixed time points during the day in adult twins and their singleton siblings. Reported time of awakening was verified with heart rate and body movement recordings. Cortisol data were available for 199 MZ twins, 272 DZ twins and 229 singleton siblings from 309 twin families. No differences in cortisol means and variances were found between twins and singleton siblings. Additionally, the correlations for DZ twins and siblings were not significantly different, indicating generalizability of twin study results to the general population. Genetic model fitting showed heritability for cortisol levels during the awakening period (34% for cortisol level at awakening and 32% for cortisol level at 30min after awakening) but not for cortisol levels later during the day. The current study shows that, while cortisol levels in the awakening period are influenced by genetic factors, cortisol levels throughout most of the day are not heritable, indicating that future gene finding studies for basal cortisol should focus on the first hour post-awakening.

High glucocorticoid stress-responses are associated with prolonged freezing reactions and decreased active approach and avoidance behavior in animals. The present study was designed to investigate the effects of cortisol responses and trait avoidance on approach–avoidance behavior in humans. Twenty individuals were administered a computerized approach–avoidance (AA)-task before and after stress-induction (Trier Social Stress Test). The AA-task involved a reaction time (RT) task, in which participants made affect congruent and affect incongruent arm movements towards positive and threatening social stimuli. Affect congruent responses involved arm extension (avoidance) in response to angry faces and arm flexion (approach) in response to happy faces. Reversed responses were made in affect incongruent instruction conditions. As expected, participants with high cortisol responses showed significantly decreased RT congruency-effects in a context of social stress. Low trait avoidance was also associated with diminished congruency-effects during stress. However, the latter effect disappeared after controlling for the effects of cortisol. In sum, in agreement with animal research, these data suggest that high cortisol responses are associated with a decrease in active approach–avoidance behavior during stress. These findings may have important implications for the study of freezing and avoidance reactions in patients with anxiety disorders, such as social phobia and post-traumatic stress disorder.

Social disparities in health persist into old age, and differences in psychophysiological responsivity may contribute to this pattern. We assessed whether higher socioeconomic status (SES) is associated with attenuated cardiovascular and neuroendocrine responses elicited by cognitive tasks in old age. We tested 132 community-dwelling men and women aged 65–80 years, divided on the basis of educational attainment into higher and lower SES groups, and compared them with 26 higher educated participants aged 27–42 years. Blood pressure, hemodynamic variables and salivary cortisol were assessed in response to the performance of three cognitive tasks, and then during recovery. Older groups showed smaller heart rate and larger cortisol changes than younger participants. Post-task recovery in heart rate, stroke volume, pre-ejection period, and systolic blood pressure was greatest in the younger group, least in the older/lower education group, and intermediate in the older/higher education group. SES did not influence the increased cortisol responsivity of older participants. The results are consistent with the notion that higher SES protects against age-related changes in cardiovascular response profiles, particularly during recovery.

Objective 
To assess whether variation in the rate of cardiovascular recovery following exposure to acute psychological stress predicts changes in blood pressure longitudinally, independently of blood pressure at baseline and other covariates.
Design 
A 3-year longitudinal study.
Participants 
A total of 209 men and women aged 45–59 years at baseline, with no history of cardiovascular disease including hypertension.
Method 
Measurement of blood pressure, heart rate, heart rate variability, cardiac index and total peripheral resistance at rest, during two moderately stressful behavioural tasks and up to 45 min post-stress. Stress reactivity was defined as the difference in values between tasks and baseline, and post-stress recovery as the difference between recovery levels and baseline.
Outcome measures 
Resting blood pressure measured at baseline and 3 years later. Seven individuals had been prescribed hypertensive medication on follow-up.
Results 
Increases in systolic blood pressure (SBP) were predicted by impaired post-stress recovery of SBP (P < 0.001), diastolic blood pressure (DBP) (P < 0.001) and total peripheral resistance (P = 0.003), independently of baseline blood pressure, age, gender, socio-economic status, hypertensive medication, body mass and smoking. The adjusted odds of an increase in SBP ≥ 5 mmHg were 3.50 [95% confidence interval (CI) 1.19 to 10.8] for individuals with poor compared with effective post-stress recovery of SBP. Three-year increases in diastolic pressure were predicted by impaired recovery of SBP (P < 0.001) and DBP (P = 0.009) pressure and by heart rate variability during tasks (P = 0.002), independently of covariates. Conclusions  Impaired post-stress recovery and less consistently heightened acute stress reactivity may index disturbances in the regulation of cardiovascular stress responses that contribute to longitudinal changes in blood pressure in middle-aged men and women.

This study assessed the heritability of ambulatory heart period, respiratory sinus arrhythmia (RSA), and respiration rate and tested the hypothesis that the well-established correlation between these variables is determined by common genetic factors. In 780 healthy twins and siblings, 24-h ambulatory recordings of ECG and thorax impedance were made. Genetic analyses showed considerable heritability for heart period (37%-48%), RSA (40%-55%), and respiration rate (27%-81%) at all daily periods. Significant genetic correlations were found throughout. Common genes explained large portions of the covariance between heart period and RSA and between respiration rate and RSA. During the afternoon and night, the covariance between respiration rate and RSA was completely determined by common genes. This overlap in genes can be exploited to increase the power of linkage studies to detect genetic variation influencing cardiovascular disease risk.

Identification of genes causing variation in daytime and nighttime respiration rates could advance our understanding of the basic molecular processes of human respiratory rhythmogenesis. This could also serve an important clinical purpose, because dysfunction of such processes has been identified as critically important in sleep disorders. We performed a sib-pair–based linkage analysis on ambulatory respiration rate, using the data from 270 sibling pairs who were genotyped at 374 markers on the autosomes, with an average distance of 9.65 cM. Uni- and multivariate variance-components–based multipoint linkage analyses were performed for respiration rate during three daytime periods (morning, afternoon, and evening) and during nighttime sleep. Evidence of linkage was found at chromosomal locations 3q27, 7p22, 10q26, and 22q12. The strongest evidence of linkage was found for respiration rate during sleep, with LOD scores of 2.36 at 3q27, 3.86 at 10q26, and 1.59 at 22q12. In a simultaneous analysis of these three loci, >50% of the variance in sleep respiration rate could be attributed to a quantitative-trait loci near marker D10S1248 at 10q. Genes in this area (GFRA1, ADORA2L, FGR2, EMX2, and HMX2) can be considered promising positional candidates for genetic association studies of respiratory control during sleep.

STUDY OBJECTIVES: It has been hypothesized that general hyperarousal, present during both sleep and wakefulness, may underlie chronic insomnia. The present study explored, under strictly controlled conditions, whether chronic insomnia is associated with altered physiologic markers of arousal, both in absolute levels and in terms of circadian rhythmicity, relative to controls.
DESIGN: A 24-hour constant-routine protocol was implemented to assess physiologic measures.
SETTING: The study was conducted in an isolated, temperature- and light-controlled, sound-attenuated sleep laboratory.
PARTICIPANTS: Eleven subjects with clinically diagnosed chronic insomnia were compared with 13 healthy matched controls.
INTERVENTIONS: The subjects underwent physiologic parameter recordings and cognitive performance testing during 24 hours of total sleep deprivation under strictly controlled circumstances.
MEASUREMENTS AND RESULTS: Cardiovascular parameters, free cortisol, and body temperature were subjected to mixed-model analysis of variance and mixed-model harmonic regression. Overall, no differences were found in either the absolute level or the circadian parameters (amplitude, phase) of these variables between the insomniacs and the control subjects.
CONCLUSIONS: Although physiologic indexes of arousal were slightly elevated in the insomnia group relative to the controls, the differences between the groups were not statistically significant. This could have been due to a lack of statistical power or could reflect the actual absence of arousal in our sample of chronic insomniacs. Systematic interindividual level differences overwhelmed any differences between the 2 groups, making it unlikely that general hyperarousal was a critical underlying factor in our sample. Earlier findings of hyperarousal in insomnia during studies that allowed sleep may have been specifically related to the sleep state.