Trait dominance is associated with vascular cardiovascular responses,and attenuated habituation,to social stress

Both exaggerated and diminished levels of cardiovascular reactivity have been associated with cardiovascular ill health. Dysregulation of hemodynamic mechanisms which control cardiovascular functioning may account for some individual differences in health outcomes. Trait dominance has also been associated with poor cardiovascular health in studies of humans and animals. The current study investigated the relationship between trait dominance and cardiovascular habituation to repeated social stress in humans.     

Individual differences in adaptation of cardiovascular responses to stress

Previous research has described patterns of adaptation of cardiovascular responses across prolonged or recurring stress. However, despite important implications for the study of reactivity, relatively little research has directly examined the antecedents or consequences of this adaptation. We present data showing that neuroticism, a personality trait associated with dispositional appraisals of stress, is associated with reductions in HR, CO, and TPR responses across stress exposures. Comparisons of reactivity curves suggest blunted initial stress responses among persons with high neuroticism, and higher initial responses followed by greater decreases among persons with low neuroticism. The data also suggest an association between adaptation of cardiovascular responses and myocardial hemodynamic responding. Such findings shed new light on previous studies detecting healthful correlates of short-term stress responding, and highlight the relevance of adaptation to future cardiovascular reactivity research.     

Stability, consistency, and heritability of electrodermal response lability in middle-aged male twins

We examined individual differences in nonspecific electrodermal response (EDR) lability in terms of retest stability, cross-situational consistency, and heritability in a sample of 345 adult monozygotic and dizygotic twin pairs. We also examined the phenotypic and genetic relationships between EDR lability and speed of habituation of the specific EDR to a nonsignal stimulus. Individual variation in EDR lability showed substantial retest stability and cross-situational consistency and also predicted resistance to specific EDR habituation. Structural equation modeling showed that the covariation among EDR lability measures and resistance to specific EDR habituation operated through a single latent phenotype, which was influenced in approximately equal measure by genetic and unique environmental factors. We discuss these findings in terms of an information processing account of individual differences in phasic EDR activation.     

Neuroendocrinological responses to alcohol intoxication in healthy males: Relationship with impulsivity,drinking behavior,and subjective effects

Ambiguous biochemical and subjective responses to alcohol may relate to preexisting individual differences in alcohol expectations, experience, or impulsivity. This study examined cortisol and alpha‐amylase responses to alcohol and their association with trait impulsivity, alcohol expectancy, and subjective reports of alcohol's effects. Eighty‐seven males assigned to an alcohol, sober, or placebo group provided biochemical and self‐report measures. Both cortisol and alpha‐amylase increased following alcohol administration. Impulsivity correlated with cortisol changes, and the greatest rise in cortisol correlated with high stimulating effects in the alcohol group. These findings emphasize the importance of individual differences in alcohol responses and support a relationship between hormonal responses and alcohol use.     

Plasma FFA responses to prolonged walking in untrained men and women

Summary Gender differences in plasma FFA responses to 90 min of treadmill walking at 35% were investigated in six men and six women following an overnight fast. The subjects represented average values for maximal oxygen uptake and body fat percentage for age and gender. Mean plasma FFA concentration at 45 and 90 min of exercise were significantly (P<0.05) higher for women (0.82 mmol·l^–01, 0.88 mmol·l^–01) than men (0.42 mmol·l^–01, 0.59 mmol·l^–1). Lower R values for women throughout the exercise period indicated a greater percentage fat in total metabolism than for men while the FFA/glycerol results supported greater lipolytic activity for women. The uniformity of percent fat in metabolism for women from rest to exercise showed that FFA release from adipose tissue increased rapidly with the onset of exercise which was not the case for men. Comparison of metabolic data as well as a statistical analysis (ANCOVA) controlling for the influence of and percentage body fat on FFA plasma concentration suggested that gender differences in FFA responses to prolonged submaximal exercise can be expected to occur in untrained subjects.     

Rat sex and strain differences in responses to stress

Sensitivity to stress has been linked to the development of a variety of physical and psychological disorders. Studies to-date have focused on extreme stress phenotypes, have studied mostly male responses, have used limited dependent variables, and have included a limited number of measurement time points. The present experiment was designed to address these limitations. Feeding, body weight, open-field activity, acoustic startle reflex (ASR), and prepulse inhibition (PPI) responses of adult male and female Sprague-Dawley and Long-Evans rats to daily immobilization stress (20 min/day) were evaluated for 3 weeks. Stress significantly decreased feeding and body weight of males but generally not of females. Effects were greatest in Long-Evans males. Stress decreased 15-min activity levels for males on Stress Day 1, but not on other days. Stress did not affect 15-min activity levels of Long-Evans females but decreased 15-min activity levels of Sprague-Dawley females on every measurement day. ASR responses to stress differed based on rat strain; percent PPI responses differed based on rat strain and sex. Stress increased startle responses of Sprague-Dawley males and females but not of Long-Evans males and females. Stress reduced PPI of Long-Evans females on every measurement day but not of other groups. These findings indicate that strain and sex of rat is important to consider in evaluating behavioral and physiological responses to stress.     

P300 amplitude reduction is associated with early‐onset and late‐onset pathological substance use in a prospectively studied cohort of 14‐year‐old adolescents

P3 amplitude reduction (P3AR) is associated with risk for adolescent‐onset pathological substance use (PSU). In this longitudinal study, data from over 1,100 adolescent twins were used to examine P3AR in relation to early adolescent onset PSU (i.e., by age 14), late adolescent onset PSU (i.e., ages 14–18), misuse of different classes of substances (PSU‐nicotine, PSU‐alcohol, PSU‐illicit), degree of PSU comorbidity, and gender differences. P3 amplitude was recorded at age 14 from two midline electrodes during a visual oddball paradigm. PSU was defined as meeting criteria for any symptom of a substance use disorder assessed using semistructured clinical interviews. P3AR was associated with degree of drug class comorbidity, early adolescent onset PSU for all three substance classes, and late adolescent onset PSU for alcohol and illicit PSU. Gender differences in P3AR were not statistically significant. These findings provide further evidence that P3AR indexes a nonspecific diathesis for adolescent‐onset PSU.     

Two‐year stability of individual differences in (para)sympathetic and HPA‐axis responses to public speaking in childhood and adolescence

Long‐term stability of individual differences in stress responses has repeatedly been demonstrated in adults, but few studies have investigated the development of stability in adolescence. The present study was the first to investigate the stability of individual differences in heart rate, parasympathetic (RMSSD, pNN50, HF), sympathetic (LF/HF, SC), and HPA‐axis (salivary cortisol) responses in a youth sample (8–19 years). Responses to public speaking were measured twice over 2 years. Stability was moderate for absolute responses and task delta responses of HR, RMSSD, pNN50, and HF. Stability was lower for SC and task delta responses of LF/HF and cortisol. Anticipation delta responses showed low stability for HR and cortisol. The latter was moderated by age or puberty, so that individual differences were more stable in more mature individuals. The results support the suggestion that stress responses may be reset during adolescence, but only for the HPA axis.     

Social neuroscience: Autonomic, neuroendocrine, and immune responses to stress

The immune system is influenced by central nervous system processes that are shaped by social and psychological factors. Considerations of social factors, intrapersonal processes, and autonomic psychophysiology therefore may contribute to a fuller understanding of both immune and brain function. Research reviewed here (a) examines the socioemotional factors that contribute to, or moderate, responses to brief and chronic stressors, (b) determines whether or not stable individual differences in heart rate reactivity predict neuroendocrine and immune responses to a brief psychological stressor and to an influenza virus vaccine, and (c) investigates the autonomic origins of individual differences in low and high heart rate reactivity and their relationship to neuroendocrine and immune responses to chronic and acute stressors. Among our findings are: (a) acute psychological stressors activate the sympathetic adrenomedullary system across individuals and affect immune function; and (b) individuals characterized by high sympathetic cardiac reactivity to acute psychological stressors also show a relative activation of the hypothalamic pituitary adrenocortical system and altered immune function.     

Self‐reported sleep quality is more closely associated with mental and physical health than chronotype and sleep duration in young adults: A multi‐instrument analysis

Sleep and circadian rhythms are considered to be important determinants of mental and physical health. Epidemiological studies have established the contribution of self‐reported sleep duration, sleep quality and chronotype to health outcomes. Mental health and sleep problems are more common in women and men are more likely to be evening types. Few studies have compared the relative strength of these contributions and few studies have assessed these contributions separately in men and women. Furthermore, sleep and circadian characteristics are typically assessed with a limited number of instruments and a narrow range of variables is considered, leaving the understanding of the relative contribution of different predictors somewhat fractionary. We compared sleep quality, sleep duration and chronotype as predictors for self‐reported mental and physical health and psychological characteristics in 410 men and 261 women aged 18 to 30. To ascertain that results were not dependent on the use of specific instruments we used a multitude of validated instruments including the Morningness‐Eveningness‐Questionnaire, Munich‐ChronoType‐Questionnaire, Pittsburgh‐Sleep‐Quality‐Index, British‐Sleep‐Survey, Karolinska‐Sleep‐Diary, Insomnia‐Severity‐Index, SF‐36‐Health Survey, General‐Health‐Questionnaire, Dutch‐Eating‐Behaviour‐Questionnaire, Big‐Five‐Inventory, Behaviour‐Inhibition‐System‐Behaviour‐Activation‐System, and the Positive‐Affect‐Negative‐Affect‐Schedule. Relative contributions of predictors were quantified as local effect sizes derived from multiple regression models. Across all questionnaires, sleep quality was the strongest independent predictor of health and in particular mental health and more so in women than in men. The effect of sleep duration and social jetlag was inconspicuous. A greater insight into the independent contributions of sleep quality and chronotype may aid the understanding of sleep‐health interactions in women and men.     

Decreased reaction time variability is associated with greater cardiovascular responses to acute stress

Cardiovascular (CV) responses to mental stress are prospectively associated with poor CV outcomes. The association between CV responses to mental stress and reaction times (RTs) in aging individuals may be important but warrants further investigation. The present study assessed RTs to examine associations with CV responses to mental stress in healthy, older individuals using robust regression techniques. Participants were 262 men and women (mean age = 63.3 ± 5.5 years) from the Whitehall II cohort who completed a RT task (Stroop) and underwent acute mental stress (mirror tracing) to elicit CV responses. Blood pressure, heart rate, and heart rate variability were measured at baseline, during acute stress, and through a 75‐min recovery. RT measures were generated from an ex‐Gaussian distribution that yielded three predictors: mu‐RT, sigma‐RT, and tau‐RT, the mean, standard deviation, and mean of the exponential component of the normal distribution, respectively. Decreased intraindividual RT variability was marginally associated with greater systolic (B = ?.009, SE = .005, p = .09) and diastolic (B = ?.004, SE = .002, p = .08) blood pressure reactivity. Decreased intraindividual RT variability was associated with impaired systolic blood pressure recovery (B = ?.007, SE = .003, p = .03) and impaired vagal tone (B = ?.0047, SE = .0024, p = .045). Study findings offer tentative support for an association between RTs and CV responses. Despite small effect sizes and associations not consistent across predictors, these data may point to a link between intrinsic neuronal plasticity and CV responses.     

Prolonged marital stress is associated with short‐lived responses to positive stimuli

Marital stress is associated with a higher incidence of psychiatric disorders, in particular major depression. One pathway through which marital stress may impact emotional health is by compromising emotion‐responding processes. We examined a longitudinal sample of adults (N = 116; 59 males; 39–84 years) to verify how marital stress predicts reactivity to, and recovery from, emotional provocation. Individuals watched positive, neutral, and negative pictures while an objective measure of affective state, corrugator supercilii muscle activity, was recorded continuously. Our results indicate that marital stress is associated with short‐lived responses to positive pictures, indexed by a less persistent decrease in corrugator activity after picture offset. Extending beyond the prior focus on negative emotional processes, these results suggest that social stress may impact health by influencing the time course of responding to positive events.     

Neuropeptide S receptor gene is associated with cortisol responses to social stress in humans

The neuropeptide S (NPS) and its receptor NPSR represent a transmitter system critically involved in the modulation of anxiety and arousal in rodents. Initial human studies indicate that the T-allele of the functional NPSR gene (NPSR1) polymorphism (rs324981), which increases NPS potency at NPSR, is associated with anxiety-related phenotypes. Since stress is critically involved in the pathogenesis of anxiety disorders, we tested the association between rs324981 and stress reactivity in 196 healthy males. Participants were exposed to the Trier Social Stress Test for Groups (TSST-G), a standardized laboratory protocol for stress exposure in a group format. Salivary cortisol and subjective stress responses were assessed. A significant genotype by time interaction and a main effect of genotype were shown, with T-allele carriers displaying larger cortisol and subjective stress responses. This is the first report to show involvement of the NPS system in the regulation of the neuroendocrine stress response in humans.     

Gambling pathology is associated with dampened cortisol response among men and women

Pathological gambling has many similarities to pharmacological addiction. Notably, both pathological gambling and drug addiction are characterized by aberrations in hypothalamic-pituitary-adrenal (HPA) axis responding. As well, there are indications that gender differences may play a role in these processes. Whether gender and/or HPA response are associated with pathological gambling was of interest. Recreational and pathological gamblers (15 men and 6 women per group) had the HPA factor, cortisol, assessed in saliva before and after watching a video of their preferred mode of gambling (slot machines, horse race betting, scratch-off tickets, blackjack, video poker, craps, sports betting, online casino games, or lottery tickets), and a video of neutral stimuli (a rollercoaster ride). Basal levels of salivary cortisol did not significantly differ among recreational and pathological gamblers. However, recreational gamblers demonstrated significantly increased salivary cortisol levels after the gambling and rollercoaster videos, whereas pathological gamblers demonstrated no salivary cortisol increase in response to either video stimulus. There was also a non-significant trend for women to have a greater cortisol response to video stimuli compared to men. These data suggest that pathological gambling is associated with hypoactive HPA response to gambling stimuli, similar to chronic drug exposure, and gender may contribute to this effect.     

Patient-centered interviewing is associated with decreased responses to painful stimuli: An initial fMRI study

Objective

To identify the functional magnetic resonance imaging (fMRI) changes associated with a patient-centered interview (PCI) and a positive provider–patient relationship (PPR).

Methods

Nine female patients participated, five randomly selected to undergo a replicable, evidence-based PCI, the other four receiving standard clinician-centered interviews (CCI). To verify that PCI differed from CCI, we rated the interviews and administered a patient satisfaction with the provider–patient relationship (PPR) questionnaire. Patients were then scanned as they received painful stimulation while viewing pictures of the interviewing doctor and control images (unknown doctor).

Results

Interview ratings and questionnaire results confirmed that PCIs and CCIs were performed as planned and PCIs led to a much more positive PPR. We found significantly reduced pain-related neural activation in the left anterior insula region in the PCI group when the interviewing doctor's picture was shown.

Conclusion

This study identifies an association between a PCI that produced a positive PPR and reduced pain-related neural responses in the anterior insula. This is an initial step in understanding the neural underpinnings of a PCI.

Practice implications

If confirmed, our results indicate one neurobiological underpinning of an effective PCI, providing an additional scientific rationale for its use clinically.     

Exhaustion is associated with reduced habituation of free cortisol responses to repeated acute psychosocial stress

We investigated the association between exhaustion and the habituation of free cortisol responses to repeated stress exposure. The study comprised 25 healthy male subjects (38-59 years) who were confronted three times with the Trier Social Stress Test. Mean cortisol responses showed the well-known general habituation effect. A two-way interaction day by exhaustion (p<0.05) indicated that mean cortisol responses vary across stress sessions depending on the extent of exhaustion. Linear regression revealed a negative dose-response relationship between exhaustion and the degree of habituation (p<0.02). We identified 19 individuals showing a response habituation (negative slope) and 6 individuals showing a response sensitization over the three sessions (positive slope) with the latter reporting higher exhaustion scores. It might be hypothesized that impaired habituation to repeated exposure to the same stressor could reflect a state of increased vulnerability for allostatic load. Absence of normal habituation might be one potential mechanism how exhaustion relates to increased disease vulnerability.     

Neural response to emotional stimuli associated with successful antidepressant treatment and behavioral activation

Background

Major Depressive Disorder (MDD) is a leading cause of disability globally. Currently available treatments have limited efficacy and combination strategies are frequently used. Several lines of research have demonstrated that MDD patients experience impairments in various components of affective processing, including regulation of affective states.

Aim

To identify baseline and 1-week neuroimaging predictors of response to a 6-week trial of fluoxetine/olanzapine combination treatment during an affective processing task.

Methods

Twenty-one MDD patients and 18 healthy controls were enrolled in the study. MDD patients were treated for 6 weeks with fluoxetine (40–60 mg/day) and olanzapine (5–12.5 mg/day). All participants viewed images from the International Affective Picture Rating System during a functional magnetic resonance (fMRI) scan at baseline and 1 week.

Results

There was a 57% response rate (defined as a 50% decrease in Hamilton Rating Scale for Depression-17 item) at 6 weeks. At baseline, responders had increased premotor activity while viewing negative images compared to non-responders and healthy controls. Higher baseline premotor activity was also predictive of greater percent change on the HAMD-17 and improvement in negative disposition and behavioral drive. Non-responders exhibited increased insular activity at baseline compared to responders. Higher activity in the posterior cingulate cortex was also predictive of greater percent change on the HAMD-17. Change from baseline to 1 week did not produce any significant predictive findings.

Conclusions

Treatment with fluoxetine/olanzapine demonstrated similar biomarkers of response to monotherapeutic strategies. In particular, posterior cingulate cortex, anterior insula, and premotor cortex may show predictive differences in their response to affective images prior to treatment. Further research needs to be conducted to determine the utility of early changes in emotion circuitry in predicting antidepressant response.