Neuroticism and cortisol: Pinning down an expected effect

Background

There are strong theoretical arguments that those high on Neuroticism (N) should normally exhibit higher prevailing levels of the stress-linked hormone cortisol (C), but findings are inconsistent, probably reflecting methodological weaknesses especially in taking account of C's diurnal cycle.

Methods

High and low N students [Total N = 118; mean age = 20.99 years] were recruited and their salivary cortisol measured, ensuring that saliva samples were numerically adequate to assess C's diurnal cycle over two days with objective verification of sample timing.

Results

Cortisol secretion was approximately 20% higher in High N than low N participants in the period of 12 h after awakening (p < .008), but no differences in secretion were evident during the first 0.75 of this period, when typically the Cortisol Awakening Response (CAR) rapidly takes cortisol to its daily peak. N effects were thus confined to the 0.75 h–12 h period (p < .007). Males had approximately 25% higher cortisol secretion levels than females, also confined to the 0.75 h–12 h period (p < .003). No significant differences between N groups were evident for dynamic measures of cortisol change, viz. the magnitude of CAR rise and subsequent diurnal fall. All effects were controlled for cohort date of study entry, age, smoking status, study day and time of awakening.

Discussion

With careful control, it appears that an important theoretically predicted effect exists, and is replicated in different student intake cohorts recruited in different years. Most importantly, findings support several lines of evidence that the period of massive rise in the brief 0–0.75 h CAR period should be seen as quite separate from the rest of the diurnal cycle, underpinned by different control mechanisms, and with potentially different correlates.     

Morningness-eveningness, habitual sleep-wake variables and cortisol level

The free cortisol rise immediately after awakening is a distinctive part of the cortisol circadian rhythm. Few studies have focused on the relationship between morningness and cortisol awakening response (CAR). As the suprachiasmatic nucleus may be of major importance for both, one may hypothesise that the CAR should also be associated with morningness. We used saliva samplings and applied questionnaires in adolescents and young adults. Saliva samplings were made at awakening (t1) and 30 min later (t2). Chronotype was measured using the Composite Scale of Morningness (CSM), and habitual time in bed was calculated from habitual rise times and bed times. In both, the adolescent sample and the young adults, positive correlations existed between cortisol measures at t1 immediately after awakening and CSM scores. Using a multivariate model controlling for age group, smoking status and time of t1, we identified CSM scores and bed times as the most relevant variables for CAR. When comparing extreme chronotypes, morning types had higher cortisol levels immediately after awakening than evening types. These results strongly suggest an association between morningness-eveningness and CAR.     

Family environment is associated with HPA-axis activity in adolescents. The TRAILS study

The purpose of the present study was to investigate the developmental programming part of the theory of biological sensitivity to context using family environmental factors and hypothalamus-pituitary-adrenal (HPA) axis functioning. Specifically, we investigated whether perceived parenting (Rejection and Emotional Warmth) and socio-economic status (SES) predicted basal cortisol levels and the cortisol awakening response (CAR). In a population-based cohort of 1594 adolescents (mean age = 11.08, SD = 0.54) we assessed salivary cortisol, SES and perceived parenting. Perceived parental Emotional Warmth showed an inverse, linear association with basal cortisol levels. In addition, there was a curvilinear relationship between SES and both basal cortisol levels and the CAR. Our findings with regard to basal cortisol levels confirmed our hypothesis: lower basal HPA-axis activity in both high and low SES families compared to intermediate SES families.     

P3 event-related potential impairments in antisocial and psychopathic individuals: A meta-analysis

Prior findings on P3 event-related potential deficits in antisocial populations are mixed and it has been suggested that these abnormalities may not apply to psychopaths. A meta-analysis of 38 studies (total N = 2616) was conducted to investigate the relationship of P3 measures to antisocial behavior. Reduced P3 amplitudes (d = 0.252, p < .001) and longer P3 latencies (d = 0.130, p = .019) were significantly associated with antisocial behavior across all electrode sites, and when using both normal and non-normal control groups. A significant moderating effect of electrode site indicated longer latencies at Fz but not Pz. Compared to non-psychopathic offenders, psychopathic offenders showed P3 amplitudes impairments in standard oddball tasks, but not other tasks. Findings suggest that reduced P3 amplitudes and prolonged P3 latencies may reflect inefficient deployment of neural resources in processing cognitive task-relevant information in individuals characterized with generic antisocial behavior (i.e., aggression, antisocial personality disorder, conduct disorder/oppositional-defiant disorder, and psychopathy), whereas this association in psychopaths may be moderated by the type of tasks.     

State, not trait, neuroendocrine function predicts costly reactive aggression in men after social exclusion and inclusion

Social exclusion increases aggressive behaviour, and the possible neuroendocrine underpinnings of the effect are largely unknown. Here, we examined the extent to which testosterone and cortisol responses to social exclusion would predict subsequent reactive aggression. Men were randomly assigned to a social exclusion (SE) or inclusion (SI) condition of ‘Cyberball’, a computer ball-toss game. Aggression was then measured using the Point Subtraction Aggression Paradigm (PSAP). Saliva was collected at three points for the measurement of testosterone and cortisol. Regression analyses indicated that testosterone concentrations 10-min into the PSAP (controlling for pre- and post-Cyberball testosterone) were positively correlated with aggressive behaviour, irrespective of SI/SE. Post hoc analyses for the conditions separately, however, suggested the relationship was stronger for SI men (R²_change = 13.3%, F_1,29 = 5.28, p = 0.03) than for SE men (R²_change = 1.8%, F_1,26 = 0.49, p = 0.49). Aggressive behaviour was also positively correlated with cortisol concentrations 10-min into the PSAP (controlling for pre- and post-Cyberball cortisol) irrespective of SE/SI. When both hormones were included in the regression model, the interaction of baseline ‘Cortisol’ × ‘Testosterone’ × ‘Experimental Group’ approached significance (R²_change = 5.4%, F_1,55 = 3.53, p = 0.07), but no significant effects were observed in either group alone. The findings add to evidence that individual differences in state neuroendocrine function map onto variability in human social behaviour.     

Day-to-day friends’ victimization,aggression perpetration,and morning cortisol activity in late adolescents

This study investigates bidirectional associations between adolescents’ daily experiences of victimization and aggression perpetration within friendships. We investigated (a) across-day associations between victimization and aggression perpetration; (b) morning cortisol activity as a moderator of cross-day victimization and aggression links; and (c) potential sex differences in these patterns. For 4 consecutive days, 99 adolescents (M_age = 18.06, SD = 1.09, 46 females) reported whether they were victimized by or aggressive toward their friends. On three of these days, adolescents provided three morning saliva samples. Multilevel path analyses showed that across days, victimization and aggression were bidirectionally linked, but only for male adolescents. Additionally, for male adolescents, morning cortisol output (but not morning cortisol increase) moderated the association between victimization and next-day aggression; victimization predicted greater next-day aggression for boys with low, but not high, morning cortisol output. Findings implicate a physiological factor that may modify daily links between victimization and aggression in male adolescent friendships.     

Children's heart rate variability as stress indicator: Association with reported stress and cortisol

Stress is a complex phenomenon coordinated by two main neural systems: the hypothalamic–pituitary–adrenal system with cortisol as classical stress biomarker and the autonomic nervous system with heart rate variability (HRV) as recently suggested stress marker. To test low HRV (5 minute measurements) as stress indicator in young children (5-10y), associations with self-reported chronic stress aspects (events, emotions and problems) (N = 334) and salivary cortisol (N = 293) were performed. Peer problems, anger, anxiety and sadness were associated with lower root mean square of successive differences (RMSSD) and high frequency power (i.e. lower parasympathetic activity). Anxiety and anger were also related to a higher low frequency to high frequency ratio. Using multilevel modelling, higher cortisol levels, a larger cortisol awakening response and steeper diurnal decline were also associated with these HRV patterns of lower parasympathetic activity. Conclusion: Low HRV (lower parasympathetic activity) might serve as stress indicator in children.     

Use of hair cortisol analysis to detect hypercortisolism during active drinking phases in alcohol-dependent individuals

The assessment of cortisol levels in human hair has recently been suggested to provide a retrospective index of cumulative cortisol exposure over periods of up to 6 months. The current study examined the utility of hair cortisol analysis to retrospectively detect hypercortisolism during active drinking phases in alcoholics in acute withdrawal (n = 23), the normalisation of cortisol output in abstinent alcoholics (n = 25) and cortisol levels in age- and gender-matched controls (n = 20). Scalp-near 3-cm hair segments were sampled and analysed for cortisol content. Results showed three to fourfold higher cortisol levels in hair samples of alcoholics in acute withdrawal than in those of abstinent alcoholics (p < .001) or controls (p < .001), with no differences between the latter two groups. The current hair cortisol findings closely mirror results of previous research using well-established measures of systemic cortisol secretion and thus provide further validation of this novel method.     

Salivary gonadal and adrenal hormone differences in boys and girls with and without disruptive behavior disorders: Contextual variants

Hormone differences by psychopathology group and gender may have implications for understanding disruptive behavior disorders (DBDs) and complexities of treatment outcomes. Current theoretical models emphasize contextual differences as moderators of hormone-behavior relations. This baseline report examined: (a) hormone differences in youth with and without DBD, and (b) contextual factors as moderators of behavior problems and hormones. 180 children and adolescents were enrolled (141 boys, mean 9.0 ± 1.7 years). DBD participants met criteria for conduct disorder (CD) and/or oppositional defiant disorder (ODD) (n = 111); 69 were recruited as healthy comparisons (HC). Saliva was collected for testosterone, cortisol, dehydroepiandrosterone and androstenedione. DBD youth had significantly higher androstenedione than the HC group. There was a group by gender interaction for basal cortisol mean with DBD boys and HC girls having lower cortisol. Moderating effects of contextual variables (e.g., family functioning, delinquent peers) were noted for cortisol and adrenal androgens. Findings argue for considering hormones as an influence on DBD beyond simple direct one-to-one associations.     

Hyperactivity of the HPA axis is related to dietary restraint in normal weight women

The objective of our study was to investigate the relationship between hypothalamus/pituitary/adrenal (HPA) axis functioning and dietary restraint in normal weight (BMI between 20 and 25 kg/m²) men and women. We therefore assessed in 38 men and 38 women HPA axis functioning, through measuring 5-hour cortisol exposure and cortisol feedback functioning through a dexamethasone (4 mg) suppression test. Eating behavior was assessed through the Three Factor Eating Questionnaire and body composition through hydro densitometry and deuterium dilution method. No relationship between HPA axis functioning and dietary restraint was found in men. Normal weight women with a restraint score ≥ 9 showed increased cortisol concentrations over a 5-hour time period, increased cortisol concentrations after a dexamethasone (4 mg) suppression test, higher BMI, and higher body fat percentage, when compared to women with a restraint score < 9. Moreover, a positive relationship was found between cortisol concentrations over a 5-hour time period and dietary restraint in combination with the disinhibition score (R² = 0.23, p < 0.001). We conclude that in normal weight women hyperactivity of the HPA-axis is related to dietary restraint especially in combination with disinhibition.     

Distinguishing the early-onset/persistent and adolescence-onset antisocial behavior types: from birth to 16 years

Moffitt's theory regarding two types of adolescent antisocial behavior was investigated using a prospective, longitudinal study of normal and abnormal development in a primarily low socioeconomic status, ethnically diverse sample. Results supported the presence of an early-onset/persistent (EOP) group and an adolescence-onset (AO) group. Groups were most reliably and significantly distinguished by indices of socioemotional history within the first 3 years, but no significant differences were found on early measures of temperament or neuropsychological functioning. EOPs scored significantly lower than other groups on measures of neuropsychological functioning only during late childhood and adolescence, suggesting that the declines in verbal functioning that have been so reliably found in this and other samples of early-starting antisocial adolescents are progressive and consequent to adverse experience. In adolescence, AOs were significantly more likely to report high levels of internalizing symptoms and life stress, suggesting that AO antisocial behavior is not a benign phenomenon. Implications of these findings for etiologic theories of adolescent antisocial behavior are discussed.     

The role of childhood abuse in HPA-axis reactivity in Social Anxiety Disorder: A pilot study

Background

Studies on depression have found that childhood abuse (CA) is associated with a persistent sensitization of the hypothalamic-pituitary-adrenal (HPA)-axis to stress in adulthood. So far, it is unknown whether this HPA-axis sensitization is specific to depression, or whether this is a more general outcome associated with CA in patients with mood and anxiety disorders. The aim of this study was to investigate whether CA is associated with enhanced cortisol reactivity to psychosocial stress in Social Anxiety Disorder (SAD).

Methods

Salivary cortisol levels before, during, and after exposure to psychosocial stress (i.e., Trier Social Stress Task, TSST) in SAD patients with a history of childhood abuse (SAD + CA, n = 9) were compared to cortisol levels in SAD patients without a history of childhood abuse (SAD − CA, n = 9), patients with PTSD related to childhood abuse (n = 16), and healthy controls without a history of childhood abuse (n = 16).

Results

Analyses showed that the SAD + CA group had a strongly increased cortisol reactivity (mean peak: 17.5 ± 1.9 nmol/l) compared to SAD − CA (mean peak: 9.0 ± 1.1 nmol/l), PTSD (mean peak: 9.0 ± 1.1 nmol/l) and healthy controls (mean peak: 9.6 ± 1.4 nmol/l), whereas baseline cortisol levels did not differ. The enhanced increase in the SAD + CA group was not explained by stronger anxiety in response to the TSST.

Conclusions

Consistent with the findings in depression, these results show for the first time that childhood abuse is also associated with strongly increased cortisol reactivity in SAD. When replicated in a larger sample, these findings may have important implications for the treatment of SAD.     

Male gamblers have significantly greater salivary cortisol before and after betting on a horse race, than do female gamblers

Prevalence rates of gambling are influenced by gender. Among normative populations, hypothalamic-pituitary-adrenal (HPA) axis response to stress is affected by gender. However, pathological, compared to recreational, gamblers demonstrate perturbations in HPA activation in response to gambling stimuli. We examined whether there were gender differences in HPA response to gambling in a naturalistic setting among horse-race bettors and scratch-off lottery bettors. Salivary cortisol was collected from horse-race gamblers (n = 32) and scratch-off lottery ticket players (n = 39) before and after (0, 10, or 20 min) betting on a horse race at an off-track betting establishment. Salivary cortisol levels were significantly higher among men than among women, both prior to and following, betting on a horse race. Among women, but not men, there was a decline in salivary cortisol across time in scratch-off bettors, whereas women horse-race bettors maintained consistent low concentrations of salivary cortisol at every time point sampled. Together these data suggest that engaging in gambling may have different effects on stress responses of men, compared to women. Whether these gender differences in HPA activation contribute to gender-related differences in gambling behavior is the subject of ongoing investigation.     

Impact of acute sleep restriction on cortisol and leptin levels in young women

Sleep restriction alters hormone patterns and appetite in men, but less is known about effects on women. We assessed effects of overnight sleep restriction on cortisol and leptin levels and on appetite in young women. Participants' baseline sleep duration and eating habits were monitored for a week before the study. Salivary cortisol and leptin were sampled from fifteen healthy women (aged 18-25) during two consecutive days: first after a 10 h overnight sleep opportunity (Baseline day) and then after a night including only 3 h sleep (Post sleep-restriction day). Participants also completed appetite questionnaires on both days. Sleep restriction significantly reduced morning cortisol levels (p = 0.02), elevated morning leptin levels (p = 0.04), elevated afternoon/evening cortisol area under the curve values (p = 0.008), and slowed the decline in cortisol concentration during the day (p = 0.04). Hunger and craving scores did not differ significantly between days. A single night of restricted sleep affected cortisol rhythms and morning leptin levels in young women.     

A novelty seeking phenotype is related to chronic hypothalamic-pituitary-adrenal activity reflected by hair cortisol

Reduced hypothalamic pituitary adrenal (HPA) activity is associated with greater novelty seeking in humans. Hair cortisol represents an integrated proxy measure of total cortisol production/release over an extended period of time and may be a valuable tool for tracking the HPA system. Sampling approaches (collection of blood, saliva, urine, or feces) for socially housed nonhuman primates present a number of technical challenges for collection particularly when repeated sampling is necessary. Herein we describe a relationship between cortisol levels measured in hair collected from 230 socially housed female vervet (Chlorocebus aethiops sabaeus) monkeys and a free-choice novelty seeking phenotype. A predator-like object was placed at the periphery of the outdoor enclosures for 30 min and speed of approach (latency to approach within 1 m) and persistence of interest (number of 1 min intervals within 1 m) were scored. A composite Novelty Seeking score, combining these two measures, was calculated. The intra-class correlation coefficient (ICC = .68) for two different objects across years indicated that this score reflects a stable aspect of temperament. Hair samples were collected from each subject approximately 3-6 months following the second assessment; cortisol levels were determined from the hair. A significant inverse relationship of Novelty Seeking score with hair cortisol level (p < .01) was noted. The high hair cortisol groups had significantly lower Novelty Seeking scores than the low cortisol groups both years (p's < .05). These results suggest that low average cortisol levels promote novelty seeking, while high average levels inhibit novelty seeking behavior.     

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.     

Disclosure and Monitoring as Predictors of Mother–Adolescent Agreement in Reports of Early Adolescent Rule-Breaking Behavior

The current study tested whether greater monitoring by mothers and greater disclosure by early adolescents was linked to greater agreement in mothers’ and adolescents’ reports of rule-breaking behavior. In doing so, the article demonstrated how polynomial regression analyses can be used to test hypotheses in which informant discrepancies serve as the dependent variable. Data were obtained from 218 mother–adolescent dyads (M adolescent age = 11.5 years, 51% female, 49% European American, 47% African American). Mothers and early adolescents provided reports of their perceptions of maternal monitoring (i.e., solicitation and control through rules), adolescent disclosure, and adolescent rule-breaking behavior. Polynomial regression models tested monitoring and disclosure as moderators of the association between mothers’ and adolescents’ reports of the adolescents’ rule-breaking behavior. Mothers’ reports of rule-breaking behavior were more strongly associated with adolescents’ reports of their own rule-breaking behavior when mothers reported engaging in more solicitation or control through rules. There was less agreement in mothers’ and adolescents’ reports of rule breaking when adolescents reported that their mothers engaged in more solicitation. Adolescent disclosure did not moderate agreement in reported rule-breaking behavior. Greater monitoring by mothers may reduce the discrepancy in mother–adolescent reports of rule-breaking behavior. Findings also demonstrate the greater validity of polynomial regression approaches over difference scores when testing hypotheses with informant agreement as the outcome.     

Combined dexamethasone suppression–corticotrophin-releasing hormone stimulation test in medication-free major depression and healthy volunteers

Background

The hypothalamic–pituitary–adrenal (HPA) axis is dysfunctional in a subgroup of mood disorders.

Methods

We compared cortisol and adrenocorticotropic hormone (ACTH) responses in major depression and healthy volunteers to the combined dexamethasone suppression–corticotrophin-releasing hormone stimulation (DEX–CRH) test. Unlike other published studies, the study patients were medication-free and the healthy volunteers did not have first-degree relatives with a mood or psychotic disorder. Demographics, DSM-IV diagnoses and other clinical parameters were evaluated in major depressive disorder (MDD) and healthy control groups. Participants received an oral dose of 1.5 mg dexamethasone at 11 pm the day before CRH administration. On the following day, at 3 pm, 100 µg of ovine CRH was infused. Blood samples for determination of cortisol and ACTH were collected every 15 min from 3 pm to 4:15 pm. Cortisol and ACTH responses were calculated as areas under the curve.

Results

Controlling for age, baseline (i.e., post-dexamethasone) ACTH levels were higher in depressed patients compared to controls (p=0.01). There was a trend for higher ACTH responses in depressed patients compared to the control group (p=0.08). In depressed patients, cortisol and ACTH responses correlated positively with age, duration of illness and number of hospitalizations.

Limitations

Because of the cross-sectional study design we can only evaluate the nature of potential HPA axis disturbances that were present in patients when they are acutely depressed.

Conclusions

Feedback inhibition of ACTH secretion by cortisol is compromised in MDD, and this is independent of an age effect on the HPA axis function.     

Self- or parent report of (co-occurring) internalizing and externalizing problems,and basal or reactivity measures of HPA-axis functioning: A systematic evaluation of the internalizing-hyperresponsivity versus externalizing-hyporesponsivity HPA-axis hypothesis

Background

Previous research findings on the link between adolescents’ psychopathology and hypothalamic–pituitary–adrenal (HPA) axis activity have been heterogeneous.

Method

Adolescents (n = 211) with a preadolescent DSM-IV diagnosis participated in a lab-based social stress task. Saliva cortisol was assessed at awakening and during social stress. It was investigated if continuous measures of internalizing and externalizing problems and their interaction, using both self- and parent report, were associated with basal or reactivity measures of HPA-axis functioning

Results

During social stress, an enhanced total release of cortisol was associated with self-reported internalizing problems and a blunted total release of cortisol with self-reported externalizing problems. Post hoc analyses revealed that the association between enhanced cortisol output and internalizing problems held for boys but not for girls. Associations with morning cortisol measures were overall weak

Conclusions

Only in the context of stress, and particularly when based on self-report, blunted cortisol output was associated with externalizing and enhanced cortisol output with internalizing problems. Our broad approach demonstrates the importance of who reports on psychopathology, the use of dimensional measures of psychopathology, simultaneous analysis of internalizing and externalizing problems, and the use of awakening and social stress related measures of cortisol.     

Blunted HPA axis response to stress is related to a persistent Dysregulation Profile in youth

The Child Behavior Checklist Dysregulation Profile (DP) in youth has been shown to be a predictor of psychopathology later in life. We examined the activity of the hypothalamic pituitary adrenal (HPA) axis in youth with remitted, new, persistent, and no DP. Data from 489 youth (47% boys) participating in a Dutch longitudinal general population study were included (Wave 1 mean age = 11.5, Wave 2 = 14.2). Wave 2 diurnal cortisol patterns and levels in response to a laboratory stress paradigm were compared in youth with DP at Wave 1 only, Wave 2 only, both Waves, and neither Wave. Youth with the DP at Wave 2 only or at both time points showed blunted cortisol responses to stress relative to the other two groups. There were no group or sex differences in diurnal cortisol activity. More research is needed to determine how the association between DP symptoms and HPA axis functioning changes over time.