Veronika Engert

Investigation into the cross-correlation of salivary cortisol and alpha-amylase responses to psychological stress

Stress is a multidimensional construct. To accurately represent stress physiology, multiple stress measures across multiple stress-related systems should be assessed. However, associations may be masked given that different systems underlie different time courses. Salivary cortisol and alpha-amylase (sAA) are reliable biological stress markers of the sympathetic nervous system (SNS) and the hypothalamus pituitary adrenal (HPA) axis, respectively. Studies examining the link between sAA and cortisol levels in response to stress have produced inconsistent results. Here, we investigated whether the covariance of stress-induced sAA and cortisol release is dependent on the distinct temporal dynamics of the two stress markers. A total of 50 male participants were exposed to a psychological laboratory stressor with high frequency (2-min interval) saliva sampling in two independent studies. Synchronized time series of sAA and cortisol measures before, during and after stress induction were obtained. Cross-correlation analysis was applied to test for the association of sAA and cortisol levels at various stages relative to the onset of the stressor. Positive and negative cross-correlations between lagged pairs of sAA and cortisol measures were found in both studies. The strongest correlation was found for sAA preceding cortisol release by 13.5 min (r = .27, p < .001). With a smaller effect size cortisol also significantly preceded sAA by 13.5 min (r = -.16, p < .001). We suggest that sAA and cortisol stress responses are reliably associated at various time lags throughout a stressful situation. As a possible connection site between HPA axis and SNS that may underlie sAA-cortisol associations, we discuss CRF neurons of the hypothalamus involved in sympathetic regulation.

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress

BACKGROUND In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic-pituitary-adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. METHODS In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. RESULTS Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. LIMITATIONS Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. CONCLUSION We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group.

Dopaminergic and noradrenergic contributions to functionality in ADHD: the role of methylphenidate.

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood psychiatric condition characterized by severe impulsiveness, inattention and overactivity. Methylphenidate (MPH), a psychostimulant affecting both the dopaminergic and the noradrenergic systems, is one of the most frequently prescribed treatments for ADHD. Despite the widespread use of MPH and its proven effectiveness, its precise neurochemical mechanisms of action are under debate. For the most part, MPH’s influence on subcortical dopamine neurotransmission is thought to play a crucial role in its behavioral and cognitive effects. In their hypothesis of biphasic MPH action, Seeman and Madras [42, 43] suggest that therapeutic doses of MPH elevate tonic dopamine while inhibiting phasic transmitter release in subcortical structures, leading to reduced postsynaptic receptor stimulation and psychomotor activation in response to salient stimuli. Volkow and colleagues [56] suggest that by amplifying a weak striatal dopamine signal, MPH increases the perception of a stimulus or task as salient. The enhanced interest for the task is thought to increase attention and improve performance. Recent animal studies have however shown that when administered at doses producing clinically relevant drug plasma levels and enhancing cognitive function, MPH preferentially activates dopamine and noradrenaline efflux within the prefrontal cortex relative to the subcortical structures [5]. Overall, we suggest that the delineated theories of MPH therapeutic action should not be discussed as exclusive. Studies are outlined that allow integrating the different findings and models.

Cortisol awakening response and hippocampal volume: vulnerability for major depressive disorder?

BACKGROUND Major depressive disorder is associated with dysregulated basal cortisol levels and small hippocampal (HC) volume. However, it is still debated whether these phenomena are a consequence of the illness or whether they may represent a vulnerability marker existing before the illness onset. Here, we aimed to examine this notion of vulnerability by assessing whether abnormalities in basal cortisol secretion and HC volumes are already present in a sample of healthy young adults who showed varying levels of depressive tendencies, but at subclinical levels. METHODS We recruited healthy young men and women from the local university. On the basis of depression scores derived from standard questionnaires, three groups were formed: a control group (n = 27), a subclinical group (n = 23), and a high-risk subclinical group (n = 9). The participants underwent a magnetic resonance imaging scan and collected saliva samples for the assessment of diurnal cortisol levels. RESULTS Both the subclinical and the high-risk subclinical group failed to show a significant increase in cortisol levels after awakening. The high-risk subclinical group also showed a lower area-under-the-curve increase of cortisol levels after awakening compared with control subjects. In addition, this group also had smaller total HC volume compared with control subjects. CONCLUSIONS The findings from this subclinical sample suggest that dysregulated cortisol awakening response and small HC volume may constitute vulnerability factors for major depressive disorder. Further investigations are needed to discern the mechanisms that may underlie these phenomena.

The interaction of acute and chronic stress impairs model-based behavioral control

It is suggested that acute stress shifts behavioral control from goal-directed, model-based toward habitual, model-free strategies. Recent findings indicate that interindividual differences in the cortisol stress response influence model-based decision-making. Although not yet investigated in humans, animal studies show that chronic stress also shifts decision-making toward more habitual behavior. Here, we ask whether acute stress and individual vulnerability factors, such as stress reactivity and previous exposure to stressful life events, impact the balance between model-free and model-based control systems. To test this, 39 male participants (21-30 years old) were exposed to a potent psychosocial stressor (Trier Social Stress Test) and a control condition in a within-subjects design before they performed a sequential decision-making task which evaluates the balance between the two systems. Physiological and subjective stress reactivity was assessed before, during, and after acute stress exposure. By means of computational modeling, we demonstrate that interindividual variability in stress reactivity predicts impairments in model-based decision-making. Whereas acute psychosocial stress did not alter model-based behavioral control, we found chronic and acute stress to interact in their detrimental effect on decision-making: subjects with high but not low chronic stress levels as indicated by stressful life events exhibited reduced model-based control in response to acute psychosocial stress. These findings emphasize that stress reactivity and chronic stress play an important role in mediating the relationship between stress and decision-making. Our results might stimulate new insights into the interplay between chronic and acute stress, attenuated model-based control, and the pathogenesis of various psychiatric diseases.

Exploring the use of thermal infrared imaging in human stress research

High resolution thermal infrared imaging is a pioneering method giving indices of sympathetic activity via the contact-free recording of facial tissues (thermal imprints). Compared to established stress markers, the great advantage of this method is its non-invasiveness. The goal of our study was to pilot the use of thermal infrared imaging in the classical setting of human stress research. Thermal imprints were compared to established stress markers (heart rate, heart rate variability, finger temperature, alpha-amylase and cortisol) in 15 participants undergoing anticipation, stress and recovery phases of two laboratory stress tests, the Cold Pressor Test and the Trier Social Stress Test. The majority of the thermal imprints proved to be change-sensitive in both tests. While correlations between the thermal imprints and established stress markers were mostly non-significant, the thermal imprints (but not the established stress makers) did correlate with stress-induced mood changes. Multivariate pattern analysis revealed that in contrast to the established stress markers the thermal imprints could not disambiguate anticipation, stress and recovery phases of both tests. Overall, these results suggest that thermal infrared imaging is a valuable method for the estimation of sympathetic activity in the stress laboratory setting. The use of this non-invasive method may be particularly beneficial for covert recordings, in the study of special populations showing difficulties in complying with the standard instruments of data collection and in the domain of psychophysiological covariance research. Meanwhile, the established stress markers seem to be superior when it comes to the characterization of complex physiological states during the different phases of the stress cycle.

Investigating the association between early life parental care and stress responsivity in adulthood

We explored the associations between early life experience, endocrine regulation, psychological health, and hippocampal integrity in 37 elderly volunteers. Specifically, a neurodevelopmental and psychological mediation model was tested: Retrospective early life parental care was hypothesized to influence hippocampal integrity and the development of self-esteem. In turn, hippocampal volume (via modulation of hypothalamic-pituitary-adrenal axis negative feedback) and self-esteem (via modulation of stress vulnerability) were suggested to influence the cortisol stress response. Results supported the two-mediator model. We propose that early life parental care impacts on an individuals developing brain and personality, which consequently contribute to the shaping of neuroendocrine stress responsivity.

Hippocampal activation during a cognitive task is associated with subsequent neuroendocrine and cognitive responses to psychological stress

Increased activation of the hypothalamus pituitary adrenal (HPA) axis, marked by increased secretion of cortisol, is a biological marker of psychological stress. It is well established that the hippocampus plays an important role in the regulation of HPA axis activity. The relationship between cortisol (stress‐related elevation or exogenous administration) and the hippocampal‐related cognitive function is often examined. However, few human studies to date have examined the effect of stress on hippocampal activity and the interactions between stress‐induced activation of the HPA axis and hippocampal function during different phases of cognitive function. On the basis of our previous work, we hypothesized that group differences in stress‐sensitivity relate to differences in hippocampal‐related stress‐integration. To test this hypothesis, we conducted a functional MRI study using tasks known to involve the hippocampal formation: novel‐picture encoding, psychological stress, and paired‐picture recognition. On the basis of their cortisol responses to stress, we divided subjects into stress‐responders (increase in cortisol, n = 9) and nonresponders (decrease in cortisol, n = 10). Responders showed higher hippocampal deactivation during the stress task and lower recognition scores due to a larger number of misses. Intriguingly, stress‐responders showed significant differences in hippocampal activation already prior to stress, with higher levels of hippocampal activity during the picture encoding. Although effects of both cortisol and hippocampal activation on recognition were present in responders, similar effects were absent in the nonresponder group. Our results indicate that hippocampus plays an important role in adaptive behavioral responses. We hypothesize that states of hippocampal activation prior to stress might reflect states of vigilance or anxiety, which might be important for determining interindividual differences in subsequent stress response and cognitive performance.

Mind your thoughts: associations between self-generated thoughts and stress-induced and baseline levels of cortisol and alpha-amylase.

Stress is a major health burden in todays society. Research shows that negative cognitive styles are associated with increased stress reactivity, low mood and accelerated cellular aging. Our study sought to unravel the relationship between the content of self-generated thoughts and psychosocial stress measured in terms of hypothalamic-pituitary-adrenal axis and sympathetic activity. Features of self-generated thoughts were assessed using thought sampling while participants performed cognitive tasks following a stress induction or in a baseline condition. More negatively toned emotional thoughts and more social temporal thoughts with a past focus were associated with increased cortisol and alpha-amylase levels, both after stress and at baseline. More social temporal thoughts with a future focus, on the other hand, had an overall attenuating effect on the levels of both stress markers. Our results indicate a fundamental link between the thoughts and stress levels we experience. Understanding the mechanisms governing this mind-body association may have important implications for understanding and counteracting the high incidence of stress-related disorders in todays society.

Effects of panel sex composition on the physiological stress responses to psychosocial stress in healthy young men and women

Men and women differ in regard to psychosocial stress responses. Biological and contextual factors are known to mediate these differences; however, few studies investigated their interaction. In the present study, we examined contributions of both contextual and biological factors to the stress response of young healthy adults. Men and women were exposed to a modified version of Trier Social Stress Test. The participants gave a speech in front of a panel of judges, composed of either male or female panelists. Both men, and women presented a cortisol increase only when exposed to opposite sex panelists. Interestingly, this effect was only observed in women in their follicular phase. This finding showed that the induction of a psychosocial stress response does not strictly rely on direct social evaluation, but also depends on the sex composition of the panel. Implications for future studies are discussed.