Marieke S. Tollenaar

Diminished cortisol responses to psychosocial stress associated with lifetime adverse events a study among healthy young subjects.

BACKGROUND Animal and human studies have found that prior stressful events can result in an altered reactivity in the HPA axis. The aim of the present study was to investigate the role of adverse events in childhood on cortisol reactivity to psychosocial stress in young healthy subjects (n=80). METHODS Salivary cortisol levels were measured before, during and after exposure to a psychosocial stress task in healthy men and women with high (n=33) and low (n=47) exposure to adverse childhood events. RESULTS A significant blunted cortisol response was found in individuals with a history of adverse events compared to individuals with no adverse life events, with no differences in baseline cortisol levels. This finding appeared to be primarily driven by men. The groups did not differ on any other physiological or subjective stress measure, including heart rate, blood pressure, and subjective tension. CONCLUSIONS These findings suggest that, at least in healthy young males, adverse childhood events are associated with changes in HPA-axis functioning. Longitudinal studies are needed to investigate whether the blunted cortisol response is a risk factor in the etiology of psychiatric disorders or rather reflects resiliency with regard to the development of psychopathology.

Immediate and prolonged effects of cortisol, but not propranolol, on memory retrieval in healthy young men.

BACKGROUND While acute cortisol administration has been found to impair retrieval of emotional memories in healthy subjects, the duration of this memory impairment is still unknown. Propranolol, on the other hand, may impair the reconsolidation of emotional memories during reactivation, although human studies examining such effects are scarce. The present investigation was therefore undertaken to examine the immediate and prolonged effects of a single administered dose of cortisol or propranolol on memory retrieval in a double-blind placebo controlled design. METHODS Eighty-five healthy male participants were asked to retrieve previously learned emotional and neutral information after ingestion of 35 mg cortisol, 80 mg propranolol or placebo. After a washout period of 1 week, recall was again tested. RESULTS Memory retrieval of neutral and emotional information was impaired by a single dose of cortisol compared to placebo. The memory impairment due to cortisol remained, even after a washout period of 1 week. No immediate or prolonged effects of propranolol on memory retrieval were found, despite significant reductions in sympathetic arousal. CONCLUSIONS These results lend support to the hypothesis that cortisol is able to attenuate (emotional) memory recall in men over longer time spans and may therefore augment the treatment of disorders like post-traumatic stress disorder and phobias, but do not clarify the mechanism(s) through which propranolol exerts its therapeutic effects.

Hydrocortisone reduces emotional distracter interference in working memory

Several studies have shown that stress and glucocorticoids can impair prefrontal-dependent working memory (WM) performance. WM is the ability to attend to the task at hand, and to maintain relevant information in mind during a delay while ignoring irrelevant stimuli. Here, it is investigated whether stress hormones impair WM by reducing the ability to suppress distracting, irrelevant neutral and emotional stimuli. Hydrocortisone (35 mg) (n=23) or placebo (n=21) was administered to young, healthy men, who performed a Sternberg WM task with neutral and emotional irrelevant distracters shown in the delay-phase of the task, between encoding and recognition of the relevant stimuli for WM. Contrary to expectations, enhanced WM performance with higher processing speed and a reduction of errors was found in the hydrocortisone group compared to placebo. Moreover, hydrocortisone significantly reduced the distraction by emotional stimuli. These findings show that cortisol effects on WM are not unambiguous and contrast with previous findings on the impairing effects of cortisol on WM. Dose-response studies could give more insight into the specific modulating effects of glucocorticoids on suppression of irrelevant emotional distraction.

Enhanced orienting of attention in response to emotional gaze cues after oxytocin administration in healthy young men

BACKGROUND Oxytocin is known to enhance recognition of emotional expressions and may increase attention to the eye region. Therefore, we investigated whether oxytocin administration would lead to increased orienting of attention in response to gaze cues of emotional faces. METHODS In a randomized placebo-controlled double-blind crossover study 20 healthy males received 24 IU of oxytocin or placebo. Thirty-five minutes after administration they performed a gaze cueing task with happy, fearful and neutral faces. Stress levels were measured throughout the study. RESULTS Oxytocin did not affect stress levels during the study, but significantly increased gaze cueing scores for happy and fearful expressions compared to placebo. No effects were found for neutral expressions. Trait anxiety or depression did not moderate the effect. CONCLUSIONS Oxytocin increases orienting of attention in response to emotional gaze cues, both for happy and fearful expressions. Replication is needed in female and clinical populations. Effects of oxytocin on early, automatic processing levels should be studied in relation to previously found pro-social and behavioral effects of oxytocin.

Long-term outcomes of memory retrieval under stress.

Previous studies have found impairing effects of stress hormones on memory retrieval. So far, it is unknown whether these impairments are temporary, persistent throughout time, or whether the strength of the memory trace changes after retrieval because of the effects of stress hormones on memory processes during retrieval. In the present study, delayed cued recall (6 months after initial learning) was compared between male participants who had retrieved previously learned word pairs during stress or a control condition. Retrieval (with or without stress) had taken place either 1 day or 5 weeks after initial encoding. The group that had retrieved words under stress 5 weeks after encoding performed worse on long-term recall than the comparable control group. However, when words were retrieved under stress 1 day after encoding, no long-term effect was found, although performance at 6 months in relation to performance under stress was slightly increased compared to the control group. These results support previous findings in animals that stress may affect memory during reactivation. It further suggests that time intervals between encoding and reactivation may play an important role.

Affect-congruent approach and withdrawal movements of happy and angry faces facilitate affective categorisation

Increasing evidence indicates that evaluation of affective stimuli facilitates the execution of affect-congruent approach and avoidance responses, and vice versa. These effects are proposed to be mediated by increases or decreases in the relative distance to the stimulus, due to the participants action. In a series of experiments we investigated whether stimulus categorisation is similarly influenced when changes in this relative distance are due to movement of the stimulus instead of movements by the participant. Participants responded to happy and angry faces that appeared to approach (move towards) or withdraw (move away) from them. In line with previous findings, affective categorisation was facilitated when the movement was congruent with stimulus valence, resulting in faster and more correct responses to approaching happy and withdrawing angry faces. These findings suggest that relative distance indeed plays a crucial role in approach–avoidance congruency effects, and that these effects do not depend on the execution of movements by the participant.

Autobiographical memory after acute stress in healthy young men

Autobiographical memories have been found to be less specific after hydrocortisone administration in healthy men, resembling memory deficits in, for example, depression. This is the first study to investigate the effects of stress-induced elevated cortisol levels on autobiographic memory specificity and experience in healthy young men. Autobiographical memories were elicited by neutral and negative cue words, with instructions to recall either recent or remote memories. No effect of psychosocial stress was found on memory specificity or experience, but cortisol increases tended to be related to less specific, recent memories elicited by neutral cue words, especially when participants were physically aroused during memory retrieval. These results indicate that autobiographical memories are fairly resistant to an acute stressor in healthy young men, but that endogenous cortisol increases might be related to autobiographical memory retrieval. More research into the relation between endogenous cortisol increases and autobiographic memory retrieval is needed, especially in stress-related disorders.

Ambulatory assessed implicit affect is associated with salivary cortisol

One of the presumed pathways linking negative emotions to adverse somatic health is an overactive HPA-axis, usually indicated by elevated cortisol levels. Traditionally, research has focused on consciously reported negative emotions. Yet, given that the majority of information processing occurs without conscious awareness, stress physiology might also be influenced by affective processes that people are not aware of. In a 24-h ambulatory study we examined whether cortisol levels were associated with two implicit measures. Implicit affect was assessed using the Implicit Positive and Negative Affect Test, and implicit negative memory bias was assessed with the word fragment completion tasks. In 55 healthy participants, we measured subjective stress levels, worries, implicit, and explicit affect each hour during waking hours. Also, saliva samples were collected at three fixed times during the day, as well as upon waking and 30 min thereafter (cortisol awakening response). Multilevel analyses of the daytime cortisol levels revealed that the presence of an implicit negative memory bias was associated with increased cortisol levels. Additionally, implicit PA and, unexpectedly, implicit NA were negatively associated with cortisol levels. Finally, participants demonstrating higher levels of implicit sadness during the first measurement day, had a stronger cortisol rise upon awakening at the next day. Contrary to previous research, no associations between explicit affect and cortisol were apparent. The current study was the first to examine the concurrent relation between implicit measures and stress physiology in daily life. The results suggest that the traditional focus on consciously reported feelings and emotions is limited, and that implicit measures can add to our understanding of how stress and emotions contribute to daily physiological activity and, in the long term, health problems.

Are psychophysiological arousal and self-reported emotional stress during an oncological consultation related to memory of medical information? : An experimental study

Abstract Patients forget 20–80% of information provided during medical consultations. The emotional stress often experienced by patients during consultations could be one of the mechanisms that lead to limited recall. The current experimental study therefore investigated the associations between (analog) patients’ psychophysiological arousal, self-reported emotional stress and their (long term) memory of information provided by the physician. One hundred and eighty one cancer-naïve individuals acted as so-called analog patients (APs), i.e. they were instructed to watch a scripted video-recoding of an oncological bad news consultation while imagining themselves being in the patient’s situation. Electrodermal and cardiovascular activity (e.g. skin conductance level and heart rate) were recorded during watching. Self-reported emotional stress was assessed before and after watching, using the STAI-State and seven Visual Analog Scales. Memory, both free recall and recognition, was assessed after 24–28 h. Watching the consultation evoked significant psychophysiological and self-reported stress responses. However, investigating the associations between 24 psychophysiological arousal measures, eight self-reported stress measures and free recall and recognition of information resulted in one significant, small (partial) correlation (r = 0.19). Considering multiple testing, this significant result was probably due to chance. Alternative analytical methods yielded identical results, strengthening our conclusion that no evidence was found for relationships between variables of interest. These null-findings are highly relevant, as they may be considered to refute the long-standing, but yet untested assumption that a relationship between stress and memory exists within this context. Moreover, these findings suggest that lowering patients’ stress levels during the consultation would probably not be sufficient to raise memory of information to an optimal level. Alternative explanations for these findings are discussed.

The association of childhood maltreatment with depression and anxiety is not moderated by the oxytocin receptor gene

BackgroundThe oxytocin receptor (OXTR) gene may be involved in resilience or vulnerability towards stress, and hence in the development of stress-related disorders. There are indications that OXTR single nucleotide polymorphisms (SNPs) interact with early life stressors in predicting levels of depression and anxiety. To replicate and extend these findings, we examined whether three literature-based OXTR SNPs (rs2254298, rs53576, rs2268498) interact with childhood maltreatment in the development of clinically diagnosed depression and anxiety disorders.MethodsWe included 2567 individuals from the Netherlands Study of Depression and Anxiety. This sample consisted of 387 healthy controls, 428 people with a current or past depressive disorder, 243 people with a current or past anxiety disorder, and 1509 people with both lifetime depression and anxiety diagnoses. Childhood maltreatment was measured with both an interview and via self-report. Additional questionnaires measured depression and anxiety sensitivity.ResultsChildhood maltreatment was strongly associated with both lifetime depression and anxiety diagnoses, as well as with depression and anxiety sensitivity. However, the OXTR SNPs did not moderate these associations nor had main effects on outcomes.ConclusionsThe three OXTR gene SNPs did not interact with childhood maltreatment in predicting lifetime depression and anxiety diagnoses or sensitivity. This stresses the importance of replication studies with regard to OXTR gene variants in general populations as well as in clearly established clinical samples.