Linn K. Kuehl

Differential physiological effects during tonic painful hand immersion tests using hot and ice water

The cold pressor test (CPT) is an empirically validated test commonly used in research on stress, pain and cardiovascular reactivity. Surprisingly, the equivalent test with water heated to noxious temperatures (hot water immersion test, HIT) has not been thoroughly investigated. The aim of the present study was to characterize the physiological effects and psychophysics of both tests and to analyze whether the autonomic responses are mainly induced by baroreflexes or a consequence of the pain experience itself. The study consisted of a single session including one CPT (4 ± 0.2 °C) and one HIT (47 ± 0.5 °C; cut‐off point 5 min) trial performed on 30 healthy drug free volunteers aged 19–57 (median 24) yrs. The sequence of both trials was alternated and participants were randomly assigned to sequence order and parallelized with respect to gender. Physiological parameters (cardiovascular, respiratory and electrodermal activity) and subjective pain intensity were continuously monitored. In addition, pain detection and tolerance thresholds as well as pain unpleasantness were assessed. Both tests were comparable with regard to the time course and intensity of subjective pain. However, a significantly higher increase of blood pressure could be observed during the CPT when compared to the HIT. The HIT appears less confounded with thermoregulatory baroreflex activity and therefore seems to be a more appropriate model for tonic pain.

Increased basal mechanical pain sensitivity but decreased perceptual wind-up in a human model of relative hypocortisolism

&NA; Clinical data have accumulated showing that relative hypocortisolism, which may be regarded as a neuroendocrinological correlate of chronic stress, may be a characteristic of some functional pain syndromes. However, it has not been clarified yet whether deregulations of the hypothalamus–pituitary–adrenal (HPA) axis may directly alter pain perception and thus be causally involved in the pathophysiology of these disorders. To test this hypothesis, we performed a randomized placebo‐controlled crossover trial in N = 20 healthy drug‐free volunteers (median age 24 yrs) and analyzed the effects of metyrapone‐induced hypocortisolism on quantitatively assessed basal mechanical pain sensitivity (1.5–13 m/s impact stimuli), perceptual wind‐up (9 m/s impact stimuli at 1 Hz) and temporal summation of pain elicited by inter‐digital web pinching (IWP; 10 N pressure stimuli for 2 min). Experimentally induced hypocortisolism significantly decreased pain detection thresholds and augmented temporal summation of IWP‐induced pain (p < .05). The latter effect was dependent on the relative reduction in cortisol levels, and seemed to rely on a potentiated sensitization and not merely on the observed changes in basal pain sensitivity. Perceptual wind‐up by contrast was reduced when cortisol synthesis was blocked (p < .05). This result is reminiscent of findings from animal studies showing a reversal of NMDA receptor activation by glucocorticoid receptor antagonists in neuropathic pain models. Our results speak in favor of a potential causal role of HPA axis alterations in pain chronicity.

Enhanced Emotional Empathy after Mineralocorticoid Receptor Stimulation in Women with Borderline Personality Disorder and Healthy Women

The mineralocorticoid receptor (MR) is highly expressed in the hippocampus and prefrontal cortex. MR have an important role in appraisal processes and in modulating stress-associated emotional reactions but it is not known whether the MR affects empathy. Borderline personality disorder (BPD) is characterized by disturbed emotion regulation and alterations in empathy. In the current study, we examined whether stimulation of the MR enhances empathy in patients with BPD and healthy individuals. In a placebo-controlled study, we randomized 38 women with BPD and without psychotropic medication, and 35 healthy women to either placebo or 0.4 mg fludrocortisone, an MR agonist. Subsequently, all participants underwent two tests of social cognition, the Multifaceted Empathy Test (MET) and the Movie for the Assessment of Social Cognition (MASC), measuring cognitive and emotional facets of empathy. Eighteen BPD patients and 18 healthy women received placebo, whereas 20 BPD patients and 17 healthy women received fludrocortisone. In the MET, fludrocortisone enhanced emotional empathy across groups, whereas cognitive empathy was not affected. In the MASC, no effect of fludrocortisone could be revealed. In both tests, BPD patients and healthy women did not differ significantly in cognitive and emotional empathy and in their response to fludrocortisone. Stimulation of MR enhanced emotional empathy in healthy women and in BPD patients. Whether fludrocortisone might have a therapeutic role in psychotherapeutic processes, remains to be elucidated.

Mineralocorticoid Receptor Stimulation Improves Cognitive Function and Decreases Cortisol Secretion in Depressed Patients and Healthy Individuals

Memory and executive function are often impaired in patients with major depression, while cortisol secretion is increased. Mineralocorticoid receptors (MR) are abundantly expressed in the hippocampus and in the prefrontal cortex, brain areas critical for memory, executive function, and cortisol inhibition. Here, we investigated whether MR stimulation with fludrocortisone (1) improves memory and executive function and (2) decreases cortisol secretion in depressed patients and healthy individuals. Twenty-four depressed patients without medication and 24 age-, sex-, and education-matched healthy participants received fludrocortisone (0.4 mg) or placebo in a randomized, double-blind, within-subject cross-over design. We measured verbal memory, visuospatial memory, executive function, psychomotor speed, and salivary cortisol secretion during cognitive testing between 1400 and 1700 hours. For verbal memory and executive function, we found better performance after fludrocortisone compared with placebo across groups. No treatment effect on other cognitive domains emerged. Depressed patients performed worse than healthy individuals in psychomotor speed and executive function. No group effect or group × treatment interaction emerged on other cognitive domains. Fludrocortisone decreased cortisol secretion across groups and there was a significant correlation between cortisol inhibition and verbal memory performance. Our data suggest a crucial role of MR in verbal memory and executive function and demonstrate the possibility to improve cognition in depressed patients and healthy individuals through MR stimulation.

Hair cortisol and cortisol awakening response are associated with criteria of the metabolic syndrome in opposite directions.

Findings on the association between hypothalamic-pituitary-adrenal (HPA) axis activity and metabolic risk are equivocal. Different methods of measuring HPA activity might indicate adverse vs. beneficial effects of HPA activity on metabolic risk thus contributing to heterogenous findings. In this study, we aimed to determine whether (1) the salivary cortisol awakening response (CAR) as a marker of awakening-induced activation of the HPA axis and (2) hair cortisol as a marker of long-term cortisol secretion are associated with criteria of the metabolic syndrome. Therefore, we recruited 41 healthy individuals (26 women, mean age: 41.2 years) and 44 patients with major depression (28 women, 41.4 years) and assessed CAR and hair cortisol values as well as all criteria of the metabolic syndrome (abdominal obesity, blood pressure, plasma glucose, triglycerides and high-density cholesterol levels) according to the International Diabetes Federation. CAR and hair cortisol values were divided into tertiles. Across groups, participants with hair cortisol or hair cortisone in the highest tertile showed significantly more criteria of the metabolic syndrome compared to participants in the medium or low tertile (F2,64=3.37, p=.04). These results were corroborated by significant positive correlations between mean hair cortisol values with waist circumference (r=.29, p=.03), triglycerides (r=.34, p=.01) and systolic blood pressure (r=.29, p=.04) and between mean hair cortisone and triglycerides (r=.46, p<.01). In contrast, mean CAR values correlated negatively with diastolic (r=-.29, p=.03) and systolic blood pressure (r=-.32, p=.02). Our results indicate that higher hair cortisol and hair cortisone levels but lower CAR values are associated with an unfavorable metabolic and cardiovascular risk profile.

Effects of stress on human mating preferences: stressed individuals prefer dissimilar mates

Although humans usually prefer mates that resemble themselves, mating preferences can vary with context. Stress has been shown to alter mating preferences in animals, but the effects of stress on human mating preferences are unknown. Here, we investigated whether stress alters mens preference for self-resembling mates. Participants first underwent a cold-pressor test (stress induction) or a control procedure. Then, participants viewed either neutral pictures or pictures of erotic female nudes whose facial characteristics were computer-modified to resemble either the participant or another participant, or were not modified, while startle eyeblink responses were elicited by noise probes. Erotic pictures were rated as being pleasant, and reduced startle magnitude compared with neutral pictures. In the control group, startle magnitude was smaller during foreground presentation of photographs of self-resembling female nudes compared with other-resembling female nudes and non-manipulated female nudes, indicating a higher approach motivation to self-resembling mates. In the stress group, startle magnitude was larger during foreground presentation of self-resembling female nudes compared with other-resembling female nudes and non-manipulated female nudes, indicating a higher approach motivation to dissimilar mates. Our findings show that stress affects human mating preferences: unstressed individuals showed the expected preference for similar mates, but stressed individuals seem to prefer dissimilar mates.

Alteration of delay and trace eyeblink conditioning in fibromyalgia patients.

Objective: Classical conditioning processes are important for the generation and persistence of symptoms in psychosomatic disorders, such as the fibromyalgia syndrome (FMS). Pharmacologically induced hyper- and hypocortisolism were shown to affect trace but not delay classical eyeblink conditioning. As previous studies revealed a relative hypocortisolism in FMS patients, we hypothesized that FMS patients also show altered eyeblink conditioning. Methods: FMS patients (n = 30) and healthy control subjects (n = 20) matched for gender and age were randomly assigned to a delay or trace eyeblink conditioning protocol, where conditioned eyeblink response probability was assessed by electromyogram. Morning cortisol levels, ratings of depression, anxiety as well as psychosomatic complaints, general symptomatology, and psychological distress were assessed. Results: As compared with healthy controls, FMS patients showed lower morning cortisol levels, corroborating previously described disturbances in neuroendocrine regulation of the hypothalamus-pituitary-adrenal axis in these patients. Trace eyeblink conditioning was facilitated in FMS patients, whereas delay eyeblink conditioning was reduced, and cortisol measures correlated significantly only with trace eyeblink conditioning. Conclusion: We conclude that FMS patients characterized by decreased cortisol levels differ in classical trace eyeblink conditioning from healthy controls, suggesting that endocrine mechanisms affecting hippocampus-mediated forms of associative learning may play a role in the generation of symptoms in these patients. CR = conditioned response; CS = conditioned stimulus; FMS = fibromyalgia syndrome; EMG = electromyogram; HPA = hypothalamus-pituitary-adrenal; SCID = Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; US = unconditioned stimulus.

Test-retest reliability of Attention Network Test measures in schizophrenia.

BACKGROUND The Attention Network Test (ANT) is a well established behavioral measure in neuropsychological research to assess three different facets of selective attention, i.e., alerting, orienting, and conflict processing. Although the ANT has been applied in healthy individuals and various clinical populations, data on retest reliability are scarce in healthy samples and lacking for clinical populations. The objective of the present study was a longitudinal assessment of relevant ANT network measures in healthy controls and schizophrenic patients. METHODS Forty-five schizophrenic patients and 55 healthy controls were tested with ANT in a test-retest design with an average interval of 7.4 months between test sessions. Test-retest reliability was analyzed with Pearson and Intra-class correlations. RESULTS Healthy controls revealed moderate to high test-retest correlations for mean reaction time, mean accuracy, conflict effect, and conflict error rates. In schizophrenic patients, moderate test-retest correlations for mean reaction time, orienting effect, and conflict effect were found. The analysis of error rates in schizophrenic patients revealed very low test-retest correlations. CONCLUSIONS The current study provides converging statistical evidence that the conflict effect and mean reaction time of ANT yield acceptable test-retest reliabilities in healthy controls and, investigated longitudinally for the first time, also in schizophrenia. Obtained differences of alerting and orienting effects in schizophrenia case-control studies should be considered more carefully. The analysis of error rates revealed heterogeneous results and therefore is not recommended for case control studies in schizophrenia.

Stimulation of the mineralocorticoid receptor improves memory in young and elderly healthy individuals

Glucocorticoids play an important role in cognitive function and act on glucocorticoid receptors and mineralocorticoid receptors (MRs) in the brain. Previously, the blockade of the MR has been shown to impair visuospatial and working memory in healthy young men. Here, we investigated the effects of the MR agonist fludrocortisone on memory in young and elderly healthy individuals. Thirty-one young (mean age 25.4 ± 4.6 years) and 22 elderly (mean age 63.2 ± 8.2 years) healthy participants received the MR agonist fludrocortisone (0.4 mg) or placebo at least 3 days apart in a randomized, double-blind within-subject cross-over design. We measured verbal memory (auditory verbal learning test), nonverbal memory (Rey/Taylor complex figure test), and working memory (digit-span task). As expected, young participants performed significantly better than elderly individuals in visuospatial memory (effect of group: F = 42.7, p < 0.01), verbal memory (F = 33.1, p < 0.01), and working memory (digit-span backward: F = 4.5, p = 0.04). For visuospatial memory (F = 5.0, p = 0.03) and short-term and working memory (digit-span forward: F = 4.2, p = 0.05), we found a significant treatment effect indicating better memory performance after fludrocortisone compared with placebo across groups. In concert with the previous studies, our data suggest a role of the MR in memory function. A cognitive enhancing effect by MR stimulation warrants future studies.

Exploring the time course of N170 repetition suppression: a preliminary study.

Several studies employed the repetition suppression paradigm to investigate the face-specific N170 component of the event-related potential (ERP), but yielded highly inconsistent results. Varying inter-stimulus intervals (ISIs) may account for inconsistencies between studies. This study aimed at exploring the time course of repetition suppression by systematically investigating the association between ISI and ERP adaptation. Fourteen healthy subjects were investigated with a passive face recognition paradigm using paired stimuli. Stimuli were presented for 500ms and ISIs parametrically varied between 400 and 2000ms. N170 was constructed to investigate adaptation effects on the level of perceptual face processing. We found an evidence for an asymptotic decay of repetition suppression over time with significant N170 adaptation effects only after the shortest ISI. Our results robustly demonstrate that N170 adaptation in a paired stimulus protocol critically depends on short ISIs, thereby explaining the inconsistencies observed in the previous studies. For future social cognition studies using neuronal adaptation to face stimuli, the current results provide a well defined ISI associated with a large N170 adaptation effect.