Hypothalamic-pituitary-adrenocortical Activity Research Articles

The differential effects of acute vs. chronic stress and their combination on hippocampal parvalbumin and inducible heat shock protein 70 expression

The hippocampus plays a central role in stress-related mood disorders. The effects of acute vs. chronic stress on the integrity of hippocampal circuitry in influencing the vulnerability to, or resiliency against, neuronal injury are poorly understood. Here we investigated whether acute vs. chronic psychosocial isolation stress or a combination of the two (chronic stress followed by acute stress) influences the expression of the interneuronal marker parvalbumin (PV) and the chaperone-inducible heat shock protein 70 (Hsp70i) in different subregions of the hippocampus. Low levels of the Ca2+-binding protein (PV) may increase the vulnerability to neuronal injury, and Hsp70i represents an indicator of intense excitation-induced neuronal stress. Adult male Wistar rats were exposed to 2h of immobilization (IM) or cold (4°C) (acute stressors), 21d of social isolation (chronic stress), or a combination of both acute and chronic stress. Both chronic isolation and the combined stressors strongly decreased the PV-immunoreactive cells in the CA1, CA3 and dentate gyrus (DG) region of the hippocampus, while acute stress did not affect PV expression. The combination of acute and chronic stress induced a dramatic increase in Hsp70i expression in the DG, but Hsp70i expression was unaffected in acute and chronic stress alone. We also monitored serum corticosterone (CORT) levels as a neuroendocrine marker of the stress response. Acute stress increased CORT levels, while chronic isolation stress compromised hypothalamic–pituitary–adrenocortical (HPA) axis activity such that the normal stress response was impaired following subsequent acute stress. These results indicate that in contrast to acute stress, chronic isolation compromises the HPA axis and generates a considerable reduction in PV expression, representing a decrease in the calcium-buffering capacity and a putatively higher vulnerability of specific hippocampal interneurons to excitotoxic injury. The induction of Hsp70i expression in response to acute and chronic isolation reveals that neurons in the DG are particularly vulnerable to an acute stressor following a chronic perturbation of HPA activity.

Tracheal occlusion conditioning causes stress, anxiety and neural state changes in conscious rats

Evidence from human and animal studies indicates that mechanical loads to breathing are stressful stimuli and evoke compensatory behaviours. Conditioning of stressful stimuli is known to cause changes in basal stress levels and behaviour. Individuals with respiratory obstructive diseases repeatedly experience bouts of airway obstruction, which may act as a form of conditioning, and often have affective disorders, such as anxiety and depression. It is unknown whether the development of affective disorders in these individuals results from the unexpected recurring respiratory perturbations. To investigate this possibility, we developed a model to elicit tracheal occlusion (TO) in conscious rats and exposed them to 10 days of TO conditioning. We hypothesized that healthy, conscious animals exposed to TO conditioning would develop stress and anxiety and would have modulated neural activity in respiratory, stress, discriminative and affective neural regions. Following TO conditioning, rats had increased basal corticosterone levels, greater adrenal weights and elevated anxiety levels compared with animals not receiving TO. Significant increases in cytochrome oxidase staining were found in brainstem respiratory nuclei, periaqueductal grey, dorsal raphe, thalamus and insular cortex. These results suggest that healthy animals develop stress and anxiety responses to respiratory load conditioning via inescapable tracheal occlusions, which may be mediated through state changes in specific brain nuclei.

Effect of repeated restraint on homotypic stress-induced nitric oxide synthases expression in brain structures regulating HPA axis

BackgroundRestraint stress (RS) markedly increases interleukin 1-β (IL-1β) generation in brain structures involved in hypothalamic-pituitary adrenocortical (HPA) axis regulation. The IL-1β-induced transient stimulation of HPA axis activity was parallel in time and magnitude to respective changes in regulation of HPA activity. In the present experiment the expression of neuron al and inducible nitric oxide synthase (nNOS and iNOS) were investigated in prefrontal cortex, hippocampus and hypothalamus in response to acute restraint stress in control and prior repeatedly restrained rats. MethodsExperiments were performed on male Wistar rats which were exposed to 10min restraint stress or restrained twice a day for 3 days, and 24h after the last stress period exposed to homotypic stress for 10min. After rapid decapitation at 0,1,2 and 3h after cessation of stress, trunk blood was collected and prefrontal cortex, hippocampus and hypothalamus were excised and frozen. Interleukin-1β, adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were determined in plasma using commercially available kits and neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in brain structure samples were analyzed by western blot procedure. ResultsPrior repeated restraint stress enhanced the acute restraint stress induced increase in IL-1β levels in all three structures examined. Restraint stress for 10min moderately decreased nNOS level in prefrontal cortex in control rats, augmented this level in hippocampus and markedly increased nNOS level in hypothalamus. Restraint itself significantly decreased iNOS level in prefrontal cortex, while it enhanced iNOS level in hippocampus and hypothalamus. Prior restraint stress for 3 days enhanced the nNOS level in prefrontal cortex and hippocampus and did not substantially affect nNOS levels response in hypothalamus. Repeated restraint stress considerably augmented the iNOS levels in both prefrontal cortex, hippocampus and hypothalamus induced by followed homotypic stress. ConclusionThese results indicate that during restraint stress nNOS regulate formation of low amount of NO and the high-output generation of NO is effected by inducible isoform of nitric oxide synthase. Prior repeated stress significantly enhances the homotypic stress-induced nNOS and iNOS responses.

Minireview: Hair Cortisol: A Novel Biomarker of Hypothalamic-Pituitary-Adrenocortical Activity

Activity of the hypothalamic-pituitary-adrenocortical (HPA) axis is commonly assessed by measuring glucocorticoids such as cortisol (CORT). For many years, CORT was obtained primarily from blood plasma or urine, whereas later approaches added saliva and feces for noninvasive monitoring of HPA functioning. Despite the value of all these sample matrices for answering many research questions, they remain limited in the temporal range of assessment. Plasma and saliva are point samples that vary as a function of circadian rhythmicity and are susceptible to confounding by environmental disturbances. Even urine and feces generally assess HPA activity over a period of only 24 h or less. We and others have recently developed and validated methods for measuring the concentration of CORT in the body hair of animals (e.g. rhesus monkeys) and scalp hair of humans. CORT is constantly deposited in the growing hair shaft, as a consequence of which such deposition can serve as a biomarker of integrated HPA activity over weeks and months instead of minutes or hours. Since the advent of this methodological advance, hair CORT has already been used as an index of chronic HPA activity and stress in human clinical and nonclinical populations, in a variety of laboratory-housed and wild-living animal species, and in archival specimens that are many decades or even centuries old. Moreover, because human hair is known to grow at an average rate of about 1 cm/month, several studies suggest that CORT levels in hair segments that differ in proximity to the scalp can, under certain conditions, be used as a retrospective calendar of HPA activity during specific time periods preceding sample collection.

Association of amygdala volumes with cortisol secretion in unipolar depressed patients

Major depressive disorder (MDD) is accompanied by morphological changes of brain structures which are of great importance in the neural circuitry mediating depression like the hippocampus and the amygdala. Hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA) system resulting in enhanced glucocorticoid secretion can often be observed during depression and has been thought to play an important role in inducing these morphological changes. We used magnetic resonance imaging to investigate alterations of amygdala and hippocampal volumes in 86 in-patients with unipolar depression and 87 healthy controls, and we then correlated amygdala and hippocampal volumes of 76 in-patients with the area under the curve of cortisol secretion in the dexamethasone/corticotropin releasing hormone (Dex/CRH) test at baseline and during short-term antidepressant therapy. In line with recently published studies both left and right amygdala volumes of patients in a first depressive episode were smaller than those of healthy controls. Patients with recurrent depressive episodes showed a reduction of hippocampal volumes, while amygdala volumes were normal. Larger left and right amygdala volumes correlated with a more pronounced reduction of HPA activity, measured by the cortisol secretion in the combined DEX/CRH test, during antidepressant therapy in patients with recurrent depressive episodes.

Lack of elevations in glucocorticoids correlates with dysphoria-like behavior after repeated social defeat

Activity of the hypothalamic–pituitary–adrenocortical (HPA) axis is often abnormal in depression and could hold clues for better treatment of this debilitating disease. However, it has been difficult to use HPA activity as a depression biomarker because both HPA hyperactivity and HPA hypoactivity have been reported in depression. Melancholic depression has typically been associated with HPA hyperactivity, while atypical depression has been linked with HPA hypoactivity. Many animal models of chronic stress recapitulate behavioral aberrations and elevated HPA activity that could represent a model for melancholic depression. However, there are no animal models that could be used to elucidate the etiology or treatment of atypical depression. We have used repeated social defeat in mice to test the hypothesis that this chronic stress would induce dysphoria-like behavior associated with HPA hypoactivity in a subset of subjects. Intruder mice were placed in the home cage of an aggressive resident mouse for 5min/d for 30days. The majority of intruder mice had elevated basal plasma corticosterone (High Morning Corticosterone, or HMC) and adrenal 11β hydroxylase mRNA levels relative to control mice that were handled daily. However, a subset of intruder mice (Low Morning Corticosterone; LMC) exhibited basal plasma corticosterone and 11β hydroxylase mRNA levels that were indistinguishable from control levels. Significant changes in emotional behavior only occurred in LMC mice, which exhibited anxiety-like increases in activity and defecation during tail suspension and anhedonia-like decreases in sucrose preference. Relative to HMC mice, LMC mice also showed increases in gene expression of mineralocorticoid receptor in CA2 hippocampus, consistent with the possibility that HPA activity in this group is constrained by increased sensitivity to glucocorticoid negative feedback. LMC mice also exhibited increased c-fos gene expression compared to HMC mice in the paraventricular hypothalamus and lateral septum suggesting that central pathways fail to habituate to chronic stress even though adrenocortical activity is not stimulated. We conclude that LMC mice showed adrenocortical hyporesponsiveness, which in combination with the behavioral abnormalities in this group may represent a model for the HPA hypoactivity associated with atypical depression.

Peer Rejection and HPA Activity in Middle Childhood: Friendship Makes a Difference

Exclusion and victimization by classmates were related to levels and diurnal change in cortisol in 97 fourth graders (53% boys, M = 9.3 years). Number and quality of friendships were considered as moderators. Salivary cortisol was collected 5 times daily on 2 school days. Excluded children had elevated cortisol levels at school and a flattened diurnal cortisol curve, suggesting hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation. This effect was weaker for children with more friends or better friendships. Victimization was not associated with cortisol level or change. The results demonstrate the role of HPA activity in peer group processes and indicate that group and dyadic factors interact in predicting stress in the peer group.

Kindergarten stressors and cumulative adrenocortical activation: The “first straws” of allostatic load?

Using an ethnically diverse longitudinal sample of 338 kindergarten children, this study examined the effects of cumulative contextual stressors on children's developing hypothalamic-pituitary-adrenocortical (HPA) axis regulation as an early life indicator of allostatic load. Chronic HPA axis regulation was assessed using cumulative, multiday measures of cortisol in both the fall and spring seasons of the kindergarten year. Hierarchical linear regression analyses revealed that contextual stressors related to ethnic minority status, socioeconomic status, and family adversity each uniquely predicted children's daily HPA activity and that some of those associations were curvilinear in conformation. Results showed that the quadratic, U-shaped influences of family socioeconomic status and family adversity operate in different directions to predict children's HPA axis regulation. Results further suggested that these associations differ for White and ethnic minority children. In total, this study revealed that early childhood experiences contribute to shifts in one of the principal neurobiological systems thought to generate allostatic load, confirming the importance of early prevention and intervention efforts. Moreover, findings suggested that analyses of allostatic load and developmental theories accounting for its accrual would benefit from an inclusion of curvilinear associations in tested predictive models.

Direct and moderating links of salivary alpha-amylase and cortisol stress-reactivity to youth behavioral and emotional adjustment

Recent studies have revealed evidence for interactions between autonomic nervous system (ANS) activity, indexed by saliva alpha amylase (sAA), and hypothalamic–pituitary–adrenocortical activity, in predicting psychological functioning. The present study extends this work by examining individual differences in sAA and cortisol stress reactivity in relation to behavioral and emotional adjustment in youth. Participants were 56 healthy children (age 7–16). sAA, cortisol, and other physiological and affective responses were measured before, during, and after stressor tasks (either performance or peer rejection). Basal and stress responsive sAA and cortisol as well as their interactions were assessed in relation to externalizing and internalizing behaviors and trait anxiety. sAA was positively related to anxiety, while sAA reactivity moderated associations between cortisol reactivity and problem behavior. Results highlight the importance of measuring multiple physiological systems to elucidate mechanisms underlying behavioral and emotional dysregulation.

Behavioral and physiological correlates of stress related to examination performance in college chemistry students

This study was designed to assess physiological and behavioral correlates of academic stress during a college course in organic chemistry in the USA. Participants (45 females, 46 males, mean age 19.88 years) were screened for their basal hypothalamic–pituitary–adrenocortical activity using saliva samples collected at the beginning of the course and after each major test. Displacement activities (DAs) were observed during each test by videotaping students' behavior when they were taking the tests. These variables were then used as predictors of the students' achievement as measured by their grade point average (GPA) scores, American College Testing (ACT) scores, and their final grade in the class. Ninety-one students, enrolled in Organic Chemistry I at Marshall University during the summer of 2009, were recruited for this study. It was found that individual differences in the physiological stress responses are a factor in predicting the students' ability to pass a challenging class. A logistic model built on GPA, DAs during stress, and salivary hormone (cortisol and dehydroepiandrosterone) concentrations was able to correctly classify almost 90% of the students passing the class. The same model was not nearly as successful in determining the possible factors behind failing the class, because the classification success was just 52%, a figure close to chance. We conclude that a clear set of characteristics related to the students' ability and resilience to psychological stress are necessary to succeed in a challenging class. The reason behind dropping or failing a class could be less defined. These data indicated that investigating the physiological and behavioral propensities associated with psychological stress can help us better understand an individual's coping responses to a long-term challenging situation.

Visually detected NREM Stage 2 sleep spindles in kindergarten children are associated with stress challenge and coping strategies

Objectives. Sleep EEG spindles are linked to efficient cortical-subcortical connectivity and intellectual abilities. The aim of the present study was to investigate the relationship of spindle activity to psychosocial stress response and coping strategies in healthy kindergarten children. Methods. In a cross-sectional study of 41 5-year old kindergarten children we examined stress-induced hypothalamic-pituitary-adrenocortical (HPA) system activity by saliva cortisol measurements and sleep regulation by sleep EEG-monitoring. Stress response was measured during the application of a standardized psychological challenge appropriate at this age. NREM S2 sleep EEG spindles were visually scored and put into relation to coping and HPA activity parameters. Results. An increased total number of NREM S2 sleep spindles correlated positively with increased high ego-involvement strategies such as “positive emotions”. By contrast, total number of NREM S2 sleep spindles correlated negatively with low ego-involvement strategies such as “denial” and “avoidance”. Stress induced HPA-activity correlated positively with coping strategies with high ego-involvement; while there was no correlation with low ego-involvement strategies. Conclusions. Total number of visually detected NREM S2 sleep spindles is elevated in children with coping involving positive, high ego-involvement; in contrast, low ego-involvement during stress is associated with reduced total number of NREM S2 sleep spindles.

Cortisol response to individualised graded insulin infusions: a reproducible biomarker for CNS compounds inhibiting HPA activation

To determine the potential of cortisol secretion, in response to a physiological stressor, as a biomarker for centrally active compounds targeting the hypothalamic-pituitary-adrenocortical (HPA) axis. Cortisol response to hypoglycaemia was measured in 26 healthy males in two stages: firstly to derive an algorithm for individualized, graded insulin infusion rates to achieve defined hypoglycaemic targets over 3 h and secondly to determine the inter- and intra-subject variability of cortisol response to hypoglycaemia over two identical periods by measuring the maximum (t(max) ), time to maximum (C(max) ) response and cortisol area under the response curve (AUC). Hypoglycaemia induced a consistent cortisol response starting at approximately 1 h, corresponding to blood glucose concentrations of approximately 3.3 mmol l⁻¹, and peaking approximately 3 h after the start of infusion. The inter- and intra-subject coefficients of variation (CVs) of cortisol response were approximately 19 and 19% (AUC), 15 and 19 % (C(max) ) and 10 and 14% (t(max) ), respectively. The intra-subject CVs for the ratio of maximum cortisol response to baseline concentration and rate of initial cortisol response between study days were more variable (32.8% and 59.0%, respectively). The blood glucose-cortisol response model derived from the study was predictive of the individual observed cortisol responses, and estimated a blood glucose EC(50) associated with onset of the cortisol response of 3.3 mmol l⁻¹. Gradual hypoglycaemia is an effective, reproducible and well-tolerated method of stimulating a cortisol response and may therefore be useful in assessing the neuroendocrine response to HPA axis inhibitors, such as corticotropin-releasing hormone-1 (CRH-1) antagonists.

PCLO rs2522833 modulates HPA system response to antidepressant treatment in major depressive disorder

Variant rs2522833 of the Piccolo-encoding gene PCLO has recently been found to be associated with major depressive disorder (MDD). PCLO encodes a presynaptic cytomatrix protein which influences monoamine neurotransmitter release. Piccolo could therefore play an important role in treatment response to antidepressant therapy and the improvement of alterations in HPA system reactivity. We investigated the influence of the coding variant rs2522833 in the PCLO gene on treatment response in 205 in-patients with unipolar depression. Treatment response was measured (1) at the level of psychopathology using the Hamilton Depression Rating Scale (HAMD) and (2) with the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, which is a refined tool for showing dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system, a neurobiological finding in depression. While we did not find an association between variation in PCLO and HAMD scores, HPA dysregulation was less pronounced in carriers of the AA genotype than in carriers of one or two C alleles. HPA activity of individuals with the AA genotype only marginally changed during 4-wk antidepressant treatment, whereas C allele carriers showed a higher hormonal secretion at admission than carriers of the AA genotype but lower responsivity to the Dex/CRH challenge after 4 wk. Our results point to a moderating role of PCLO SNP rs2522833 on HPA regulation during antidepressant treatment, which may represent a neurobiological feature of stability of clinical response.

Central Deficiency of Corticotropin-Releasing Hormone Receptor Type 1 (CRH-R1) Abolishes Effects of CRH on NREM But Not on REM Sleep in Mice

Corticotropin-releasing hormone (CRH) is the major activator of the hypothalamic-pituitary-adrenocortical (HPA) system and orchestrates the neuroendocrine, autonomous as well as behavioral responses to stress. Many studies suggest an influence of CRH on sleep-wake regulation even in the absence of stressors. However, none of these studies yet clearly distinguished between central and peripheral effects of CRH. Therefore, we investigated in CNS-specific CRH receptor type 1 deficient mice whether centrally administered CRH could induce its sleep-wake modulatory effects without peripheral induction of HPA activity. Male mice (C57BL/6J, CNS-specific CRH-R1 knockout [CKO] mice and their control littermates [CL]) were intracerebroventricularily (i.c.v.) injected with vehicle or 3 different doses of CRH shortly before the beginning of the light period. Electroencephalogram (EEG) and electromyogram (EMG) were monitored to compare the effects of CRH on vigilance states with or without presence of central CRH-R1. To quantify HPA-axis reactivity to CRH injections in CKO and CL animals, blood samples were analyzed to determine plasma corticosterone concentrations. I.c.v. injections of CRH promoted wakefulness while decreasing NREMS in C57BL/6J and CRH-R1 CL animals, whereas such changes were not exerted in CKO mice. However, REMS suppression after CRH application persisted in all animals. I.c.v. injected CRH increased plasma corticosterone levels in both CL and CKO mice. The results demonstrated that CRH has a major impact on wake and NREMS regulation which is predominantly mediated through central CRH-R1. Peripheral actions of CRH, i.e., elevated HPA activity, may interfere with its central effects on REMS but not on NREMS suppression.

Sleep actigraphy pattern and behavioral/emotional difficulties in kindergarten children: Association with hypothalamic-pituitary-adrenocortical (HPA) activity

Background Various studies of adult endocrinology and sleep show close connections between poor sleep quality, deterioration of the HPA axis and negative psychological characteristics. However, the extent to which these associations may have already emerged and developed in childhood remains unclear. Methods A total of 82 preschoolers (age 4.91 ± 0.48) underwent activity monitoring for seven consecutive days and nights, wearing a digital movement-measuring instrument. Additionally, on the first and on the last morning of sleep registration, the activity of the HPA axis was assessed via the amount of cortisol in the saliva. Psychological and behavioral assessments were also made. Results Three sub-groups of good (22%), normal (58.5%) and poor (19.5%) sleepers were distinguished. Poor sleep patterns were associated with higher HPA activity and with behavioral/emotional difficulties. Conclusions The interplay between unfavorable sleep patterns, deterioration of the HPA axis and behavioral/emotional difficulties is already apparent in pre-school children.

Long-term anxiolytic and antidepressant-like behavioural effects of tiagabine, a selective GABA transporter-1 (GAT-1) inhibitor, coincide with a decrease in HPA system activity in C57BL/6 mice

Gamma-aminobutyric acid (GABA) system plays a pivotal role in the pathophysiology of anxiety and mood disorders. This study was aimed to assess the anxiolytic and antidepressant-like properties of tiagabine, an inhibitor of the GABA transporter-1 (GAT-1), after acute and chronic administration in C57BL/6JOlaHsD mice with paroxetine as a positive control. In first experiments, the acute administration of tiagabine (7.5 mg/kg, orally [PO]) and paroxetine (10 mg/kg PO) induced anxiolytic effects in the elevated plus maze test and the modified hole board test and an antidepressant-like effect in the forced swim test. Chronic application of tiagabine (7.5 mg/kg PO) and paroxetine (10 mg/kg PO) for 22 days revealed an anxiolytic and antidepressant-like efficacy of tiagabine only. In a further experiment, we analysed the impact of chronic tiagabine versus paroxetine treatment on the hypothalamic-pituitary-adrenocortical (HPA) system regulation. GAT-1 blockade induced a setpoint-shift of the stress hormone system toward lower levels as indicated by decreased plasma corticosterone concentrations and attenuated gene expression levels of corticotropin-releasing factor in the paraventricular nucleus of the hypothalamus and of hippocampal steroid receptors. This data indicate that both acute and long-term anxiolytic and antidepressant-like properties of brain GAT-1 inhibition coincide with a reduction in HPA system activity in mice.

Coregulation in Salivary Cortisol During Maternal Holding of Premature Infants

The purpose of this study was to examine coregulation between mothers and preterm infants in hypothalamic-pituitary-adrenocortical (HPA) system activity, as indicated by salivary cortisol levels, while mothers held their infants. The research questions were (a) does mother-infant coregulation in HPA activity occur during holding? and (b) if mother- infant coregulation in HPA activity exists during holding, do type of holding, antenatal steroids, sound level, and maternal touch influence this coregulation? The sample consisted of 20 mother- infant dyads with infants at a mean postconceptional age of 34.7 weeks (+0.7) and average postnatal age of 15 days (+9) at the time of cortisol sampling. The design was exploratory using convenience sampling. Maternal and infant cortisol levels were obtained at Time 1 (baseline) and Time 2 (end of holding); at each time, the absolute differences in levels between mother and infant were determined. Coregulation was operationalized as less difference between maternal-infant cortisol levels immediately after holding (Time 2) as compared to before holding (Time 1). The two variables with the highest correlation with the Time 1/Time 2 difference score included antenatal steroids and ambient sound level, which were entered into a linear regression equation as predictor variables. A coregulatory relationship in cortisol levels existed between mothers and infants during holding, which was moderated by sound levels. Nurses in the neonatal intensive care unit (NICU) can facilitate the mother-infant relationship, as reflected in coregulatory measures, by promoting a quiet environment, particularly around mothers who are holding their infants.

Comparison Of Stress Response Performing Endotracheal Intubation By Direct Laryngoscopy, Fibreoptic Intubation And Intubation By The Glidescope Laryngoscope

Comparison Of Stress Response Performing Endotracheal Intubation By Direct Laryngoscopy, Fibreoptic Intubation And Intubation By The Glidescope Laryngoscope Stress response is regulated by two primary neuroendocrine systems—the hypothalamuspituitary- adrenocortical (HPA) and sympathetic adrenomedullary (SAM) systems. Salivary alphaamylase (AA) levels can be used as an index of the SAM activity, and serum cortisol as an index of HPA activity. The aim of the study was to compare patient stress response to different intubation techniques. Sixty adult patients, ASA I-III, scheduled for elective abdominal surgery were included in this study, with median age of 54±18 years. Patients were prospectively randomly divided into three groups-intubation with a GlideScope (GS), Macintosh laringoscope (ML) and PENTAX fibreoptic bronchoscope (FB). After preoxygenation for 3 min anaesthesia was induced with fentanyl 2 mkg/kg, mivacuronium 0.2 mg/kg and propofol 2 mg/kg, injected intravenously over 20 seconds. Intubation was started 2 min after mivacuronium injection. Anaesthesia was maintained with sevoflurane 1-2 vol% and fentanyl 1 mkg/kg as needed. Intubation time (IT) was measured, blood and saliva samples were collected before and shortly after intubation. Haemodynamic response was recorded. Intubation time was statistically significantly longer in the FB group (120±65 s) versus the ML group (29±5 s) and GS group (26±9 s), P < 0.05. In the three patients groups the initial AA level was similar (54±20 KU/ml, P > 0.05). In GS patients the alpha amylase level after intubation significantly decreased (42±15 KU/ml, P < 0.05), but in ML and FB patients—significantly increased (68±24 KU/ml and 73±32 KU/ml, respectively, P < 0.05). After intubation, blood cortisol did not differ between the ML (377±181 U/ml) and GS (484±61 U/ml) patient groups, but was significantly higher (P < 0.05) in the FB group (530±79 U/ml). Both heart rate and blood pressure increased during intubation, the difference between groups was not significant. All intubations were successful, but in the FB patient group IT was significantly longer than in the ML and GS patient group. IT in the GS and FB patient groups did not statistically significantly differ. In our opinion, shorter and more confident intubations with a GlideScope produce less nociceptive stimulus and less stress to the patient. Intubations using GlideScope videolaryngoscope causes lesser stress response in comparison to intubation with a Macintosh laryngoscope or fibreoptic bronchoscope.

Noradrenaline and cortisol changes in response to low-grade cognitive stress differ in migraine and tension-type headache

The goal of this study was to explore the relationship between indicators of sympathoneural, sympathomedullar and hypothalamic-pituitary-adrenocortical (HPA) activity and stress-induced head and shoulder-neck pain in patients with migraine or tension-type headache (TTH). We measured noradrenaline, adrenaline and cortisol levels before and after low-grade cognitive stress in 21 migraineurs, 16 TTH patients and 34 controls. The stressor lasted for 60 min and was followed by 30 min of relaxation. Migraine patients had lower noradrenaline levels in blood platelets compared to controls. Pain responses correlated negatively with noradrenaline levels, and pain recovery correlated negatively with the cortisol change in migraineurs. TTH patients maintained cortisol secretion during the cognitive stress as opposed to the normal circadian decrease seen in controls and migraineurs. There may therefore be abnormal activation of the HPA axis in patients with TTH when coping with mental stress, but no association was found between pain and cortisol. A relationship between HPA activity and stress in TTH patients has to our knowledge not been reported before. In migraine, on the other hand, both sympathoneural activation and HPA activation seem to be linked to stress-induced muscle pain and recovery from pain respectively. The present study suggests that migraineurs and TTH patients cope differently with low-grade cognitive stress.

Acute psychosocial challenge and cardiac autonomic response in women: The role of estrogens, corticosteroids, and behavioral coping styles

Theoretical statements, as well as clinical and experimental data, suggest that the amplitude of cardiovascular reactivity to acute stressors can be a good predictor of preclinical and clinical cardiovascular states. The aim of the present study is to investigate the role of estrogens, the hypothalamic-pituitary-adrenocortical activity, and the behavioral profile in individual cardiac autonomic reactivity to brief laboratory stressors in women. Thirty-six adult, healthy women were exposed to a stress interview and a mental task test, each lasting 5 min. They were assigned to two experimental groups: D4, i.e. 4 days after menses beginning (follicular phase, n=18), and D14, i.e. 14 days after menses beginning (ovulatory phase, n=18). The cardiac measurements in the baseline, stress and recovery periods consisted in heart rate (average R-R interval) and parasympathetic tone (r-MSSD) quantification, while the HPA axis activity and stress reactivity were assessed via plasma cortisol and dehydroepiandrosterone concentrations. The ethological profile during the interview was drawn by means of non-verbal behavior analysis. The cardiac, adrenocortical and behavioral responses to the two stressors were similar in groups D4 and D14, despite significantly higher estradiol levels in the latter. Subjects with higher pre-stress cortisol levels had higher heart rate and lower vagal activity in the baseline, stress and recovery phases. Women showing higher level of submission were characterized by higher heart rate acceleration and vagal withdrawal during both the interview and the recovery phase. In addition, the subjects that exhibited greater displacement during the interview were also characterized by lower heart rate increments and less pronounced vagal suppression during post-stress recovery. In conclusion, the present results do not support a clear buffering role of estrogens in cardiovascular response to acute stressors. However, they confirm that baseline HPA axis activity can be predictive of cardiac autonomic activity and stress responsiveness. They also highlight the modulating role of the individual style of behavioral coping in cardiac sympathovagal stress reactivity. Therefore, the objective assessment of the individual behavioral profile via the analysis of non-verbal communication patterns might represent a powerful tool for identifying subjects with higher risk of cardiac events.