Gloria-Beatrice Wintermann

Blunted salivary and plasma cortisol response in patients with panic disorder under psychosocial stress

BACKGROUND Panic disorder (PD) has been associated with an altered activity of the hypothalamic-pituitary-adrenal-cortical (HPA) axis. Recent findings from a patient sample with PD with secondary depression on psychotropic medication using salivary cortisol as outcome measure suggest a non-responsiveness of the HPA-axis under acute psychosocial stress. Salivary cortisol does not necessarily reflect the total plasma cortisol due to interfering variables. Whether the present findings can be replicated on a patient sample with pure PD using both salivary cortisol and total plasma cortisol as outcome variables remains to be elucidated. METHODS For this study, the Trier Social Stress Test (TSST) was implemented to assess the HPA-axis reactivity indicated by the plasma adreno-corticotropin-hormone (ACTH), plasma cortisol, and salivary cortisol release. The sample included 32 patients diagnosed with PD in a Structured Clinical Interview (SCID). Twelve male and fifteen female patients [mean age=32.87years, SD=11.23] were matched with 32 healthy controls by age and gender. RESULTS The plasma ACTH, total plasma cortisol and salivary cortisol release increased significantly in both groups due to the psychosocial stress test. The patients with PD showed a decreased plasma and salivary cortisol response as compared to the healthy controls. Plasma cortisol and salivary cortisol were highly correlated in both groups. CONCLUSION These findings provide strong evidence for a hypo-responsiveness of the HPA-axis as measured in both blood and saliva. Salivary and total plasma cortisol showed a strong concordance of results. Thus, future investigations could consider salivary cortisol as reliable marker of the HPA-axis under psychosocial stress.

Dissociation between ACTH and cortisol response in DEX–CRH test in patients with panic disorder

BACKGROUND Panic disorder (PD) has been associated with the altered circadian rhythm of the hypothalamic-pituitary-adrenocortical (HPA) axis. The findings regarding the stress-specific functioning of the HPA-system are inconsistent. It is also unclear whether the HPA-system response after the Corticotropin-Releasing-Hormone (CRH) challenge becomes altered. METHODS For this study, the dexamethasone-corticotropin-releasing-hormone (DEX-CRH) test was implemented to assess the HPA-axis reactivity indicated by the plasma adreno-corticotropin-hormone (ACTH) and the cortisol release. The sample included 32 patients diagnosed with PD in a Structured Clinical Interview (SCID). Fourteen male and eighteen female patients, [mean age = 33.50 years, SD = 12.76] were matched with 32 healthy controls by age and gender. Moreover, a sample of patients with unipolar depression (n = 21, ten females) was examined as a clinical control group. RESULTS In healthy controls as well as in patients with PD and patients with unipolar depression, the ACTH and the cortisol response increased significantly due to the CRH injection after dexamethasone pre-treatment. There were differences between the healthy controls and the patients with PD in the plasma cortisol response pattern, however, not in the ACTH. The patients with PD showed a decreased CRH-induced plasma cortisol response. A median-split gave evidence that patients suffering from PD longer than two years showed a remarkably higher HPA-axis reactivity under CRH-injection than patients suffering from PD two years or less. CONCLUSION These findings provide strong evidence that patients with PD show some dissociation between ACTH and cortisol response under the DEX-CRH test with strong indicators that the length of the duration of the psychopathology is a risk factor for an increased reactivity of the HPA-axis in patients with PD.

Stress disorders following prolonged critical illness in survivors of severe sepsis.

Objectives:To examine the frequency of acute stress disorder and posttraumatic stress disorder in chronically critically ill patients with a specific focus on severe sepsis, to classify different courses of stress disorders from 4 weeks to 6 months after transfer from acute care hospital to postacute rehabilitation, and to identify patients at risk by examining the relationship between clinical, demographic, and psychological variables and stress disorder symptoms. Design:Prospective longitudinal cohort study, three assessment times within 4 weeks, 3 months, and 6 months after transfer to postacute rehabilitation. Setting:Patients were consecutively enrolled in a large rehabilitation hospital (Clinic Bavaria, Kreischa, Germany) admitted for ventilator weaning from acute care hospitals. Patients:We included 90 patients with admission diagnosis critical illness polyneuropathy or critical illness myopathy with or without severe sepsis, age between 18 and 70 years with a length of ICU stay greater than 5 days. Interventions:None. Measurements and Main Results:Acute stress disorder and posttraumatic stress disorder were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria by a trained and experienced clinical psychologist using a semistructured clinical interview for Diagnostic and Statistical Manual of Mental Disorders. We further administered the Acute Stress Disorder Scale and the Posttraumatic Symptom Scale-10 to assess symptoms of acute stress disorder and posttraumatic stress disorder. Three percent of the patients had an acute stress disorder diagnosis 4 weeks after transfer to postacute rehabilitation. Posttraumatic stress disorder was found in 7% of the patients at 3-month follow-up and in 12% after 6 months, respectively. Eighteen percent of the patients showed a delayed onset of posttraumatic stress disorder. Sepsis turned out to be a significant predictor of posttraumatic stress disorder symptoms at 3-month follow-up. Conclusions:A regular screening of post-ICU patients after discharge from hospital should be an integral part of aftercare management. The underlying mechanisms of severe sepsis in the development of posttraumatic stress disorder need further examination.

Altered Olfactory Processing of Stress-Related Body Odors and Artificial Odors in Patients with Panic Disorder

Background Patients with Panic Disorder (PD) direct their attention towards potential threat, followed by panic attacks, and increased sweat production. Onés own anxiety sweat odor influences the attentional focus, and discrimination of threat or non-threat. Since olfactory projection areas overlap with neuronal areas of a panic-specific fear network, the present study investigated the neuronal processing of odors in general and of stress-related sweat odors in particular in patients with PD. Methods A sample of 13 patients with PD with/ without agoraphobia and 13 age- and gender-matched healthy controls underwent an fMRI investigation during olfactory stimulation with their stress-related sweat odors (TSST, ergometry) as well as artificial odors (peach, artificial sweat) as non-fearful non-body odors. Principal Findings The two groups did not differ with respect to their olfactory identification ability. Independent of the kind of odor, the patients with PD showed activations in fronto-cortical areas in contrast to the healthy controls who showed activations in olfaction-related areas such as the amygdalae and the hippocampus. For artificial odors, the patients with PD showed a decreased neuronal activation of the thalamus, the posterior cingulate cortex and the anterior cingulate cortex. Under the presentation of sweat odor caused by ergometric exercise, the patients with PD showed an increased activation in the superior temporal gyrus, the supramarginal gyrus, and the cingulate cortex which was positively correlated with the severity of the psychopathology. For the sweat odor from the anxiety condition, the patients with PD showed an increased activation in the gyrus frontalis inferior, which was positively correlated with the severity of the psychopathology. Conclusions The results suggest altered neuronal processing of olfactory stimuli in PD. Both artificial odors and stress-related body odors activate specific parts of a fear-network which is associated with an increased severity of the psychopathology.

Chewing after stress: psychosocial stress influences chewing frequency, chewing efficacy, and appetite.

BACKGROUND Psychosocial stress is accompanied by an increase in the activity of the hypothalamic-pituitary-adrenocortical (HPA)-axis and by an increase in food intake. At present, no studies have been conducted to examine the impact of a potent laboratory stress test on the chewing frequency. METHODS Thirty-one healthy participants (14 females, mean age 27.13) were compared after they had fulfilled the protocol of a standardized psychosocial stress test, the Trier Social Stress Test (TSST), and after a resting condition of silent reading in reference to their chewing frequency, chewing efficacy, food intake, and eating preferences. As part of the design free salivary cortisol levels and heart rate variability were measured repeatedly before and after the TSST and the resting condition. RESULTS After the TSST, the participants exhibited a significantly higher mean chewing frequency than after the resting condition (F(2,60)=3.600, p=.035, η(2)=.107). The testing condition had no influence on the amount of food intake. Following the psychosocial stress, however, the participants reported a significantly less general appetite (Z=-3.921, p<.001) and less of an appetite for eggs (Z=-2.023, p=.043) than after their resting condition. No correlation was found between the salivary cortisol response and the chewing frequency. CONCLUSION The results indicated that psychosocial stress is associated with an increase in chewing frequency, as measured with a sound-based apparatus, and with a decrease in appetite.

Salivary alpha-amylase response following repeated psychosocial stress in patients with panic disorder

BACKGROUND This study examined autonomic responses (salivary alpha-amylase, sAA; heart rate, HR) to repeated psychosocial stress as a candidate mechanism linking autonomic hyper-arousal and sensitization to the occurrence of panic disorder (PD). METHODS Thirty-three patients with PD and 34 healthy controls were exposed to the Trier Social Stress Test (TSST) twice on consecutive days. RESULTS sAA changes were comparable between PD and controls on both testing days with overall decreasing sAA responses (delta) on day two. In contrast, HR delta increased on day two in both groups. This sensitization was driven by female controls while male PD showed most pronounced HR changes to the first TSST. CONCLUSIONS Overall, a general autonomic hyper-arousal in PD could not be confirmed. In contrast, sAA responses slightly habituated to repeated stress. Whether sAA findings mirror assumed habituation effects of repeated stress exposure on normalizing autonomic reactivity remains to be investigated in longitudinal studies.

Predisposition or side effect of the duration: the reactivity of the HPA-axis under psychosocial stress in panic disorder.

BACKGROUND Panic disorder (PD) has been associated with an altered reactivity of the hypothalamic–pituitary–adrenocortical (HPA) system under psychosocial stress. Until now it remains unclear whether a diminished cortisol release is an early risk factor predisposing for PD or a consequence of PD. In order to unravel this point, the present study compares the cortisol secretion between patients with a recent onset and a chronic course of PD. METHODS The Trier Social Stress Test (TSST) was applied in patients with a duration of PD ≤ 1.5 years (N = 35), patients with a duration of PD > 1.5 years (N = 56) and healthy controls (N = 95). Salivary cortisol and heart rate (HR) were assessed as primary outcomes. RESULTS According to baseline cortisol/baseline HR and HR response there was no significant difference. Both patient groups (≤ 1.5/> 1.5 years) showed a blunted cortisol response with no significant group difference. In multiple linear regression models the attenuation of the HPA-axis was largely accounted for by group, smoking status, use of contraceptive pill and the interaction group by gender. Female patients with a chronic course showed the lowest cortisol response under the TSST. CONCLUSIONS It might be assumed that a decreased reactivity of the HPA-axis could be considered as etiological risk factor in the preliminary stages of PD. Above, female gender, smoking status and the use of contraceptive pill seem to further moderate the attenuated HPA-axis response pattern in patients with PD.

Pre-hospital discharge testing of defibrillator without anesthesia: effects on psychological symptoms during clinical follow-up.

Objective After the implantation of an implantable cardioverter-defibrillator (ICD), patients often fear therapeutic shock. The extent to which the experience of pre–hospital discharge (PHD) testing without anesthesia after ICD implantation, under observation by a physician, affects shock-related anxiety symptoms on follow-up has not been investigated as yet. Methods In a prospective, randomized controlled trial, 44 patients with a primary prevention indication for an ICD were randomly assigned to experience PHD testing without anesthesia (n = 23) or with anesthesia (n = 21). Patients were longitudinally evaluated before (T1), shortly after (T2), and 3 months after (T3) PHD testing. During the respective PHD testings, the course of patients’ serum cortisol release was measured. Results During PHD testing, patients without anesthesia showed a significantly higher serum cortisol release than patients with anesthesia (F(4,152) = 22.227, p < .001). Patients who experienced PHD testing without anesthesia felt significantly safer with the ICD (U = 165.000, p = .040), would significantly more often recommend other patients to undergo PHD testing without anesthesia (&khgr;2 = 12.013, p = .002), and showed significantly lower levels of general shock-related anxiety shortly afterward (F(1,42) = 6.327, p = .02) and 3 months after PHD testing (F(1,41) = 8.603, p = .005). Conclusions The implementation of PHD testing without anesthesia is associated with lower anxiety concerning therapeutic shock. Patients should be advised about the effects of PHD testing without anesthesia on their psychological well-being in the long run.

Predictors of Major Depressive Disorder following Intensive Care of Chronically Critically Ill Patients

Objective Major depressive disorder (MDD) is a common condition following treatment in the Intensive Care Unit (ICU). Long-term data on MDD in chronically critically ill (CCI) patients are scarce. Hence, the primary aim of the present study was to investigate the frequency and predictors of MDD after intensive care of CCI patients. Materials and Methods In a prospective cohort study, patients with long-term mechanical ventilation requirements (n=131) were assessed with respect to a diagnosis of MDD, using the Structured Clinical Interview for DSM-IV, three and six months after the transfer from acute ICU to post-acute ICU. Sociodemographic, psychological, and clinical risk factors with p values ≤ 0.1 were identified in a univariate logistic regression analysis and entered in a multivariable logistic regression model. A mediator analysis was run using the bootstrapping method, testing the mediating effect of perceived helplessness during the ICU stay, between the recalled traumatic experience from the ICU and a post-ICU MDD. Results 17.6% (n=23) of the patients showed a full- or subsyndromal MDD. Perceived helplessness, recalled experiences of a traumatic event from the ICU, symptoms of acute stress disorder, and the diagnosis of posttraumatic stress disorder (PTSD) after ICU could be identified as significant predictors of MDD. In a mediator analysis, perceived helplessness could be proved as a mediator. Conclusions Every fifth CCI patient suffers from MDD up to six months after being discharged from ICU. Particularly, perceived helplessness during the ICU stay seems to mainly affect the long-term evolvement of MDD. CCI patients with symptoms of acute stress disorder/PTSD should also be screened for MDD.

Risk Factors of Delayed Onset Posttraumatic Stress Disorder in Chronically Critically Ill Patients

Abstract The main aim of this study was to investigate factors associated with a delayed-onset posttraumatic stress disorder (PTSD) after the intensive care unit (ICU) treatment of patients with a chronic critical illness (CCI). Patients (n = 97) with critical illness polyneuropathy or critical illness myopathy were interviewed via the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. The diagnosis of the acute stress disorder was assessed within 1 month (t1), the diagnosis of PTSD at 3 (t2) and 6 (t3) months after transfer from the acute care ICU to the post-acute ICU. Patients showing a delayed-onset or persistent course of PTSD were subsumed in one group; 24.7% (n = 24) showed a delayed-onset PTSD. Significant risk factors were as follows: the severity of the medical illness, the perceived fear of dying at the ICU, the number of traumatic memories from the ICU, and the presence of a coronary heart disease. Every fourth patient with CCI showed a delayed-onset PTSD up to 6 months after the ICU treatment. Markers for a delayed-onset PTSD should already be assessed at the time of discharge from the ICU.