Psychosocial stress affects the change of mental distress under dermatological treatment-A prospective cohort study in patients with psoriasis.

Psoriasis is a chronic-inflammatory, immune-mediated disease leading to a state of increased systemic inflammation. Mental comorbidities often occur in the patients and may additionally affect the therapy outcome. Currently, it is unknown whether the disease severity, psychosocial stress or health-related quality of life determines the manifestation of anxiety/depression, or vice versa, in psoriasis. The interplay between these variables during the dermatological treatment of psoriasis remains to be elucidated in order to initiate appropriate psychological interventions and to identify patients at risk for comorbid anxiety/depression. In a prospective cohort study, the impact of disease severity, health-related quality of life and psychosocial stress on anxiety/depression were examined during the dermatological treatment in patients with moderate to severe psoriasis (patients with psoriasis = PSO). Patients were examined before (T1) and about 3 months after (T2) the beginning of a new treatment episode, in most cases by means of systemic therapy. Data were analysed, exploratory, using Bivariate Latent Change Score Models and mediator analyses. Assessments included patient-reported outcomes (Hospital Anxiety and Depression Scale/HADS, Perceived Stress Scale/PSS, Childhood Trauma Questionnaire/CTQ, Dermatology Life Quality Index-DLQI, Body Surface Area-BSA), at both T1 and T2. 83 PSO patients (37.3% women, median age 53.7, IQR 37.8-62.5, median BSA 18.0, IQR 9.0-40.0) with complete data of HADS and DLQI were included. In the total group, a higher anxiety/depression at T1 was associated with a lower improvement in psoriasis severity in the course of the dermatological treatment (γBSA  = 0.50, p < 0.001). In subgroups of PSO with low/high CTQ scores, anxiety/depression at T1 had no impact on the change in psoriasis severity. Only by tendency, in CTQ subgroups, a higher psoriasis severity at T1 was linked with a higher improvement in anxiety/depression at T2 (low/high CTQ, γHADS  = -0.16/-0.15, p = 0.08). An improvement in the health-related quality of life was positively associated with an improvement in anxiety/depression (Pearson's r = 0.49, p = 0.02). Here, the reduction of acute psychosocial stress seems to be a decisive factor, mediating this association (ß = 0.20, t [2,60] = 1.87; p = 0.07, 95% CI -0.01, 0.41). The results allude, that the initial severity of anxiety/depression may presumably have an impact on the treatment outcome in the total group. In contrast, analysing subgroups of patients with high/low childhood trauma, the impact of the initial disease severity on the course of anxiety/depression after a switch to a new dermatological treatment could not be conclusively ruled out. The latter results from the latent change score modelling should be treated cautiously because of the small sample size. A common aetiopathological mechanism for psoriasis and anxiety/depression might be assumed with impact of dermatological treatment on both. The change in perceived stress seems to play an important role in the manifestation of anxiety/depression, substantiating the need for adequate stress management in patients with increased psychosocial stress during their dermatological treatment.

Mental distress of physicians in the outpatient care throughout the COVID-19 pandemic: emotional and supportive human relations matter - Cross-sectional results of the VOICE-study.

BACKGROUND: The aim of this cross-sectional study was to evaluate the course of self-reported mental distress and quality of life (QoL) of physicians, working in the outpatient care (POC). Outcomes were compared with a control group of physicians working in the inpatient care (PIC), throughout the Corona Virus Disease (COVID)-19 pandemic. The impact of risk and protective factors in terms of emotional and supportive human relations on mental distress and perceived QoL of POC were of primary interest. METHODS: Within the largest prospective, multi-center survey on mental health of health care workers (HCW), conducted during the first (T1) and second (T2) wave of the COVID-19 pandemic in Europe, we investigated the course of current burden (CB), depression (Patient Health Questionnaire-2), anxiety (Generalized Anxiety Disorder-2) and QoL, cross-sectionally, in n = 848 POC (T1: n = 536, T2: n = 312). The primary outcomes were compared with an age- and gender-matchted control group of n = 458 PIC (T1: n = 262, T2: n = 196). COVID-19-, work-related, social risk and protective factors were examined. RESULTS: At T1, POC showed no significant differences with respect to CB, depression, anxiety, and QoL, after Bonferroni correction. Whereas at T2, POC exhibited higher scores of CB (Cohen´s d/ Cd = .934, p < .001), depression (Cd = 1.648, p < 001), anxiety (Cd = 1.745, p < .001), work-family conflict (Cd = 4.170, p < .001) and lower QoL (Cd = .891, p = .002) compared with PIC. Nearly all assessed parameters of burden increased from T1 to T2 within the cohort of POC (e.g. depression: CD = 1.580, p < .001). Risk factors for mental distress of POC throughout the pandemic were: increased work-family conflict (CB: ß = .254, p < .001, 95% CI: .23, .28; PHQ-2: ß = .139, p = .011, 95% CI: .09, .19; GAD-2: ß = .207, p < .001, 95% CI: .16, .26), worrying about the patients´ security (CB: ß = .144, p = .007, 95% CI: .07, .22; PHQ-2: ß = .150, p = .006, 95% CI: .00, .30), fear of triage situations (GAD-2: ß = .132, p = .010, 95% CI: -.04, .31) and burden through restricted social contact in spare time (CB: ß = .146, p = .003, 95% CI: .07, .22; PHQ-2: ß = .187, p < .001, 95% CI: .03, .34; GAD-2: ß = .156, p = .003, 95% CI: -.01, .32). Protective factors for mental distress and QoL were the perceived protection by local authorities (CB: ß = -.302, p < .001, 95% CI: -.39, -.22; PHQ-2: ß = -.190, p < . 001, 95% CI: -.36, -.02; GAD-2: ß = -.211, p < .001, 95% CI: -.40, -.03; QoL: ß = .273, p < .001, 95% CI: .18, .36), trust in colleagues (PHQ-2: ß = -.181, p < .001, 95% CI: -.34, -.02; GAD-2: ß = -.199, p < .001, 95% CI: -.37, -.02; QoL: ß = .124, p = .017, 95% CI: .04, .21) and social support (PHQ-2: ß = -.180, p < .001, 95% CI: -.22, -.14; GAD-2: ß = -.127, p = .014, 95% CI: -.17, -.08; QoL: ß = .211, p < .001, 95% CI: .19, .23). CONCLUSIONS: During the pandemic, the protective role of emotional and supportive human relations on the mental distress and quality of life of POC should be taken into account more thoroughly, both in practice and future research.

Rates and predictors of mental health care utilisation in patients following a prolonged stay on intensive care unit: a prospective cohort study.

OBJECTIVES: An acute critical illness and secondary complications may necessitate a prolonged treatment on an intensive care unit (ICU). As long-term consequences, ICU survivors may suffer from both physical and psychological sequelae. To improve the aftercare of these patients, the present study aimed to assess the use of mental healthcare and associated factors following prolonged ICU stay. METHODS: N=197 patients with a primary diagnosis of critical illness polyneuropathy/myopathy were enrolled within 4 weeks (T1) and interviewed three (T2) and six (T3) months following the transfer from acute-care to postacute ICU. Symptoms and a current diagnosis of major depression/post-traumatic stress disorder (PTSD) were assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders. The potential need for mental healthcare, its current and past use and reasons for non-use were raised. RESULTS: Full syndromal and subsyndromal major depression/PTSD were diagnosed in 8.3%/15.6% at T2, 12.2%/23.5% at T3. About 29% of the patients reported mental healthcare utilisation. Considering somatic complaints, more important was a common reason for the non-use of mental healthcare. Female gender, previous mental healthcare, number of sepsis episodes and pension receipt increased the chance for mental healthcare utilisation, a pre-existing mental disorder decreased it. CONCLUSION: Every fourth patient surviving prolonged ICU treatement makes use of mental healthcare . Particularly male patients with pre-existing mental disorders should be targeted preventively, receiving specific psychoeducation about psychological long-term sequelae and mental healthcare options post-ICU.Trial registration numberDRKS00003386.

Cortisol response under low intensity exercise during cognitive-behavioral therapy is associated with therapeutic outcome in panic disorder-an exploratory study.

OBJECTIVES: Patients with Panic Disorder (PD) show an abnormal stress-induced functioning of the Hypothalamic-Pituitary-adrenal (HPA)-axis. Different protocols for stress induction are of rather low relevance for the psychotherapeutic treatment. In practice, interoceptive exposure is often realized as Low Intensity Exercise (LIE), as compared to an incremental cycle exercise test to exhaustion. Currently, it is not known, whether LIE displays an effective interoceptive stressor 1.) leading to a significant anxiety induction; 2.) a comparable HPA- and Sympathetic-Adreno-Medullar (SAM)-axis response in both patients and healthy controls; 3.) stress responses under LIE are associated with treatment outcomes. PATIENTS AND METHODS: N = 20 patients with PD and n = 20 healthy controls were exposed to ten minutes of LIE on an exercise bike. LIE was applied as part of the interoceptive exposure, during an intensive Cognitive-Behavioral Therapy (CBT) in a day clinic. Heart rate was monitored and salivary cortisol samples collected. Before and after the LIE, state anxiety/ arousal were assessed. In order to evaluate psychopathology, the Panic and Agoraphobia Scale, Mobility Inventory, Agoraphobic Cognitions Questionnaire and Body Sensations Questionnaire were applied, before (T1) and after five weeks (T2) of an intensive CBT. RESULTS: LIE led to a significant and similar heart rate increase in both groups. Cortisol decreased over time in both groups, especially in male patients. A higher psychopathology before, and after CBT, was associated with a significantly lower cortisol response under LIE. CONCLUSIONS: In the present study, LIE led to a divergent stress response: while there was a significant heart rate increase, cortisol decreased over time, particularly in male patients. A lower reactivity of the HPA-axis seems to be associated with a lower treatment outcome, which may affect extinction based learning. The findings suggest, that interoceptive stimuli should be designed carefully in order to be potent stressors.

Childhood Trauma and Psychosocial Stress Affect Treatment Outcome in Patients With Psoriasis Starting a New Treatment Episode.

Objective: Traumatic childhood experiences and psychosocial stress may predispose the evolvement of somatic diseases. Psoriasis is a multifactorial chronic inflammatory skin disease that often associates with current and past stress. Both may entail pathological alterations in major stress axes and a balance shift in the level of T helper type 1 (Th1) and 2 (Th2) cytokines, affecting the development and course of psoriasis. Until now, it is unclear whether traumatic stress experiences during the childhood or current stress are more frequent in psoriatic compared to skin-healthy individuals, and if they interact with treatment outcome. Method: In a prospective cohort study, the impact of acute and early childhood stress on the course of dermatological treatment were studied in patients with moderate to severe psoriasis (PSO). Patients were examined before (T1) and about 3 months after (T2) the beginning of a new treatment episode. Assessments included clinical outcomes (Psoriasis Area and Severity Index-PASI, Structured Clinical Interview SCID-I) and patient-reported outcomes (PRO) (Childhood Trauma Questionnaire-CTQ, Perceived Stress Scale-PSS, itching/scratching, Dermatology Life Quality Index-DLQI, Hospital Anxiety and Depression Scale, Body Surface Area, Self-Administered PASI). Results: N = 83 PSO patients (median age 53.7, IQR 37.8, 62.5) and n = 66 skin-healthy control subjects (HC) (median age 51.5, IQR 33.3, 59.2) participated. PSO had higher CTQ physical neglect than HC, as well as higher PRO levels. The positive impact of improved skin on the skin-related quality of life was moderated by the perceived stress. Acute stress at T1 had a positive effect both on the skin severity and the skin-related quality of life. CTQ total closely interacted with baseline psoriasis severity, and was associated with higher improvement from T1 to T2. Conclusion: One might tentatively conclude, that chronic psychosocial stressors like childhood maltreatment may predispose the manifestation of psoriasis. The latter may be amplified by acute psychological stressors. In addition, the present evidence suggests that systemic therapies work well in PSO, with childhood trauma and acute psychosocial stress. Both should therefore be routinely assessed and addressed in PSO.

Single assessment of delirium severity during postacute intensive care of chronically critically ill patients and its associated factors: post hoc analysis of a prospective cohort study in Germany.

OBJECTIVES: To assess the delirium severity (DS), its risk factors and association with adverse patient outcomes in chronically critically ill (CCI) patients. DESIGN: A prospective cohort study. SETTING: A tertiary care hospital with postacute intensive care units (ICUs) in Germany. PARTICIPANTS: N=267 CCI patients with critical illness polyneuropathy and/or critical illness myopathy, aged 18-75 years, who had undergone elective tracheotomy for weaning failure. INTERVENTIONS: None. MEASURES: Primary outcomes: DS was assessed using the Confusion Assessment Method for the Intensive Care Unit-7 delirium severity score, within 4 weeks (t1) after the transfer to a tertiary care hospital. In post hoc analyses, univariate linear regressions were employed, examining the relationship of DS with clinical, sociodemographic and psychological variables. Secondary outcomes: additionally, correlations of DS with fatigue (using the Multidimensional Fatigue Inventory-20), quality of life (using the Euro-Quality of Life) and institutionalisation/mortality at 3 (t2) and 6 (t3) months follow-up were computed. RESULTS: Of the N=267 patients analysed, 9.4% showed severe or most severe delirium symptoms. 4.1% had a full-syndromal delirium. DS was significantly associated with the severity of illness (p=0.016, 95% CI -0.1 to -0.3), number of medical comorbidities (p<0.001, 95% CI .1 to .3) and sepsis (p<0.001, 95% CI .3 to 1.0). Patients with a higher DS at postacute ICU (t1), showed a higher mental fatigue at t2 (p=0.008, 95% CI .13 to .37) and an increased risk for institutionalisation/mortality (p=0.043, 95% CI 1.1 to 28.9/p=0.015, 95% CI 1.5 to 43.2). CONCLUSIONS: Illness severity is positively associated with DS during postacute care in CCI patients. An adequate management of delirium is essential in order to mitigate functional and cognitive long-term sequelae following ICU. TRIAL REGISTRATION NUMBER: DRKS00003386.

Impact of post-traumatic stress symptoms on the health-related quality of life in a cohort study with chronically critically ill patients and their partners: age matters.

BACKGROUND: Survivors of an acute critical illness with continuing organ dysfunction and uncontrolled inflammatory responses are prone to become chronically critically ill. As mental sequelae, a post-traumatic stress disorder and an associated decrease in the health-related quality of life (QoL) may occur, not only in the patients but also in their partners. Currently, research on long-term mental distress in chronically critically ill patient-partner dyads, using appropriate dyadic analysis strategies (patients and partners being measured and linked on the same variables) and controlling for contextual factors, is lacking. METHODS: The present study investigates the interdependence of post-traumatic stress symptoms (PTSS) and the health-related QoL in n = 70 dyads of chronically critically ill patients and their partners, using the Actor-Partner-Interdependence Model (APIM) under consideration of contextual factors (age, gender, length of partnership). The Post-traumatic Stress Scale (PTSS-10) and Euro-Quality of Life (EQ-5D-3L) were applied in both the patients and their partners, within up to 6 months after the transfer from acute care ICU to post-acute ICU. RESULTS: Clinically relevant post-traumatic stress symptoms were reported by 17.1% of the patients and 18.6% of the partners. Both the chronically critically ill patients and their partners with more severe post-traumatic stress symptoms also showed a decreased health-related QoL. The latter was more pronounced in male partners compared to female partners or female patients. In younger partners (≤ 57 years), higher values of post-traumatic stress symptoms were associated with a decreased QoL in the patients. CONCLUSIONS: Mental health screening and psychotherapeutic treatment options should be offered to both the chronically critically ill patients and their partners. Future research is required to address the special needs of younger patient-partner dyads, following protracted ICU treatment. TRIAL REGISTRATION: German Clinical Trials Register No. DRKS00003386 . Registered 13 November 2011.

Neural Responses to Faces of Attachment Figures and Unfamiliar Faces: Associations With Organized and Disorganized Attachment Representations.

The neural response to faces of attachment figures compared with unfamiliar faces still remains elusive. In particular, the modulation of the neural response by the organized (secure, insecure) compared with disorganized attachment representation of the subject investigated is unknown. For the present study, 38 healthy participants (age range, 21-71 years) were recruited. Three attachment groups (secure, n = 14; insecure, n = 15; disorganized, n = 9) were assessed using the Adult Attachment Projective. The participants were shown pictures of the faces of attachment figures (romantic partner/parents) and unfamiliar faces in a blocked factorial design, using functional magnetic resonance imaging. Showing pictures of attachment figures activated parts of a neural social judgment network, important for inferring others' affective and cognitive mental states (e.g., inferior parietal lobe/superior temporal gyrus) in securely attached healthy individuals. In contrast, disorganized attached individuals with the experience of unresolved attachment trauma in their biography showed deactivations in these areas.

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.

Self-reported fatigue following intensive care of chronically critically ill patients: a prospective cohort study.

BACKGROUND: Protracted treatment on intensive care unit (ICU) sets the patients at increased risk for the development of chronic critical illness (CCI). Muscular and cardio-respiratory deconditioning are common long-term sequelae, going along with a state of chronic fatigue. At present, findings regarding the frequency, long-term course, and associated factors of self-reported fatigue following ICU treatment of CCI patients are lacking. METHODS: CCI patients with the diagnosis of critical illness polyneuropathy/myopathy (CIP/CIM) were assessed at three time points. Four weeks following the discharge from ICU at acute care hospital (t1), eligibility for study participation was asserted. Self-reported fatigue was measured using the Multidimensional Fatigue Inventory (MFI-20) via telephone contact at 3 (t2, n = 113) and 6 months (t3, n = 91) following discharge from ICU at acute care hospital. RESULTS: At both 3 and 6 months, nearly every second CCI patient showed clinically relevant fatigue symptoms (t2/t3: n = 53/n = 51, point prevalence rates: 46.9%/45.1%). While total fatigue scores remained stable in the whole sample, female patients showed a decrease from 3 to 6 months. The presence of a coronary heart disease, the perceived fear of dying at acute care ICU, a diagnosis of major depression, and the perceived social support were confirmed as significant correlates of fatigue at 3 months. At 6 months, male gender, the number of medical comorbidities, a diagnosis of major depression, and a prior history of anxiety disorder could be identified. A negative impact of fatigue on the perceived health-related quality of life could be ascertained. CONCLUSIONS: Nearly every second CCI patient showed fatigue symptoms up to 6 months post-ICU. Patients at risk should be informed about fatigue, and appropriate treatment options should be offered to them. TRIAL REGISTRATION: The present study was registered retrospectively at the German Clinical Trials Register (date of registration: 13th of December 2011; registration number: DRKS00003386). Date of enrolment of the first participant to the present trial: 09th of November 2011.

Fatigue in chronically critically ill patients following intensive care - reliability and validity of the multidimensional fatigue inventory (MFI-20).

BACKGROUND: Fatigue often occurs as long-term complication in chronically critically ill (CCI) patients after prolonged intensive care treatment. The Multidimensional Fatigue Inventory (MFI-20) has been established as valid instrument to measure fatigue in a wide range of medical illnesses. Regarding the measurement of fatigue in CCI patients, the psychometric properties of the MFI-20 have not been investigated so far. Thus, the present study examines reliability and validity of the MFI-20 in CCI patients. METHODS: A convenience sample of n = 195 patients with Critical Illness Polyneuropathy (CIP) or Myopathy (CIM) were recruited via personal contact within four weeks (t1) following the transfer from acute care ICU to post-acute ICU at a large rehabilitation hospital. N = 113 (median age 61.1 yrs., 72.6% men) patients were again contacted via telephone three (t2) and six (t3) months following the transfer to post-acute ICU. The MFI-20, the Euro-Quality of Life (EQ-5D-3 L) and the Structured Clinical Interview for the Diagnostic and Statistical Manual of mental disorders DSM-IV (SCID-I) were applied within this prospective cohort study. RESULTS: The internal consistency Cronbach's α was adequate for the MFI-total and all but the subscale Reduced Motivation (RM) (range: .50-.91). Item-to-total correlations (range: .22-.80) indicated item redundancy for the subscale RM. Confirmatory Factor analyses (CFAs) revealed poor model fit for the original 5-factor model of the MFI-20 (t2/t3, Confirmatory Fit Index, CFI = .783/ .834; Tucker-Lewis Index, TLI = .751/ .809; Root Mean Square Error of Approximation, RMSEA = .112/ .103). Among the alternative models (1-, 2-, 3-factor models), the data best fit to a 3-factor solution summarizing the highly correlated factors General -/ Physical Fatigue/ Reduced Activity (GF/ PF/ RA) (t2/ t3, CFI = .878/ .896, TLI = .846/ .869, RMSEA = .089/ .085, 90% Confidence Interval .073-.104/ .066-.104). The MFI-total score significantly correlated with the health-related quality of life (range: -.65-(-).66) and the diagnosis of major depression (range: .27-.37). CONCLUSIONS: In the present sample of CCI patients, a reliable and valid factor structure of the MFI-20 could not be ascertained. Especially the subscale RM should be revised. Since the factors GF, PF and RA cannot be separated from each other and the unclear factorial structure in the present sample of CCI patients, the MFI-20 is not recommended for use in this context. TRIAL REGISTRATION: German Clinical Trials Registration DRKS00003386 . Registered 13 December 2011, retrospectively registered.

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

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.

Effects of Mental Stress Induction on Heart Rate Variability in Patients with Panic Disorder.

Reduced heart rate variability (HRV) constitutes a widely used marker of cardiac autonomic inflexibility which has been linked to disorders such as panic disorder (PD). To date, the pathophysiological mechanisms whereby panic leads to attenuated HRV are not fully elucidated. We aimed to investigate the hypothesis that PD patients show pathological reactivity both in response to interoceptive and psychosocial stress in comparison to healthy individuals. We performed a controlled study on 38 patients diagnosed with PD [20 males and 18 females aged 35.55 ± 10.12 years, mean ± standard deviation] and 23 age and gender matched healthy control participants. Distress was induced using the Trier Social Stress Test (TSST) and the dexamethasone-corticotropin-releasing-hormone (DEX-CRH) test. We assessed HRV prior to, during, and post-stress induction using the root mean square successive differences (RMSSD) as well as spectral analysis (high frequency; HF and low frequency; LF). Statistical analyses revealed significant main effects of time for mean heart rate (HR), HF, LF (solely DEX-CRH), LFHF-ratio (solely TSST) and the RMSSD. Significant interaction effects were observed with more pronounced increases in mean HR (TSST) and LFHF-ratio (DEX-CRH) in the healthy control participants. No significant main effects of group were observed. Overall, our results indicate "normal" HRV parameters in patients with PD. The HRV of PD patients is no worse than that of healthy control participants since the HRV profiles were similar between the study groups. The current study is one of rather rarely published studies which was unable to show an influence of PD on HRV. Implications for future studies are under discussion.

Predictors of posttraumatic stress and quality of life in family members of chronically critically ill patients after intensive care.

BACKGROUND: Prolonged mechanical ventilation for acute medical conditions increases the risk of chronic critical illness (CCI). Close family members are confronted with the life-threatening condition of the CCI patients and are prone to develop posttraumatic stress disorder affecting their health-related quality of life (HRQL). Main aim of the present study was to investigate patient- and family-related risk factors for posttraumatic stress and decreased HRQL in family members of CCI patients. METHODS: In a cross-sectional design nested within a prospective longitudinal cohort study, posttraumatic stress symptoms and quality of life were assessed in family members of CCI patients (n = 83, aged between 18 and 72 years) up to 6 months after transfer from ICU at acute care hospital to post-acute rehabilitation. Patients admitted a large rehabilitation hospital for ventilator weaning. The Posttraumatic Stress Scale-10 and the Euro-Quality of life-5D-3L were applied in both patients and their family members via telephone interview. RESULTS: A significant proportion of CCI patients and their family members (14.5 and 15.7 %, respectively) showed clinically relevant scores of posttraumatic stress. Both CCI patients and family members reported poorer HRQL than a normative sample. Factors independently associated with posttraumatic stress in family members were the time following ICU discharge (ß = .256, 95 % confidence interval .053-.470) and the patients' diagnosis of PTSD (ß = .264, 95 % confidence interval .045-.453). Perceived satisfaction with the relationship turned out to be a protective factor for posttraumatic stress in family members of CCI patients (ß = -.231, 95 % confidence interval -.423 to -.015). Regarding HRQL in family members, patients' acute posttraumatic stress at ICU (ß = -.290, 95 % confidence interval -.360 to -.088) and their own posttraumatic stress 3 to 6 months post-transfer (ß = -.622, 95 % confidence interval -.640 to -.358) turned out to be significant predictors. CONCLUSIONS: Posttraumatic stress and HRQL should be routinely assessed in family members of CCI patients at regular intervals starting early at ICU. Preventive family-centered interventions are needed to improve posttraumatic stress and HRQL in both patients and their family members.

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 hypothalamic­pituitary­adrenocortical (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.

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.

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.

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.

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.