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Genetic variations affecting the course of depressive symptoms in patients with coronary artery disease (CAD) have not yet been well studied. Therefore, we set out to investigate whether distinct haplotypes of the two insertion/deletion polymorphisms in the serotonin-transporter-linked polymorphic region (5-HTTLPR) and the angiotensin I-converting enzyme (ACE) gene located on chromosome 17 can be identified as risk factors for trajectories of depression. Clinical and genotyping data were derived from 507 depressed CAD patients participating in the randomized, controlled, multicenter Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD) trial, of whom the majority had an acute cardiac event before study inclusion. Depression scores on the Hospital Anxiety and Depression Scale (HADS) were assessed at baseline and at five follow-up time points up to 2 years after study entrance. At baseline, depression scores did not significantly differ between patients carrying the risk haplotype ACE D/D, 5-HTTLPR I/I (n = 46) and the non-risk haplotypes (n = 461, 10.9 ± 2.7 versus 10.4 ± 2.5, p = 0.254). HADS-depression scores declined from study inclusion during the first year irrespective of the genotype. At each follow-up time point, HADS-depression scores were significantly higher in ACE D/D, 5-HTTLPR I/I carriers than in their counterparts. Two years after study inclusion, the mean HADS depression score remained 1.8 points higher in patients with the risk haplotype as compared to subjects not carrying this haplotype (9.9 ± 4.2 versus 8.1 ± 4.0, p = 0.009). In summary, the presence of the ACE D/D, 5-HTTLPR I/I haplotype may be a vulnerability factor for comorbid depressive symptoms in CAD patients.

Background Depressive symptoms are common in patients with coronary artery disease (CAD) and are associated with an unfavourable outcome. Establishing prognostic patient profiles prior to the beginning of mental health care may facilitate higher efficacy of targeted interventions. The aim of the current study was to identify sociodemographic and somatic predictors of depression outcome among depressed patients with CAD. Methods Based on the dataset of the multicentre SPIRR-CAD randomised controlled trial (n = 570 patients with CAD and ≥ 8 points on the Hospital Anxiety and Depression Scale (HADS)), 141 potential sociodemographic and somatic predictors of the change in the HADS-D depression score from baseline to 18-month-follow-up were derived in two different ways. We screened for univariable association with response, using either analysis of (co)variance or logistic regression, respectively, both adjusted for baseline HADS-D value and treatment group. To guard against overfitting, multivariable association was evaluated by a linear or binomial (generalised) linear model with lasso regularisation, a machine learning approach. Outcome measures were the change in continuous HADS-D depression scores, as well as three established binary criteria. The Charlson Comorbidity Index (CCI) was calculated to assess possible influences of comorbidities on our results and was also entered in our machine learning approach. Results Higher age (p = 0.002), unknown previous myocardial infarction (p = 0.013), and a higher heart rate variability during numeracy tests (p = .020) were univariably associated with a favourable depression outcome, whereas hyperuricemia (p ≤ 0.003), higher triglycerides (p = 0.014), NYHA class III (p ≤ 0.028), state after resuscitation (p ≤ 0.042), intake of thyroid hormones (p = 0.007), antidiabetic drugs (p = 0.015), analgesic drugs (p = 0.027), beta blockers (p = 0.035), uric acid drugs (p ≤ 0.039), and anticholinergic drugs (p = 0.045) were associated with an adverse effect on the HADS-D depression score. In all analyses, no significant differences between study arms could be found and physical comorbidities also had no significant influence on our results. Conclusion Our findings may contribute to identification of somatic and sociodemographic predictors of depression outcome in patients with CAD. The unexpected effects of specific medication require further clarification and further research is needed to establish a causal association between depression outcome and our predictors. Trial registration www.clinicaltrials.gov NCT00705965 (registered 27th of June, 2008). www.isrctn.com ISRCTN76240576 (registered 27th of March, 2008).

INTRODUCTION A hyper-coagulant state is a biological mechanism that triggers cardiac events in patients with coronary artery disease (CAD). Depressive symptoms and anxiety predict an unfavourable course of CAD. The SPIRR-CAD-RCT examined the effects of a psychological intervention and provided the opportunity to explore cross-sectional associations between indices of psychological strain and coagulation parameters, as well as prospective changes in depression scores and coagulation parameters. METHODS In this secondary analysis, we investigated 253 CAD patients (194 male; age m 58.9, SD 8.3 yrs.) with mild to moderate depression (≥8 on the HADS-D) at baseline and at follow-up 18 months later: TF, fibrinogen, D-dimer, VWF, FVII and PAI-1 and the course of depression (HAM-D), vital exhaustion (VE) and anxiety scores (HADS-A) were examined by ANOVA in the total and younger age groups (≤ 60). RESULTS HAM-D at baseline was correlated with TF (corr. R2 = 0.27; F = 9.31, p = 0.001). HADS anxiety was associated with fibrinogen (corr. R2.20; F = 7.27, p = 0.001). There was no detectable therapeutic effect on coagulation. Fibrinogen and VWF decreased within 18 months (time effect; p = 0.02; p = 0.04), as did HADS-D in both treatment groups (p

Natriuretic peptides (NP) are involved in the regulation of blood pressure and blood volume, and are elevated in patients with coronary artery disease (CAD). They are used as markers for illness severity, but their role in mental health is not well understood. Recently, A-type NP (ANP) has been associated with reduced anxiety in studies on cardiac patients; however, this study is the first to assess this effect for B-type NP (BNP) and for further dimensions of well-being and mental health. Depression, anxiety, and distress are more common in CAD patients than in the general population and are most likely not only influenced by psychological adaptation but also by neurobiological processes. We used baseline N-terminal proBNP (NT-proBNP) samples and psychometric assessments of 529 at least mildly depressed (Hospital Anxiety and Depression Scale, depression score ≥ 8) CAD patients from the multicenter Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD) trial. Psychosocial status was assessed using standardized self-rating questionnaires on anxiety, depression, coping with illness, vital exhaustion, type D personality, and quality of life. Separate linear regression models for each psychometric scale revealed significant negative correlations of NT-proBNP with anxiety, depression, vital exhaustion, depressive coping, and negative affectivity. Moreover, patients with higher levels of NT-proBNP experienced less bodily pain and had a better self-rated mental health, despite worse physical functioning. Linear regression adjusted for age, sex, and physical functioning (Short Form Health Survey [SF-36]) revealed NT-proBNP to be a significant predictor for all tested measures of the patients' psychosocial status. These results indicate that NT-proBNP is not only positively associated with greater disease severity in mildly to moderately depressed CAD patients but also with better psychosocial status and mental well-being. Possible mechanisms of this effect are discussed.

BACKGROUND: Depression predicts adverse prognosis in patients with coronary artery disease (CAD), but previous treatment trials yielded mixed results. We tested the hypothesis that stepwise psychotherapy improves depressive symptoms more than simple information. METHODS: In a multicenter trial, we randomized 570 CAD patients scoring higher than 7 on the Hospital Anxiety and Depression Scale-depression subscale to usual care plus either one information session (UC-IS) or stepwise psychotherapy (UC-PT). UC-PT patients received three individual psychotherapy sessions. Those still depressed were offered group psychotherapy (25 sessions). The primary outcome was changed in the Hospital Anxiety and Depression Scale-depression scores from baseline to 18 months. Preplanned subgroup analyses examined whether treatment responses differed by patients' sex and personality factors (Type D). RESULTS: The mean (standard deviation) depression scores declined from 10.4 (2.5) to 8.7 (4.1) at 18 months in UC-PT and from 10.4 (2.5) to 8.9 (3.9) in UC-IS (both p < .001). There was no significant group difference in change of depressive symptoms (group-by-time effect, p = .90). Preplanned subgroup analyses revealed no differences in treatment effects between men versus women (ptreatment-by-sex interaction = .799) but a significant treatment-by-Type D interaction on change in depressive symptoms (p = .026) with a trend for stronger improvement with UC-PT than UC-IS in Type D patients (n = 341, p = .057) and no such difference in improvement in patients without Type D (n = 227, p = .54). CONCLUSIONS: Stepwise psychotherapy failed to improve depressive symptoms in CAD patients more than UC-IS. The intervention might be beneficial for depressed CAD patients with Type D personality. However, this finding requires further study. TRIAL REGISTRATION: www.clinicaltrials.gov NCT00705965; www.isrctn.com ISRCTN76240576.

Patients with coronary heart disease (CHD) suffer from physical limitations, but also from psychological distress. Natriuretic peptides may be involved in the neurobiological processes that modulate psychological adaptation, as they are increased in heart disease and seem to have an anxiolytic-like function. Longitudinal data on this association are scarce.To assess the relationship between NT-proBNP and anxiety (Hospital Anxiety and Depression Scale (HADS)), we used secondary data from a multicenter trial from baseline to 24 months. Patients (N = 308, 80.8% male, mean age 60.1 years) had stable CHD and moderate levels of depression (HADS ≥8).Multiple linear regression adjusted for age, sex, BMI, and physical functioning revealed NT-proBNP as a significant predictor for anxiety at baseline, 1, 6, 12, 18, and 24 months (all p .05). Linear mixed model analysis with the six anxiety measures as level-1 variable and NT-proBNP as fixed factor revealed a significant time*NT-proBNP interaction (t(1535.99) = -2.669, p = .01) as well as a significant time*NT-proBNP*sex interaction (t(1535.99) = 3.277, p = .001), when NT-proBNP was dichotomized into lowest vs. the three highest quartiles.Our results indicate a stable negative association of baseline NT-proBNP with anxiety over two years. In men and women, different pathways modulating this relationship appear to be in effect. Female patients with very low NT-proBNP levels, despite their cardiac disease, show persistently higher levels of anxiety compared to women with higher levels of NT-proBNP and compared to men. Trial name: A Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD).www.clinicaltrials.govNCT00705965; www.isrctn.com ISRCTN76240576.

Introduction The biological and psychosocial risk profile differs between women and men with coronary artery disease (CAD). Depressive symptoms and Vital Exhaustion (VE) predict an unfavourable course of CAD. The secondary analysis of the SPIRR-CAD trial offered the possibility to examine gender as exposure variable of the clinical and psychological situation at baseline and in a variety of psychosocial measures as outcomes. Methods In this trial, 450 men (78.9%) and 120 women (21.1%) with CAD (age ≤ 75 y), with mild to moderate depression (scoring ≥8 on the HADS), were randomized to usual care with or without a stepwise psychotherapy intervention. Beside clinical measures exhaustion and other indicators of depressive symptoms were collected at baseline and 18-month follow up. Results Men had more signs and symptoms of heart disease at baseline, whereas women had higher psychosocial burden (e.g. negative affect). Women were more likely to live alone, had lower educational levels and employment rates and higher levels of depression and exhaustion. The psychotherapy intervention differed as a function of gender: In women, VE decreased from 29.4 ± 8.1 to 22.1 ± 11.7 in the intervention group (IG) and from 29.2 ± 8.2 to 25.1 ± 11.3 in the control group (CG). In men VE decreased from 23.3 + −10.8 to 21.2 ± 9.7 in the IG and from 23.6 ± 10.7 to 19.3 ± 11.3 in the CG (time x intervention x gender; F = 4.97; p = .026). Discussion Women had a higher psychosocial burden than men. VE compared to other rating instruments of depressive symptoms suggested a stronger response to the intervention in women. VE may help to understand gender differences in psychotherapeutic treatment studies of CAD. ISRCTN:76240576; clinicaltrials.gov

Coffee is one of the most widely consumed beverages worldwide. Aim of this study was to investigate short-term effects of espresso coffee on heart rate variability (HRV), a marker of vagal activity, in healthy habitual and non-habitual coffee consumers.Seventy-seven healthy subjects (38 habitual and 39 non-habitual coffee consumers, 74% women, mean age 26.97 ± 6.88 years) took part in three laboratory sessions in a randomized order. In condition 1, subjects consumed espresso; in condition 2, subjects consumed decaffeinated espresso; and in condition 3, subjects consumed warm water. HRV and blood pressure were assessed at rest before and after ingestion of the respective beverage.HRV was significantly increased after consumption of caffeinated espresso, decaffeinated espresso, or water, indicating increased vagal activity in the course of the experiments. In the habitual coffee consumers, the increase in vagally mediated HRV was significantly lower after consumption of decaffeinated espresso compared to caffeinated espresso. Increases of systolic blood pressure were only found in the non-habitual consumers.We found no evidence for specific short-term effects of caffeinated espresso on vagal activity in healthy subjects. Instead, consumption of decaffeinated espresso inhibited vagal activity in habitual consumers. This may be explained by an attempt of the organism to establish a sympathovagal equilibrium comparable to that after caffeine consumption. In the absence of caffeine-induced sympathetic activation, this may have been achieved by relative vagal withdrawal.

Background: Salt-sensitive normotensive men exhibit an enhanced pressor and heart rate (HR) response to mental stress. Stress-induced HR acceleration may result from sympathetic activation or vagal withdrawal. We studied the importance of vagal withdrawal for the increased stress responsiveness of salt-sensitive subjects. Methods: We studied cardiovascular reactivity to mental challenge in 17 salt-sensitive healthy white male students and 56 salt-resistant control subjects who were comparable with respect to age, body mass index, and physical fitness. Salt sensitivity was determined by a 2-week dietary protocol (20 mmol v 240 mmol sodium/day). Mental stress was induced by a computerized information-processing task (manometer test). Electrocardiogram and finger blood pressure (BP; Finapres, Ohmeda, Louisville, CO) were registered continuously to determine HR and interbeat-interval length. Time and frequency domain (spectral power) based measures of respiratory-related heart rate variability (HRV) were calculated to estimate vagal cardiac control; diastolic BP reactivity was assessed to estimate peripheral sympathetic effects. Results: Stress-induced increase in HR was higher in salt-sensitive than in salt-resistant subjects. Salt-sensitive subjects, in comparison to salt-resistant subjects, showed significantly reduced respiratory-related HRV during baseline and mental stress conditions (P < .01). The increase in diastolic BP during mental challenge was significantly greater in salt-sensitive subjects (P < .05). Conclusions: Our findings suggest reduced vagal and increased sympathetic tone during mental challenge in salt-sensitive subjects. Altered autonomic nervous system function may contribute to later development of hypertension in salt-sensitive individuals. Am J Hypertens 2003; 16:531-536 @ 2003 American Journal of Hypertension, Ltd

Anxiety is associated with worse outcomes in patients with coronary heart disease (CHD). A dysregulation of the HPA axis is a potential mechanism linking psychological factors and coronary disease. No study has yet investigated the relationship between anxiety and cortisol among patients with established CHD.The aim of this study was to assess the association between anxiety and the cortisol awakening response in patients with CHD.Four salivary cortisol samples were used to assess two measures of the cortisol awakening response (CAR) in 47 patients with established CHD. Anxiety was measured using the Hospital Anxiety and Depression Scale (HADS).Higher anxiety values were associated with a higher total output of cortisol in the first hour after awakening (AUCg, area under the curve with respect to ground) (p = 0.04) and a nonsignificant trend towards a more pronounced increase (AUCi, area under the curve with respect to increase) (p = 0.08). In patients who had a history of myocardial infarction (MI), the cortisol output was lower compared to patients who had no previous MI (p = 0.02). In linear regression analyses, anxiety emerged as significant predictor of AUCg and AUCi after controlling for MI, ejection fraction (LVEF, left ventricular ejection fraction), and depression.Our results provide further indications for an association between anxiety and a dysregulation of the HPA axis. History of MI emerged as second predictor of cortisol output in the morning.

Objective Depressive symptoms are highly relevant for the quality of life, health behavior, and prognosis in patients with coronary artery disease (CAD). However, previous psychotherapy trials in depressed CAD patients produced small to moderate effects on depression, and null effects on cardiac events. In this multicentre psychotherapy trial, symptoms of depression are treated together with the Type D pattern (negative affectivity and social inhibition) in a stepwise approach. Methods Men and women (N=569, age 18–75 years) with any manifestation of CAD and depression scores ≥ 8 on the Hospital Anxiety and Depression Scale (HADS), will be randomized (allocation ratio 1:1) into the intervention or control group. Patients with severe heart failure, acutely life-threatening conditions, chronic inflammatory disease, severe depressive episodes or other severe mental illness are excluded. Both groups receive usual medical care. Patients in the intervention group receive three initial sessions of supportive individual psychotherapy. After re-evaluation of depression (weeks 4–8), patients with persisting symptoms receive an additional 25 sessions of combined psychodynamic and cognitive–behavioral group therapy. The control group receives one psychosocial counseling session. Primary efficacy variable is the change of depressive symptoms (HADS) from baseline to 18 months. Secondary endpoints include cardiac events, remission of depressive disorder (SCID) and Type D pattern, health-related quality of life, cardiovascular risk profile, neuroendocrine and immunological activation, heart rate variability, and health care utilization, up to 24 months of follow-up (ISRCTN: 76240576; NCT00705965). Funded by the German Research Foundation.

We have previously shown that acute psychological stress alerts the adaptive immune response causing an increase in antigen-experienced effector T cells in the peripheral blood. T regulatory cells (Tregs) play a central role in maintaining self-tolerance and controlling autoimmune responses. Here, we analyzed for the first time the behaviour of Tregs in the context of a stress-induced activation of the adaptive immune response. 31 healthy young males underwent a brief laboratory stressor and, in a crossover design, served as their own unstressed controls. We quantified effects of acute stress on CD4(+)FOXP3(+) T regulatory cells and other T cell subpopulations using flow cytometry. In addition, the expression of Treg-related effector molecules and stress hormone receptors were analyzed in the subjects' peripheral T cells. We confirmed our previous observation of a stress-induced decrease in CD45RA(+)CCR7(+) "naïve" and CD45RA(-)CCR7+ "central memory" T cells while CD45RA(-)-CCR7(-) "memory effector" and CD45RA(+)CCR7(-) "terminally differentiated" effector T cells remained stable or increased. Importantly, we found acute psychological stress to cause a concomitant decrease in CD4(+)FOXP3(+) Tregs and in CD4(+) T cells expressing Treg-related effector molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and latency associated peptide (LAP). Finally, we observed beta(1)-adrenergic and glucorticoid alpha receptors to be overexpressed in Tregs, suggesting that these molecules might mediate stress-related effects on Tregs. In conclusion, inhibiting components of the adaptive immune response, like Tregs, are down-regulated during a stress-induced activation of the adaptive immune response. In situations of chronic stress, this scenario might result in an exacerbation of inflammatory conditions such as autoimmune diseases.

Research suggests equivocal findings on associations of catecholamines and mood. Our study investigated the associations of emotional state, blood pressure and catecholamines in 55 healthy males undergoing mental stress. We especially checked the reported link between norepinephrine (NE) and emotional irritation. Blood pressure (SBP, DBP) and heart rate (HR) were continuously monitored. NE and epinephrine (EPI) were measured before, after, and 20 minutes after stress. Participants were divided into irritated versus non-irritated and anxious versus non-anxious subjects by median split on their baseline questionnaires. The task elicited significant cardiovascular, hormonal, and psychological stress responses. NE levels were significantly correlated with irritation before stress. Irritated subjects showed significantly higher DBP and NE than non-irritated subjects. The higher NE and DBP levels in the irritated participants suggest detrimental psycho-physiological interrelations promoting the development of stress-mediated cardiovascular diseases. Heightened emotional irritation before stress may be regarded as a psychological risk factor.

Background: Few published studies examine the influence of psychological treatment on health care utilization in Crohn's disease. Methods: The present substudy of a prospective, randomized, multicenter trial conducted in 69 of 488 consecutive Crohn's disease (CD) patients was designed to investigate the way in which healthcare utilization is influenced by psychotherapy and relaxation in addition to standardized glucocorticoid therapy. Before and after a 1-year period of standardized somatic treatment the psychotherapy and control groups were compared with regard to hospital and sick-leave days. Predictors of healthcare utilization were analyzed. Results: The comparison between groups before and after psychological treatment showed a significantly higher decrease of mean hospital days (P < 0.03) and sick-leave days in the treatment group compared with the controls. When a covariate analysis was applied to compare the data at randomization, the difference in hospital days remained statistically a trend (P < 0.1). Multivariate regression analysis detected a significant gender and depression effect for hospital days (cor r2 = 0.114) and a significant gender and age effect for sick-leave days (cor r2 = 0.112). Conclusion: A significant drop in healthcare utilization after psychological treatment demonstrates a clear benefit of this additional therapy. This is important, since the study failed to demonstrate significant changes in the psychosocial status or somatic course of study patients. Clinical and psychological factors influencing these outcomes are discussed. (Inflamm Bowel Dis 2007)

Blood pressure reactivity to mental stress in hypertensives is much higher than in normotensives. The authors' aim in this study was to examine whether different cardiovascular responses can be induced by various stimuli in hypertensive subgroups. The authors matched 10 essential hypertensives (EHs), 10 renal hypertensives (RHs), and 10 normotensives (Ns) according to age and gender examined them during an emotion-stimulating interview, and measured blood pressure (BP) and heart rate (HR) during the phases of the interview. They observed differences in BP reactivity between EHs/RHs and Ns under some stimuli but not between EHs and RHs, as well as a marked difference in the product of systolic BP (SBP) and HR between both hypertensive groups in the anger/rage phase (p = .028) and the baseline 2 (p = .02). This shows a higher cardiovascular activation under mental stress and a lower recovery in EHs and more sensitivity to perturbation or higher central tension compared with RHs.

Introduction. Patients with essential hypertension react more strongly to mental stress than normotensives. This may be related to the type of stress coping or to increased reactivity associated with the disease. The aim of our study was to examine whether patients with essential or secondary hypertension differ in their reaction to mental stress. Methods. Seventeen patients with essential hypertension (EH), 9 patients with renal hypertension (RH), and 22 normotensive controls (N) with no circulatory disorders were subjected to a psychophysiological examination under mental stress. Blood pressure (BP), heart rate (HR) and electrodermal activity (EDA) were measured. Results. The two hypertensive groups differed in their BP reaction to mental stress from the control group but not from each other. The product of heart rate and systolic blood pressure during the matrix test was significantly higher in essential than renal hypertensives (EH median: 13344; RH median: 12154.5; p = 0.04). This also holds true for the number of spontaneous fluctuations of EDA in the resting phase after the experiment (EH. median: 3.2; RH. median: 1.3; p = 0.01). Conclusion. The results suggest that not only a high blood pressure level but also the sympathetic nervous tone are responsible for the blood pressure response to mental stress. Due to very different (perhaps psychosocially triggered) conditions, essential hypertension leads to a stronger cardiovascular reaction under mental stress than renal hypertension.

Influences of psychological stress on the acquired immune system have not consequently been investigated. We found acute psychological stress to cause an increase in CD56+ and CCR5+ effector T cells in the peripheral blood of healthy human subjects (N=22), while skin-homing CLA+ T cells decreased. At the same time, we observed a stress-induced decrease in CD45RA+/CCR7+ naive and CD45RA-/CCR7+ central memory T cells, while CD45RA-/CCR7- effector memory and CD45RA+/CCR7- terminally differentiated T cells increased. This T cell redistribution translated into an increase in T cells expressing perforin/granzyme B and in Epstein-Barr virus-specific, cytomegalovirus-specific and influenza virus-specific CD8+ T cells. Thus, acute stress seems to promote the retention of less mature T cells within lymphoid tissue or skin while effector-type T cells are mobilized into the blood in order to be able to rapidly migrate into peripheral tissues.

We tested the hypothesis that a suggestive placebo intervention can reduce the subjective and neurobiological stress response to psychosocial stress. Fifty-four healthy male subjects with elevated levels of trait anxiety were randomly assigned in a 4:4:1 fashion to receive either no treatment (n = 24), a placebo pill (n = 24), or a herbal drug (n = 6) before undergoing a stress test. We repeatedly measured psychological variables as well as salivary cortisol, alpha-amylase, and heart rate variability prior to and following the stress test. The stressor increased subjective stress and anxiety, salivary cortisol, and alpha-amylase, and decreased heart rate variability (all P < .001). However, no significant differences between subjects receiving placebo or no treatment were found. Subjects receiving placebo showed increased wakefulness during the stress test compared with no-treatment controls ( P < .001). Thus, the suggestive placebo intervention increased alertness, but modulated neither subjective stress and anxiety nor the physiological response to psychosocial stress.

In the last decades the number of obese and pre-obese patients in Western industrial nations increased. Obese patients have been largely unsuccessful in losing weight over time, but the causes of their difficulties and the causes of their obesity have remained unclear. We examined whether the attachment style and its interaction with interpersonal processes would shed light on this question. We analyzed 107 obese or pre-obese patients before the start of a weight loss intervention program. We used the Adult Attachement Prototype Rating (AAPR)-interview and related questionnaires (Helping Alliance Questionnaire (HAQ), Inventory of Interpersonal Problems (IIP-D), Brief Symptom Inventory (BSI)). According to the AAPR-rating 54% of the patients were secure and 46% insecure attached. The results suggest that insecure attachment style has an impact on psychic strain in obese patients unrelated to weight, gender and age. Additionally the insecure attachment style influences the therapeutic alliance experienced by patients and the therapist.

Objective: The authors investigated the hypothesis that in acute anorexia nervosa a low body weight predicts a poor weight prognosis for the future. Method: The body mass indexes at referral of 272 female patients were examined in relation to the body mass indexes of these patients after a mean follow-up of 9.5 years. Results: The overall correlation between body mass indexes at referral and at follow-up was r=0.33. Despite this low correlation, the 100 patients with body mass indexes less than 13 kg/m 2 at referral had low weights at long-term follow-up. Eleven of the 12 deceased patients were among these 100 patients, as were 24 of the 46 surviving patients whose body mass indexes were 17.5 kg/m 2 or less at follow-up. Conclusions: For patients with anorexia nervosa, a body mass index less than 13 kg/m 2 at referral indicates a substantial risk for chronic anorexia nervosa and death related to emaciation. (Am J Psychiatry 1997; 154:566‐569)

Acute psychological stress has primarily been investigated regarding its effects on conventional lymphocytes such as natural killer (NK) cells and CD4(+) and CD8(+) T cells. However, it might be important to focus on more "specialized" lymphocyte subsets, playing a role, for instance, in allergic conditions and autoimmunity, to identify links between stress, the immune system and somatic diseases. Using flow cytometry we determined frequencies of circulating T helper (Th)1-type (CD226(+)) and Th2-type (CRTH2(+)) T cells, γδ T cells, conventional CD56(+) natural killer T (NKT) cells and invariant NKT cells (iNKT) in healthy young males (N = 31; median age 26 years) undergoing a laboratory computer-based stressor lasting 12 min. We found that acute psychological stress induced a prolonged increase in CD4(+) and CD8(+) T cells expressing a Th2 phenotype. We also detected an acute increase in CD4(-) and CD8(-) double negative γδ T cells. Finally, we found that the well-known increase in NK cells under stressful conditions was paralleled by a significant increase in numbers of conventional CD56(+) NKT cells. In contrast, numbers of iNKT was not altered by stress. This study adds further evidence to a psychoneuroimmunological model proposing that under stressful conditions certain lymphocyte subsets, including iNKT and less mature T cells, are retained in lymphoid tissues while antigen-experienced effector-type T cells with a Th2 phenotype, γδ T cells and conventional CD56(+) NKT cells are mobilized into the peripheral blood. We suggest that in the case of frequent stress exposure, this might result in the promotion of, for example, allergic conditions.

Objective Placebo effects on pain and other subjective parameters are well-established, but the evidence for placebo effects on autonomic functions is scarce. Our randomized-controlled trial aimed to investigate autonomic responses after a suggestive placebo intervention intended to increase or decrease blood pressure (BP). Methods 92 healthy subjects inhaled a placebo spray with the prior suggestion that it contained an effective drug to either increase or decrease BP, or the information that a placebo was administered (controls). BP, heart rate, stroke volume, peripheral resistance, heart rate variability and skin conductance level were monitored 30 min before and after placebo administration. The expected and the subjectively perceived drug effect were measured by means of visual analog scales. Results We found no statistically significant differences between the groups with respect to BP, heart rate, stroke volume, total peripheral resistance and heart rate variability responses to the verbal suggestions. Skin conductance response was more pronounced in the BP decrease group compared with controls (p = 0.04), but this finding might be due to chance, given the multiple tests. Within the total study sample, BP, total peripheral resistance, low frequency power of heart rate variability and skin conductance were significantly higher after the placebo spray independent of the associated suggestions. Subjects in the BP increase and BP decrease condition had higher ratings of the expected and the subjectively perceived drug effect compared with controls (all p Conclusion We found no evidence that specific verbal suggestions during placebo interventions affect BP in healthy subjects.

Background Patients with psychosocial problems often present somatic symptoms in primary care. Objective The authors compare interventions and outcomes of emotionally-distressed patients by presenting physical disease, somatoform symptoms, or psychological symptoms. Method General practitioners (N = 191) documented data from 1,286 patients with psychosocial problems. Experts rated the presented reasons for encounter. Results Somatoform symptoms, as well as physical disease, result in patients’ receiving physical treatments. Psychologicallyoriented treatment is more likely with psychological presentation, but not significantly related to somatoform symptoms. Conclusion These findings underline the importance of a specific treatment approach for patients with somatoform symptoms, so as to avoid inappropriate treatment.

Anger has been implicated in the etiology of hypertensive disease. Trait anger has been linked to enhanced cardiovascular responsiveness. However, whether this association reflects differences in context appraisal or a general hyper-reactivity of the cardiovascular system remains unclear. We studied the cardiovascular response to acoustic startle probes in 76 healthy Caucasian males in different affective contices (pleasant, neutral, and unpleasant). All participants completed the State-Trait-Anger-Expression-Inventory (STAXI) by Spielberger and the results were analysed with stepwise regression analysis according to the anger scores and traditional risk factors for hypertension. Our study reveals differential modulation of the cardiovascular response to startle stimuli by affective pictures in the dimensions "valence" for heart rate and "arousal" for blood pressure. Anger-in was identified as the most important determinant for blood pressure responses in unpleasant context, while anger-out was associated with less cardiovascular activation in neutral context. This is the first study that relates trait anger to cardiovascular reactivity and affective reflex modulation in normotensive subjects. We could demonstrate an interaction of affective context and trait anger for cardiovascular (hyper-)reactivity. Increased cardiovascular reactivity for higher scores of anger-in in unpleasant context may indicate enhanced sympathetic reactivity and constitute a risk factor for the development of essential hypertension.

The study examines the effectiveness of applying the Life-Stressor Checklist (LSC-R) in diagnosing trauma-related disease. The validity of a quantitative analysis of the checklist is evaluated in consideration of the dose-response effect between the number of different traumatic stressor expositions and the degree of trauma-related symptoms. The trauma checklist LSC-R was applied to 130 patients. Data on psychological symptoms was collected with the help of IES-R (PTSD symptoms) and SCL-90-R, the relevance of traumatic experiences for the genesis of disorders was assessed by expert evaluation. The dose effect replicated clearly with r=0.714 and a cut-off of ≥6 yielded a 75% agreement with the expert evaluation. The total value of the trauma checklist showed a differentiation within high-risk groups and also agreement with the severity of the traumatization. The quantitative analysis of the trauma checklist permits an effective screening for identifying trauma-related disease.

Reduced heart rate variability (HRV) and delayed blood pressure recovery are associated with increased cardiovascular risk. Besides this evident link, the vagus is thought to play an inhibitory role in the regulation of other allostatic systems, including inflammation and the hypothalamic-pituitary-adrenal (HPA) axis. However, human evidence is scarce. To further explore these associations and with special regard to the postulated mediating role of the vagus, we hypothesised that subjects with low vagal tone as indexed by reduced resting HRV would show impaired post-stress recovery of cardiovascular, endocrine and immune system markers involved in cardiovascular pathology. 44 healthy men underwent a standardised mental stress test. Besides continuous measurement of systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and HRV serum cortisol, tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured before, after, 20, and 60 min after stress. Low versus high HRV groups was defined by median split on resting HRV (RMSSD). The task elicited significant time effects for SBP, DBP, HR, HRV, cortisol, and TNF-alpha. Subjects with low baseline HRV showed almost no modulation of HRV coupled with overall reduced HRV levels, and impaired recovery of DBP, cortisol, and TNF-alpha. Confirming our hypothesis, low vagal tone was associated with impaired recovery of cardiovascular, endocrine, and immune markers in healthy males. The data support an inhibitory role of the vagus in the regulation of allostatic systems as described in the neurovisceral integration model. We posit reduced resting HRV as a risk marker for future cardiovascular and other stress-related disease.

In this pilot study we examined the natural course of depressive and anxiety symptoms in patients with coronary heart disease over a period of 1(1/2) years. Additionally, we examined patients' interest in participation in a group-psychotherapy. The intervention and its effects on symptom reduction were tested in a subgroup of patients.Assessment of anxiety and depression (HADS) in 58 cardiology inpatients at 3 time points (t1 after one year, t2 after 1(1/2) years). N = 9 patients were additionally included in a 6-month psychotherapy intervention and compared to N = 14 untreated patients.79 % of the patients were interested in beginning a psychotherapy intervention. Without psychotherapeutic treatment, the average psychological strain remained stable over the time of investigation. Intervention-group patients, however, achieved a significant (60 %) reduction in depression and anxiety scores. Implications for the clinical practice and further investigations are discussed.

Salt sensitivity (SS) represents a risk factor for essential hypertension, which has been related to enhanced cardiovascular stress reactivity possibly mediated by increased noradrenergic susceptibility. We investigated biophysiological responses to mental stress in salt-sensitive (ss) and salt-resistant (sr) subjects, hypothesizing lower heart rate variability (HRV) and higher cortisol in the ss. A total of 48 healthy normotensive Caucasian men (age 25.6+/-2.6, body mass index 22.9+/-2.3) were phenotyped for SS (defined as significant drop in mean arterial pressure>3 mm Hg under the low-salt diet) by a 2-week high- versus low-salt diet. Subjects underwent a standardized mental stress task with continuous cardiovascular monitoring before, during and after the test (Finapres; Ohmeda, Louisville, CO, USA). Blood samples were drawn to examine cortisol and catecholamines before, after and 20 min after stress. The task elicited significant increases of systolic blood pressure (SBP), diastolic BP (DBP) and heart rate (HR) and a significant decrease of HRV (all time effects P

The objective of the study was to identify predictors of health-care utilization in Crohn's disease.Therefore, data of 499 patients was collected over a 2-year period. A sample of 87 patients was taken and analyzed. Health-care utilization was measured as work disability days and hospital bed days. Sociodemographic, mental as well as somatic variables were used as possible predictors of health-care utilization.In a linear regression model with work disability days, the variables gender (b = 43.01; p = 0.032) and depressiveness (b = 2.949; p = 0.014) turned out to be significant (R(2) = 0.189). In a linear regression model with hospital bed days, the variables gender (b = 19.863; p = 0.006) and age (b = 0.785; p = 0.029) proved to be significant (R(2) = 0.114). No significant result was found for somatic variables such as severity of disease.Psychosocial variables such as depressiveness, gender and age have, therefore, a low but measurable impact on health-care utilization of patients with Crohn's disease. Increased consideration of these variables in clinical practice would not only improve the quality of life of these patients but also reduce health-care utilization.

Changes in the German hospital system like the introduction of the DRG compensation system suggest the usefulness of considering the modification of inpatient psychosomatic treatment options. Patients in a university hospital underwent diagnosis-related psychosomatic treatment in the wards of other departments after instituting the allocated bed model. The report presented here points out chances and risks of such a change. First psychodiagnostic assessments indicate a significant improvement of symptoms in these patients. Despite the overall positive result obtained thus far, the institutional and administrative framework conditions for such a change should be carefully considered and further evaluated.

Possible effects of psychological stress on the function of phagocytic cells have thus far hardly been investigated. In this study, we examined the phagocytic production of reactive oxygen species (ROS) in 10 healthy subjects undergoing a brief mental stressor. In a crossover design, the same subjects served as their own unstressed controls on a second experimental date. The acute laboratory stress resulted in a suppressed circadian rhythm of ROS production and in a decreased overall formation of ROS throughout the day. Especially under conditions of chronic stress, this finding may be of importance for the host's defense against infectious diseases.

Psychophysiological course studies are still the exception in AP hospitalized for psychotherapy. The aim of this study was to perform a more precise psychophysiological analysis of anxiety patients (AP) before and after hospital treatment. From a sample of 28 AP, 13 were psychophysiologically and psychodiagnostically examined and compared to controls (CG) at the beginning and end of in-patient psychotherapy and 4 months later. APs showed higher heart rate (HR) and electrodermal spontaneous fluctuation (SF) than control patients but did not differ in their resting systolic (SBP) and diastolic blood pressure (DBP). Under cognitive stress, the controls had a significantly stronger HR and SBP reaction, while the AP showed more SF during the tone sequence and while being asked about their subjectively experienced anxiety. Following inpatient psychotherapy, the two groups showed correlation in their vegetative reaction patterns. The study clearly demonstrates the effectiveness of the applied depth psychology-oriented multimodal therapy from a psychophysiological standpoint.

Background: Numerous studies have described distinctive immunological findings in patients with depression. In contrast, only very little is known about the possible influence of anxiety disorders on the immune system. It is also unknown whether treatment with psychotherapy alone has any influence on immunological variations in patients with psychiatric disorders. Methods: We measured immunological and psychological parameters in patients with minor depression (N=10) or anxiety disorder (N=13) over an 8-week course of inpatient psychotherapy. Data for patients and a group of healthy controls (N=11) were recorded three times in 4-week intervals. A FACS analysis revealed the composition of lymphocyte subpopulations. The production of reactive oxygen species (ROS) by phagocytes was analyzed using lucigenin-enhanced chemiluminescence. Results: On admission, patients with anxiety disorder showed a markedly elevated ratio of CD4+ (T helper) versus CD8+ (T suppressor/cytotoxic) lymphocytes compared to healthy controls (P

The influences of physicians' and patients' gender on the prescription behaviour seems to be important in background of epidemiology, economy and medicine.Dataset of 24 physicians (general and internal medicine) and their 11 322 patients in 1995 and 1996 were examined focusing the prescription of psychopharmaceuticals, analgesics and hypnoticals.Distinct effects of physicians gender were shown: Male physicians prescribed more frequently drugs in all three groups (p0,001). In the prescription of analgesics, male physicians prescribed significantly more daily defined doses (DDD) (p = 0,001). Concerning the patients' gender it was shown, that female patients received psychopharmaceuticals significantly more frequently than male patients.The results point out that there are differences in the prescribing behaviour of psychopharmaceuticals, analgesics and hypnoticals. This surprising result should be taken into consideration in research and training of physicians.

The aetiopathogenesis of essential hypertension has been more intensively investigated in recent years mainly in genetic high-risk groups and patients with transitory and early forms of essential hypertension. A group of 29 patients with mild hypertension according to the WHO criteria were submitted to hypertensiological, psychological and psychophysiological specification in this study. Twenty-four hour blood measurements were performed for this purpose. The group could thus be divided into 18 patients with white-coat hypertension (WH) and 11 patients with real mild hypertension (H). Contrary to expectations, mild hypertensives had weaker systolic (p0.05) and diastolic (p0.01) blood pressure reactions to mental stress than white-coat hypertensives. Their cardiovascular recovery was not reduced after stress. Psychological differences between the groups were only found with respect to irritability (FP1: H 6.9 sd 2.1, WH 5.2 sd 2.1 stanine) and hypertensives compared to the reference random sample on the FPI scale emotional instability (6.5 stanine). Other psychosomatic studies should replicate the results obtained in this study in larger patient populations with white-coat and mild hypertension.

Few studies have been published on the influence of psychotherapy on the physical and psychosocial course of Crohn's disease (CD).The present study, a prospective, randomized multicenter investigation conducted with 108 of 488 consecutive CD patients, was designed to investigate the influence of short-term psychodynamic therapy and relaxation in addition to a standardized glucocorticoid therapy on the somatic course of the disease as well as on patient psychosocial status. Based on the same standardized somatic treatment, the psychotherapy and control groups were compared after a 1-year treatment period and a follow-up of another year with regard to somatic course and psychosocial situation.A total of 81 (75%) of 108 randomized patients completed the psychosocial follow-up. The comparison between the therapy groups after 1 year showed no significant differences in the four main target criteria of psychosocial status (depression, anxiety, psychosocial-communicative status and health-related quality of life). The mean Beck's Depression Inventory (BDI) score at admission was 12.3 in the psychotherapy group and 8.7 in the control group. At the 1-year follow-up, the scores for depression have been 7.8 (psychotherapy group) and 7.8 (control group). In the 2-year follow-up, 84 patients were classified into four groups on the basis of somatic course; 23% of the control group and 30% of the psychotherapy group showed episode-free courses, 29% and 17% respectively underwent surgery due to failure of immunosuppressive or medical therapy, and a further subranking showed no significant differences between the two groups (P=.125). At the 1-year follow-up, the scores for depression of patients with an active episode respective remission were 14.6 vs. 5.8. From the patient's point of view, at the end of the 2-year follow-up, the overall subjective evaluation of the effectiveness of psychotherapy was positive.The patients included showed no psychosocial disturbances of clinical relevance. Although a tendency toward fewer surgical interventions, fewer relapses and reduction of depression was noted, the analysis was unable to demonstrate any benefit from psychosocial intervention on hypothesized parameters of psychosocial status and somatic course. Further studies should be performed to identify patient subgroups that may benefit from psychosocial intervention.

Salt-sensitive normotensive men exhibit an enhanced pressor response to mental stress. Although an enhanced pressor response is associated with higher affective startle modulation in men, an association between salt sensitivity of blood pressure and affective startle modulation has not been studied so far. We studied reactivity to mental stress and startle modulation in 14 salt-sensitive healthy white male students and 14 salt-resistant control subjects, who were well matched for age, body mass index, physical fitness, and family history of hypertension. Subjects performed a computerized information-processing task under time pressure (manometer test), while heart rate and blood pressure were continuously registered. In a separate session, subjects viewed a series of 42 pictures of the International Affective Picture System (IAPS), varying in pleasure and arousal, while acoustic startle probes were administered randomly, and electromyogram activity of the orbicular eye muscle was continuously recorded. Startle modulation was calculated as the difference between startle responses under negative and positive affective stimuli. In contrast to salt-resistant subjects, salt-sensitive subjects showed significantly enhanced startle amplitudes under negative stimuli and diminished amplitudes under positive stimuli. Thus, salt-sensitive subjects displayed a significantly higher startle modulation than did salt-resistant subjects ( P

To evaluate the psychophysiological response to mental stress of young healthy salt-sensitive normotensive subjects.Thirty-two healthy volunteers who had previously been phenotyped for salt sensitivity were selected for the study. The 16 salt-sensitive and 16 salt-resistant subjects, who were matched for age, body mass index and family history of hypertension, underwent a mental stress test consisting of an information-processing task performed under time pressure (the Manometer test). During the experimental session the blood pressure, heart rate and pulse-wave velocity were registered continuously. Before and after the mental task subjects were instructed to complete several standardized psychological state and trait questionnaires.Mental stress resulted in a greater rise in blood pressure (P0.05) and in pulse-wave velocity (P0.01) in salt-sensitive than in salt-resistant individuals. Salt-sensitive subjects also displayed significantly higher levels of anxiety (P0.01) and a lower level of control of anger (P0.01) than did salt-resistant subjects. Furthermore, the level of irritation of the salt-sensitive subjects was higher both before (P0.01) and after (P0.05) the stress testAn increased responsiveness of the blood pressure to mental stress and an increased level of irritation are associated with salt sensitivity in normotensive subjects. These findings are in line with the hypothesis that psychophysiological traits play a role in the development of salt-sensitive hypertension.

Of 103 patients with anorexia nervosa, 50 women and 5 men were followed-up on the average 11.8 year after clinical presentation with a differentiated method for body awareness according to Askevold. A considerable number of women with body image disturbances, however, largely corresponded to those of a healthy female control group. Both the male anorexia nervosa patients and the healthy male controls had normal findings. Applying to touch-induced stimulus, the body assessment indices only increased in former male anorexia patients but remained the same in female anorexia patients, while they clearly normalized in the sense of a realistic assessment in the two healthy control groups. Surprisingly, there was only little correlation between the visually measured body perception disorder and the self (EDI) and expert assessment (Sianex) at the time of follow-up (exception: the EDI scale 3 [dissatisfaction with one's own body). The global expert rating of body image disturbances at clinical presentation was important as a predictor for the severity of anorexia nervosa after 12 years. The findings were discussed under methodological and clinical aspects.

The present study includes 40 patients with Crohn's disease who underwent an internal and psychodiagnostic examination over a period of 5 to 8 weeks. On the average, there were only minor psychic symptoms were recorded in the psychodiagnostic instruments. The fewest symptoms were seen in the recurrence-free interval, a moderate number at the beginning of intermittent inpatient treatment and the largest number of symptoms in patients transferred to a psychosomatic department. While decreasing significantly from high levels under internal intensive care and at the beginning of inpatient depth-analysis-based psychotherapy, symptoms of depression and anxiety dropped only slightly from initially low levels in outpatients. In addition, there were first changes in the patients personality profile during psychotherapy. The findings are discussed under diagnostic and therapeutic aspects.

It was the aim of the present study to identify correlations between social, psychological and physical findings in 57 unselected patients with Crohn's disease from a gastroenterological outpatient department. Social support was registered using the confidant rating and the social network using a network questionnaire. Additional internal-medical and psychodiagnostic test instruments were used for a specific description of the sample. Anxieties, depressive moods and emotional lability were significantly less pronounced in patients with a confidant than in those without or with a less supportive partner. And the former also seemed to be more able to adequately cope with the disease than the patients of the other groups. With respect to the physical findings, the differences between the groups were less pronounced: Nevertheless, patients who were supported by a partner tended to show lower activity levels for Crohn's disease (Best index) than the others. The results obtained by the network questionnaire were less specific but altogether confirmed the results of the confidant rating. The study confirms the results of comparable investigations done in other clinical patient groups. The construct of social support is discussed critically with respect to psychoanalytical and family-dynamic concepts.