Heart rate variability in patients with post-traumatic stress disorder or borderline personality disorder: relationship to early life maltreatment.

Traumatic experiences have severe impact on the autonomous nervous system. Heart rate variability (HRV) is a reliable psychophysiological marker for the autonomous nervous system functioning. Reduced vagally mediated HRV has been found in patients with post-traumatic stress disorder (PTSD) and, in some studies, in patients with borderline personality disorder (BPD). In this study, we compared HRV parameters of patients with PTSD, current BPD, and BPD in remission with healthy volunteers in a 5 min resting-state electrocardiogram recording. 91 unmedicated female participants took part in the study (18 with PTSD, 27 with the current BPD, 23 with BPD in remission, and 23 healthy volunteers). We found significant group differences in both time-domain and frequency-domain (total power, low-frequency and high-frequency power) HRV parameters. Root mean square of the successive differences (RMSSD) was lowest in patients with PTSD (M = 48.6 ms, SD = 23.5 ms) followed by patients with BPD in remission (M = 57.7 ms, SD = 31.5 ms) and patients with the current BPD (M = 71.1 ms, SD = 44.5 ms), while the highest RMSSD was found in healthy volunteers (M = 84.1 ms, SD = 41.7 ms). Variance of HRV was higher in patients with BPD than in patients with PTSD. In addition, RMSSD was significantly negatively correlated with self-reported early life maltreatment assessed with the Childhood Trauma Questionnaire. Our findings point out a complex interaction between traumatic experiences, the functioning of the autonomic nervous system, and psychopathology. Alterations in HRV might be related to early life maltreatment or associated psychological factors rather than diagnostic entities.

Grey matter abnormalities within cortico-limbic-striatal circuits in acute and weight-restored anorexia nervosa patients.

Functional disturbances within cortico-striatal control systems have been implicated in the psychobiology (i.e. impaired cognitive-behavioral flexibility, perfectionist personality) of anorexia nervosa. The aim of the present study was to investigate the morphometry of brain regions within cortico-striatal networks in acute anorexia nervosa (AN) as well as long-term weight-restored anorexia nervosa (AN-WR) patients. A total of 39 participants: 12 AN, 13 AN-WR patients, and 14 healthy controls (HC) underwent high-resolution, T1-weighted magnetic resonance imaging (MRI), a cognitive-behavioral flexibility task, and a psychometric assessment. Group differences in local grey matter volume (GMV) were analyzed using whole brain voxel-based morphometry (VBM) and brain-atlas based automatic volumetry computation (IBASPM). Individual differences in total GMV were considered as a covariate in all analyses. In the regional brain morphometry, AN patients, as compared to HC, showed decreased GMVs (VBM and volumetry) in the anterior cingulate cortex (ACC), the supplementary motor area (SMA), and in subcortical regions (amygdala, putamen: VBM only). AN-WR compared to HC showed decreased GMV (VBM and volumetry) in the ACC and SMA, whereas GMV of the subcortical region showed no differences. The findings of the study suggest that structural abnormalities of the ACC and SMA were independent of the disease stage, whereas subcortical limbic-striatal changes were state dependent.

Temporal relationships of emotional avoidance in a patient with anorexia nervosa--a time series analysis.

OBJECTIVE: Anorexia nervosa (AN) is a serious eating disorder marked by self-induced underweight. In patients with AN, the avoidance of emotions appears to be a central feature that is reinforced during the acute state of the disorder. This single case study investigated the role of emotional avoidance of a 25-year-old patient with AN during her inpatient treatment. METHOD: Throughout the course of 96 days, the patient answered questions daily about her emotional avoidance, pro-anorectic beliefs, perfectionism, and further variables on an electronic diary. The patient's daily self-assessment of emotional avoidance was described in terms of mean value, range, and variability for the various treatment phases. Temporal relationships between emotional avoidance and further variables were determined using a time series approach (vector autoregressive (VAR) modelling). RESULTS: Diary data reflect that the patient's ability to tolerate unpleasant emotions appeared to undergo a process of change during inpatient treatment. Results of the time series analysis indicate that the more the patient was able to deal with negative emotions on any one day (t-1), the less she would be socially avoidant, cognitively confined to food and eating, as well as feeling less secure with her AN, and less depressive on the following day (t). CONCLUSIONS: The findings show that for this patient emotional avoidance plays a central role in the interacting system of various psychosocial variables. Replication of these results in other patients with AN would support the recommendation to focus more on emotional regulation in the treatment of AN.

Immunogenicity and safety of H1N1 vaccination in anorexia nervosa--results from a pilot study.

OBJECTIVE: In anorexia nervosa (AN) patients immunologic alterations are known, although their clinical significance remains a matter of debate. Currently, no recommendation can be given on the safety and immunogenicity of indicated vaccinations in this malnourished population. METHOD: In this exploratory study, 10 AN patients' (eight female, two male, mean age 31.1 years, SD 16.3 years; mean BMI 14.8 kg/m(2), SD 1.6 kg/m(2)) antibody levels against H1N1 influenza were measured before vaccination, and were followed-up for two and three weeks after vaccination. They were compared with the immunological response in normal weight population, as reported in the literature. Clinical and socio-demographical data were collected. RESULTS: In the AN group, H1N1 vaccination showed to be sufficiently immunogenic and safe, comparable to published data of normal weight population. DISCUSSION: The findings provide preliminary evidence that vaccination seems recommendable even in extremely underweight AN patients. Further studies are needed to corroborate the present findings.

Elevated myocardial enzymes and natriuretic peptides in anorexia nervosa: prototypic condition for the pathophysiology of cachexia?

We report on a patient suffering from chronic anorexia nervosa who in the course of treatment showed elevated high-sensitive troponin T, creatine kinase and most markedly N-terminal pro-brain natriuretic peptide (NT-proBNP). Elevated enzymes improved significantly throughout the course of treatment without cardiac specific medication but exceeded the normal range for weeks. Abnormally high myocardial enzymes and NT-proBNP in cachectic anorectic patients might resemble conditions of cardiac cachexia. A review of the available literature is provided. Further research is required to explain the pathophysiological meaning of the abnormal laboratory findings.

[Patients' perspectives on behavioral and cognitive changes after hospitalization: a 3-month follow-up cohort study using qualitative and quantitative research methods]. / Verhaltens- und Einstellungsänderungen nach Behandlung auf einer internistichen beziehungsweise internistisch-psychosomatischen Akutstation - eine qualitative und quantitative naturalistische Katamnesestudie.

OBJECTIVES: To describe patients' subjective perspectives on hospitalization at time of admission, to prospectively investigate patients' views on changes actually achieved after discharge, and to identify predictors of subjective changes 3 months after hospitalization. METHODS: We conducted a 3-month follow-up cohort study using qualitative and quantitative research methods. Consecutive adult inpatients of an internal medicine ward and a ward integrating internal and psychosomatic medicine were included. They answered open-ended questions concerning their motivation for change at the time of admission (N = 639) using self-report questionnaires and 3 months post hospitalization via a telephone interview (N = 389). Qualitative content analysis was performed. Predictors of subjective change 3 months after hospitalization were identified using multivariate logistic regression analyses. RESULTS: At admission, more psychosomatic patients than internal-medicine ward patients wanted to achieve change (58% vs. 44 %). Patients expressed desires that were assigned to three main categories: to pay more attention to one's physical health (40 %), to change one's perceptions (32 %), and to change one's way of life (16 %). Three months after discharge, 52 % of patients had experienced cognitive and behavioral changes they attributed to their hospitalization. 31 % of the patients reported continuing to implement changes that had begun during hospitalization. Predictors of subjective change 3 months after hospitalization included high educational level (OR = 2.04, 95 %-CI 1.27-3.26), young age (OR = 0.98, 95 %-CI 0.97-1.00), and length of hospitalization (OR = 1.03, 95 %-CI 1.00-1.05). CONCLUSIONS: There is considerable motivation for behavioral and cognitive change among inpatients following admission; this deserves the attention of healthcare professionals. An integrated psychosomatic setting would appear to support cognitive and behavioral changes more effectively than a classical internal medicine ward.

[Outcome of simultaneous psychosomatic/internal-medicine inpatient care--a naturalistic follow-up study]. / Behandlungsverlauf stationär-internistisch-psychosomatischer Versorgung--eine prospektive, naturalistische Studie.

OBJECTIVES: The effectiveness of simultaneous psychosomatic and internal-medicine inpatient care has not yet been satisfyingly investigated. What outcome is found in patients treated in a psychosomatic/internal medicine setting? Can we predict a reduction in depression and symptom severity? METHODS: The study design is prospective and naturalistic. Patients from a psychosomatic/internal-medicine setting and a solely internal-medicine ward filled in self-report questionnaires on the day of admission, five days thereafter, and three months after discharge. RESULTS: A total of 221 patients from a psychosomatic/internal-medicine setting and 418 patients from a solely internal-medicine ward were included. Patient characteristics differed significantly between the two wards. Treatment was associated with a reduction of depression and somatic symptom severity over time. Depression severity improved more in the psychosomatic/internal-medicine setting than in the internal-medicine ward (ES = 0.37 vs. ES = 0.65). The strongest predictor of improvement of depression and somatic symptom severity was the patients' belief that their physical well-being was influenced by psychological factors (B = 1.44 and 1 = 0.65). CONCLUSIONS: The results document a differential approach to admission in an integrated psychosomatic/internal medicine setting and underline the favourable course for psychological and somatic symptoms.

Neural correlates of impaired cognitive-behavioral flexibility in anorexia nervosa.

OBJECTIVE: Impaired cognitive-behavioral flexibility is regarded as a trait marker in anorexia nervosa patients. The authors sought to investigate the neural correlates of this deficit in executive functioning in anorexia nervosa. METHOD: Fifteen women with anorexia nervosa and 15 age-matched healthy comparison women underwent event-related functional MRI while performing a target-detection task. The task distinguished between shifts in behavioral response and shifts in cognitive set. It involved infrequent target and non-target distractor stimuli embedded in a sequence of prepotent standard stimuli. RESULTS: Relative to comparison subjects, anorexia nervosa patients showed a significantly higher error rate in behavioral response shifting, independent of whether those runs also involved cognitive set shifting. During behavioral response shifting, patients showed reduced activation in the left and right thalamus, ventral striatum, anterior cingulate cortex, sensorimotor brain regions, and cerebellum that differed significantly from the comparison group but showed dominant activation in frontal and parietal brain regions. These differential activations in patients and comparison subjects were specific to shifts in behavioral response: except for thalamic activation, they were not observed in response to non-target distractor trials that required no alteration in behavioral response. CONCLUSION: Impaired behavioral response shifting in anorexia nervosa seems to be associated with hypoactivation in the ventral anterior cingulate-striato-thalamic loop that is involved in motivation-related behavior. In contrast, anorexia nervosa patients showed predominant activation of frontoparietal networks that is indicative of effortful and supervisory cognitive control during task performance.

Risk factors of symptom underestimation by physicians.

OBJECTIVE: The aims of this study were to characterize patient-physician agreement on various psychological and somatic symptoms in internal medicine inpatients and to identify predictors of symptom severity underestimation by physicians. METHODS: Consecutive adult inpatients of two internal medicine wards of a university hospital completed visual analogue scales (VASs) for severity of disability, anxiety, depression, somatic symptoms, and pain at the time of admission (n=639, participation rate=70%) and 5 days thereafter (n=401, participation rate=82%). In addition, the Patient Health Questionnaire 9 (PHQ-9) depression scale and the Clinical Global Impression Scale--Revised were used. At the same time, the six treating physicians independently rated the complaints of their patients using the same VAS. Rates of overestimation, concordance, and underestimation of symptom severity were analyzed. Logistic regression analyses were used to identify predictors of symptom underestimation by physicians. RESULTS: Concordance between patients and physicians regarding disability, anxiety, depression, somatic symptom severity, and pain reached 50-60%. Symptom severity of patients suffering from major depressive episode was significantly more often underestimated than that of nondepressed patients (all P<.01). Of all the variables, greater depression on the PHQ depression score was the most important risk factor for symptom underestimation by physicians (OR ranging from 1.29 to 1.57; all P<.05, except underestimation of disability). Symptom underestimation of pain severity was also associated with panic disorder symptoms (odds ratio, 2.44; P=.01). CONCLUSION: Depressed patients seem to be at greater risk of symptom underestimation by their physicians--a finding bearing implications for avoidance of underdiagnosis and insufficient treatment. Mutual understanding could be improved by better doctor-patient communication skills. Brief self-report depression screeners might help to reliably identify patients at risk for symptom underestimation by physicians.

IL-10 inhibits endothelium-dependent T cell costimulation by up-regulation of ILT3/4 in human vascular endothelial cells.

Effects of IL-10 on endothelium-dependent T cell activation have not been investigated in detail. We confirm expression of the IL-10 receptor and effective signaling via STAT-3 in human umbilical vein endothelial cells (HUVEC). In CD4 T cell cocultures with HUVEC, pretreatment of endothelial cells with IL-10 resulted in significant dose-dependent inhibition of CD4 T cell proliferation, which also occurred when IL-10 was removed after pretreatment before starting cocultures. Th1/Th2 polarization of proliferated T cells, endothelial nitric oxide (NO), or IL-12 production were unchanged. However, IL-10 stimulation resulted in up-regulation of SOCS-3, a negative regulator of cytokine secretion, and induction of the inhibitory surface molecules immunoglobulin-like transcript 3 and 4 (ILT3/ILT4) in EC, potentially involving glucocorticoid-induced leucine zipper (GILZ). Addition of blocking antibodies against ILT3/ILT4 to EC/T cell cocultures resulted in nearly complete reestablishment of T cell proliferation. In contrast, addition of soluble ILT3 or overexpression of ILT3 in cocultures significantly reduced T cell proliferation. No induction of foxp3+ regulatory T cells was seen. In conclusion, the T cell costimulatory potential of human EC is markedly suppressed by IL-10 due to up-regulation of ILT3/ILT4, obviously not involving generation of Treg. This identifies a novel action of IL-10 in EC and a potential therapeutical target for local immunomodulation.