Publications by authors named "Martin Siepmann"

39 Publications

Effect of a biofeedback intervention on heart rate variability in individuals with panic disorder: A randomized controlled trial.

Psychosom Med 2021 Oct 12. Epub 2021 Oct 12.

Medical Psychology and Medical Sociology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany Clinic for Psychotherapy and Psychosomatic Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany Department of Psychosomatic Medicine und Psychotherapy, University Bonn, Bonn, Germany.

Objective: Some individuals with panic disorder (PD) display reduced heart rate variability, which may result in an increased risk of cardiovascular mortality. Heart rate variability-biofeedback (HRV-BF) training has been shown to improve the modulation of the autonomic activity. Therefore, this randomized controlled trial was conducted to investigate the effect of a four-week HRV-BF intervention in individuals with PD. Heart rate variability-biofeedback (HRV-BF) training improved the modulation of the autonomic activity. Therefore, with this randomized controlled trial we aimed to investigate the effect of a four-week HRV-BF intervention in people with PD.

Methods: Thirty-six women and sixteen men with PD (mean age: 35.85 ± 15.60 years) were randomly allocated either to HRV-BF with 0.1 Hz breathing as intervention group or to HRV-Sham-BF as active control group. HRV-BF was performed over four weeks while HRV was measured both during a short-term resting condition as well as during a paced breathing condition before and after intervention.

Results: HRV-BF with 0.1 Hz breathing increased HRV and reduced panic symptoms in individuals with PD. HRV-BF with 0.1 Hz breathing demonstrated an increase in the time and frequency domain parameters of HRV during the short-term resting condition (ΔPost-Pre RMSSD: 5.87 ± 14.03 ms; ΔPost-Pre SDNN: 11.63 ± 17.06 ms; ΔPost-Pre Total Power: 464.88 ± 1825.47 ms2; ΔPost-Pre LF: 312.73 ± 592.71 ms2), a decrease in the heart rate during the paced breathing condition (ΔPost-Pre: -5.87 ± 9.14 b/min), and a decrease in the Panic & Agoraphobia Scale (ΔPost-Pre: -3.64 ± 6.30). There was no intervention effect in the HRV-Sham-BF group.

Conclusions: HRV-BF as a non-invasive and non-pharmacological treatment seems to be an important intervention option to improve reduced HRV and decrease panic symptoms in individuals with PD. Future studies are needed to establish whether these effects translate to reductions in the risk of cardiovascular disease in PD.
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http://dx.doi.org/10.1097/PSY.0000000000001031DOI Listing
October 2021

Myxedema Psychosis: Systematic Review and Pooled Analysis.

Neuropsychiatr Dis Treat 2021 18;17:2713-2728. Epub 2021 Aug 18.

Department of Health Care Sciences, Center for Clinical Research and Management Education, Dresden International University, Dresden, Germany.

Background And Objective: The term myxedema psychosis (MP) was introduced to describe the occurrence of psychotic symptoms in patients with untreated hypothyroidism, but the optimal assessment and treatment of this condition are unclear. We aimed to synthesize data from the literature to characterize the clinical presentation and management of MP.

Methods: We performed a systematic review according to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines in PubMed (Medline), Embase, Google Scholar, and Cochrane databases, including observational studies, case series, and case reports published from 1/1/1980 to 31/12/2019 in the English language. Descriptive statistics along with univariate and multivariate analysis were used for data synthesis.

Results: Out of 1583 articles screened, 71 case reports met our inclusion criteria providing data on 75 MP cases. The median age at diagnosis was 42 years [32-56]. About 53% had no prior hypothyroidism diagnosis. Delusions occurred in 91%, with a predominance of persecutory ideas (84%), while hallucinations occurred in 78%. Physical symptoms and signs of hypothyroidism were absent in 37% and 26%, respectively. If symptoms occurred, nonspecific fatigue was seen most frequently (63%). The median thyroid-stimulating hormone value was 93 mIU/L [60-139]. Thyroid peroxidase antibodies were found positive in 75% (23/33) of reported cases. Creatinine kinase was reported abnormal in seven cases. Cranial imaging (CT or MRI) and electroencephalogram were normal in 89%, 75%, and 73% of the cases reported. The majority of patients were treated orally with thyroxine in combination with short-term antipsychotics. More than 90% of them showed complete recovery. Univariate analysis revealed a trend towards a shorter duration of psychosis with IV thyroid hormone therapy (= 0.0502), but the effect was not consistent in a multivariate analysis.

Conclusion: While we identified a substantial lack of published research on MP, our pooled analysis of case observations suggests that the condition presents a broad spectrum of psychiatric and physical symptoms lending support to the value of screening for thyroid dysfunction in patients with first-ever psychosis.

Prospero Registration Number: CRD42020160310.
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http://dx.doi.org/10.2147/NDT.S318651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382967PMC
August 2021

Comparison of the HRV of Emergency Physicians in the HEMS During Helicopter Operations: Analysis of Differences as a Function of Number of Operations and Workload.

Appl Psychophysiol Biofeedback 2020 12;45(4):249-257

Medical Psychology & Medical Sociology, University Medical Center of the Johannes Gutenberg - University Mainz, Duesbergweg 6, 55128, Mainz, Germany.

Chronic stress can lead to physiological illness. Emergency physicians in danger of developing such illnesses due to their demanding working environment. The aim of this study was to investigate the physiological stress level of emergency physicians (EPs) of the Helicopter Emergency Medical Service (HEMS) between emergency operations in one shift. Furthermore, the phases of the operations were compared with respect to the activity of the autonomic nervous system. The physiological and self-perceived stress levels of 20 EPs were recorded on a HEMS air-rescue-day (age: M = 44.95, SD = 4.80). The measurement of the heart rate variability (HRV) was performed during a complete air-ambulance day and examined using analyses of variance. The heart rate rises significantly at the beginning of the emergency operation to its highest value after landing at the operation site. The HRV parameter standard deviation of all NN intervals shows a significant decrease between the alarm phase and the end of the operation. Furthermore, high values were reached regarding chronic stress. On the Symptom Checklist-90 the EPs show lower values than the norm sample. In conclusion, over the course of three emergency operations, no physiological fatigue indicators were found. In contrast, the subjective stress load was assessed as high among EPs and on average higher than the norm sample. Compared to standard values, the EPs showed lower HRV values, which indicates a strong activation of the autonomic nervous system. These lower HRV findings might be caused by a high psychological stress load.
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http://dx.doi.org/10.1007/s10484-020-09480-1DOI Listing
December 2020

Randomized controlled three-arm study of NADA acupuncture for alcohol addiction.

Addict Behav 2020 11 31;110:106488. Epub 2020 May 31.

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. Electronic address:

Introduction: Alcohol addiction compromises cardiovascular health, possibly due to impaired control of the heart and vasculature by the autonomic nervous system. We aimed to assess the effects of National Acupuncture Detoxification Association (NADA) acupuncture on cardiovascular autonomic functions, psychiatric comorbidities and abstinence in patients addicted to alcohol.

Material And Methods: A randomized sham controlled three-arm study was undertaken in 72 patients (nine females, aged 43.7 ± 9.2 years, mean ± SD) undergoing in-patient rehabilitation for alcohol addiction. Patients were randomly allocated (1:1:1) to receive twenty 30-minute NADA or sham acupuncture sessions within six weeks or no intervention. They were evaluated for craving, depression, anxiety and autonomic control of the heart (heart rate variability, HRV), vasculature (laser Doppler flowmetry) and sweat glands (sympathetic skin response). Testing was performed at baseline, immediately post intervention (sham intervention or control period, respectively) and another four weeks later. Abstinence was assessed one year after study completion.

Results: Patients in the NADA arm displayed increased HRV immediately post-intervention compared to baseline (SDNN: 72.8 ms ± 34.2 ms vs. 57.9 ms ± 31.2 ms, p = 0.001). This increase was sustained four weeks later (66.2 ms ± 32.4 ms, p = 0.015). HRV remained unaltered following sham or no acupuncture (p = n.s.). Autonomic function of vasculature and sweat glands, psychiatric comorbidities and one-year abstinence did not differ between study arms.

Conclusions: NADA acupuncture may improve autonomic cardiac function. However, this improvement appears not to translate into alleviation of psychiatric comorbidities or sustained abstinence.
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http://dx.doi.org/10.1016/j.addbeh.2020.106488DOI Listing
November 2020

Continuous HRV analysis of HEMS emergency physicians to specify the work load over the different working days.

Int Arch Occup Environ Health 2020 05 16;93(4):525-533. Epub 2019 Dec 16.

Medical Psychology and Medical Sociology, Clinic and Policlinic for Psychosomatic Medicine and Psychotherapy, University Medicine Mainz, Duesbergweg 6, 55128, Mainz, Germany.

Introduction: Up to date, there has been little research about the acute stress load of emergency physicians of the Helicopter Emergency Medical Service (HEMS). Therefore, this study investigates the physiological stress level between an air-rescue day, a clinic day, and a day off (control day). Furthermore, phases of activity and resting were compared to assess the activity of the autonomic nervous system (ANS).

Methods: In this field study (within-subjects design), heart rate variability (HRV) and self-perceived stress levels were monitored on an air-rescue day, a clinic day, and a control day of 20 HEMS EPs [three females, 17 males; age: mean (M) = 44.95, standard deviation (SD) = 4.80].

Results: When comparing the activity phases, significant differences were found for HR and HRV. The highest HR was found on the air-rescue day during the phase of landing at the operation site with M = 107.30 bpm (SD = 22.66 bpm), which was significantly higher than during activity phases of the clinic day (M = 88.28 bpm, SD = 11.81 bpm) and the control day (M = 83.28 bpm, SD = 14.83 bpm). The SDNN is significantly higher on the air-rescue day for the phase before the alarm (M = 72.23 ms, SD = 38.60 ms), the phase of the alarm (M = 77.52 ms, SD = 40.52 ms), and the average of all phases (M = 60.04 ms, SD = 34.07 ms) than on the clinic day (M = 38.42 ms, SD = 15.16 ms) and the control day, where the lowest value was reached (M = 39.11 ms, SD = 17.65 ms). The highest LF/HF was found during activity phases of the clinic day with M = 1281.84% (SD = 587.33%), which was significantly higher than the first five phases of the emergency operations and the average of all phases of the emergency operations of the air-rescue day, where a maximum of M = 896.57 ms (SD = 681.79 ms) during the phase before the alarm and a minimum of M = 764.69 ms (SD = 372.28 ms) during the phase of landing at the operation site. The lowest LF/HF for all testing days was found during the activity phases of the control day with M = 693.74% (SD = 404.73%). Overall, 60 observations were analyzed. In the psychological assessment, on average, the EPs shows lower values than the norm sample.

Discussion: In the comparison of the activity phases, significant effects were found on the clinic day and during the phases of the emergency operations of the air-rescue day for the HR and HRV. Hereby, a significant activation of the EPs ANS and an outweigh of the sympathetic nervous system could be shown, whereby the subjective stress load was reported mainly as low. For the resting phases, no significant differences were found between all testing days. We interpret this as a good sign for the ability of regeneration between the phases of high stress load.
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http://dx.doi.org/10.1007/s00420-019-01507-3DOI Listing
May 2020

Improving the Course of Depressive Symptoms After Inpatient Psychotherapy Using Adjunct Web-Based Self-Help: Follow-Up Results of a Randomized Controlled Trial.

J Med Internet Res 2019 10 24;21(10):e13655. Epub 2019 Oct 24.

Department of Psychosomatic Medicine and Psychotherapy, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.

Background: We recently showed in a randomized controlled trial that Web-based self-help as an adjunct improved the effectiveness of multimodal inpatient psychotherapy for depression.

Objective: The aims of this study were (1) to determine whether a Web-based self-help adjunctive to multimodal inpatient psychotherapeutic treatment could also improve the course of depressive symptoms and (2) to identify predictors of residual depressive symptoms at follow-up.

Methods: Overall, 229 patients were randomized either to the Web-based self-help intervention group (Deprexis) or an active control group (Web-based information about depression and depressive symptoms) in addition to multimodal inpatient psychotherapy. Participants in both groups were able to access their respective Web-based programs for 12 weeks, which meant that they typically had access after discharge from the inpatient unit (mean hospitalization duration: 40 days, T1). Follow-up was performed 6 months after study intake (T3).

Results: At follow-up, participants of the Web-based self-help group had considerably lower symptom load regarding depressive symptoms (d=0.58) and anxiety (d=0.46) as well as a better quality of life (d=0.43) and self-esteem (d=0.31) than participants of the control group. Nearly 3 times as many participants of the intervention group compared with the control group achieved remission in accordance with less deterioration. The number needed to treat based on the Beck Depression Inventory-II (BDI-II) improved over time (T1: 7.84, T2: 7.09, and T3: 5.12). Significant outcome predictors were BDI at discharge and treatment group.

Conclusions: Web-based self-help as an add-on to multimodal inpatient psychotherapy improved the short-term course of depressive symptoms beyond termination. Residual symptoms at discharge from inpatient treatment and utilization of the Web-based self-help were the major predictors of depressive symptoms at follow-up. Challenges and barriers (eg, costs, therapists' concerns, or technical barriers) of adding Web-based interventions to inpatient treatment have to be addressed.

Trial Registration: ClinicalTrials.gov NCT02196896; https://clinicaltrials.gov/ct2/show/NCT02196896.
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http://dx.doi.org/10.2196/13655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838691PMC
October 2019

Cardiac dysautonomia in depression - heart rate variability biofeedback as a potential add-on therapy.

Neuropsychiatr Dis Treat 2019 17;15:1287-1310. Epub 2019 May 17.

Division of Health Care Sciences, Dresden International University, Dresden, Germany.

Depressive disorders are among the most important health problems and are predicted to constitute the leading cause of disease burden by the year 2030. Aside significant impact on quality of life, psychosocial well-being and socioeconomic status of affected patients, depression is associated with impaired cardiovascular health and increased mortality. The link between affective and cardiovascular disease has largely been attributed to dysregulation of the autonomic nervous system resulting in a chronic shift toward increased sympathetic and decreased parasympathetic activity and, consecutively, cardiac dysautonomia. Among proposed surrogate parameters to capture and quantitatively analyze this shift, heart rate variability (HRV) and baroreflex sensitivity have emerged as reliable tools. Attenuation of these parameters is frequently seen in patients suffering from depression and is closely linked to cardiovascular morbidity and mortality. Therefore, diagnostic and therapeutic strategies were designed to assess and counteract cardiac dysautonomia. While psychopharmacological treatment can effectively improve affective symptoms of depression, its effect on cardiac dysautonomia is limited. HRV biofeedback is a non-invasive technique which is based on a metronomic breathing technique to increase parasympathetic tone. While some small studies observed beneficial effects of HRV biofeedback on dysautonomia in patients with depressive disorders, larger confirmatory trials are lacking. We reviewed the current literature on cardiac dysautonomia in patients suffering from depression with a focus on the underlying pathophysiology as well as diagnostic workup and treatment.
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http://dx.doi.org/10.2147/NDT.S200360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529729PMC
May 2019

Early maladaptive schemas in patients with somatoform disorders and somatization.

Clin Psychol Psychother 2019 Jul 1;26(4):418-429. Epub 2019 Apr 1.

Department of Psychotherapy and Psychosomatic Medicine, University Hospital Dresden, Dresden, Germany.

Maladaptive schemas are stable relational patterns that develop through harmful childhood experiences with primary caregivers. Schemas within somatoform disorders are rarely explored even though these disorders are clinically important due to high prevalence, co-morbidity, and cost for the health care system. This study investigates schemas according to Young's schema theory in patients with somatoform disorders in comparison with healthy controls and patients with depressive or anxiety disorders. Further associations between schemas and somatization were explored. We included 134 patients with a somatoform disorder and 39 age-matched healthy controls, 83 patients with a unipolar depression, and 34 patients with an anxiety disorder. The clinical sample consists of day care patients, diagnosed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, but without a personality disorder. Primary measures were the Young Schema Questionnaire (YSQ-S2), the Screening for Somatoform Disorders (SOMS-7T), the Beck Depression Inventory, Second Edition, and the Childhood Trauma Questionnaire. Analyses of variance indicated that somatoform patients scored higher on almost all schemas than do healthy controls (p < 0.001, η  = 0.148). The highest mean scores were reached for the schemas "self-sacrifice" and "unrelenting standards," with significant higher values in the patient sample. However, when compared with patients with depressive or anxiety disorders, somatoform patients scored equally or even lower. High somatization was associated with generally higher schema activation. This effect was to a great extent mediated by depressive symptoms. Only the schema "vulnerability to harm or illness" was exclusively related to somatization. These findings suggest that schemas should be systematically assessed within psychotherapy of somatoform patients.
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http://dx.doi.org/10.1002/cpp.2363DOI Listing
July 2019

[Rehabilitants' Expectations and Informational Needs Concerning Inpatient Psychosomatic Rehabilitation - Results of a Qualitative Analysis].

Rehabilitation (Stuttg) 2019 Oct 5;58(5):304-311. Epub 2018 Oct 5.

Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie der Universitätsmedizin der Johannes Gutenberg-Universität Mainz.

Aim Of The Study: In order to develop an online portal for the preparation for inpatient psychosomatic rehabilitation, information requirements as well as the online use behavior of rehabilitants were determined first.

Methods: Four focus groups with rehabilitants (N=31) as well as two with the treatment team (N=18) were performed and evaluated qualitatively.

Results: A total of 419 statements by rehabilitants and 333 statements by the treatment team were coded and assigned to categories. Current information materials on rehabilitation have been regarded as too extensive and difficult to understand by rehabilitants. They were uncertain regarding the effectiveness and sustainability of the treatment. While practitioners assumed that rehabilitants expect wellness and relaxation during rehabilitation, rehabilitants themselves reported more of an active treatment orientation.

Conclusion: Online portals for preparation should address the effectiveness and sustainability of psychosomatic rehabilitation by means of illustrative case studies.
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http://dx.doi.org/10.1055/a-0645-9142DOI Listing
October 2019

Online Self-Help as an Add-On to Inpatient Psychotherapy: Efficacy of a New Blended Treatment Approach.

Psychother Psychosom 2017 3;86(6):341-350. Epub 2017 Nov 3.

Department of Psychosomatic Medicine and Psychotherapy, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.

Background: Depression is one of the most frequent and costly mental disorders. While there is increasing evidence for the efficacy of online self-help to improve depression or prevent relapse, there is little evidence in blended care settings, especially combined with inpatient face-to-face psychotherapy. Therefore, we evaluated whether an evidence-based online self-help program improves the efficacy of inpatient psychotherapy.

Methods: A total of 229 depressed patients were randomly allocated either to an online self-help program (intervention group [IG]; Deprexis) or an active control group (CG; weekly online information on depression) in addition to inpatient psychodynamic psychotherapy. Both groups had access to their respective experimental intervention for 12 weeks, regardless of inpatient treatment duration. Reduction of depressive symptoms, as measured with the Beck Depression Inventory-II, was the primary outcome at the end of the intervention (T2).

Results: Depressive symptoms were statistically significantly lower in the IG compared to the active CG at T2 with a moderate between-group effect size of d = 0.44. The same applied to anxiety (d = 0.33), quality of life (d = 0.34), and self-esteem (d = 0.38) at discharge from inpatient treatment (T1). No statistically significant differences were found regarding dysfunctional attitudes (d = 0.14) and work ability (d = 0.08) at T1.

Conclusions: This is the first evidence for blended treatment combining online self-help with inpatient psychotherapy. The study opens new and promising avenues for increasing the efficacy of inpatient psychotherapy. Future studies should determine how integration of online self-help into the therapeutic process can be developed further.
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http://dx.doi.org/10.1159/000481177DOI Listing
September 2018

Effect of short-term heart rate variability biofeedback on long-term abstinence in alcohol dependent patients - a one-year follow-up.

BMC Psychiatry 2017 09 6;17(1):325. Epub 2017 Sep 6.

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.

Background: A randomized controlled study (RCT) recently showed that short-term heart rate variability (HRV) biofeedback in addition to standard rehabilitation care for alcohol dependence can reduce craving, anxiety and improve cardiovascular autonomic function. In this one-year follow-up study we aimed to explore whether completion of 2-week HRV-Biofeedback training is associated with long-term abstinence. Furthermore, we sought to identify potential predictors of post-treatment abstinence.

Methods: We conducted a survey on abstinence in patients with alcohol dependence 1 year after completion of an RCT comparing HRV-biofeedback in addition to inpatient rehabilitation treatment alone (controls). Abstinence rates were compared and analysed for association with demographic data as well as psychometric and autonomic cardiac assessment before and after completion of the biofeedback training using bivariate and multivariate regression analyses.

Results: Out of 48 patients who participated in the RCT, 27 patients (9 females, ages 42.9 ± 8.6, mean ± SD) completed our one-year follow-up. When including in the analysis only patients who completed follow-up, the rate of abstinence tended to be higher in patients who underwent HRV-biofeedback 1 year earlier compared to those who received rehabilitative treatment alone (66.7% vs 50%, p = ns). This non-significant trend was also observed in the intention-to-treat analysis where patients who did not participate in the follow-up were assumed to have relapsed (46,7% biofeedback vs. 33.3% controls, p = ns). Neither cardiac autonomic function nor psychometric variables were associated with abstinence 1 year after HRV-biofeedback.

Conclusion: Our follow-up study provide a first indication of possible increase in long-term abstinence after HRV-biofeedback for alcohol dependence in addition to rehabilitation.

Trial Registration: The original randomized controlled trial was registered in the German Clinical Trials Register ( DRKS00004618 ). This one-year follow-up survey has not been registered.
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http://dx.doi.org/10.1186/s12888-017-1480-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585893PMC
September 2017

Evaluation of a transdiagnostic psychodynamic online intervention to support return to work: A randomized controlled trial.

PLoS One 2017 8;12(5):e0176513. Epub 2017 May 8.

Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

Objectives: Given their flexibility, online interventions may be useful as an outpatient treatment option to support vocational reintegration after inpatient rehabilitation. To that purpose we devised a transdiagnostic psychodynamic online intervention to facilitate return to work, focusing on interpersonal conflicts at the workplace often responsible for work-related stress.

Research Design And Methods: In a randomized controlled trial, we included employed patients from cardiologic, psychosomatic and orthopedic rehabilitation with work-related stress or need for support at intake to inpatient rehabilitation after they had given written consent to take part in the study. Following discharge, maladaptive interpersonal interactions at the workplace were identified via weekly blogs and processed by written therapeutic comments over 12 weeks in the intervention group (IG). The control group (CG) received an augmented treatment as usual condition. The main outcome, subjective prognosis of gainful employment (SPE), and secondary outcomes (psychological complaints) were assessed by means of online questionnaires before, at the end of aftercare (3 months) and at follow-up (12 months). We used ITT analyses controlling for baseline scores and medical group.

Results: N = 319 patients were enrolled into IG and N = 345 into CG. 77% of the IG logged in to the webpage (CG 74%) and 65% of the IG wrote blogs. Compared to the CG, the IG reported a significantly more positive SPE at follow-up. Measures of depression, anxiety and psychosocial stressors decreased from baseline to follow-up, whereas the corresponding scores increased in the CG. Correspondingly, somatization and psychological quality of life improved in the IG.

Conclusions: Psychodynamic online aftercare was effective to enhance subjective prognosis of future employment and improved psychological complaints across a variety of chronic physical and psychological conditions, albeit with small effect sizes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176513PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421767PMC
September 2017

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

Appl Psychophysiol Biofeedback 2017 06;42(2):95

Department of Psychotherapy and Psychosomatic Medicine, University Hospital Carl Gustav Carus Dresden, Technische Universitaet Dresden, Fetscherstr. 74, 01307, Dresden, Germany.

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http://dx.doi.org/10.1007/s10484-017-9357-1DOI Listing
June 2017

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

Appl Psychophysiol Biofeedback 2017 Jun;42(2):85-94

Department of Psychotherapy and Psychosomatic Medicine, University Hospital Carl Gustav Carus Dresden, Technische Universitaet Dresden, Fetscherstr. 74, 01307, Dresden, Germany.

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.
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http://dx.doi.org/10.1007/s10484-016-9346-9DOI Listing
June 2017

Evaluation of a video-based Internet intervention as preparation for inpatient psychosomatic rehabilitation: study protocol for a randomized controlled trial.

Trials 2016 06 13;17(1):287. Epub 2016 Jun 13.

Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg-University, Untere Zahlbacher Str. 8, 55131, Mainz, Germany.

Background: Patients' treatment expectations are a key factor in psychotherapy. Several studies have linked higher expectations to better treatment success. Therefore, we want to evaluate the impact of a targeted video-based intervention on patients' expectations and the treatment success of inpatient rehabilitation.

Methods/design: All patients who will be referred to inpatient psychosomatic rehabilitation in three clinics will receive a study flyer with information about how to log in to the study platform together with the usual clinic information leaflet. Patients will receive the study information and informed consent upon login and will be randomized into the intervention or the control group. The intervention group (n = 394) will get access to our virtual online clinic, containing several videos about inpatient rehabilitation, until their admission to inpatient rehabilitation. The control group (n = 394) will receive no special treatment preparation. Questionnaires will be given at study inclusion (T0), two weeks before admission to (T1), and at the end of (T2) inpatient rehabilitation. The primary outcome is the outcome expectancy measured with the Credibility Expectancy Questionnaire at T1. Secondary outcomes include treatment motivation, mental health, work ability, depression, anxiety, and satisfaction with and usage of the Internet platform.

Discussion: We expect the intervention group to benefit from the additional preparation concerning their outcome expectancy. If successful, this approach could be used in the future to enhance the efficacy of inpatient rehabilitation.

Trial Registration: ClinicalTrials.gov: NCT02532881 . Registered on 25 August 2015.
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http://dx.doi.org/10.1186/s13063-016-1417-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4906995PMC
June 2016

Heart rate variability biofeedback in patients with alcohol dependence: a randomized controlled study.

Neuropsychiatr Dis Treat 2015 9;11:2619-27. Epub 2015 Oct 9.

Department of Psychotherapy and Psychosomatic Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Saxony, Germany.

Background And Objective: In patients with alcohol dependence, ethyl-toxic damage of vasomotor and cardiac autonomic nerve fibers leads to autonomic imbalance with neurovascular and cardiac dysfunction, the latter resulting in reduced heart rate variability (HRV). Autonomic imbalance is linked to increased craving and cardiovascular mortality. In this study, we sought to assess the effects of HRV biofeedback training on HRV, vasomotor function, craving, and anxiety.

Methods: We conducted a randomized controlled study in 48 patients (14 females, ages 25-59 years) undergoing inpatient rehabilitation treatment. In the treatment group, patients (n=24) attended six sessions of HRV biofeedback over 2 weeks in addition to standard rehabilitative care, whereas, in the control group, subjects received standard care only. Psychometric testing for craving (Obsessive Compulsive Drinking Scale), anxiety (Symptom Checklist-90-Revised), HRV assessment using coefficient of variation of R-R intervals (CVNN) analysis, and vasomotor function assessment using laser Doppler flowmetry were performed at baseline, immediately after completion of treatment or control period, and 3 and 6 weeks afterward (follow-ups 1 and 2).

Results: Psychometric testing showed decreased craving in the biofeedback group immediately postintervention (OCDS scores: 8.6±7.9 post-biofeedback versus 13.7±11.0 baseline [mean ± standard deviation], P<0.05), whereas craving was unchanged at this time point in the control group. Anxiety was reduced at follow-ups 1 and 2 post-biofeedback, but was unchanged in the control group (P<0.05). Following biofeedback, CVNN tended to be increased (10.3%±2.8% post-biofeedback, 10.1%±3.5% follow-up 1, 10.1%±2.9% follow-up 2 versus 9.7%±3.6% baseline; P=not significant). There was no such trend in the control group. Vasomotor function assessed using the mean duration to 50% vasoconstriction of cutaneous vessels after deep inspiration was improved following biofeedback immediately postintervention and was unchanged in the control group (P<0.05).

Conclusion: Our data indicate that HRV biofeedback might be useful to decrease anxiety, increase HRV, and improve vasomotor function in patients with alcohol dependence when complementing standard rehabilitative inpatient care.
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http://dx.doi.org/10.2147/NDT.S84798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624058PMC
November 2015

The effects of heart rate variability biofeedback in patients with preterm labour.

Appl Psychophysiol Biofeedback 2014 Mar;39(1):27-35

Clinic for Psychotherapy and Psychosomatic Medicine, Carl Gustav Carus Medical School, Dresden University of Technology, Fetscherstr. 74, 01307, Dresden, Germany,

Preterm birth is a highly prevalent phenomenon that was shown to be associated with mental stress during pregnancy (Rich-Edwards and Grizzard in Am J Obstet Gynecol 192(5 Suppl):S30-S35, 2005). We aimed to assess the effects of heart rate variability (HRV)-biofeedback in patients with preterm labour. Therefore, we conducted a controlled randomized parallel group study in 48 female patients aged 19-38 years (median = 29) with preterm labour at gestational week 24th-32nd (median = 29th). In this study, one group (n = 24) attended six sessions of HRV-biofeedback over 2 weeks whereas patients of the other group (n = 24) were assigned to control sessions. In the HRV-biofeedback treated group, perception of chronic stress was decreased 4 weeks after completion of training compared to baseline (p < 0.05) but there was no change in the control group. In the HRV-biofeedback group, preterm birth was seen in 3 patients (13 %) whereas in the control group, preterm delivery occurred in 8 patients (33 %, p = n.s.). There was no difference in birth weight between groups and HRV remained unchanged. In conclusion, our study demonstrates that HRV-biofeedback can reduce chronic stress in patients with preterm labour when administered as an adjunct to routine care. However, it remains unclear whether stress reduction through HRV-biofeedback has a beneficial effect on preterm birth.
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http://dx.doi.org/10.1007/s10484-013-9238-1DOI Listing
March 2014

Cortisol response to repeated psychosocial stress.

Appl Psychophysiol Biofeedback 2012 Jun;37(2):103-7

Clinic for Psychotherapy and Psychosomatic Medicine, Medical School Carl Gustav Carus, Technische Universität Dresden, Germany.

Psychosocial stress plays a major role in the etiology and the course of mental disorders that often show an altered activation of the hypothalamus-pituitary-adrenal (HPA) axis. The Trier Social Stress Test (TSST) reliably activates the HPA axis and reflects real life stress exposure. However, habituation may confound the results of clinical trials that apply TSST. The present study investigates the cortisol response after repeated psychosocial stress induction with short-term and long-term intervals between repeated testing sessions. Forty-one healthy subjects were exposed to the TSST four times with an interval of 24 h between the first and the second testing session (t1 and t2). The 3rd and the 4th testing session (t3 and t4) were also separated by a 24-hour interval whereas there were 10 weeks between t2 and t3. A significant decrease in the salivary cortisol responses was noticed from testing session t1 to t2 as well as from testing session t3 to t4. By contrast, there were no differences in the HPA axis reactivity between testing session t2 and t3. Our results demonstrated the habituation of the HPA axis to a standardized psychosocial stress test when testing was repeated after 24 h. By contrast, a renewed challenge with a ten-week-interval in-between activated the HPA axis in a similar manner as before. It is suggested that studies designed to investigate the HPA axis activity under repeated psychosocial stress conditions should apply the TSST three times in order to separate habituation from intervention effects.
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http://dx.doi.org/10.1007/s10484-012-9183-4DOI Listing
June 2012

Phosphorylation of amyloid-β peptide at serine 8 attenuates its clearance via insulin-degrading and angiotensin-converting enzymes.

J Biol Chem 2012 Mar 20;287(11):8641-51. Epub 2012 Jan 20.

Department of Neurology, University of Bonn, 53127 Bonn, Germany.

Accumulation of amyloid-β peptides (Aβ) in the brain is a common pathological feature of Alzheimer disease (AD). Aggregates of Aβ are neurotoxic and appear to be critically involved in the neurodegeneration during AD pathogenesis. Accumulation of Aβ could be caused by increased production, as indicated by several mutations in the amyloid precursor protein or the γ-secretase components presenilin-1 and presenilin-2 that cause familial early-onset AD. However, recent data also indicate a decreased clearance rate of Aβ in AD brains. We recently demonstrated that Aβ undergoes phosphorylation by extracellular or cell surface-localized protein kinase A, leading to increased aggregation. Here, we provide evidence that phosphorylation of monomeric Aβ at Ser-8 also decreases its clearance by microglial cells. By using mass spectrometry, we demonstrate that phosphorylation at Ser-8 inhibited the proteolytic degradation of monomeric Aβ by the insulin-degrading enzyme, a major Aβ-degrading enzyme released from microglial cells. Phosphorylation also decreased the degradation of Aβ by the angiotensin-converting enzyme. In contrast, Aβ degradation by plasmin was largely unaffected by phosphorylation. Thus, phosphorylation of Aβ could play a dual role in Aβ metabolism. It decreases its proteolytic clearance and also promotes its aggregation. The inhibition of extracellular Aβ phosphorylation, stimulation of protease expression and/or their proteolytic activity could be explored to promote Aβ degradation in AD therapy or prevention.
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http://dx.doi.org/10.1074/jbc.M111.279133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318721PMC
March 2012

Casein kinase 2 dependent phosphorylation of neprilysin regulates receptor tyrosine kinase signaling to Akt.

PLoS One 2010 Oct 1;5(10). Epub 2010 Oct 1.

Department of Neurology, Molecular Cell Biology, University of Bonn, Bonn, Germany.

Neprilysin (NEP) is a type II membrane metalloproteinase that cleaves physiologically active peptides at the cell surface thus regulating the local concentration of these peptides available for receptor binding and signal transduction. In addition, the cytoplasmic N-terminal domain of NEP interacts with the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) thereby regulating intracellular signaling via Akt. Thus, NEP serves dual functions in extracellular and intracellular signal transduction. Here, we show that NEP undergoes phosphorylation at serine residue 6 within the N-terminal cytoplasmic domain. In vitro and cell culture experiments demonstrate that Ser 6 is efficiently phosphorylated by protein kinase CK2. The phosphorylation of the cytoplasmic domain of NEP inhibits its interaction with PTEN. Interestingly, expression of a pseudophosphorylated NEP variant (Ser6Asp) abrogates the inhibitory effect of NEP on insulin/insulin-like growth factor-1 (IGF-1) stimulated activation of Akt. Thus, our data demonstrate a regulatory role of CK2 in the interaction of NEP with PTEN and insulin/IGF-1 signaling.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0013134PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948513PMC
October 2010

Statins promote the degradation of extracellular amyloid {beta}-peptide by microglia via stimulation of exosome-associated insulin-degrading enzyme (IDE) secretion.

J Biol Chem 2010 Nov 28;285(48):37405-14. Epub 2010 Sep 28.

Departments of Neurology, University of Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.

Epidemiological studies indicate that intake of statins decrease the risk of developing Alzheimer disease. Cellular and in vivo studies suggested that statins might decrease the generation of the amyloid β-peptide (Aβ) from the β-amyloid precursor protein. Here, we show that statins potently stimulate the degradation of extracellular Aβ by microglia. The statin-dependent clearance of extracellular Aβ is mainly exerted by insulin-degrading enzyme (IDE) that is secreted in a nonconventional pathway in association with exosomes. Stimulated IDE secretion and Aβ degradation were also observed in blood of mice upon peripheral treatment with lovastatin. Importantly, increased IDE secretion upon lovastatin treatment was dependent on protein isoprenylation and up-regulation of exosome secretion by fusion of multivesicular bodies with the plasma membrane. These data demonstrate a novel pathway for the nonconventional secretion of IDE via exosomes. The modulation of this pathway could provide a new strategy to enhance the extracellular clearance of Aβ.
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http://dx.doi.org/10.1074/jbc.M110.149468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988346PMC
November 2010

[Psychosomatic aspects of cardiac arrhythmias].

Med Klin (Munich) 2010 Jul 30;105(7):479-84. Epub 2010 Jul 30.

Institut für Klinische Pharmakologie, Medizinische Fakultät der TU Dresden, Dresden, Germany.

Emotional stress facilitates the occurrence of cardiac arrhythmias including sudden cardiac death. The prevalence of anxiety and depression is increased in cardiac patients as compared to the normal population. The risk of cardiovascular mortality is enhanced in patients suffering from depression. Comorbid anxiety disorders worsen the course of cardiac arrhythmias. Disturbance of neurocardiac regulation with predominance of the sympathetic tone is hypothesized to be causative for this. The emotional reaction to cardiac arrhythmias is differing to a large extent between individuals. Emotional stress may result from coping with treatment of cardiac arrhythmias. Emotional stress and cardiac arrhythmias may influence each other in the sense of a vicious circle. Somatoform cardiac arrhythmias are predominantly of psychogenic origin. Instrumental measures and frequent contacts between physicians and patients may facilitate disease chronification. The present review is dealing with the multifaceted relationships between cardiac arrhythmias and emotional stress. The underlying mechanisms and corresponding treatment modalities are discussed.
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http://dx.doi.org/10.1007/s00063-010-1083-xDOI Listing
July 2010

[Chlorambucil treatment of Behçet's syndrome. Retrospective evaluation of two cases].

Med Klin (Munich) 2010 Jan 3;105(1):20-5. Epub 2010 Feb 3.

Rehabilitationsklinik Nordfriesland, Sankt Peter-Ording, Germany.

Background: Behçet's syndrome rarely occurs in North America and Central Europe (incidence: 1 : 500,000), whereas it is more frequently seen in Japan and Mediterranean countries (incidence: 1 : 10,000). The diagnosis is based on the detection of symptoms and clinical signs. Orogenital aphthosis, anterior and posterior uveitides that frequently cause loss of vision are considered to be primary symptoms. Dermatologic manifestations, i.e., erythema nodosum, vascular lesions (angio-Behçet's syndrome), gastrointestinal ulcers and neurologic involvement, can be observed. HLA B5 is found in some of the patients with Behçet's syndrome. Administration of chlorambucil, a cytotoxic compound, is an effective form of treatment of symptoms and complications of Behçet's syndrome.

Case Reports: The present article describes the course of a female and a male patient who were 39 and 23 years old when Behçet's syndrome was diagnosed for the first time. Treatment with chlorambucil was started in the early 1990s and continued for a period of 9 1/2 and 3(3/4) years, respectively, with the symptoms remitting during and after this therapy. Approximately 10 years after the start of treatment with chlorambucil, the patients' symptoms changed. The female patient who was first diagnosed having Behçet's syndrome at the age of 39 years developed rheumatoid arthritis with joint destruction. Her symptoms could be controlled in the long term by oral administration of prednisone, at doses below the Cushing threshold combined with methotrexate. The male patient who was first diagnosed having Behçet's syndrome at the age of 23 years developed systemic vasculitis remitting during low-dose treatment with prednisone.

Conclusion: Immunosuppressive therapy with chlorambucil administered over several years often induces remission of Behçet's syndrome. However, both case reports indicate that symptoms can change from Behçet's syndrome to systemic vasculitis or rheumatoid arthritis.
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http://dx.doi.org/10.1007/s00063-010-1003-0DOI Listing
January 2010

Pharmacokinetic/pharmacodynamic modelling of venlafaxine: pupillary light reflex as a test system for noradrenergic effects.

Clin Pharmacokinet 2008 ;47(11):721-31

Department of Clinical Pharmacy, Institute of Pharmacy, University of Bonn, Bonn, Germany.

Background And Objective: Venlafaxine and its major active metabolite O-desmethylvenlafaxine selectively inhibit serotonin and norepinephrine reuptake from the synaptic gap. The inhibition of norepinephrine uptake is assumed to enhance antidepressant efficacy when venlafaxine is given at higher therapeutic doses. Thus investigation of the concentration-response relationship of noradrenergic effects is of clinical interest. We used pupillography as a test system for the pharmacodynamic response to venlafaxine, since it had been shown to be useful for assessment of noradrenergic effects on the autonomous nervous system. The aim of the study was to develop a pharmacokinetic/pharmacodynamic model by means of nonlinear mixed-effects modelling in order to describe the time course of the noradrenergic response to venlafaxine.

Subjects And Methods: Twelve healthy male subjects received venlafaxine 37.5 mg or placebo orally twice daily for 7 days and subsequently 75 mg or placebo twice daily for another 7 days. After a 14-day washout phase, the two groups were crossed over. After the last dose of venlafaxine or placebo on day 14, blood samples were drawn to determine venlafaxine and O-desmethylvenlafaxine concentrations and the amplitude and recovery time of the pupillary light reflex were measured. A pharmacokinetic/pharmacodynamic model was developed to describe the data using nonlinear mixed-effects modelling.

Results: The pharmacokinetic part of the model could be simultaneously fitted to both venlafaxine and O-desmethylvenlafaxine data, yielding precise parameter estimates that were similar to published data. The model detected high variability of the intrinsic clearance of venlafaxine (94.8%), most likely due to cytochrome P450 2D6 polymorphism. Rapid development of tolerance of the pupillary light reflex parameters was seen and could be successfully accounted for in the pharmacodynamic part of the model. The half-life of development and regression of tolerance was estimated to be 30 minutes for the amplitude and 40 minutes for the recovery time.

Conclusion: The time course of the effect and the concentration-response relationship were successfully described by a pharmacokinetic/pharmacodynamic model that takes into account the rapid development of tolerance of pupillary light reflex parameters. This provides a basis for further investigations of the applicability of pupillography as a surrogate measurement of the effectivity of antidepressant drugs with norepinephrine reuptake-inhibiting properties.
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http://dx.doi.org/10.2165/00003088-200847110-00003DOI Listing
January 2009

A pilot study on the effects of heart rate variability biofeedback in patients with depression and in healthy subjects.

Appl Psychophysiol Biofeedback 2008 Dec 19;33(4):195-201. Epub 2008 Sep 19.

Clinic for Psychotherapy and Psychosomatic Medicine, Medical School, Technical University, Dresden, Germany.

Decreased vagal activity and increased sympathetic arousal have been proposed as major contributors to the increased risk of cardiovascular mortality in patients with depression. It was aim of the present study to assess the feasibility of using heart rate variability (HRV) biofeedback to treat moderate to severe depression. This was an open-label study in which 14 patients with different degrees of depression (13 f, 1 m) aged 30 years (18-47; median; range) and 12 healthy volunteers attended 6 sessions of HRV biofeedback over two weeks. Another 12 healthy subjects were observed under an active control condition. At follow up BDI was found significantly decreased (BDI 6; 2-20; median 25%-75% quartile) as compared to baseline conditions (BDI 22;15-29) in patients with depression. In addition, depressed patients had reduced anxiety, decreased heart rate and increased HRV after conduction of biofeedback (p < 0.05). By contrast, no changes were noted in healthy subjects receiving biofeedback nor in normal controls. In conclusion, HRV biofeedback appears to be a useful adjunct for the treatment of depression, associated with increases in HRV.
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http://dx.doi.org/10.1007/s10484-008-9064-zDOI Listing
December 2008

Modelling anxiety in humans for drug development.

Curr Neuropharmacol 2007 Mar;5(1):65-72

Institute of Clinical Pharmacology, Medical Faculty, Technical University, Fiedlerstr. 27, 01307 Dresden, Germany.

Animal behavioural profiles are commonly employed to investigate new therapeutic agents to treat anxiety disorders as well as to investigate the mechanism of action of anxiolytic drugs. However, many clinically important symptoms of anxiety can not be modelled directly in animals. Human models of anxiety should bridge between animal models and anxiety disorders. Experimental anxiety states in humans can be induced by either pharmacological means such as CO(2) inhalation or psychological means such as aversive conditioning of skin conductance responses to tones. Investigation of these models may contribute to a better understanding of anxiety disorders, both from a biological and behavioural point of view. In a comprehensive review existing models of human experimental anxiety states are summarized and validity is discussed.
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http://dx.doi.org/10.2174/157015907780077114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2435339PMC
March 2007

The effects of sildenafil on heart rate variability in healthy subjects.

J Cardiovasc Pharmacol 2007 Nov;50(5):598-600

Institute of Clinical Pharmacology, Medical Faculty, Technical University, Dresden, Germany.

The effects of sildenafil on heart rate variability were investigated in 20 healthy male subjects aged 24 (21 to 32) years (median; range). Subjects orally received single 100-mg doses of sildenafil and placebo under randomized double-blind crossover conditions on 2 separate study days. Time domain measures of heart rate variability were assessed under conditions of relaxed rest, metronomic breathing (6 cycles per minute), and bicycle ergometry before administration of sildenafil and placebo as well as 60 minutes afterwards. Sildenafil did not alter heart rate nor heart rate variability to a significant extent (P > 0.05).
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http://dx.doi.org/10.1097/FJC.0b013e318148b23dDOI Listing
November 2007

The effects of venlafaxine on autonomic functions in healthy volunteers.

J Clin Psychopharmacol 2007 Dec;27(6):687-91

Institute of Clinical Pharmacology, Medical Faculty, Technical University, Fiedlerstrasse 27, Dresden, Germany.

Antidepressants that block norepinephrine uptake may cause unwanted effects on autonomic functions such as reduction of heart rate variability. This randomized, double-blind, placebo-controlled study examined the effects of venlafaxine on heart rate variability, vasoconstrictory responses (VRs) of cutaneous blood vessels, and pupillary light reflex in humans. Twelve healthy male subjects aged 23 to 32 years (mean +/- SD, 26 +/- 3 years) orally received 37.5 mg of venlafaxine BID for 7 days and subsequently 75 mg BID for another 7 days. After a 14-day washout phase, placebo was administered to the subjects for 14 days under randomized double-blind crossover conditions. Heart rate variability was diminished, and the dilation phase of VR was prolonged during multiple dosing with venlafaxine (P < 0.05). A significant increase in resting pupil diameter, a decrease in amplitude, an increase in latency, and a shortening of the 33% recovery time of the pupillary light reflex were noted with the drug, whereas no changes were observed under placebo condition. Sustained VR and shortening of the recovery time of the pupillary light reflex are consistent with sympathetic potentiation resulting from noradrenaline reuptake blockade in cutaneous blood vessels and iris. The decrease in amplitude and increase in latency of the pupillary light reflex could be indicative of centrally mediated parasympathetic inhibition.
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http://dx.doi.org/10.1097/jcp.0b013e31815a255bDOI Listing
December 2007

The effects of acetylic salicylic acid on heart rate variability in healthy subjects.

Clin Auton Res 2007 Apr 28;17(2):115-7. Epub 2007 Mar 28.

Institute of Clinical Pharmacology, Medical Faculty, Technical University, Fieldlerstrasse 27, Dresden, Germany.

In this placebo controlled double blind cross over study multiple daily dosing with 500 mg acetylic salicylic acid did not influence heart rate variability in 16 healthy male volunteers aged 25 (22-28) years (median; range) to a relevant extent (p > 0.05).
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http://dx.doi.org/10.1007/s10286-007-0408-1DOI Listing
April 2007

The effects of lorazepam on skin conductance responses to aversive stimuli in healthy subjects.

Clin Auton Res 2007 Jun 27;17(3):160-4. Epub 2007 Mar 27.

Institute of Clinical Pharmacology, Medical Faculty, Technical University, 01307, Dresden, Germany.

Background: Autonomic responses to aversive stimuli are widely used to model anxiolytic drug effects in healthy humans. Benzodiazepine anxiolytics dose dependently attenuate autonomic responses to aversive stimuli by their anxiolytic as well as sedative action. The present study aimed to examine the effects of non-sedative doses of lorazepam on skin cutaneous responses to aversive stimuli and subjective mood.

Methods: A randomized, double blind, cross over study of 12 healthy male volunteers aged 24 years (23-32; median; range) was carried out. Subjects received single oral doses of 0.5 and 1.0 mg lorazepam as well as placebo on three different occasions with at least 5 days in-between. Skin conductance responses (SCRs) to unpleasant pictures and noises, pupillary unrest index as well as subjective levels of anxiety were measured repeatedly before and after drug administration.

Results: SCRs were found significantly lower 2 hours following ingestion of 0.5 mg lorazepam as well as 1, 2 and 3 hours after 1.0 mg lorazepam were given as compared to baseline conditions. By contrast, administration of placebo did not influence SCRs to a significant extent. Both doses of lorazepam did not change pupillary unrest index nor subjective mood.

Conclusions: Lorazepam may attenuate SCRs to aversive stimuli without affecting vigilance nor subjective mood. Attenuation of autonomic responses to aversive stimuli may not be specific for an anxiolytic effect.
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http://dx.doi.org/10.1007/s10286-007-0407-2DOI Listing
June 2007
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