Effects of Post-awakening Light Exposure on Heart Rate Variability in Healthy Male Individuals.

Light-induced effects on the autonomic nervous system (ANS) are assumed to be mediated by retinal projections to the hypothalamic suprachiasmatic nucleus (SCN) via different routes. Light information for the circadian system is detected by a subset of intrinsically photosensitive retinal ganglion cells (ipRGCs), however, inconsistency exists in research concerning the effects of light exposure on heart rate variability (HRV). Two within-subject experiments were conducted in a standardized sleep laboratory to investigate effects of light intensity (study I, n = 29: 2 days dim vs. bright light) and spectral composition (study II, n = 24: 3 days using red vs. blue vs. green light) on HRV parameters (RMSSD, LF, HF-HRV, LF/HF ratio). Light exposure was conducted for one-hour in the post-awakening phase at 5:00 AM. Results revealed no significant light intensity effect comparing dim light versus bright white light on HRV parameters. Light color of different wavelengths significantly influenced all HRV parameters except the low frequency, with moderate to large effect sizes. RMSSD values were elevated for all three colors compared to norm values, indicating stronger parasympathetic activation. LED light of different spectral compositions demonstrated bidirectional effects on spectral components of the HRV. Red light decreased the LF/HF ratio within 30 min, whereas with blue light, LF/HF ratio consistently increased across 40 min of light exposure.

Effect of a Biofeedback Intervention on Heart Rate Variability in Individuals With Panic Disorder: A Randomized Controlled Trial.

OBJECTIVE: Some individuals with panic disorder (PD) display reduced heart rate variability (HRV), 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 4-week HRV-BF intervention in individuals with PD. HRV-BF training improved the modulation of the autonomic activity. Therefore, with this randomized controlled trial, we aimed to investigate the effect of a 4-week HRV-BF intervention in people with PD. METHODS: Thirty-six women and 16 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 for 4 weeks, whereas HRV was measured both during a short-term resting condition and 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 root mean square successive differences: 5.87 [14.03] milliseconds; ΔPost-Pre standard deviation of all NN intervals: 11.63 [17.06] milliseconds; ΔPost-Pre total power: 464.88 [1825.47] milliseconds2; ΔPost-Pre power in low-frequency range 0.04-0.15 Hz: 312.73 [592.71] milliseconds2), a decrease in the heart rate during the paced breathing condition (ΔPost-Pre: -5.87 [9.14] beats/min), and a decrease in the Panic and Agoraphobia Scale (ΔPost-Pre: -3.64 [6.30]). There was no intervention effect in the HRV-Sham-BF group. CONCLUSIONS: HRV-BF as a noninvasive and nonpharmacological 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.

Heart Rate Variability: A Measure of Cardiovascular Health and Possible Therapeutic Target in Dysautonomic Mental and Neurological Disorders.

Mental illness such as depression and anxiety as well as cerebrovascular disease are linked to impairment of neurocardiac function mediated by changes to the autonomic nervous system with increased sympathetic and decreased parasympathetic activity. Autonomic neurocardiac function can be evaluated by computing heart rate variability (HRV). Over the past decades, research has demonstrated the diagnostic value of HRV as independent predictor of cardiovascular mortality and as disease marker in progressive autonomic nervous system disorders such as Parkinson's disease. Here we summarize our studies on HRV and its therapeutic modulation in the context of psychopharmacology as well as psychiatric and neurological disorders to honor the life of Professor Evgeny Vaschillo, the true pioneer of HRV research who sadly passed away on November 21st, 2020.

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

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.

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.

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.

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

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.

Early maladaptive schemas in patients with somatoform disorders and somatization.

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, η2  = 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.

[Rehabilitants' Expectations and Informational Needs Concerning Inpatient Psychosomatic Rehabilitation - Results of a Qualitative Analysis]. / Erwartungen und Informationsbedarf von Rehabilitanden bezüglich stationärer psychosomatischer Rehabilitation.

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.

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

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.

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

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.

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

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

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

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.

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

Accumulation of amyloid-ß peptides (Aß) in the brain is a common pathological feature of Alzheimer disease (AD). Aggregates of Aß are neurotoxic and appear to be critically involved in the neurodegeneration during AD pathogenesis. Accumulation of Aß 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 Aß in AD brains. We recently demonstrated that Aß undergoes phosphorylation by extracellular or cell surface-localized protein kinase A, leading to increased aggregation. Here, we provide evidence that phosphorylation of monomeric Aß 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 Aß by the insulin-degrading enzyme, a major Aß-degrading enzyme released from microglial cells. Phosphorylation also decreased the degradation of Aß by the angiotensin-converting enzyme. In contrast, Aß degradation by plasmin was largely unaffected by phosphorylation. Thus, phosphorylation of Aß could play a dual role in Aß metabolism. It decreases its proteolytic clearance and also promotes its aggregation. The inhibition of extracellular Aß phosphorylation, stimulation of protease expression and/or their proteolytic activity could be explored to promote Aß degradation in AD therapy or prevention.

Cortisol response to repeated psychosocial stress.

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.

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

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 ß-peptide (Aß) from the ß-amyloid precursor protein. Here, we show that statins potently stimulate the degradation of extracellular Aß by microglia. The statin-dependent clearance of extracellular Aß is mainly exerted by insulin-degrading enzyme (IDE) that is secreted in a nonconventional pathway in association with exosomes. Stimulated IDE secretion and Aß 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 Aß.

Myxedema Psychosis: Systematic Review and Pooled Analysis.

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 (p= 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.

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

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.

The middle domain of Hsp90 acts as a discriminator between different types of client proteins.

The mechanism of client protein activation by Hsp90 is enigmatic, and it is uncertain whether Hsp90 employs a common route for all proteins. Using a mutational analysis approach, we investigated the activation of two types of client proteins, glucocorticoid receptor (GR) and the kinase v-Src by the middle domain of Hsp90 (Hsp90M) in vivo. Remarkably, the overall cellular activity of v-Src was highly elevated in a W300A mutant yeast strain due to a 10-fold increase in cellular protein levels of the kinase. In contrast, the cellular activity of GR remained almost unaffected by the W300A mutation but was dramatically sensitive to S485Y and T525I exchanges. In addition, we show that mutations S485Y and T525I in Hsp90M reduce the ATP hydrolysis rate, suggesting that Hsp90 ATPase is more tightly regulated than assumed previously. Therefore, the activation of GR and v-Src has various demands on Hsp90 biochemistry and is dependent on separate functional regions of Hsp90M. Thus, Hsp90M seems to discriminate between different substrate types and to adjust the molecular chaperone for proper substrate activation.

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

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.