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Abstract: Objective: Sleep deprivation (SD) can induce a prompt decrease in depressive symptoms within 24h. Following the recovery night, however, a relapse into depression occurs in most patients. Recovery sleep, naps and even very short episodes of sleep (microsleep; MS) during SD have been shown to provoke a rapid relapse into depression. This study tested the hypothesis that modafinil reduces MS during SD and stabilizes the treatment response to PSD compared to placebo. Methods: A total of 28 patients (13 men, 15 women; age 45.1±12.1years) with a major depressive episode and a cumulative daytime microsleep of five or more minutes were investigated using a double-blind placebo-controlled study design. All patients were treated with a stable mirtazapine monotherapy. A partial SD (PSD) was performed after one week. Additional morning treatment with modafinil vs. placebo started during PSD and was maintained over two weeks. Sleep-EEG and MS episodes were recorded with a portable EEG. Depression severity was assessed using the Hamilton Depression Rating Scale before, during and after PSD and at follow-ups after one and two weeks. Results: Patients treated with modafinil showed significantly reduced microsleep during PSD (11.63±15.99min) compared to the placebo group (47.77±65.31min). This suppression of MS was not associated with the antidepressive effect of PSD. Conclusions: Compared to placebo, modafinil was efficient in reducing daytime microsleep following partial sleep deprivation but did not enhance the antidepressive effects of PSD and did not stabilize antidepressive effects over two weeks. [Copyright &y& Elsevier]

Aims: Lectins, and especially galectins, appear to be important in malignancy-associated processes. The aim was to analyse comprehensively the presence of galectins in urothelial tumours. Methods and results: Non-cross-reactive antibodies against seven family members from the three subgroups (prototype: galectin-1, -2 and -7; chimera type: galectin-3; tandem-repeat type: galectin-4, -8 and -9) were used. Gene expression was monitored in specimens of normal urothelium, fresh tumour tissue and cell lines by real-time polymerase chain reaction (PCR). The presence and evidence of tumour-associated up-regulation were shown for galectin-1 and -3. This was less clear-cut for galectin-4 and -8. Galectin-7 was expressed in all cell lines; galectin-2 and -9 were detected at comparatively low levels. Galectin-2, -3 and -8 up-regulation was observed in superficial tumours, but not in muscle-invasive tumours ( P < 0.05). Immunoreactivity correlated with tumour grading for galectin-1, -2 and -8, and disease-dependent mortality correlated with galectin-2 and -8 expression. Binding sites were visualized using labelled galectins. Conclusions: The results demonstrate a complex expression pattern of the galectin network in urothelial carcinomas. Galectin-1, -2, -3 and -8 are both potential disease markers and also possible targets for bladder cancer therapy. [ABSTRACT FROM AUTHOR]

B Introduction: b To date, the medication treatment of major depression is associated with unsatisfactory response rates, delayed treatment improvements, unpleasant side effects, and a high burden of disease. Only in the IG, the cordance was provided prospectively for guidance of treatment: Physicians were told to adapt antidepressant treatment strategy in case of predicted non-response, or to maintain treatment strategy in case of predicted response. [Extracted from the article]

B Background: b Previous research has demonstrated that in trials studying the effect of exercise on depression improvement of cardiorespiratory fitness measured by maximal oxygen uptake (VO2max) might be associated with improvement of depression severity and subjective sleep complaints [1]. Our analysis also showed an association of increase in VO2max with decreased REM-latency, one of the distinct sleep-related features of depression [4]. [Extracted from the article]

B Objectives: b Postpartum Depression (PPD) is a depressive episode occurring after childbirth. [4] The aim of this study was to examine, if 1) PPD was associated with decreased sBDNF cross-sectionally, and 2) if prenatal sBDNF could predict PPD twelve weeks after delivery. [Extracted from the article]

The protein brain derived neurotrophic factor (BDNF) is a major contributor to neuronal plasticity. There is numerous evidence that BDNF expression is decreased by experiencing psychological stress and that accordingly a lack of neurotrophic support causes depression. The use of serum BDNF concentration as a potential indicator of brain alteration is justified through extensive evidence. Recently, we reported, for the first time, a relationship between BDNF and insomnia, since we could show that reduced levels of serum BDNF are correlated with sleep impairment in control subjects, while partial sleep deprivation was able to induce a fast increase in serum BDNF levels in depressed patients. Using a bi-directional stress model as an explanation approach, we propose the hypothesis that chronic stress might induce a deregulation of the HPA system leading in the long term to sleep disturbance and decreased BDNF levels, whereas acute sleep deprivation, can be used as therapeutical intervention in some insomniac or depressed patients as compensatory process to normalize BDNF levels. Indeed, partial sleep deprivation (PSD) induced a very fast increase in BDNF serum levels within hours after PSD which is similar to effects seen after ketamine infusion, another fast-acting antidepressant intervention, while traditional antidepressants are characterized by a major delay until treatment response as well as delayed BDNF level increase. Moreover, we revealed that stress experience and subjective sleep perception interact with each other and affect serum BDNF levels. We identified sleep as a mediator of the association between stress experience and serum BDNF levels. [ABSTRACT FROM AUTHOR]

Introduction: Frowning expresses negative emotions like anger, fear, and sadness. According to the facial feedback hypothesis, suppression of frowning will also diminish the corresponding negative emotions. Hence, mood improvement has been observed in patients who underwent treatment of glabellar frown lines with botulinum neurotoxin. This observation suggests the possibility that the intervention may be employed for the management of psychiatric disorders associated with negative emotions. Preliminary data from an open case series indicate that the intervention might improve the symptoms of depression. Aims & objectives: To test whether an onabotulinumtoxinA injection into the glabellar region is benefical as an adjunctive treatment of major depression within a clinical trial. Methods: We used a randomized, double-blinded, placebo-controlled study design (n=30; ClinicalTrials.gov, number, NCT00934687). Results: We show that a single onabotulinumtoxinA treatment shortly leads to a strong and sustained improvement in partly chronic major depression that did not respond sufficiently to previous treatment. As for the primary end-point, Hamilton Depression Rating Scale (HAM-D17) six weeks after treatment compared to baseline, scores of onabotulinumtoxinA recipients showed 37.9% (8.34 points) more improvement than those of placebo-treated participants (F=12.30, p=0.002, η2 =0.31, d=1.28). Conclusion: Our findings support the concept that the facial musculature not only expresses, but also regulates, mood states. As it stands, treatment of glabellar frown lines with botulinum neurotoxin can be considered for depressed patients with the objective of inducing mood-lifting effects. [ABSTRACT FROM AUTHOR]

Introduction: Major depressive disorders (MDD) are a leading health concern worldwide. While first line medication treatments may fall short of desired therapeutic outcomes, physical activity (PA) interventions appear to be a promising and cost-effective add-on to improve symptoms of depression. This study aimed to address challenges in the assessment of PA in inpatients treated for MDD by examining the correspondence of self-reported and accelerometer-based PA., Methods: In 178 inpatients treated for MDD (mean age: M  = 41.11 years, SD = 12.84; 45.5% female) and 97 non-depressed controls (mean age: M  = 35.24 years, SD = 13.40; 36.1% female), we assessed self-reported PA via the Simple Physical Activity Questionnaire (SIMPAQ) for one week, followed by a week where PA was monitored using an accelerometer device (Actigraph wGT3x-BT). Additionally, we examined correlations between PA levels assessed with the SIMPAQ and exercise determinants in both groups., Results: Descriptively, inpatients treated for MDD showed lower levels of light PA on accelerometer-based measures, whereas they self-reported increased levels of certain types of PA on the SIMPAQ. More importantly, there was only a small degree of correspondence between self-reported and actigraphy-based PA levels in both in patients ( r  = 0.15, p  < 0.05) and controls ( r  = 0.03, ns). Only few significant correlations were found for self-reported PA (SIMPAQ subscores) and perceived fitness, whereas self-reported PA and estimated VO 2 max were unrelated. Furthermore, only weak (and mostly statistically non-significant) correlations were found between exercise determinants and SIMPAQ-based exercise behavior in both populations., Discussion: Our findings emphasize the intricate challenges in the assessment of PA, not only in inpatients treated for MDD, but also in non-depressed controls. Our findings also underline the necessity for a diversified data assessment. Further efforts are needed to refine and improve PA questionnaires for a more accurate data assessment in psychiatric patients and healthy controls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Schilling, Cody, Kreppke, Faude, Beck, Brand, Donath, Hatzinger, Imboden, Lang, Mans, Mikoteit, Oswald, Schweinfurth-Keck and Gerber.)

Over 300 million individuals worldwide suffer from major depressive disorder (MDD). Individuals with MDD are less physically active than healthy people which results in lower cardiorespiratory fitness (CRF) and less favorable perceived fitness compared with healthy controls. Additionally, individuals with MDD may show autonomic system dysfunction. The purpose of the present study was to evaluate the CRF, perceived fitness and autonomic function in in-patients with MDD of different severity compared with healthy controls. We used data from 212 in-patients (age: 40.7 ± 12.6 y, 53% female) with MDD and from 141 healthy controls (age: 36.7 ± 12.7 y, 58% female). We assessed CRF with the Åstrand-Rhyming test, self-reported perceived fitness and autonomic function by heart rate variability (HRV). In specific, we used resting heart rate, time- and frequency-based parameters for HRV. In-patients completed the Beck Depression Inventory-II (BDI-II) to self-assess the subjectively rated severity of depression. Based on these scores, participants were grouped into mild, moderate and severe MDD. The main finding was an inverse association between depression severity and CRF as well as perceived fitness compared with healthy controls. Resting heart rate was elevated with increasing depression severity. The time-based but not the frequency-based autonomic function parameters showed an inverse association with depression severity. The pattern of results suggests that among in-patients with major depressive disorder, those with particularly high self-assessed severity scores show a lower CRF, less favorable perceived fitness and partial autonomic dysfunction compared to healthy controls. To counteract these conditions, physical activity interventions may be effective., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. The PACINPAT trial is funded by the Swiss National Science Foundation (grant number: 321003B-179353). The authors JB, MH, CI, UEL, SM, TM, AO, AR and NS supported the patient screening and recruitment processes on the four study sites. JNK and RC recruited the participants and collected the data. EHT, LD, AE, SB, LZ and MG offered thematic support. JNK and OF were responsible for conceptualizing the manuscript. JNK conducted the statistical analyses. JNK wrote the first draft of the manuscript with assistance of OF. All listed co-authors read, contributed to and approved the final manuscript., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Anxiety is a common and disabling condition that significantly impacts quality of life. Subsyndromal anxiety (SSA) refers to anxiety symptoms that do not meet the full diagnostic criteria for an anxiety disorder but pose a risk for developing such disorders. We aimed to provide practical recommendations for the treatment of SSA in primary care settings., Methods: A narrative review was conducted to identify strategies for recognizing and treating patients with SSA., Results: The recommendations for treating SSA include lifestyle modifications such as exercise and stress reduction techniques, psychotherapy, and pharmacological treatments, including natural compounds like the lavender oil extract Silexan. Regular follow-up care is essential to monitor treatment response and address ongoing symptoms. Additionally, the use of the GAD-7 tool is recommended for accurately identifying patients with SSA., Conclusion: Implementing these recommendations in primary care can lead to effective treatment of SSA, preventing the development of more severe anxiety disorders. An integrative approach, combining lifestyle modifications, psychotherapy, and pharmacotherapy, including natural compounds, offers significant benefits for managing anxiety.

Major depressive disorder (MDD) is an increasingly common psychiatric illness associated with a high risk of insufficient physical activity, which in turn is associated with negative mental and physical health outcomes. Theory-based, individually tailored, in-person and remote physical activity counseling has the potential to increase physical activity levels in various populations. Given this, the present study investigated the effect of such a physical activity intervention on the physical activity behavior of in-patients with MDD. This was a multi-center, two-arm randomized controlled trial including initially insufficiently physically active adult in-patients with MDD from four study sites in Switzerland. The sample consisted of 220 participants (M age  = 41 ± 12.6 years, 52% women), 113 of whom were randomized to the intervention group and 107 to the control group. The main outcome, moderate-to-vigorous physical activity (MVPA), was assessed at three time points via hip-worn accelerometer. According to accelerometer measures, there was no significant difference in minutes spent in MVPA over a 12-month intervention period when comparing the intervention with the control group (β = -1.02, 95% CI = -10.68 to 8.64). Higher baseline physical activity significantly predicted physical activity at post and follow-up. This study showed that it is feasible to deliver an individually tailored, theory-based physical activity counseling intervention to in-patients with MDD, however yielding no significant effects on accelerometer-based MVPA levels. Further efforts are warranted to identify efficacious approaches.Trial registration: ISRCTN, ISRCTN10469580, registered on 3rd September 2018, https://www.isrctn.com/ISRCTN10469580 ., (© 2024. The Author(s).)

Introduction: The «Recommendations for the Diagnosis and Treatment of Behavioral and Psychological Symptoms of Dementia (BPSD)» were developed in parallel with the Swiss National Dementia Strategy 2014-2019 under the auspices of the Swiss Society for Geriatric Psychiatry and Psychotherapy (SGAP) and mark the beginning of a series of recommendations for geriatric psychiatric disorders. They depict the evidence-based state of knowledge about diagnostics and therapy, based on the clinical experience of the experts, and are designed for interprofessional and interdisciplinary use. The non-pharmacological intervention options and pharmacotherapy are discussed in detail. This paper is the revised version of the 2014 publication and compiles the development in this area for everyday clinical practice., Competing Interests: Es bestehen keine Interessenskonflikte., (© 2024 Aerzteverlag medinfo AG.)

Objectives: Thus far, the diagnosis of insomnia is based on purely clinical criteria. Although a broad range of altered physiological parameters has been identified in insomniacs, the evidence to establish their diagnostic usefulness is very limited. Purpose of this WFSBP Task Force consensus paper is to systematically evaluate a series of biomarkers as potential diagnostic tools for insomnia., Methods: A newly created grading system was used for assessing the validity of various measurements in establishing the diagnosis of insomnia; these measurements originated from relevant studies selected and reviewed by experts., Results: The measurements with the highest diagnostic performance were those derived from psychometric instruments. Biological measurements which emerged as potentially useful diagnostic instruments were polysomnography-derived cyclic alternating pattern, actigraphy, and BDNF levels, followed by heart rate around sleep onset, deficient melatonin rhythm, and certain neuroimaging patterns (mainly for the activity of frontal and pre-frontal cortex, hippocampus and basal ganglia); yet, these findings need replication, as well as establishment of commonly accepted methodology and diagnostic cut-off points. Routine polysomnography, EEG spectral analysis, heart rate variability, skin conductance, thermoregulation, oxygen consumption, HPA axis, and inflammation indices were not shown to be of satisfactory diagnostic value., Conclusions: Apart from psychometric instruments which are confirmed to be the gold standard in diagnosing insomnia, six biomarkers emerge as being potentially useful for this purpose.

Introduction: Compared to the general population, individuals with depression have an increased risk for cardiovascular diseases. Nevertheless, little is known so far whether cardiorespiratory fitness (CRF) moderates this relationship. Therefore, we examined whether common physiological cardiovascular risk factors differ between patients with depression and healthy (non-depressed) controls, whether patients and controls differ in CRF, and whether higher CRF is associated with a lower cardiovascular risk in both patients and healthy controls. Additionally, we examined whether within the patient sample, cardiovascular risk factors differ between patients with mild, moderate and severe depression, and whether the relationship between symptom severity and cardiovascular risk is moderated by patients' CRF levels., Methods: Data from a multi-centric, two-arm randomized controlled trial (RCT) was analyzed, including 210 patients (F32, single episode: n  = 72, F33, recurrent major depression: n  = 135, F31-II, bipolar type II: n  = 3) and 125 healthy controls. Waist circumference, body mass index, body fat, blood pressure, cholesterol levels, triglycerides, and blood glucose were considered as cardiovascular risk markers. CRF was assessed with a submaximal ergometer test. Differences between groups were examined via χ 2 -tests and (multivariate) analyses of covariance., Results: Compared to healthy controls, patients with depression had a higher cardiovascular risk as evident from about half of the examined indicators. In the total sample, participants with good CRF had more favourable scores across nearly all risk markers than counterparts with poor CRF. For most variables, no interaction occurred between group and fitness, indicating that in patients and controls, similar differences existed between participants with poor and good CRF. Few differences in risk markers were found between patients with mild, moderate and severe depression, and no interaction occurred between depression severity and CRF., Discussion: Patients with depression and healthy controls differ in several cardiovascular risk markers, putting patients at increased risk for CVDs. In contrast, people with good CRF show more favourable cardiovascular risk scores, a relationship which was observed in both healthy controls and patients with depression. Physical health of psychiatric patients should receive the clinical attention that it deserves. Lifestyle interventions targeting healthy diet and/or physical activity are recommended as a physically active and healthy lifestyle contributes equally to patients' mental well-being and cardiovascular health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gerber, Cody, Beck, Brand, Donath, Eckert, Hatzinger, Imboden, Kreppke, Lang, Ludyga, Mans, Mikoteit, Oswald, Schweinfurth-Keck, Zahner and Faude.)

Background: Patients with major depressive disorder (MDD) are characterized by neurocognitive impairments and show deficits in various cognitive performance indicators, including executive function. We examined whether sustained attention and inhibitory control differ between patients with MDD and healthy controls, and whether differences exist between patients with mild, moderate, and severe depression., Methods: Clinical in-patients ( N = 212) aged 18-65 years with a current diagnosis of MDD and 128 healthy controls were recruited. Depression severity was assessed using the Beck Depression Inventory, and sustained attention and inhibitory control were assessed using the oddball and flanker tasks. The use of these tasks promises insights into executive function in depressive patients that are not biased by verbal skills. Group differences were tested via analyses of covariance., Results: Patients with MDD showed slower reaction times in both the oddball and flanker task, independent of the executive demands of the trial types. Younger participants achieved shorter reaction times in both inhibitory control tasks. After correcting for age, education, smoking, BMI, and nationality, only differences in reaction times in the oddball task were statistically significant. In contrast, reaction times were not sensitive to the symptom severity of depression., Conclusion: Our results corroborate deficits in basic information processing and specific impairments in higher-order cognitive processes in MDD patients. As difficulties in executive function underlie problems in planning, initiating, and completing goal-directed activities, they may jeopardize in-patient treatment and contribute to the recurrent nature of depression.

Background: The physical activity counseling for in-patients with major depression (PACINPAT) randomized controlled trial was launched to tackle physical inactivity for in-patients with major depressive disorder. Evidence shows that despite potential treatment effects, physical inactivity is prevalent in this population. To contribute to the assessment of how this in-person and remote, theory-based, individually tailored intervention was designed, received and effected behavior, the aim of this study was to evaluate its implementation., Methods: This implementation evaluation was conducted within a multi-center randomized controlled trial according to the Process Evaluation Framework by the Medical Research Council including the analysis of reach, dose, fidelity and adaptation. Data were collected from the implementers and the participants randomized to the intervention group of the trial., Results: The study sample comprised 95 physically inactive in-patients (mean age: 42 years, 53% women) with diagnosed major depressive disorder. The intervention reached the intended population (N = 95 in-patients enrolled in the study). The intervention dose varied between early dropouts (counseling sessions, M = 1.67) and study completers with some participants receiving a low dose (counseling sessions, M = 10.05) and high dose (counseling sessions, M = 25.37). Differences in the attendance groups were recognizable in the first two counseling sessions (duration of counseling session about 45 min in early dropouts versus 60 min for study completers). Fidelity of the in-person counseling content was partly achieved and adapted, whereas that of the remote counseling content was well achieved. Participants (86% at follow up) reported satisfaction with the implementers of the intervention. Adaptations were made to content, delivery mode and dose., Conclusion: The PACINPAT trial was implemented in the intended population, in varying doses and with adaptations made to in-person counseling content and remote counseling dose. These findings are key to understanding outcome analyses within the PACINPAT trial, further developing interventions and contributing to implementation research among in-patients with depressive disorders., Trial Registration: ISRCTN, ISRCTN10469580 , registered on 3 rd September 2018., (© 2023. The Author(s).)

Individuals diagnosed with major depressive disorder (MDD) and social phobia (SP) have difficulties in social interactions. It is unknown, however, whether such difficulties prevent them from helping others, thereby depriving them of the natural benefits of helping, such as receiving gratitude. Using event sampling methodology (ESM), individuals (MDD, n = 118; SP, n = 47; and control group, n = 119) responded to questions about the frequency of helping, in total at 5333 time points, and their well-being. Contrary to our hypothesis, individuals in the MDD, SP and control group did not differ in their helping frequency. Results did show an association between helping and well-being, such that helping is related to well-being and well-being to helping. Understanding the complex relation of helping others and well-being and how this might be used during therapy and prevention programmes are discussed., (© 2022 British Psychological Society.)

Background: Within the spectrum of emotional competencies, callous-unemotional traits are socially discouraged, while empathy is considered a socially much more accepted emotional trait. This holds particularly true for adolescents, who are still building up their social and emotional competencies. The aims of the present study were two-fold: First, longitudinally, to identify traits of behavioral problems and objective sleep dimensions at the age of 5 years to predict callous-unemotional traits and empathy at the age of 14 years. Second, cross-sectionally, to associate callous-unemotional traits and empathy with current insomnia, stress, and mental toughness., Methods: Preschoolers at the age of 5 years were contacted nine years later at the age of 14 years. At 5 years, parents rated their children's behavior (Strength and Difficulties Questionnaire, SDQ); in parallel, children underwent a one-night sleep-EEG assessment. At the age of 14 years, adolescents completed a series of questionnaires covering callous-unemotional traits, insomnia, empathy, stress, and mental toughness., Results: A total of 77 adolescents (38.1% females) took part in the present study. Longitudinally, higher scores for hyperactivity at age 5 significantly predicted higher callous-unemotional traits at age 14. A higher score for negative peer relationships at age 5 significantly predicted lower scores for cognitive empathy at age 14. Further, objective sleep-EEG measures showed that a higher sleep efficiency and a shorter sleep latency was associated with lower scores for callousness. Cross-sectionally, higher scores for callous-unemotional traits were associated with higher insomnia and stress, while lower insomnia was associated with higher empathy. Mental toughness was unrelated to callous-unemotional traits and empathy., Conclusions: It appears that hyperactivity traits and negative peer relationships and more unfavorable objective sleep patterns at 5 years predicted socially discouraged callous-unemotional traits and low empathy during adolescence. Further, cross-sectionally at the age of 14, callous-unemotional traits, subjective poor sleep, and higher stress were associated.

Introduction: A physical activity counseling intervention based on a motivation-volition model was developed and delivered to in-patients with Major Depressive Disorders with the aim of increasing lifestyle physical activity. The aim of this study is to evaluate the short-term outcomes of this intervention., Methods: A multi-center randomized controlled trial was conducted in four Swiss psychiatric clinics. Adults who were initially insufficiently physically active and were diagnosed with Major Depressive Disorder according to ICD-10 were recruited. The sample consisted of 113 participants in the intervention group ( M age = 42 years, 56% women) and 107 in the control group ( M age = 40 years, 49% women). Motivation and volition determinants of physical activity were assessed with questionnaires. Implicit attitudes were assessed with an Implicit Association Test. Physical activity was self-reported and measured with hip-worn accelerometers over 7 consecutive days starting on the day following the data collection., Results: According to accelerometer measures, step count decreased on average 1,323 steps less per day (95% CI = -2,215 to -431, p < 0.01) over time in the intervention group compared to the control group. A trend was recognized indicating that moderate-to-vigorous physical activity decreased on average 8.37 min less per day (95% CI = -16.98 to 0.23, p < 0.06) over time in the intervention group compared to the control group. The initial phase of the intervention does not seem to have affected motivational and volitional determinants of and implicit attitudes toward physical activity., Conclusion: Physical activity counseling may be considered an important factor in the transition from in-patient treatment. Methods to optimize the intervention during this period could be further explored to fulfill the potential of this opportunity., Clinical Trial Registration: https://www.isrctn.com/ISRCTN10469580, identifier ISRCTN10469580., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cody, Beck, Brand, Donath, Faude, Hatzinger, Imboden, Kreppke, Lang, Ludyga, Mans, Mikoteit, Oswald, Schweinfurth, Zahner and Gerber.)

Objectives: Silexan is an orally administered, proprietary essential oil from Lavandula angustifolia with significant anxiolytic and sleep improving properties. Here we present a narrative review that provides an overview of the available evidence of the effects of silexan on sleep., Methods: We start with a summary of the pharmacological background and continue with presenting sleep-related results from controlled clinical trials with silexan. Then we report on a meta-analysis of item 'insomnia' from the Hamilton Anxiety Scale, which includes data from all randomised, placebo-controlled clinical trials with silexan in which the scale was administered. Finally, we summarise the results of a mediation analysis that was performed to elucidate the pathway of the effect of silexan on sleep., Results: In randomised, placebo-controlled trials in patients suffering from anxiety disorders silexan had a significant anxiolytic effect and improved sleep along with recovery from anxiety. Mediation analysis demonstrates that more than 98% of the effect of silexan on sleep was mediated by its anxiolytic effect while the direct effect on sleep was marginal., Conclusions: Silexan improves sleep as a result of its anxiolytic effect.

Genetic predisposition is one factor influencing interindividual drug response. Pharmacogenetic information can be used to guide the selection and dosing of certain drugs. However, the implementation of pharmacogenetics (PGx) in clinical practice remains challenging. Defining a formal structure, as well as concrete procedures and clearly defined responsibilities, may facilitate and increase the use of PGx in clinical practice. Over 140 patient cases from an observational study in Switzerland formed the basis for the design and refinement of a pharmacist-led pharmacogenetics testing and counselling service (PGx service) in an interprofessional setting. Herein, we defined a six-step approach, including: (1) patient referral; (2) pre-test-counselling; (3) PGx testing; (4) medication review; (5) counselling; (6) follow-up. The six-step approach supports the importance of an interprofessional collaboration and the role of pharmacists in PGx testing and counselling across healthcare settings.

Background: It is known that only 50% of patients diagnosed with major depressive disorders (MDD) respond to the first-line antidepressant treatment. Accordingly, there is a need to improve response rates to reduce healthcare costs and patient suffering. One approach to increase rates of treatment response might be the integration of pharmacogenetic (PGx) testing to stratify antidepressant drug selection. The goal of PGx assessments is to identify patients who have an increased risk to experience adverse drug reactions or non-response to specific drugs. Especially for antidepressants, there is compiling evidence on PGx influencing drug exposure as well as response., Methods: This study is an open-label, randomized controlled trial conducted in two study centers in Switzerland: (1) the Psychiatric Clinic of Solothurn and (2) the Private Clinic Wyss in Münchenbuchsee. Adult inpatients diagnosed with a unipolar moderate or severe depressive episode are recruited at clinic admission and are included in the study. If the adjustment to a new antidepressant pharmacotherapy is necessary, the participants are randomized to either Arm A (intervention group) or Arm B (control group). If no new antidepressant pharmacotherapy is introduced the participants will be followed up in an observational arm. The intervention is the service of pharmacist-guided pre-emptive PGx testing to support clinical decision making on antidepressant selection and dosing. As a comparison, in the control group, the antidepressant pharmacotherapy is selected by the treating physician according to current treatment guidelines (standard of care) without the knowledge of PGx test results and support of clinical pharmacists. The primary outcome of this study compares the response rates under antidepressant treatment after 4 weeks between intervention and control arm., Discussion: The findings from this clinical trial are expected to have a direct impact on inter-professional collaborations for the handling and use of PGx data in psychiatric practice., Trial Registration: ClinicalTrials.gov NCT04507555 . Registered on August 11, 2020. Swiss National Clinical Trials Portal SNCTP000004015 . Registered August 18, 2020., (© 2021. The Author(s).)

Introduction: Major depression is a psychiatric disease associated with physical inactivity, which in turn affects mental and physical health. A randomized controlled trial is being implemented to facilitate physical activity in people with major depression. In March 2020, Swiss state authorities temporarily legislated a lockdown to contain the Coronavirus disease-19 (COVID-19), which influenced health, behavior and research. The aim of this study was to find out whether data gathered before and during/after the lockdown among in-patients with major depression differ with regard to psychosocial health, physical activity and related attitudes and to establish whether baseline data have been affected by the lockdown. Methods: This is a cross-sectional analysis within a randomized controlled trial. Physically inactive, adult in-patients diagnosed with major depression were recruited from four Swiss psychiatric clinics between January 2019 and December 2020. Psychosocial health was measured with questionnaires pertaining to stress, sleep and health-related quality of life. Physical activity was measured with the Simple Physical Activity Questionnaire. Explicit attitudes were measured with seven questionnaires pertaining to physical activity-related motivation and volition. Implicit attitudes toward physical activity were captured with a single target implicit association test. Results: The sample consisted of 165 participants ( n = 119 before lockdown, n = 46 during/after lockdown). No statistically significant differences were found between in-patients with major depression assessed before and during/after the COVID-19 lockdown with regard to psychosocial health (stress, p = 0.51; sleep, p = 0.70; physical component of health-related quality of life, p = 0.55; mental component of health-related quality of life, p = 0.64), self-reported physical activity ( p = 0.16) and explicit as well as implicit attitudes toward physical activity ( p = 0.94). Hence, the COVID-19-induced lockdown seems not to have led to group differences. Conclusion: Baseline data gathered in in-patients suffering from major depression who are physically inactive upon admission to in-patient treatment in Switzerland seem to be unaffected by the COVID-19-induced lockdown. To assess changes in said population regarding psychosocial health and physical activity patterns over time, longitudinal data are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cody, Kreppke, Beck, Donath, Eckert, Imboden, Hatzinger, Holsboer-Trachsler, Lang, Ludyga, Mans, Mikoteit, Oswald, Rogausch, Schweinfurth, Zahner, Faude and Gerber.)

Though it is thousands of years old, prostate cancer (PCa) has only been known for 200 years. Until about 50 years ago, the diagnosis could only be made by digital rectal examination. Although the first prostate biopsies were already implemented in the beginning of the last century, it only obtained importance with the introduction of prostate-specific antigen (PSA) testing in the early screening for PCa and the pathologist, thus, became an essential partner for the urologist. In more recent years, specific MRI has significantly increased the accuracy of prostate biopsies. Thus, the question arises whether this technique is going to be so meaningful one day that prostate biopsy and the associated pretherapeutic histology are going to be redundant., (© 2020. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Humans need meaningful social interactions, but little is known about the consequences of not having them. We examined meaningful social interactions and the lack thereof in patients diagnosed with major depressive disorder (MDD) or social phobia (SP) and compared them to a control group (CG). Using event-sampling methodology, we sampled participants' everyday social behavior 6 times per day for 1 week in participants' natural environment. We investigated the quality and the proportion of meaningful social interactions (when they had meaningful social interactions) and degree of wishing for and avoidance of meaningful social interactions (when they did not have meaningful social interactions). Groups differed on the quality and avoidance of meaningful social interactions: Participants with MDD and SP reported perceiving their meaningful social interactions as lower quality (in terms of subjective meaningfulness) than the CG, with SP patients reporting even lower quality than the MDD patients. Further, both MDD and SP patients reported avoiding meaningful social interactions significantly more often than the CG. Although the proportion of meaningful social interactions was similar in all groups, the subjective quality of meaningful social interactions was perceived to be lower in MDD and SP patients. Future research might further identify what variables influenced the reinforcement of the MDD and SP patients so that they engaged in the same number of meaningful social interactions even though the quality of their meaningful social interactions was lower. Increasing awareness of what happens when patients do or do not have meaningful social interactions will help elucidate a potentially exacerbating or maintaining factor of the disorders., Competing Interests: The authors have declared that no competing interests exist.

A meta-analysis was performed to examine therapeutic effects of Silexan on somatic symptoms, including insomnia/fatigue, and physical health in patients with anxiety disorders. Five randomized, placebo-controlled trials were included in this analysis: The efficacy of Silexan (80 mg/day) was investigated in patients with subthreshold anxiety disorders (three trials) and in patients with generalized anxiety disorder (two trials). Silexan was superior to placebo in terms of the mean change from baseline in the Hamilton Anxiety Rating Scale (HAMA) subscore somatic anxiety at week 10 with a standardized mean difference of -0.31 [95% Cl: -0.52 to -0.10, p = .004]. Treatment effects of silexan on somatic anxiety were independent of gender and age. Statistically significant differences were also shown for single HAMA items somatic muscular, cardiovascular, respiratory, and genitourinary symptoms, indicating clinical relevance with small to medium effects of Silexan. Similar clinically meaningful effects of Silexan on SF-36 physical health, including reduced bodily pain and improved general health, and on insomnia complaints and fatigue, were demonstrated. In this meta-analysis including all placebo-controlled clinical trials in patients with anxiety disorders to date, statistically significant and clinically meaningful advantages of Silexan over placebo treatment were found in improving somatic symptoms and physical health., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

(1) Background: While the antidepressant effects of aerobic exercise (AE) are well documented, fewer studies have examined impact of AE as an add-on treatment. Moreover, various effects on neurobiological variables have been suggested. This study examines effects of AE on Cortisol Awakening Reaction (CAR), serum Brain Derived Neurotrophic Factor (sBDNF), Tumor Necrosis Factor alpha (TNF-alpha) and sleep. (2) Methods: Inpatients with moderate-to-severe depression ( N = 43) were randomly assigned to the AE or stretching condition (active control) taking place 3x/week for 6 weeks. CAR, sBDNF and TNF-alpha were assessed at baseline, after 2 weeks and post-intervention. The 17-item Hamilton Depression Rating Scale (HDRS17), subjective sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) were obtained at baseline and post-intervention. (3) Results: Stress axis activity decreased in both groups from baseline to post-intervention. sBDNF showed a significant increase over time, whereas the number of awakenings significantly decreased. No significant time by group interactions were detected for any of the study variables. Correlational analyses showed that higher improvements in maximum oxygen capacity (VO 2 max) from baseline to post-intervention were associated with reduced scores on the HDRS17, PSQI and REM-latency post-intervention. (4) Conclusions: While some neurobiological variables improved during inpatient treatment (CAR, sBDNF), no evidence was found for differential effects between AE and an active control condition (stretching). However, patients in which cardiorespiratory fitness increased showed higher improvements in depression severity and depression-related sleep-parameters.

Introduction and Hypothesis: To determine in patients with overactive bladder (OAB), urodynamic differences as well to compare the characteristics of patient's, with presence of detrusor overactivity on urodynamics with those with absence of detrusor overactivity., Methods: Taking into account the urodynamic findings, the patients with OAB symptoms were categorized into one of two groups: group 1 (with detrusor overactivity) or group 2 (without detrusor overactivity), and comparative analyses for both groups were performed (epidemiological data, patient history, urodynamic criteria, bladder diaries, IC-OAB, IC-OABqol - questionnaires)., Results: There was a significant difference in age as well in the disease duration between group 1 and group 2. Although the mean number of micturitions and nocturia episodes was comparable, the numbers of urgency episodes differed significantly. The number of 'wet' patients was significantly higher in the group 1 with the significantly higher number of incontinence episodes. Group 1 demonstrated higher OAB symptom scores and higher impact on the patients' quality of life., Conclusions: More than half of the patients complaining of urgency-frequency do not have detrusor overactivity upon urodynamic testing, and only half have detrusor overactivity that correlates with urge perception. The patients with no detrusor overactivity appear to be significantly younger and have fewer symptoms, with a less pronounced impact on quality of life. They also have significantly higher maximal bladder capacity. This data supports the hypothesis that both conditions are different phases (early and late) of the same pathological state, or may be two different subtypes of OAB.

Introduction: Stress and social isolation are potent predictors of negative health outcomes and are impacted in mood and anxiety disorders. Difficulties in social interactions have been particularly noted in people diagnosed with major depression disorder (MDD) and social phobia (SP). It remains poorly understood, however, how these variables interact on a moment-to-moment basis and which variables moderate this relationship. Psychological flexibility, or the ability to be open to experiences while maintaining engagement in valued activities, may help moderate the relationship between stress and social interaction., Objective: This study examined these variables in participants diagnosed with MDD and SP and compared them to a control group., Methods: Participants were diagnosed with a mental disorder (n = 118 MDD; n = 47 SP) or were in the control group consisting of participants without MDD or SP (n = 119). Using the event sampling methodology (ESM), participants were queried six times per day for 7 days about stress, social interactions, and emotional response (rigid vs. flexible)., Results: Higher current stress levels were related to more social interactions. This relationship was even stronger in situations when response flexibility was increased, especially in the clinical groups., Conclusions: Data suggest that a healthy psychological process (flexible emotional responding) buffers the relationship between stress and social interactions. We discuss how these variables interact and whether these patterns may paradoxically contribute to the maintenance of psychopathology., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Background: Post-event processing (PEP) after social interactions (SIs) contributes to the persistence of social phobia (SP). This study investigated whether PEP as a transdiagnostic process also occurs in major depressive disorder (MDD) and controls. We also tested to what extent PEP was explained by trait levels of social anxiety (SA) or depression., Method: For seven days, a total of n = 165 patients (n = 47 SP, n = 118 MDD) and n = 119 controls completed five surveys per day on their smartphones. Event-based experience sampling was used. PEP was assessed following subjective embarrassment in SIs with two reliable items from the Post-Event Processing Questionnaire. Data were analysed via multilevel regression analyses., Results: Individuals with SP or MDD experienced more embarrassing SIs than controls and, accordingly, more PEP. The relative frequency of PEP after embarrassing SIs was equally high in all groups (86-96%). The groups did not differ regarding the amount of time PEP was experienced. After controlling trait depression, embarrassment occurred more frequently only in SP compared to controls. When controlling trait SA, between-group differences in indications of embarrassment, and consequently in PEP, dissipated., Conclusions: PEP could be interpreted as a common coping strategy among all individuals, while more frequent embarrassment might be specific for clinical groups. Embarrassment was primarily driven by SA. The alleviation of SA could lead to the reduction of embarrassment and, further, of PEP. On this basis, a model describing PEP in MDD is proposed, while current models of PEP in SP are complemented., Competing Interests: The authors have declared that no competing interests exist.

We report the case of a patient with major depression treated with high-dose bupropion due to prior detected subtherapeutic blood concentrations at standard dosing. Pharmacogenetic panel testing identified the patient as a carrier of the CYP2B6 *6 allele, which has been associated with reduced bupropion metabolism and decreased concentrations of the pharmacologically active metabolite hydroxybupropion. Interestingly, we also found the patient to be homozygous for the CYP2C19 *17 allele, predicting an ultra rapid metabolizer phenotype. We propose a combined effect of the detected CYP2C19 and CYP2B6 genetic variants on bupropion metabolism. This case underlines the potential benefit of pre-emptive pharmacogenotyping but also the yet still fragmentary evidence making precise pharmacogenotype guided antidepressant selection and dosing challenging.