An implementation evaluation of the physical activity counseling for in-patients with major depressive disorder (PACINPAT) intervention: a randomized controlled trial.

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 3rd September 2018.

How Response Styles Moderate the Relationship between Daily Stress and Social Interactions in Depression, Social Phobia, and Controls.

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.

Severe Adverse Drug Reactions to Quetiapine in Two Patients Carrying CYP2D6*4 Variants: A Case Report.

We report two cases of patients who developed severe adverse drug reactions including persistent movement disorders, nausea, and vertigo during treatment with quetiapine at maximum daily doses ranging between 300 and 400 mg. The extensive hepatic metabolism of quetiapine is mainly attributed to cytochrome P450 3A4 (CYP3A4). However, there is recent evidence supporting the idea of CYP2D6 playing a role in the clearance of the quetiapine active metabolite norquetiapine. Interestingly, both patients we are reporting of are carriers of the CYP2D6*4 variant, predicting an intermediate metabolizer phenotype. Additionally, co-medication with a known CYP2D6 inhibitor and renal impairment might have further affected quetiapine pharmacokinetics. The herein reported cases could spark a discussion on the potential impact of a patient's pharmacogenetic predisposition in the treatment with quetiapine. However, further studies are warranted to promote the adoption of pharmacogenetic testing for the prevention of drug-induced toxicities associated with quetiapine.

The effect of anticipatory stress and openness and engagement on subsequently perceived sleep quality-An Experience Sampling Method study.

High stress levels can influence sleep quality negatively. If this also applies to anticipatory stress is poorly documented, however. Across insomnia severity levels, this study examined participants' evening levels of (a) anticipatory stress and (b) their skills hypothesized to downregulate the impact of stress, namely openness to internal experiences and continuous engagement in meaningful activities (openness and engagement) and their association with the quality of the subsequent night's sleep. The moderating role of insomnia severity was also tested. We used a quasi-experimental longitudinal design with Experience Sampling Method using smartphones over the course of 1 week (3,976 assessments; 93.2% of prompted queries). Participants recorded their sleep quality, anticipatory stress, and openness and engagement within their daily context. Participants included in the study were diagnosed with major depressive disorder (n = 118), social phobia (n = 47) or belonged to the control group (n = 119). Both anticipatory stress and openness and engagement predicted subsequent sleep quality. Diagnostic group was associated with overall sleep quality, but did not interact with the predictors. These findings were invariant across levels of self-reported insomnia severity. Furthermore, openness and engagement and anticipatory stress did not interact in their effect on sleep quality. The results suggest that both stress reduction and increased openness and engagement are associated with improved subjective sleep quality on a day to day basis, regardless of insomnia severity. Targeting these variables may help improve sleep quality. Future research should disentangle the effects of openness and engagement on anticipatory stress.

General or specific? The memory-experience gap for individuals diagnosed with a major depressive disorder or a social phobia diagnosis, and individuals without such diagnoses.

Psychological treatment and assessment necessarily rely on patients' recall. Yet several empirical studies have documented a gap between memory and real-life experience (i.e., memory-experience gap; MeG). We investigated and compared the MeG of sadness, social anxiety, happiness, and physical activity for participants diagnosed with a major depressive disorder (MDD), a social phobia (SP), and participants without such diagnoses (CG). The study included 118 participants diagnosed with a MDD, 47 with a SP, and 119 CG. Using event-sampling methods (ESM), participants were asked via smartphone to report their experiences throughout a week and then to recall those again retrospectively at the end of the study week. Results indicate significant differences in the MeG with respect to the experience that was salient to them (e.g., MDD group - sadness; SP group - social anxiety; CG group - happiness). Furthermore, all groups showed a MeG for physical activity and, the results indicate significant group differences in the magnitude of the MeGs. This study demonstrated the presence of a MeG in individuals in a MDD, SP, and CG group and in positive and negative affective experiences. Differential patterns across the samples contribute to a better understanding of this gap and its implications.

[Sleep and Psychological Functioning of Children and Adolescents - a Narrative Review]. / Schlaf und Befindlichkeit bei Kindern und Jugendlichen ­ ein narratives Review.

Sleep and Psychological Functioning of Children and Adolescents - a Narrative Review Children and adolescents need sufficient and restoring sleep to improve their cognitive, emotional, social and behavioral performance. The present narrative review describes the associations between children's and adolescents' sleep patterns and a broad variety of topics; these topics were chosen at the authors' discretion and does not claim to be exhaustive. After a short introduction, we describe the associations between (adolescent) children's sleep in tight relation to the family functioning. Specifically, (adolescent) children's sleep and psychological functioning appears to be related to mothers' sleep and psychological functioning. Findings from longitudinal studies are reported, which underline that poor sleep at childhood increases the risk of poor sleep and somatic and psychological health issues later in life. Excessive screen time in the evening increases the risk of shorter sleep duration and increased daytime sleepiness; on the flip side, it also appears the excessive screen time might be a coping strategy to deal with symptoms of anxiety; further, using social media in the evening seems to be associated with the adolescents' need to stay in touch with their peers. While physical inactivity and sedentary behavior is a serious health concern, in children and adolescents, regular physical activity is associated with improved subjective and objective sleep and a broad variety of psychological health outcomes. Further selective topics are: While children and adolescents with repaired cleft did not show disadvantages in their sleep and psychological functioning compared to their counterparts without clefts, at the age of seven to nine years, very preterm children show unfavorable sleep patterns and psychological functioning, compared to typically developing children.

Improved Alertness Is Associated with Early Increase in Serum Brain-Derived Neurotrophic Factor and Antidepressant Treatment Outcome in Major Depression.

BACKGROUND/AIMS: In major depression cognitive impairment is common and may persist despite improvement in psychopathology. So far it is unclear how closely related improvement in cognitive functioning is to the clinical course of depression. Further, it is unclear whether recovery from cognitive impairment is linked to changes in serum brain-derived neurotrophic factor (sBDNF). The objectives of this study were (1) to explore the predictive value of cognitive impairment for therapeutic outcome, and (2) to assess the association between cognitive performance and sBDNF levels over a 6-week course of antidepressant treatment. METHODS: Twenty-five adult patients suffering from major depression underwent standardized treatment with duloxetine. Both severity of depression as assessed by the Hamilton Depression Rating Scale and sBDNF levels were measured at baseline, and after 1, 2 and 6 weeks of treatment. Cognitive performance, i.e. alertness, working memory, and divided attention, was assessed at baseline, after 1 week, and at the end of treatment after 6 weeks. RESULTS: Higher performance in alertness and divided attention at baseline correlated with less severe depression at week 6. During the first week of treatment, a greater increase in sBDNF was associated with a greater improvement in alertness at week 6. CONCLUSION: Greater alertness at baseline was a predictor of favorable antidepressive treatment outcome. Moreover, the early increase in sBDNF correlated with improvement in attention functioning. Thus, recovery from cognitive impairment and an early increase in sBDNF seem to be associated.

Recurrent high creatine kinase levels under clozapine treatment - a case report assessing a suspected adverse drug reaction.

Suspected adverse drug reactions (ADRs) during treatment with clozapine often prompt therapeutic drug monitoring (TDM) in clinical practice. Currently, there is no official recommendation for pharmacogenetic (PGx) testing in the context of clozapine therapy. In this case report, we demonstrate and discuss the challenges of interpreting PGx and TDM results highlighting the possibilities and limitations of both analytical methods. A 36-year-old male patient with catatonic schizophrenia was treated with clozapine. He experienced multiple hospitalizations due to elevated creatine kinase (CK) levels (up to 9000 U/L, reference range: 30-200 U/L). With no other medical explanation found, physicians suspected clozapine-induced ADRs. However, plasma levels of clozapine were consistently low or subtherapeutic upon admission, prompting us to conduct a PGx analysis and retrospectively review the patient's TDM data, progress notes, and discharge reports. We investigated two possible hypotheses to explain the symptoms despite low clozapine plasma levels: Hypothesis i. suggested the formation and accumulation of a reactive intermediate metabolite due to increased activity in cytochrome P450 3A5 and reduced activity in glutathione S-transferases 1, leading to myotoxicity. Hypothesis ii. proposed under-treatment with clozapine, resulting in ineffective clozapine levels, leading to a rebound effect with increased catatonic symptoms and CK levels. After considering both data sources (PGx and TDM), hypothesis ii. appeared more plausible. By comprehensively assessing all available TDM measurements and examining them in temporal correlation with the drug dose and clinical symptoms, we observed that CK levels normalized when clozapine plasma levels were raised to the therapeutic range. This was achieved through hospitalization and closely monitored clozapine intake. Therefore, we concluded that the symptoms were not an ADR due to altered clozapine metabolism but rather the result of under-treatment. Interpreting TDM and PGx results requires caution. Relying solely on isolated PGx or single TDM values can result in misinterpretation of drug reactions. We recommend considering the comprehensive patient history, including treatment, dosages, laboratory values, clinic visits, and medication adherence.

Correspondence between the Simple Physical Activity Questionnaire (SIMPAQ) and accelerometer-based physical activity in inpatients treated for major depressive disorders in comparison to non-depressed controls.

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 VO2max 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.

Long-term outcomes of physical activity counseling in in-patients with major depressive disorder: results from the PACINPAT randomized controlled trial.

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 (Mage = 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 (ß = -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 .

Cardiorespiratory fitness, perceived fitness and autonomic function in in-patients with different depression severity compared with healthy controls.

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.

Visually detected NREM Stage 2 sleep spindles in kindergarten children are associated with current and future emotional and behavioural characteristics.

Sleep electroencephalogram spindles are associated with efficient cortical-subcortical connectivity, and intellectual and learning abilities. In the present study, we assessed healthy preschoolers with a twofold aim: (i) to explore associations of non-rapid eye movement S2 spindles with emotional/behavioural characteristics cross-sectionally; and (ii) longitudinally. A total of 43 children who were 5 years old underwent objective sleep electroencephalogram monitoring in their homes. Emotional and behavioural dimensions were assessed by parents and teachers with the Strengths & Difficulties Questionnaire at baseline and at follow-up 1 year later. Non-rapid eye movement S2 spindles were visually scored and compared with Strengths & Difficulties Questionnaire dimensions. High non-rapid eye movement S2 spindle density was associated with less internalizing behaviour, more prosocial behaviour and a low total problem score. In girls, high non-rapid eye movement S2 spindle density was related to low hyperactivity, while in boys it was associated with less internalizing behaviour, more externalizing behaviour and more hyperactivity. Longitudinally, a higher number of non-rapid eye movement S2 spindles at 5 years old predicted fewer peer problems 12 months later. In kindergarten children, high non-rapid eye movement S2 spindle density is associated with observable current and future favourable emotional/behavioural patterns. However, gender differences were also found, as should be taken into account in future studies.

The Origins of the Dark-Hyperactivity and Negative Peer Relationships, an Objectively Lower Sleep Efficiency, and a Longer Sleep Onset Latency at Age Five Were Associated with Callous-Unemotional Traits and Low Empathy at Age 14.

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.

Is helping you helping me? The assessment of helping others using event sampling methodology in a clinical and a non-clinical sample.

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.

Differences in Selective Attention and Inhibitory Control in Patients with Major Depressive Disorder and Healthy Controls Who Do Not Engage in Sufficient Physical Activity.

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.

Cardiorespiratory fitness and cardiovascular risk among in-patients with depression compared to healthy controls.

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 χ2-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.

The potential of biomarkers for diagnosing insomnia: Consensus statement of the WFSBP Task Force on Sleep Disorders.

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.

Case report: Non-response to fluoxetine in a homozygous 5-HTTLPR S-allele carrier of the serotonin transporter gene.

We report the case of a 50-year-old male with major depressive disorder (MDD) to illustrate the challenge of finding effective antidepressant pharmacotherapy and the role that the patient's genetic makeup may play. Recent treatment attempts before clinic admission included venlafaxine and fluoxetine. Venlafaxine was discontinued due to lack of response, and subsequently switched to fluoxetine based on pharmacogenotyping of the P-glycoprotein transporter (P-gp, encoded by ABCB1) by the outpatient psychiatrist. Despite steady state serum levels within the therapeutic range, the patient did not benefit from fluoxetine either, necessitating admission to our clinic. Here a clinical pharmacist-led medication review including additional pharmacogenetic (PGx) analysis resulted in the change of the antidepressant therapy to bupropion. Under the new regimen, established in the in-patient-setting, the patient remitted. However, based on the assessed pharmacokinetics-related gene variants, including CYPs and ABCB1, non-response to fluoxetine could not be conclusively explained. Therefore, we retrospectively selected the serotonin transporter (SERT1, encoded by SLC6A4) for further genetic analysis of pharmacodynamic variability. The patient presented to be a homozygous carrier of the short allele variant in the 5-HTTLPR (S/S) located within the SLC6A4 promoter region, which has been associated with a reduced expression of the SERT1. This case points out the potential relevance of panel PGx testing considering polymorphisms in genes of pharmacokinetic as well as pharmacodynamic relevance.

Short-term outcomes of physical activity counseling in in-patients with Major Depressive Disorder: Results from the PACINPAT randomized controlled trial.

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.

A Guide to a Pharmacist-Led Pharmacogenetic Testing and Counselling Service in an Interprofessional Healthcare Setting.

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.