Predictors of valproic acid steady-state serum levels in adult and pediatric psychiatric inpatients: a comparative analysis.

RATIONALE: Valproic acid (VPA) is commonly used as a second-line mood stabilizer or augmentative agent in severe mental illnesses. However, population pharmacokinetic studies specific to psychiatric populations are limited, and clinical predictors for the precision application of VPA remain undefined. OBJECTIVES: To identify steady-state serum VPA level predictors in pediatric/adolescent and adult psychiatric inpatients. METHODS: We analyzed data from 634 patients and 1,068 steady-state therapeutic drug monitoring (TDM) data points recorded from 2015 to 2021. Steady-state VPA levels were obtained after tapering during each hospitalization episode. Electronic patient records were screened for routine clinical parameters and co-medication. Generalized additive mixed models were employed to identify independent predictors. RESULTS: Most TDM episodes involved patients with psychotic disorders, including schizophrenia (29.2%) and schizoaffective disorder (17.3%). Polypharmacy was common, with the most frequent combinations being VPA + quetiapine and VPA + promethazine. Age was significantly associated with VPA levels, with pediatric/adolescent patients (< 18 years) demonstrating higher dose-adjusted serum levels of VPA (ß = 7.6±2.34, p < 0.001) after accounting for BMI. Women tended to have higher adjusted VPA serum levels than men (ß = 5.08±1.62, p < 0.001). The formulation of VPA (Immediate-release vs. extended-release) showed no association with VPA levels. Co-administration of diazepam exhibited a dose-dependent decrease in VPA levels (F = 15.7, p < 0.001), suggesting a potential pharmacokinetic interaction. CONCLUSIONS: This study highlights the utility of population-specific pharmacokinetic data for VPA in psychiatric populations. Age, gender, and co-administration of diazepam were identified as predictors of VPA levels. Further research is warranted to establish additional predictors and optimize the precision application of VPA in psychiatric patients.

Patient-reported experience measures (PREMs) in outpatient psychiatry - is there an association to perceived discrimination and devaluation?

Patient-Reported Experience Measures (PREMs) are gaining significance in the field of psychiatry, with patient satisfaction being a key measure. However, it is unclear if patient satisfaction in psychiatry is influenced by variables outside the treatment setting. This brief report thus examines the possible impact of perceived discrimination and devaluation (PDD) on patient satisfaction in the psychiatric outpatient setting. Data from 1,126 individuals who were undergoing or had recently completed treatment at 15 outpatient centers of the Psychiatric University Clinic in Basel, Switzerland, was analyzed. Patient satisfaction was assessed using the Münsterlingen Patient Satisfaction Questionnaire (MüPF), and perceived stigma was measured with the Perceived Discrimination Devaluation Scale. The results revealed a positive small effect size relationship between MüPF and PDD, suggesting that patients who perceived less stigma report higher treatment satisfaction. This relationship may affect most ratings, with the total MüPF score remaining relatively robust against this potential influence. Linear regression analysis indicated that a one-unit increase in PDD score could lead to a maximum change of 1.8 points on the 7-point Likert scale for the MüPF item correlating highest with PDD and 0.4 points on the total MüPF score. These findings highlight the importance of considering perceived stigma when evaluating patient satisfaction with psychiatric outpatient treatment. Future research should investigate associations between stigma, patient satisfaction, treatment outcome, as well as other external factors that may influence patient satisfaction in psychiatric settings.

Treatment-seeking threshold and accessibility of psychiatric outpatient services in Switzerland: the relationship with stigma and self-esteem.

Perceived stigmatization and low self-esteem are linked to poorer mental health outcomes, but their impact on treatment-seeking thresholds and the importance of outpatient service location remain unclear. The study included 525 outpatients of the University Psychiatric Clinic (UPK) Basel, Switzerland, of whom 346 were treated at inner city services and 179 at services located on the main site of the UPK at the outer city limits. Perceived discrimination and devaluation (PDD), self-esteem (SE), treatment-seeking threshold (TST), and accessibility were measured via a self-reported questionnaire. The PDD consisted of 12 items evaluating beliefs about the level of stigma towards individuals with mental illness in the general population on a 5-point Likert scale. SE, TST and accessibility were assessed through single-item 7-point Likert scales. PDD and SE were positively correlated (p < 0.001), suggesting that lower perceived stigma was linked to higher self-esteem, and were not associated with TST. The relationship between PDD and SE remained consistent after controlling for age, gender, and nationality. Age was negatively correlated with TST (p = 0.022), while gender did not significantly influence any of the variables. There was little variation regarding PDD, with emergencies at the site of the psychiatric clinic and substance use disorder (SUD) patients reporting higher levels of stigmatization. Emergency patients and those with SUD and personality disorder reported the lowest SE ratings. TST showed a broad range and was highest for emergency services and transcultural psychiatry patients. Differences in accessibility were mainly linked to the location, with outpatient service users in the inner city reporting better accessibility (p < 0.001) and higher SE (p = 0.009). In comparison to patients using services with planned contacts only, patients in emergency settings differed by higher TST (p = 0.018) and better ratings of accessibility (p = 0.004). In conclusion, there was a relevant amount of stigmatization, impaired self-esteem, and, for some outpatient services, high thresholds to seek treatment. Future research should explore other factors influencing TST. The findings highlight the need to address stigmatization and accessibility when planning mental health services.

Comparing the latent state-trait structure of the PANSS in cariprazine-medicated and placebo-controlled patients with acute schizophrenia.

After over a hundred years of research, the question whether the symptoms of schizophrenia are rather trait-like (being a relatively stable quality of individuals) or state-like (being substance to change) is still unanswered. To assess the trait and the state component in patients with acute schizophrenia, one group receiving antipsychotic treatment, the other not. Data from four phase II/III, 6-week, randomized, double-blind, placebo-controlled trials of similar design that included patients with acute exacerbation of schizophrenia were pooled. In every trial, one treatment group received a third-generation antipsychotic, cariprazine, and the other group placebo. To assess symptoms of schizophrenia, the Positive and Negative Symptom Scale (PANSS) was applied. Further analyses were conducted using the five subscales as proposed by Wallwork and colleagues. A latent state-trait (LST) model was developed to estimate the trait and state components of the total variance of the observed scores. All symptom dimensions behaved more in a trait-like manner. The proportions of all sources of variability changed over the course of the observational period, with a bent around weeks 3 and 4. Visually inspected, no major differences were found between the two treatment groups regarding the LST structure of symptom dimensions. This high proportion of inter-individual stability may represent an inherent part of symptomatology that behaves independently from treatment status.

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 .

Aging effects on the encoding/retrieval flip in associative memory: fMRI evidence from incidental contingency learning.

Introduction: Associative memory is arguably the most basic memory function and therein constitutes the foundation of all episodic and semantic memory processes. At the same time, the decline of associative memory represents a core feature of age-related cognitive decline in both, healthy and pathological (i.e., dementia-related) aging. The neural mechanisms underlying age-related impairments in associative memory are still not fully understood, especially regarding incidental (i.e., non-intentional) learning. Methods: We investigated the impact of age on the incidental learning and memory retrieval of face-name combinations in a total sample of 46 young (N = 23; mean age = 23.39 years) and elderly (N = 22, mean age = 69.05 years) participants. More specifically, particular interest was placed in age-related changes in encoding/retrieval (E/R) flips, which denote a neural antagonism of opposed activation patterns in the same brain region during memory encoding and retrieval, which were assessed using fMRI. Results: According to our hypothesis, the results showed a significant age-related decline in the retrieval performance in the old group. Additionally, at the neural level, we discovered an abolished E/R flip in the right anterior insula and a joint but reduced E/R flip activation magnitude in the posterior middle cingulate cortex in older subjects. Discussion: In conclusion, the present findings suggest that the impaired neural modulation of the E/R flip in the right aIC might be a sensitive marker in the early detection of neural aging.

Listening to music during intranasal (es)ketamine therapy in patients with treatment-resistant depression correlates with better tolerability and reduced anxiety.

Background: Although the effectiveness of (es)ketamine for therapy-resistant depression (TRD) has been established, potential treatment-limiting factors include side effects like dissociation, anxiety, or elevated blood pressure. Music can reduce stress and negative emotions as anxiety. This study aimed to investigate the impact of listening to music during intranasal (es)ketamine administration on both tolerability and efficacy. Methods: Records of 494 sessions (of 37 patients) with intranasal (es)ketamine administration, each containing data of blood pressure measurements, DSS-IV (dissociation symptoms scale-IV), anxiety and euphoria analogue scale, MADRS (Montgomery-Åsberg Depression Rating Scale) and BDI (Beck's Depression Inventory) were evaluated. Results: The between-group analysis, comparing participants who listened to music with those who did not, revealed significant differences in the administered dose (p-value: 0.003, mean: 131.5 mg with music vs. 116.7 mg without music), scores on the DSS Item 1 (p-value: 0.005, mean: 3 points vs. 2.4 points), levels of anxiety (p-value: <0.001, mean: 0.4 points vs. 1.4 points), and measurements of maximal systolic blood pressure after administration (p-value: 0.017, mean: 137.9 mmHg vs. 140.3 mmHg). Listening to music had no impact on the MARDS-change score between the sessions. Limitations: Key limitations include a non-randomized naturalistic design and the non-standardized selection of music, which was based on individual patient preferences. Conclusion: Listening to music during intranasal (es)ketamine therapy appears to be linked to reduced anxiety and lower blood pressure, stable or increased dissociation levels, and improved tolerance for higher doses. These findings could potentially contribute to the optimization of (es)ketamine therapy, both in terms of treatment efficacy and managing side effects.

Implementation of a Budo group therapy for psychiatric in- and outpatients: a feasibility study.

Introduction: Physical exercise has been shown to have numerous health benefits on co-morbid somatic conditions in psychiatry and can also enhance mental health. Thus, it is not difficult to recommend physical training programs as part of an integrated and holistic treatment approach for mental health disorders. However, getting patients to participate and keeping them engaged is a major challenge. Programs based on martial arts training could be interventions improving physical and mental health with higher attachment rates. The structured discipline, holistic approach integrating physical and mental elements, and empowering activities, may explain higher participant attachment rates. Methods: Thus, the main objective of this feasibility study is to describe a newly established group therapy program incorporating interventions from martial arts training with its physical and philosophical parts including mindfulness and breath work. Results: During the 14-month study period from April 2021 to May 2022, a Budo group therapy was used by 215 individual persons with a total of 725 group therapy participations. Retention in the program was good across all settings and very good for persons who participated as outpatients. The mean age of the participants was 33.5 years with a range from 14 to 69 years of age, and about 41% of the participants were female. The therapy program was able to address patients over the whole spectrum of psychiatric diagnoses. Satisfaction and motivation were uniformly self-reported as very good. Patients self-reported improved mental and physical health after participating in a Budo session compared to pre-session. Discussion: Budo group therapy thus can be seen as a feasible, well-accepted and promising new transdiagnostic treatment approach, combining physical activation with resilience enhancement. With minimal contraindications, a broad spectrum of individuals seeking mental health support can engage in this group therapy.

Just Not Enough: Utilization of Outpatient Psychotherapy Provided by Clinical Psychologists for Patients With Psychosis and Bipolar Disorder in Switzerland.

Treatment guidelines state that evidence-based psychotherapy is effective for people with psychosis and bipolar disorder and should be offered during every phase of the treatment process. However, research has indicated a lack of outpatient psychotherapeutic services for this patient group, for example, in the United States or Germany. We extend this finding by presenting survey data from Switzerland. We surveyed 112 inpatients with a diagnosis of a schizophrenia spectrum disorder or bipolar disorder and assessed outpatient treatment over the 5 years prior to their index hospitalization by using retrospective self-reports. The survey focused on psychotherapy provided by clinical psychologists. Results indicate that only 23.2% of participants retrospectively reported having utilized any outpatient psychotherapy within the reporting period and only 8% of participants reported having received a number of outpatient sessions that reaches recommended levels of psychotherapy. Exploratory analyses did not detect a significant association between self-reported utilization of outpatient psychotherapy sessions and most demographic, psychiatric, and psychological attributes, but patients with a bipolar disorder diagnosis (vs schizophrenia spectrum diagnosis) reported having utilized outpatient treatment more often. These findings are preliminary. When replicated they highlight the need for increased access to outpatient psychotherapy and better alignment between guideline recommendations and outpatient supply.

How mood is affected by environment and upsetting events: The moderating role of psychological flexibility.

OBJECTIVE: Patients suffering from psychological disorders report decreased quality of life and low mood. The relationship of these symptoms to daily upsetting events or environments, and in the context of active coping mechanisms is poorly understood. The present study thus investigates the association between mood, psychological flexibility, upsetting events, and environment in the daily life of outpatients. METHOD: We investigated 80 outpatients at the beginning of treatment, using event sampling methodology (ESM). Patients' mood, occurrence of upsetting events, current environment, and psychological flexibility were sampled six times per day during a one-week intensive longitudinal examination. Data were analyzed using linear mixed models (LMMs). RESULTS: Participants reported worse mood the more upsetting events they experienced. Further, participants reported better mood when in private environments (e.g., with friends), and worse mood when at the hospital, compared to being at home. Higher levels of psychological flexibility, however, were associated with better mood, irrespective of the occurrence of upsetting events or current environment. CONCLUSION: Results suggest that mood is positively associated with psychological flexibility, not despite, but especially during the dynamic and context-specific challenges of daily life. Psychological flexibility may thus potentially act as a buffer against distress-provoking situations as patients go about their daily lives. TRIAL REGISTRATION: ISRCTN.org identifier: ISRCTN11209732.

Exploring the Therapeutic Potential of Gamma-Aminobutyric Acid in Stress and Depressive Disorders through the Gut-Brain Axis.

Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABAA receptors) responsible for mediating GABAergic inhibition. Furthermore, there is substantial evidence supporting the significant role of GABA in regulating stress within the brain, which is a pivotal vulnerability factor in mood disorders. GABA is readily available and approved as a food supplement in many countries. Although there is substantial evidence indicating that orally ingested GABA may affect GABA receptors in peripheral tissues, there is comparatively less evidence supporting its direct action within the brain. Emerging evidence highlights that oral GABA intake may exert beneficial effects on the brain and psyche through the gut-brain axis. While GABA enjoys wide consumer acceptance in Eastern Asian markets, with many consumers reporting favorable effects on stress regulation, mood, and sleep, rigorous independent research is still largely lacking. Basic research, coupled with initial clinical findings, makes GABA an intriguing neuro-nutritional compound deserving of clinical studies in individuals with depression and other psychological problems.

The association between the admission to wards with open- vs. closed-door policy and the use of coercive measures.

Introduction: Psychiatric treatment on a ward with open-door policy is associated with reduced numbers of coercive measures. The effect of the door policy of previous stays, however, has not been investigated. Methods: The data set consisted of 22,172 stays by adult inpatients in a psychiatric university hospital between 2010 and 2019. Pairs of consecutive stays were built. The outcome variable was the occurrence of coercive measures during the second stay. Results: Compared to treatments on wards with a closed-door policy at both stays, treatments on wards with an open-door policy at the second stay had smaller odds for coercive measures (OR ranging between 0.09 and 0.33, p < 0.01). In addition, coercive measures were more frequent in treatment histories where patients previously treated on a closed ward were admitted to a ward with an open-door policy and subsequently transferred to a ward with a closed-door policy at the second stay (OR=2.97, p = 0.046). Discussion: Treatment under open-door policy is associated with fewer coercive measures, even in patients with previous experience of closed-door settings. The group of patients who were admitted to a ward with an open-door, then transmitted to a ward with a closed-door policy seem to be prone to experience coercive measures. Clinical strategies to keep these patients in treatment in an open-door setting could further reduce coercive measures.

Shifting drug markets in North America - a global crisis in the making?

Understanding drug market dynamics and their underlying driving factors is paramount to developing effective responses to the overdose crisis in North America. This paper summarises the distinct drug market trends observed locally and internationally over the past decade to extrapolate future drug market trajectories. The emergence of fentanyl on North American street markets from 2014 onwards led to a shift of street drug use patterns. Previously perceived as contaminants, novel synthetic opioids became the drugs of choice and a trend towards higher potency was observed across various substance classes. The diversification of distribution strategies as well as the regionalisation and industrialisation of production followed basic economic principles that were heavily influenced by prosecution and policy makers. Particularly, the trend towards higher potency is likely most indicative of what to expect from future illicit drug market developments. Nitazenes and fentanyl-analogues, several times more potent than fentanyl itself, are increasingly detected in toxicological testing and have the potential of becoming the drugs of choice in the future. The dynamic of drug import and local production is less clear and influenced by a multitude of factors like precursor availability, know-how, infrastructure, and the success of local drug enforcement strategies. Drug market dynamics and the current trajectory towards ultrapotent opioids need to be recognised by legislation, enforcement, and the health care system to prepare effective responses. Without significant improvements in treatment access, the implementation of preventative approaches and early warning systems, the mortality rate will continue to increase. Furthermore, there is no mechanism in place preventing the currently North American focused overdose crisis to spread to other parts of the globe, particularly Europe. A system of oversight, research, and treatment is needed to address mortality rates of historic proportions and prevent further harm.

Folate and Its Significance in Depressive Disorders and Suicidality: A Comprehensive Narrative Review.

Depressive disorders pose significant challenges to global public health, necessitating effective prevention and management strategies. Notably, the occurrence of suicide frequently coincides with depressive episodes. Suicide is as a paramount global health concern that demands efficacious preventive strategies. Current psychiatric approaches heavily rely on pharmacological interventions but have had limited success in addressing the global burden of mental health issues. Suboptimal nutrition, with its impact on the neuroendocrine system, has been implicated in the underlying pathology of depressive disorders. Folate, a group of water-soluble compounds, plays a crucial role in various central nervous system functions. Depressed individuals often exhibit low levels of serum and red blood cell folate. Multiple studies and systematic reviews have investigated the efficacy of folic acid and its derivative, L-methylfolate, which can cross the blood-brain barrier, as stand-alone or adjunct therapies for depression. Although findings have been mixed, the available evidence generally supports the use of these compounds in depressed individuals. Recent studies have established links between the one-carbon cycle, folate-homocysteine balance, immune system function, glutamate excitation via NMDA (N-methyl-D-aspartate) receptors, and gut microbiome eubiosis in mood regulation. These findings provide insights into the complex neurobiological mechanisms underlying the effects of folate and related compounds in depression. Through a comprehensive review of the existing literature, this study aims to advance our understanding of the therapeutic potential of folic acid and related compounds in depression treatment. It also seeks to explore their role in addressing suicidal tendencies and shed light on the neurobiological mechanisms involved, leveraging the latest discoveries in depression research.

Sexual dysfunction prevalence, risk factors, and help-seeking behavior in opioid agonist treatment and general psychiatry: a cross-sectional study.

Background: Mental disorders pose a high risk for the occurrence of sexual dysfunctions (SD). This study aimed to investigate prevalence of risk factors and help-seeking behavior for sexual dysfunctions in patients with opioid use disorder compared to patients seeking psychotherapeutic help. Methods: Ninety-seven patients at two opioid agonist treatment (OAT) centers and 65 psychotherapeutic patients from a psychiatric practice (PP) in Switzerland were included in the study. Self-report assessments comprised sexual functioning (IIEF: International Index of Erectile Function; FSFI: Female Sexual Function Index), depressive state, psychological distress, alcohol consumption, nicotine use, and a self-designed questionnaire on help-seeking behavior. We used chi-squared and Mann-Whitney U tests for group comparisons and binary logistic regression models to identify variables predicting the occurrence of sexual dysfunctions. Results: There was no statistically significant difference (p = 0.140) in the prevalence of SD between OAT (n = 64, 66.0%) and PP sample (n = 35, 53.8%). OAT patients scored significantly higher in scales assessing nicotine use (p < 0.001) and depressive state (p = 0.005). Male OAT patients scored significantly worse on the Erectile Function scale (p = 0.005) and female PP patients scored significantly worse on the FSFI Pain domain (p = 0.022). Opioid use disorder, higher age, and being female predicted the occurrence of SD in the total sample. In the OAT sample, only higher age remained predictive for the occurrence of SD. A lack of help-seeking behavior was observed in both groups, with only 31% of OAT patients and 35% of PP patients ever having talked about their sexual health with their treating physician. Conclusion: SD are common among psychiatric patients receiving OAT and general psychiatric patients seeking psychotherapy. Professionals providing mental healthcare to patients must emphasize prevention and routine assessments of sexual functioning needs.

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.

Benzodiazepine use, quality of life and psychiatric symptom burden in oral and injectable opioid agonist treatment: a cross-sectional study.

BACKGROUND: Use of benzodiazepines (BZD) in patients receiving opioid agonist treatment (OAT) is common and associated with a variety of negative health and social outcomes. This cross-sectional study investigates the impact of BZD use in OAT patients on their quality of life (QoL). METHODS: A convenience sample of patients receiving oral OAT or heroin-assisted treatment in two outpatient centres in Basel, Switzerland was investigated. Participants (n = 141) completed self-report questionnaires on psychiatric symptoms and psychological distress (The Symptom Checklist 27, SCL-27), depressive state (German version of the Center for Epidemiological Studies Depression Scale), quality of life (Lancashire Quality of Life Profile, LQOLP) and use of BZD and other drugs (self-report questionnaire). Substance use was assessed by urine toxicology testing. RESULTS: In bivariate analysis, total QoL scores were significantly lower for lifetime, current, and prolonged BZD users compared to participants without the respective use patterns. There was no significant relationship between BZD dose and QoL. In multivariable linear regression models controlling for psychiatric symptom load and depressive state, only lifetime use predicted lower QoL, whereas other BZD use patterns were not significantly associated. CONCLUSIONS: The association of lower QoL and BZD use in OAT patients is strongly confounded by co-occurring depressive state and psychiatric symptoms. Careful diagnosis and treatment of co-occurring mental disorders in OAT is paramount to improve QoL in this patient population and may also help reduce BZD use.

Potential links between brown adipose tissue, circadian dysregulation, and suicide risk.

Circadian desynchronizations are associated with psychiatric disorders as well as with higher suicidal risk. Brown adipose tissue (BAT) is important in the regulation of body temperature and contributes to the homeostasis of the metabolic, cardiovascular, skeletal muscle or central nervous system. BAT is under neuronal, hormonal and immune control and secrets batokines: i.e., autocrine, paracrine and endocrine active substances. Moreover, BAT is involved in circadian system. Light, ambient temperature as well as exogen substances interact with BAT. Thus, a dysregulation of BAT can indirectly worsen psychiatric conditions and the risk of suicide, as one of previously suggested explanations for the seasonality of suicide rate. Furthermore, overactivation of BAT is associated with lower body weight and lower level of blood lipids. Reduced body mass index (BMI) or decrease in BMI respectively, as well as lower triglyceride concentrations were found to correlate with higher risk of suicide, however the findings are inconclusive. Hyperactivation or dysregulation of BAT in relation to the circadian system as a possible common factor is discussed. Interestingly, substances with proven efficacy in reducing suicidal risk, like clozapine or lithium, interact with BAT. The effects of clozapine on fat tissue are stronger and might differ qualitatively from other antipsychotics; however, the significance remains unclear. We suggest that BAT is involved in the brain/environment homeostasis and deserves attention from a psychiatric point of view. Better understanding of circadian disruptions and its mechanisms can contribute to personalized diagnostic and therapy as well as better assessment of suicide risk.

Therapeutic leave and direct inpatient healthcare costs in inpatients with mental illness.

AIMS: Balancing the economic costs related to mental illness is a pressing matter globally. Scarce monetary and staff resources impose an ongoing challenge. Therapeutic leaves (TL) are an established clinical tool in psychiatry possibly improving therapy outcome and potentially lowering direct mental healthcare costs in the long term. We thus examined the association between TL and direct inpatient healthcare costs. METHODS: We analyzed the association between the number of TL and direct inpatient healthcare costs in a sample of 3151 inpatients, using a tweedie multiple regression model, including eleven confounders. Using multiple linear (bootstrap) and logistic regression models we assessed the robustness of our results. RESULTS: The tweedie model showed that the number of TL was associated with lower costs following the initial inpatient stay (B = -.141, CI 95% = [-0.225, -.057], p < 0.001). Results of the multiple linear and the logistic regression models matched those of the tweedie model. CONCLUSION: Our findings suggest a link between TL and direct inpatient healthcare costs. TL might lower direct inpatient healthcare costs. In the future RCTs might examine whether an increased utilization of TL leads to a reduction of outpatient treatment costs and evaluate the association of TL with outpatient treatment costs and indirect costs. The systematic use of TL during inpatient treatment could reduce healthcare costs following the initial inpatient stay which is highly relevant due to global rise of mental illness and the associated financial pressure on healthcare systems.