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Alterations in peripheral serotonin concentrations and an imbalanced immune system have been reported in patients with a depressive disorder. Cytokines and T regulatory (Treg) cells may play an important role in the development of depression. This study investigates levels of cytokines and Treg cells, as well as the concentration of serotonin (5-HT) in the blood of 89 patients suffering from a depressive disorder and 89 healthy participants between two acquisitions. We investigated the state of health before (T1) and after (T2) psychological and pharmacological therapy. Both cytokine (IL-6, IL-10, TNF-α, and INF-γ) and 5-HT levels in the blood were measured by enzyme-linked immunosorbent assays (ELISAs). The levels of CD4+ CD25+ Treg cells were determined by flow cytometric analysis (FACS). Patients with a depressive disorder showed significantly higher serum levels of IL-6 and INF-γ, no altered serum levels of IL-10 and TNF-α, and decreased platelet and serum 5-HT levels compared to healthy participants at the first acquisition. In addition, the symptoms of depression and anxiety, the TNF-α level, and the amount of CD4+ CD25+ cells in the blood were decreased from the first to the second acquisition. Further, a correlation between IL-6 and platelet 5-HT has been observed in patients. An imbalance of the immune system in patients with a depressive disorder and an association of the serotonergic system and cytokines were observed. These results indicate that the development of a depressive disorder might be related to several interacting proteins, including cytokines and 5-HT, and the treatment affects imbalances of these factors.

As early detection of symptoms in the subclinical to clinical psychosis spectrum may improve health outcomes, knowing the probabilistic susceptibility of developing a disorder could guide mitigation measures and clinical intervention. In this context, polygenic risk scores (PRSs) quantifying the additive effects of multiple common genetic variants hold the potential to predict complex diseases and index severity gradients. PRSs for schizophrenia (SZ) and bipolar disorder (BD) were computed using Bayesian regression and continuous shrinkage priors based on the latest SZ and BD genome-wide association studies (Psychiatric Genomics Consortium, third release). Eight well-phenotyped groups (n = 1580; 56% males) were assessed: control (n = 305), lower (n = 117) and higher (n = 113) schizotypy (both groups of healthy individuals), at-risk for psychosis (n = 120), BD type-I (n = 359), BD type-II (n = 96), schizoaffective disorder (n = 86), and SZ groups (n = 384). PRS differences were investigated for binary traits and the quantitative Positive and Negative Syndrome Scale. Both BD-PRS and SZ-PRS significantly differentiated controls from at-risk and clinical groups (Nagelkerke’s pseudo-R2: 1.3–7.7%), except for BD type-II for SZ-PRS. Out of 28 pairwise comparisons for SZ-PRS and BD-PRS, 9 and 12, respectively, reached the Bonferroni-corrected significance. BD-PRS differed between control and at-risk groups, but not between at-risk and BD type-I groups. There was no difference between controls and schizotypy. SZ-PRSs, but not BD-PRSs, were positively associated with transdiagnostic symptomology. Overall, PRSs support the continuum model across the psychosis spectrum at the genomic level with possible irregularities for schizotypy. The at-risk state demands heightened clinical attention and research addressing symptom course specifiers. Continued efforts are needed to refine the diagnostic and prognostic accuracy of PRSs in mental healthcare.

In current diagnostic systems, schizophrenia and bipolar disorder are still conceptualized as distinct categorical entities. Recently, both clinical and genomic evidence have challenged this Kraepelinian dichotomy. There are only few longitudinal studies addressing potential overlaps between these conditions. Here, we present design and first results of the PsyCourse study (N = 891 individuals at baseline), an ongoing transdiagnostic study of the affective-to-psychotic continuum that combines longitudinal deep phenotyping and dimensional assessment of psychopathology with an extensive collection of biomaterial. To provide an initial characterization of the PsyCourse study sample, we compare two broad diagnostic groups defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) classification system, that is, predominantly affective (n = 367 individuals) versus predominantly psychotic disorders (n = 524 individuals). Depressive, manic, and psychotic symptoms as well as global functioning over time were contrasted using linear mixed models. Furthermore, we explored the effects of polygenic risk scores for schizophrenia on diagnostic group membership and addressed their effects on nonparticipation in follow-up visits. While phenotypic results confirmed expected differences in current psychotic symptoms and global functioning, both manic and depressive symptoms did not vary between both groups after correction for multiple testing. Polygenic risk scores for schizophrenia significantly explained part of the variability of diagnostic group. The PsyCourse study presents a unique resource to research the complex relationships of psychopathology and biology in severe mental disorders not confined to traditional diagnostic boundaries and is open for collaborations.

Attention deficit hyperactivity disorder (ADHD) is a common pediatric psychiatric disorder, frequently treated with methylphenidate (MPH). Recently, MPH&rsquo, s cardiovascular safety has been questioned by observational studies describing an increased cardiovascular risk in adults and blood pressure alterations in children. We considered members of the L-arginine (Arg)/nitric oxide (NO) pathway as possible early cardiovascular risk factors in pediatric ADHD children. They include the NO metabolites, nitrite and nitrate, the NO precursor Arg, and asymmetric dimethylarginine (ADMA), an endogenous NO synthase (NOS) inhibitor and a cardiovascular risk factor in adults. We conducted a prospective clinical trial with 42 ADHD children (aged 6&ndash, 16 years) with (n = 19) and without (n = 23) MPH treatment. Age-matched children without ADHD (n = 43) served as controls. All plasma and urine metabolites were determined by gas chromatography-mass spectrometry. We observed higher plasma nitrite and lower plasma ADMA concentrations in the ADHD children. MPH-treated ADHD children had higher plasma nitrite concentrations than MPH-untreated ADHD children. As NOS activity is basally inhibited by ADMA, MPH treatment seems to have decreased the inhibitory potency of ADMA. Percentiles of systolic blood pressure were higher in MPH-treated ADHD children. The underlying mechanisms and their implications in the MPH therapy of pediatric ADHD with MPH remain to be elucidated in larger cohorts.

IMPORTANCE: Identifying psychosis subgroups could improve clinical and research precision. Research has focused on symptom subgroups, but there is a need to consider a broader clinical spectrum, disentangle illness trajectories, and investigate genetic associations. OBJECTIVE: To detect psychosis subgroups using data-driven methods and examine their illness courses over 1.5 years and polygenic scores for schizophrenia, bipolar disorder, major depression disorder, and educational achievement. DESIGN, SETTING, AND PARTICIPANTS: This ongoing multisite, naturalistic, longitudinal (6-month intervals) cohort study began in January 2012 across 18 sites. Data from a referred sample of 1223 individuals (765 in the discovery sample and 458 in the validation sample) with DSM-IV diagnoses of schizophrenia, bipolar affective disorder (I/II), schizoaffective disorder, schizophreniform disorder, and brief psychotic disorder were collected from secondary and tertiary care sites. Discovery data were extracted in September 2016 and analyzed from November 2016 to January 2018, and prospective validation data were extracted in October 2018 and analyzed from January to May 2019. MAIN OUTCOMES AND MEASURES: A clinical battery of 188 variables measuring demographic characteristics, clinical history, symptoms, functioning, and cognition was decomposed using nonnegative matrix factorization clustering. Subtype-specific illness courses were compared with mixed models and polygenic scores with analysis of covariance. Supervised learning was used to replicate results in validation data with the most reliably discriminative 45 variables. RESULTS: Of the 765 individuals in the discovery sample, 341 (44.6%) were women, and the mean (SD) age was 42.7 (12.9) years. Five subgroups were found and labeled as affective psychosis (n = 252), suicidal psychosis (n = 44), depressive psychosis (n = 131), high-functioning psychosis (n = 252), and severe psychosis (n = 86). Illness courses with significant quadratic interaction terms were found for psychosis symptoms (R(2) = 0.41; 95% CI, 0.38-0.44), depression symptoms (R(2) = 0.28; 95% CI, 0.25-0.32), global functioning (R(2) = 0.16; 95% CI, 0.14-0.20), and quality of life (R(2) = 0.20; 95% CI, 0.17-0.23). The depressive and severe psychosis subgroups exhibited the lowest functioning and quadratic illness courses with partial recovery followed by reoccurrence of severe illness. Differences were found for educational attainment polygenic scores (mean [SD] partial η(2) = 0.014 [0.003]) but not for diagnostic polygenic risk. Results were largely replicated in the validation cohort. CONCLUSIONS AND RELEVANCE: Psychosis subgroups were detected with distinctive clinical signatures and illness courses and specificity for a nondiagnostic genetic marker. New data-driven clinical approaches are important for future psychosis taxonomies. The findings suggest a need to consider short-term to medium-term service provision to restore functioning in patients stratified into the depressive and severe psychosis subgroups.

Introduction Dietary supplements are very widely used in the general population and there is a growing market for them, which is against the recommendations of the German Society for Nutrition. There is some evidence that dietary supplements are useful additions in the treatment of psychiatric disorders. This review is an overview of available practical knowledge regarding the use of supplements in psychiatric treatment. In particular, the review focused on the diagnosis of depression and anxiety in terms of supplement treatment. Methods This is a narrative review of the evidence regarding supplements for treating anxiety and depression. We searched PubMed to 2018. Two reviewers screened the citations and abstracted the data. Phytopharmaceutical attends and animal-based data were excluded. Results There are strong indications regarding the impact of supplements on the selected psychiatric disorders, but at this time, there only a few randomized clinical studies available, so evidence for these findings is quite low. However, it must be noted that there are strong hints for a relationship between vitamin D level and depression. Furthermore, various supplements have got potentially an influence on the characteristics of depression. Discussion This review summarizes the current knowledge about supplements when used for some psychiatric conditions, but the data does not provide compelling evidence in any direction. There are only indications that there is an influence of supplements on psychiatric diseases. In support of this, there is further need for high-quality studies in this field. Reviews on other diagnoses, such as schizophrenia and dementia, will be part of further work.

Background: Patients with severe mental illness (SMI) have worse physical health and reduced life expectancy compared to the general population. Individuals with mental disorders also more often suffer from influenceable risk factors such as obesity, smoking, diabetes, arterial hypertension and dyslipidaemia. Moreover, they have more difficulties to access health services and fewer opportunity for cardiovascular risk screening and prevention than would be expected in a non-psychiatric population. Therefore, we aimed to investigate the somatic care situation of psychiatric patients. Methods: This study used a 14-item-questionnaire to survey the physical status of hospital patients with SMI. Main subjects were psychiatric and somatic diagnoses, metabolic risk factors, regular somatic care (by general practitioners and specialists), and routine check-ups. Data collection underwent pseudonymisation and descriptive analysis. Outcome: 350 patients (49.1% male, mean age 46,31 ±16,02 years) were included. More than three quarters had access to a general practitioner (78.2%), whom most of the patients reported to see quite regularly. Patients with affective and anxiety disorders reported significantly more contact with medical specialists for somatic diseases, compared to other diagnostic subgroups. Nearly all of the patients received psychiatric medication, but some had never before a blood sample taken or received an ecq. Interpretation: Although the access to a general practitioner is quite high, it can be concluded, that the interaction of patient, provider, and system factors has created a situation in which access to and quality of health care is problematic for individuals with especially a SMI. Funding: None. Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: The analysis has been performed in accordance with the Declaration of Helsinki. The Ruhr-University Bochum ethics committee approved the analysis, and written informed consent was obtained from the patient.

In current diagnostic systems, schizophrenia and bipolar disorder are still conceptualized as distinct categorical entities. Recently, both clinical and genetic evidence have challenged this Kraepelinian dichotomy. There are only few longitudinal studies addressing the potential overlaps between these conditions. Here, we present design and first results of the PsyCourse study, an ongoing transdiagnostic study of the affective-to-psychotic continuum that combines longitudinal deep phenotyping and dimensional assessment of psychopathology with an extensive collection of biomaterial. Within the DSM-IV framework, we compare two broad diagnostic groups: one consisting of predominantly affective and one of predominantly psychotic disorders. Depressive, manic, and psychotic symptoms as well as global functioning over time were analyzed. Furthermore, we explore the effects of polygenic risk scores for schizophrenia on diagnostic group membership and address their effects on non-participation in follow-up visits. While phenotypic results show differences in both current psychotic and manic symptoms, depressive symptoms did not vary between both groups. Polygenic risk scores for schizophrenia significantly explained part of the variability of the diagnostic group. Furthermore, there was a trend that a higher polygenic loading for schizophrenia was associated with attrition. Because of its unique properties, the PsyCourse study presents a prime resource for the interrogation of complex genotype-phenotype relationships.

Background: Germany provides a wide range of highly developed mental health care to its citizens. The aim of this study was to identify factors influencing the voluntariness of admissions to psychiatric hospitals. Especially the impact of demographic factors of the region, characteristics of the psychiatric hospitals and characteristics of the psychosocial services was analyzed. Method: A retrospective analysis of hospital admission registers from 13 German adult psychiatric hospitals in 2009 was conducted. Public data on the regional psychiatric accommodation and demographic situation were added. Hospitals were dichotomously divided according to their index of involuntary admissions. Group comparisons were performed between the clinics with low and high involuntary admission indices. Analysis was conducted with clinical, psychiatric provision and demographic data related to inpatients in the Landschaftsverbands Westfalen-Lippe (LWL)-PsychiatryNetwork. Results: Especially the range of services provided by the social-psychiatric services in the region such as number of supervised patients and home visits had an influence on the proportion of involuntary admissions to a psychiatric hospital. Some demographic characteristics of the region such as discretionary income showed further influence. Contrary to our expectations, the characteristics of the individual hospital seem to have no influence on the admission rate. Conclusion: Social-psychiatric services show a preventive impact on involuntary acute psychiatry interventions. Sociodemographic factors and patient variables play a role with regard to the number of involuntary hospitalizations, whereas characteristics of hospitals seemed to play no role.

Ziel: In dieser Studie wurden 40 untergebrachte Patienten durchschnittlich 3 Wochen nach erfolgter Zwangsmasnahme zu ihrem Erleben befragt. Methode: Der Fragebogen umfasste 31 Items zu demografischen und krankheitsbezogenen Daten, Modalitaten der Unterbringung, Zwangsmasnahmen im Rahmen der Unterbringung und ihre Empfindung sowie Patientenzufriedenheit. Letzteres wurde bisher nicht detailliert untersucht. Schlussfolgerung: Als fuhrende Emotionen in der Zwangssituation wurden Wut, Arger und Verzweiflung benannt, retrospektiv jedoch auch Verstandnis. Klinisch stabilere Patienten bewerteten das Erlebte insgesamt negativer.

Background & aims: Hepatocyte apoptosis is a key event in non-alcoholic steatohepatitis (NASH). We studied the effect of obesity on free fatty acid (FFA) levels, fatty acid transport proteins (FATPs) and on extrinsic and intrinsic activation of apoptosis in the liver. Methods: Liver biopsies were harvested from 52 morbidly obese patients [body mass index (BMI): 53.82±1.41; age: 45±10.50; 15 males/37 females] undergoing bariatric surgery, and were scored for NASH, evaluated for fibrosis, and investigated for intrahepatic expression of FATPs, death receptors and cytosolic apoptosis-related molecules. Findings were correlated with serum FFA levels and the degrees of intrahepatic (terminal dUTP nick end labelling) and systemic (M30) apoptosis. Results: In patients' liver sections, FATPs as well as select parameters of extrinsic and intrinsic apoptosis were found to be upregulated (CD36/FAT: × 11.56; FATP-5: × 1.33; CD95/Fas: × 3.18; NOXA: × 2.79). These findings correlated with significantly elevated serum FFAs (control: 14.72±2.32 mg/dl vs. patients: 23.03±1.24 mg/dl) and M30 levels (control: 83.12±7.46 U/L vs. patients: 212.61±22.16 U/L). We found correlations between FATPs and apoptosis mediators as well as with histological criteria of NASH and fibrosis. Conclusions: Increased FFA and FATPs are associated with extrinsically and intrinsically induced apoptosis, liver damage and fibrosis in obese patients. Thus, FATPs may offer an interesting new approach to understand and potentially intervene NASH pathogenesis.

Involuntary psychiatric admission is a central issue in mental health care, especially in the treatment of children and adolescents. Its legal regulations do not only differ between European countries, but also on a federal level. Only few studies so far dealt with rates of involuntary admission (RIA), mainly focusing on adults, rather than children and adolescents. None of the studies analyzed this topic in a large cohort. The aim of this regional cross-sectional study was to compare voluntary and involuntary admissions in child and adolescent psychiatry (CAP) regarding personal and admission characteristics. Furthermore, risk factors and predictors of involuntary admission should be identified. A retrospective analysis of hospital admission registers from three major German CAP hospitals over a period of 6 years (2004-2009) was conducted (N = 10,547 inpatients). Group comparisons between involuntarily and voluntarily treated minors and a logistic regression to determine predictors of legal status were performed. Information on harm to self or others prior to the admission, medication and clinical outcome was not available due to data structure. 70.8 % of patients were voluntarily and 29.2 % involuntarily admitted. Both subsamples comprised more males. The RIA decreased consistently over the years, ranging from 25.7 to 32.4 %. The strongest predictor of being admitted involuntarily was suffering from mental retardation (OR = 15.74). Adolescence, substance abuse, psychotic disorders and admission on duty time were also strongly associated (OR > 3). In this first large cohort study on involuntary treatment of children and adolescents in Germany, about every fourth patient was treated involuntarily. Certain personal and disease-related factors increased the risk. Commitment laws and other legal instruments for regulating involuntary placements are inconsistent and a standardized description or systematic analysis is needed. The influence of demographic, institutional variables and care and health services aspects should also be investigated.

Background Despite marked costs and limited evidence regarding effectiveness, occupational therapy (OT) is widely applied in psychiatric settings and financed by health insurance companies in European countries. This pilot study investigated the antidepressive effects of adjuvant OT for patients with major depression in a 6-week inpatient setting, stratified for females and males. Methods A total of 114 inpatients with major depression were assigned to either a standard OT group (using basic handcraft) or an active control group that played board games (2 h daily, 5 days a week). HAMD-21 scores were assessed as the primary outcome parameter after 3–6 weeks. Results The OT intervention was not superior to “board game” (BG) activities in reducing depressive symptoms. However, significant interaction effects were found in favor of the OT group regarding anxiety measures and other variables. Male participants displayed more significant interaction effects than female participants. Conclusions OT as an adjuvant short-term treatment for inpatients with major depression may be more efficacious than game interventions in terms of reducing anxiety and other symptoms, particularly in males. Trial registration The study was registered in the EU Clinical Trials Register as a multicenter trial (EudraCT Number 2009-016463-10; https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-016463-10/DE#A) However, because of the elaborate setting requirements, the original study design with four centers was transformed into a solution with those two centers facilitating the pertinent resources. Furthermore, “mono-therapy with mirtazapine” was changed into “preferably mono-therapy with any antidepressant drug”.

Background Coercive measures in psychiatry are a controversial topic and raise ethical, legal and clinical issues. Involuntary admission of patients is a long-lasting problem and indicates a problematic pathway to care situations within the community, largely because personal freedom is fundamentally covered by the UN declaration of human rights and the German constitution. Methods In this study, a survey on a large and comprehensive population of psychiatric in-patients in the eastern part of North Rhine-Westphalia, Germany, was carried out for the years 2004–2009, including 230.678 treatment cases. The data were collected from the dataset transferred to health insurance automatically, which, since 2004 is available in an electronic form. In addition, a wide variety of information on treatment, sociodemographic and illness-related factors were collected and analysed. Data were collected retrospectively and analyses were calculated using statistical software (IBM SPSS Statistics 19.0®). Quantitative data are presented as mean and standard deviation. Due to the unequal group sizes, group differences were calculated by means of Chi-square tests or independent sample t tests. A Bonferroni correction was applied to control for multiple comparisons. Results We found an over-representation of involuntary admissions in young men (