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Abstract: Benzodiazepines (BZD) and Z-drugs (ZD) are often prescribed to treat psychiatric disorders. Despite the risk of dependency and serious adverse events, they are increasingly prescribed to outpatients. Yet little is known about the prescription to inpatients. In this article, we analyze the BZD and ZD prescription patterns in the routine data of 913 psychiatric and somatic inpatients treated in Bochum, Germany. BZD were prescribed more often as regular medication in psychiatry and ZD in somatic hospitals. ZD were more often used on demand, by female patients, and combined with other substances. Both were frequently prescribed to older adults, especially as part of somatic treatment and in combination with opioids. Prescription of sedative hypnotics is frequent in psychiatric and somatic inpatients. Their use seems to be partially independent of recorded psychiatric indications.

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.

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.

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.

The development of efficient and specific vector systems remains a central issue in gene therapy. Several different adeno-associated virus (AAV) serotypes have so far been characterized so far which show different tissue tropisms.The vectors used here contained AAV2 transgene cassette containing green fluorescent protein (GFP) in AAV1, AAV2, or AAV5 capsids, producing the recombinant pseudotypes rAAV2/1, rAAV2/2, and rAAV2/5. The transduction efficiency of the different pseudotyped AAV vectors was tested in vitro in pancreatic and colon cancer cells lines (HT-29, BXPC3, and Hs766T).For all three serotypes, the percentage of GFP-positive cells was below 10% at multiplicities of infection (MOI) 100 rAAV vectors when used alone for infection. However, transduction efficiency for rAAV vectors increased dramatically when the cells were co-infected with wild-type adenovirus (wtAd). The percentage of GFP-positive cells ranged from 19.8-65.3% for AAV2/1 and 16.9-70.2% for AAV2/5, respectively. It was highest for rAAV2/2, at 40.9-88.4%. Variation between the cell lines was observed, with BXPC3 scoring the highest transduction rates and HT-29 the lowest.This study indicates that vectors based on distinct AAV serotypes 1, 2, and 5 all transduce pancreatic and colon cell lines poorly when used alone. Co-infection with wtAd increase transduction rates dramatically indicating that slow second-strand synthesis is a reason for the poor transduction efficiency. Due to the poor transduction rates, none of the rAAV serotypes tested here seem to be feasible for the treatment of malignant tumors.

Objective. Hematopoietic progenitor cells are a promising source for generation of genetically modified dendritic cells. A prerequisite for using these cells in therapeutic approaches is stable vector-mediated transgene expression during and after cell maturation. We investigated the expression of enhanced green fluorescence protein (EGFP) mediated by retroviral vectors in dendritic cells and other hematopoietic cells differentiated in vitro. Material and Methods. CD34 + cells were efficiently transduced with retroviral vector constructs known to mediate different expression levels due to distinct cis -acting elements. EGFP + cells were purified by cell sorting and differentiated to monocytes, granulocytes, dendritic cells, and erythrocytes. Coexpression of EGFP and cell type-specific markers was analyzed by flow cytometry. Results. Transgene expression from various retroviral vectors was silenced exclusively in dendritic cells, but not in other mature myeloid cells. Loss of EGFP was most pronounced in cells initially displaying low expression levels. This was confirmed by using a retroviral vector coding for a variant of EGFP with significantly reduced half-life. In contrast, a majority of dendritic cells showed stable expression when a self-inactivating retroviral construct using an internal cytomegalovirus promotor was used. Conclusions. We suggest that expression from the retroviral long terminal repeat is silenced during dendritic cell differentiation in vitro. High levels of stable transgene product in progenitor cells may mask a loss of expression. An improvement of retroviral vectors mediating stable transgenic expression is necessary for therapeutic approaches using gene-modified dendritic cells.

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 (