Search

Background: Self-binding directives (SBDs) are psychiatric advance directives that include a clause in which mental health service users consent in advance to involuntary hospital admission and treatment under specified conditions. Medical ethicists and legal scholars identified various potential benefits of SBDs but have also raised ethical concerns. Until recently, little was known about the views of stakeholders on the opportunities and challenges of SBDs. Aims: This article aims to foster an international exchange on SBDs by comparing recent empirical findings on stakeholders views on the opportunities and challenges of SBDs from Germany, the Netherlands, and the United Kingdom. Method: Comparisons between the empirical findings were drawn using a structured expert consensus process. Results: Findings converged on many points. Perceived opportunities of SBDs include promotion of autonomy, avoidance of personally defined harms, early intervention, reduction of admission length, improvement of the therapeutic relationship, involvement of trusted persons, avoidance of involuntary hospital admission, addressing trauma, destigmatization of involuntary treatment, increase of professionals confidence, and relief for proxy decisionmakers. Perceived challenges include lack of awareness and knowledge, lack of support, undue influence, inaccessibility during crisis, lack of cross-Agency coordination, problems of interpretation, difficulties in capacity assessment, restricted therapeutic flexibility, scarce resources, disappointment due to non-compliance, and outdated content. Stakeholders tended to focus on practical challenges and did not often raise fundamental ethical concerns. Conclusions: Stakeholders tend to see the implementation of SBDs as ethically desirable, provided that the associated challenges are addressed.

BACKGROUND: Joint Crisis Plans (JCP) and crisis cards (CC) are both instruments designed to improve the management of future psychiatric crisis situations, but they differ, for example, in terms of resource use, legal validity, and aims. International research findings for JCP are inconsistent.; METHODS: From January 2018 to December 2020, a single-blinded, two-armed multicenter RCT was carried out, with assessments at T0 (baseline) and T1 (18 months later). The patients included had schizophrenia or schizoaffective disorder and were aged between 18 and 62 years. The primary outcome was the cumulative duration of inpatient treatment (voluntary/involuntary), and coercive measures comprised the secondary outcome. Trial registration: DRKS00013985.; RESULTS: Of the 266 study participants, 157 completed the study. In the CC group 57.8% and in the JCP group 64.9% were admitted to psychiatric hospitals between the index treatment and T1 (p = 0.367); 8.4% of the CC group and 12.2% of the JPC group were admitted against their will (p = 0.441). The cumulative treatment duration was not significantly shorter (p = 0.631) in the JPC group (mean 42.43 days, SD = 48.60) than in the CC group (50.16 days, SD = 74.16). Thus, JPCs did not achieve the expected improvement with regard to the primary endpoint. There were also no relevant differences regarding the secondary endpoint. Major effects in favor of the JCP were observed, however, in patients' development of conficence in the treatment teams and in their active participation in the treatment procedure.; CONCLUSION: Although the study showed no superiority of JCP over CC with regard to the primary and secondary outcomes, JCP should be used more frequently in routine practice as an intervention to support a participative approach to treatment.

BACKGROUND: Joint Crisis Plans (JCP) and crisis cards (CC) are both instruments designed to improve the management of future psychiatric crisis situations, but they differ, for example, in terms of resource use, legal validity, and aims. International research findings for JCP are inconsistent. METHODS: From January 2018 to December 2020, a single-blinded, two-armed multicenter RCT was carried out, with assessments at T0 (baseline) and T1 (18 months later). The patients included had schizophrenia or schizoaffective disorder and were aged between 18 and 62 years. The primary outcome was the cumulative duration of inpatient treatment (voluntary/involuntary), and coercive measures comprised the secondary outcome. Trial registration: DRKS00013985. RESULTS: Of the 266 study participants, 157 completed the study. In the CC group 57.8% and in the JCP group 64.9% were admitted to psychiatric hospitals between the index treatment and T1 (p = 0.367); 8.4% of the CC group and 12.2% of the JPC group were admitted against their will (p = 0.441). The cumulative treatment duration was not significantly shorter (p = 0.631) in the JPC group (mean 42.43 days, SD = 48.60) than in the CC group (50.16 days, SD = 74.16). Thus, JPCs did not achieve the expected improvement with regard to the primary endpoint. There were also no relevant differences regarding the secondary endpoint. Major effects in favor of the JCP were observed, however, in patients’ development of conficence in the treatment teams and in their active participation in the treatment procedure. CONCLUSION: Although the study showed no superiority of JCP over CC with regard to the primary and secondary outcomes, JCP should be used more frequently in routine practice as an intervention to support a participative approach to treatment.

This descriptive study examined patient characteristics, treatment characteristics, and short-term outcomes among patients with Anorexia Nervosa (AN) and Bulimia Nervosa (BN) in routine clinical care. Results for patients receiving full-time treatment were contrasted with results for patients receiving ambulatory treatment. Data of a clinical trial including 116 female patients (18-35 years) diagnosed with AN or BN were subjected to secondary analyses. Patients were voluntarily admitted to one of nine treatment facilities in Germany and Switzerland. Patients received cognitive-behavioral interventions in accordance with the national clinical practice guidelines for the treatment of EDs under routine clinical care conditions, either as full-time treatment or ambulatory treatment. Assessments were conducted after admission and three months later. Assessments included a clinician-administered diagnostic interview (DIPS), body-mass-index (BMI), ED pathology (EDE-Q), depressive symptoms (BDI-II), symptoms of anxiety (BAI), and somatic symptoms (SOMS). Findings showed that treatment intensity differed largely by setting and site, partly due to national health insurance policies. Patients with AN in full-time treatment received on average 65 psychotherapeutic sessions and patients with BN in full-time treatment received on average 38 sessions within three months. In comparison, patients with AN or BN in ambulatory treatment received 8-9 sessions within the same time. Full-time treatment was associated with substantial improvements on all measured variables for both women with AN (d = .48-.83) and BN (d = .48-.81). Despite the relatively small amount of psychotherapeutic sessions, ambulatory treatment was associated with small increases in BMI (d = .37) among women with AN and small improvements on all measured variables among women with BN (d = .27-.43). For women with AN, reduction in ED pathology were positively related to the number of psychotherapeutic sessions received. Regardless of diagnosis and treatment setting, full recovery of symptoms was rarely achieved within three months (recovery rates ranged between 0 and 4.4%). The present study shows that a considerable amount of patients with EDs improved after CBT-based ED treatment in routine clinical care within three months after admission. Intensive full-time treatment may be particularly effective in quickly improving ED-related pathology, although full remission of symptoms is typically not achieved. A small amount of ambulatory sessions may already produce considerable improvements in BN pathology and weight gain among women with AN. As patient characteristics and treatment intensity differed largely between settings, results should not be interpreted as superiority of one treatment setting over another. Furthermore, this study shows that treatment intensity is quite heterogeneous, indicating the possibility for increasing effectiveness in the treatment of EDs in routine clinical care.

In psychiatry, there has been a growing focus on identifying at-risk populations. For schizophrenia, these efforts have led to the development of early recognition and intervention measures. Despite a similar disease burden, the populations at risk of bipolar disorder have not been sufficiently characterized. Within the BipoLife consortium, we used magnetic resonance imaging (MRI) data from a multicenter study to assess structural gray matter alterations in N = 263 help-seeking individuals from seven study sites. We defined the risk using the EPIbipolar assessment tool as no-risk, low-risk, and high-risk and used a region-of-interest approach (ROI) based on the results of two large-scale multicenter studies of bipolar disorder by the ENIGMA working group. We detected significant differences in the thickness of the left pars opercularis (Cohen’s d = 0.47, p = 0.024) between groups. The cortex was significantly thinner in high-risk individuals compared to those in the no-risk group (p = 0.011). We detected no differences in the hippocampal volume. Exploratory analyses revealed no significant differences in other cortical or subcortical regions. The thinner cortex in help-seeking individuals at risk of bipolar disorder is in line with previous findings in patients with the established disorder and corresponds to the region of the highest effect size in the ENIGMA study of cortical alterations. Structural alterations in prefrontal cortex might be a trait marker of bipolar risk. This is the largest structural MRI study of help-seeking individuals at increased risk of bipolar disorder.

\(\bf Background\) Child maltreatment has been shown to be associated with a wide range of mental disorders, including bipolar disorders. In this 2-year follow-up study, recollections of emotional, physical and sexual abuse were related to bipolar symptoms, namely depressive, hypomanic and manic symptoms. \(\bf Methods\) The sample consists of 134 students who took part at five measurement times within the 2-year period. Data were collected with self-report scales. \(\bf Results\) The results show that recollections of abuse, particularly emotional abuse, were associated with more severe depressive symptoms; this finding, however, only applied to women. Hypomanic and manic symptoms were not associated with recollections of abuse. For hypomanic symptoms, however, a significant decrease over the 2 years was observed. \(\bf Conclusions\) The findings of this study suggest that recollections of abusive experiences in childhood combined with female gender increase the risk for depression, whereas hypomanic and manic states are probably better predicted by other factors, such as current life circumstances.

There are controversial data on the efficacy and safety profile of selective serotonin reuptake inhibitors (SSRIs) to prevent post-stroke depression (PSD). We performed a systematic search in MEDLINE and SCOPUS databases to identify randomized-controlled trials questioning the use of early SSRI therapy in the post-stroke population and its effect on PSD incidence. We included 6 studies with 6560 participants. We extracted the data on PSD occurrence in association with the treatment arm (SSRI versus placebo), as reported by each study. For safety analysis, we extracted the information on adverse events. A random-effects model was used to calculate the pooled relative risk estimates. Early SSRI therapy was associated with a significant reduction of PSD occurrence compared to placebo (10.4% versus 13.8%; relative risk: 0.75 [95% CI, 0.66–0.86]; absolute risk reduction: 3.4%). SSRI therapy increases the risk of bone fracture (RR 2.28 [95% CI, 1.58–3.30]) and nausea (RR 2.05 [95% CI, 1.10–3.82]) in the post-stroke population. Considering the risk-benefit ratio of early SSRI therapy in the post-stroke population, future research should identify high-risk patients for PSD to improve the risk-benefit consideration of this therapy for use in clinical practice.

There are controversial data on the efficacy and safety profile of selective serotonin reuptake inhibitors (SSRIs) to prevent post-stroke depression (PSD). We performed a systematic search in MEDLINE and SCOPUS databases to identify randomized-controlled trials questioning the use of early SSRI therapy in the post-stroke population and its effect on PSD incidence. We included 6 studies with 6560 participants. We extracted the data on PSD occurrence in association with the treatment arm (SSRI versus placebo), as reported by each study. For safety analysis, we extracted the information on adverse events. A random-effects model was used to calculate the pooled relative risk estimates. Early SSRI therapy was associated with a significant reduction of PSD occurrence compared to placebo (10.4% versus 13.8%; relative risk: 0.75 [95% CI, 0.66-0.86]; absolute risk reduction: 3.4%). SSRI therapy increases the risk of bone fracture (RR 2.28 [95% CI, 1.58-3.30]) and nausea (RR 2.05 [95% CI, 1.10-3.82]) in the post-stroke population. Considering the risk-benefit ratio of early SSRI therapy in the post-stroke population, future research should identify high-risk patients for PSD to improve the risk-benefit consideration of this therapy for use in clinical practice.

Suizidales Erleben und Verhalten ist in klinischen Kontexten sehr verbreitet. Während international diverse Messinstrumente zur Erfassung von Suizidalität entwickelt und validiert wurden, gibt es nur wenige deutsche Messinstrumente. In der vorliegenden Studie wurde die neu entwickelte Skala Suizidales Erleben und Verhalten (SSEV) in fünf Stichproben mit insgesamt \(\it N\) = 1 099 Proband_innen im Hinblick auf ihre psychometrischen Eigenschaften untersucht. Die faktorenanalytische Untersuchung (explorative und konfirmatorische Faktorenanalyse) ergab eine eindimensionale Struktur des Fragebogens. Die interne Konsistenz der SSEV ist hoch und es zeigten sich erwartungsgemäß positive Zusammenhänge zu diversen Maßen aktueller Theoriemodelle suizidalen Erlebens und Verhaltens, sowie zu Depressivität, Angst und Stress. Weitere Analysen zeigten erwartungskonform negative Zusammenhänge mit sozialer Unterstützung und positiver mentaler Gesundheit. Insgesamt verweisen die Ergebnisse darauf, dass es sich beim SSEV um ein reliables und valides Instrument zur Erfassung von akutem suizidalem Erleben und Verhalten handelt, welches in der Forschung und der klinischen Praxis angewendet werden kann. Suicide ideation and suicide behavior occur commonly in clinical contexts. While various instruments for the assessment of suicidality have been developed and validated internationally, only few German instruments are presently available. The present study examines the psychometric properties of the newly developed Scale for Suicidal Experience and Behavior (SSEV) in five samples with \(\it N\) = 1 099 subjects. Exploratory and confirmatory factor analysis revealed a one-dimensional structure of the scale. The internal consistency of the scale is high, and strong positive associations were found with various measures of current theoretical models of suicide as well as with depression, anxiety, and distress. Further analyses exhibited negative correlations with social support and positive mental health. Overall, the results indicate that the SSEV is a reliable and valid instrument for measuring acute suicidality and can be applied in research and clinical practice.

Aim Depression and suicidal ideation (SUI) and behaviour are more prevalent in females than males, and common in clinical high-risk (CHR) patients. Childhood adversities and trauma (CAT) are associated with adult depression and SUI. The role of gender as a moderator and depression as a mediator for the effect of CAT on SUI has not been explored in CHR patients. Methods In all, 245 young help-seeking CHR patients were assessed for SUI (thoughts of killing themselves) with the Beck Depression Inventory at baseline, 9-month and 18-month follow-ups. At baseline, clinical depression was assessed by the Structured Clinical Interview for DSM-IV (SCID-I), and CAT by the Trauma and Distress Scale (TADS) which includes the five domains of emotional, physical and sexual abuse, emotional and physical neglect. Results CAT total and all domains except physical neglect predicted SUI over the study period. The effect of CAT on SUI was mediated via clinical depression and concurrent depression symptoms differently for females and males. In females, the effect of emotional abuse and neglect on SUI was mediated via baseline depression. In males, emotional and physical abuse had a direct effect on SUI, and the effect of sexual abuse and emotional neglect was partly mediated via concurrent depression symptoms. Conclusions For CHR females, the effect of CAT on adult SUI is mediated via depression, while for males, CAT and its domains have mainly direct effects in maintaining SUI. These gender differences should be taken into account when treating CHR patients with SUI.

\(\textbf {Background:}\) Ethics consultation has been advocated as a valuable tool in ethically challenging clinical situations in healthcare. It is paramount for the development and implementation of clinical ethics support services (CESS) in psychiatry that interventions can address the moral needs of mental health professionals adequately and communicate the nature of the services clearly. This study explores types of ethical problems and concepts of ethical expertise as core elements of CESS in mental healthcare with the aim of contributing to the further development of ethical support in psychiatry. \(\textbf {Methods:}\) We conducted 13 semi-structured interviews with mental health professionals and CESS members and triangulated them with four non-participant observations of ethical case consultations in psychiatry. Data were analyzed according to principles of grounded theory and are discussed from a normative perspective. \(\textbf {Results:}\) The analysis of the empirical data reveals a typology of three different ethical problems professionals want to refer to CESS: (1) Dyadic problems based on the relationship between patients and professionals, (2) triangular problems, where a third party is involved and affected as a side effect, and (3) problems on a systemic level. However, CESS members focus largely on types (1) and (2), while the third remains unrecognized or members do not feel responsible for these problems. Furthermore, they reflect a strong inner tension connected to their role as ethical experts which can be depicted as a dilemma. On the one hand, as ethically trained people, they reject the idea that their judgments have expert status. On the other hand, they feel that mental health professionals reach out for them to obtain guidance and that it is their responsibility to offer it. \(\textbf {Conclusion:}\) CESS members and professionals in mental healthcare have different ideas of the scope of responsibility of CESS. This contains the risk of misunderstandings and misconceptions and may affect the quality of consultations. It is necessary to adapt concepts of problem solving to practitioners' needs to overcome these problems. Secondly, CESS members struggle with their role as ethical experts. CESS members in psychiatry need to develop a stable professional identity. Theoretical clarification and practical training are needed.

Perineuronal nets (PNNs) are specialized, reticular structures of the extracellular matrix (ECM) that can be found covering the soma and proximal dendrites of a neuronal subpopulation. Recent studies have shown that PNNs can highly influence synaptic plasticity and are disrupted in different neuropsychiatric disorders like schizophrenia. Interestingly, there is a growing evidence that microglia can promote the loss of PNNs and contribute to neuropsychiatric disorders. Based on this knowledge, we analyzed the impact of activated microglia on hippocampal neuronal networks in vitro. Therefore, primary cortical microglia were cultured and stimulated via polyinosinic-polycytidylic acid (Poly I:C; 50 μg/ml) administration. The Poly I:C treatment induced the expression and secretion of different cytokines belonging to the CCL- and CXCL-motif chemokine family as well as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, the expression of matrix metalloproteinases (MMPs) could be verified via RT-PCR analysis. Embryonic hippocampal neurons were then cultured for 12 days in vitro (DIV) and treated for 24 h with microglial conditioned medium. Interestingly, immunocytochemical staining of the PNN component Aggrecan revealed a clear disruption of PNNs accompanied by a significant increase of glutamatergic and a decrease of γ-aminobutyric acid-(GABA)ergic synapse numbers on PNN wearing neurons. In contrast, PNN negative neurons showed a significant reduction in both, glutamatergic and GABAergic synapses. Electrophysiological recordings were performed via multielectrode array (MEA) technology and unraveled a significantly increased spontaneous network activity that sustained also 24 and 48 h after the administration of microglia conditioned medium. Taken together, we could observe a strong impact of microglial secreted factors on PNN integrity, synaptic plasticity and electrophysiological properties of cultured neurons. Our observations might enhance the understanding of neuron-microglia interactions considering the ECM.

\(\textbf {Background:}\) Individual staff factors, such as personality traits and attitudes, are increasingly seen as an important factor in the reduction of coercion in mental health services. At the same time, only a few validated instruments exist to measure those factors and examine their influence on the use of coercion. \(\textbf {Aim:}\) The present study aimed to develop and validate a German version of the Staff Attitude to Coercion Scale (SACS). \(\textbf {Methods:}\) The original English version of the SACS published was translated into German. Subsequently, it was empirically validated on a sample of \(\textit {N = 209}\) mental health professionals by conducting an exploratory factor analysis. \(\textbf {Results:}\) The three-factor structure in the original version of the SACS, consisting of critical, pragmatic and positive attitudes toward the use of coercion, could not be replicated. Instead, the German version revealed one factor ranging from rejecting to approving the use of coercion. \(\textbf {Conclusion:}\) The SACS is one of the first instruments created to assess staff attitudes toward coercion in a validated way. The version of the instrument developed in this study allows for a validated assessment of those attitudes in German. Our results highlight the ethical importance of using validated measurements in studies on the role of staff factors in the reduction of coercion.

Additional file 1: Appendix S1. Magnet Resonance Imaging protocol sequences of each center.

Peer support workers (PSWs) use their experiential knowledge and specific skills to support patients in their recovery process. The aim of our study was to examine the integration and role-finding process of PSWs in adult psychiatric hospitals in Germany. We conducted open nonparticipant observations of 25 multiprofessional team meetings and 5 transregional peer support worker meetings over a period of six months. The data were analyzed using qualitative content analysis. Regarding the integration of PSWs into multiprofessional teams, we identified three subcategories: "Features of success", "challenges" and "positioning between team and patients". Concerning the PSWs' roles, we developed two subcategories: "Offers" and "self-perception." The PSWs' specific roles within a multiprofessional mental healthcare team evolve in a process over a longer period of time. This role-finding process should be supported by a framework role description which leaves sufficient freedom for individual development. Regular opportunities for mutual exchange among PSWs can help to address specific support needs at different points in time.

Executive functions are metacognitive capabilities that control and coordinate mental processes. In the transdiagnostic PsyCourse Study, comprising patients of the affective-to-psychotic spectrum and controls, we investigated the genetic basis of the time course of two core executive subfunctions: set-shifting (Trail Making Test, part B (TMT-B)) and updating (Verbal Digit Span backwards) in 1338 genotyped individuals. Time course was assessed with four measurement points, each 6 months apart. Compared to the initial assessment, executive performance improved across diagnostic groups. We performed a genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with performance change over time by testing for SNP-by-time interactions using linear mixed models. We identified nine genome-wide significant SNPs for TMT-B in strong linkage disequilibrium with each other on chromosome 5. These were associated with decreased performance on the continuous TMT-B score across time. Variant rs150547358 had the lowest P value = 7.2 × 10−10 with effect estimate beta = 1.16 (95% c.i.: 1.11, 1.22). Implementing data of the FOR2107 consortium (1795 individuals), we replicated these findings for the SNP rs150547358 (P value = 0.015), analyzing the difference of the two available measurement points two years apart. In the replication study, rs150547358 exhibited a similar effect estimate beta = 0.85 (95% c.i.: 0.74, 0.97). Our study demonstrates that longitudinally measured phenotypes have the potential to unmask novel associations, adding time as a dimension to the effects of genomics.

Biological research and clinical management in psychiatry face two major impediments: the high degree of overlap in psychopathology between diagnoses and the inherent heterogeneity with regard to severity. Here, we aim to stratify cases into homogeneous transdiagnostic subgroups using psychometric information with the ultimate aim of identifying individuals with higher risk for severe illness. 397 participants of the PsyCourse study with schizophrenia- or bipolar-spectrum diagnoses were prospectively phenotyped over 18 months. Factor analysis of mixed data of different rating scales and subsequent longitudinal clustering were used to cluster disease trajectories. Five clusters of longitudinal trajectories were identified in the psychopathologic dimensions. Clusters differed significantly with regard to Global Assessment of Functioning, disease course, and-in some cases-diagnosis while there were no significant differences regarding sex, age at baseline or onset, duration of illness, or polygenic burden for schizophrenia. Longitudinal clustering may aid in identifying transdiagnostic homogeneous subgroups of individuals with severe psychiatric disease.

Background: The interpersonal theory of suicide (IPTS) is one of the most intensively researched contemporary theories on the development of suicidal ideation and behaviour. However, there is a lack of carefully conducted prospective studies. Aims: To evaluate the main predictions of the IPTS regarding the importance of perceived burdensomeness, thwarted belongingness and capability for suicide in predicting future suicide attempts in a prospective design. Method: Psychiatric in-patients (n = 308; 53.6% (n = 165) female; mean age 36.82 years, s.d. = 14.30, range 18-81) admitted for severe suicidal ideation (n = 145, 47.1%) or a suicide attempt completed self-report measures of thwarted belongingness, perceived burdensomeness, capability for suicide, hopelessness, depression and suicidal ideation as well as interviews on suicide intent and suicide attempts and were followed up for 12 months. Logistic regression and receiver operating characteristics (ROC) analysis were conducted. Results: The interaction of perceived burdensomeness, thwarted belongingness and capability for suicide was not predictive of future suicide attempts, but perceived burdensomeness showed a significant main effect (z = 3.49, P < 0.01; OR = 2.34, 95% CI 1.59-3.58) and moderate performance in screening for future suicide attempts (area under the curve AUC = 0.729, P < 0.01). Conclusions: The results challenge the theoretical validity of the IPTS and its clinical utility - at least within the methodological limitations of the current study. Yet, findings underscore the importance of perceived burdensomeness in understanding suicidal ideation and behaviour. OA Förderung 2020

Additional file 1. Supporting methods, Figures S1-S13, and Tables S1-S3.

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 (R2 = 0.41; 95% CI, 0.38-0.44), depression symptoms (R2 = 0.28; 95% CI, 0.25-0.32), global functioning (R2 = 0.16; 95% CI, 0.14-0.20), and quality of life (R2 = 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 η2 = 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.

Objective: To investigate the impact of expressed emotion (EE) on the risk of developing the first psychotic episode (FEP). Method: The European Prediction of Psychosis Study (EPOS) investigated 245 patients who were at clinical high risk (CHR) of psychosis. The predictive value of EE alone and as a part of the multivariate EPOS model was evaluated. Results: "Perceived irritability", a domain of the Level of Expressed Emotion Scale (LEE), was found to be predictive for the First Psychotic Episode (FEP), even as an individual variable. Furthermore, it was selected in the multivariate EPOS prediction model, thereby replacing two of the original predictor variables. This led to an improved revised version that enabled the identification of three significantly different risk classes with a hazard rate of up to 0.911. Conclusions: CHR subjects who perceive the most important person in their individual social environment to be limited in their stress coping skills had a higher risk of conversion to the first psychotic episode. The importance of this risk factor was further demonstrated by an improvement of risk estimation in the original EPOS predictor model. Perceiving a reference person as stress-prone and thus potentially unreliable might amplify self-experienced uncertainty and anxiety, which are often associated with the prodromal phase. Such an enforcement of stress-related processes could promote a conversion to psychosis. (c) 2018 Elsevier B.V. All rights reserved.

\(\textit {Hintergrund:}\) Die Befunde der bisherigen Untersuchungen legen nahe, dass die Angst vor dem Tod ein wichtiger Faktor bei der Entstehung psychischer Erkrankungen ist. Insbesondere die Terror-Management-Theorie geht davon aus, dass Menschen zwei verschiedene Strategien anwenden, um mit Todesangst umzugehen: (1) Sie versuchen, ihren Selbstwert zu steigern; (2) sie halten die Werte ihrer Kultur hoch. \(\textit {Patienten und Methoden:}\) Im Rahmen einer prospektiven Studie wurden 56 ambulante Psychotherapie-Patienten (29 Frauen, Alter 42,8 Jahre, SD 13,8) vornehmlich mit depressiven Störungen mittels Interview/Fragebögen u.a. zu Angst vor dem Tod (BOFRETTA) sowie Religiosität untersucht. \(\textit {Ergebnisse:}\) Die Angst vor dem Tod korrelierte signifikant mit der Schwere der psychischen Symptomatik (BDI), Neurotizismus (NEO-FFI) sowie dem Hochhalten kultureller Werte (LeBe). Erwartungsgemäß zeigte sich ein signifikanter negativer Zusammenhang von Selbstwert und Angst vor dem Tod. Dieser zeigte sich nicht bei Vergleichsvariablen wie Lebenssinn, Religiosität und Spiritualität. \(\textit {Diskussion und Schlussfolgerungen:}\) Die Angst vor dem Tod spielt bei der Entstehung und Aufrechterhaltung psychischer Probleme eine wesentliche Rolle. Ein wichtiger protektiver Faktor gegen diese scheint das Selbstwertgefühl zu sein. Es lässt sich vermuten, dass das Hochhalten kultureller Werte zwar ein unbewusster Versuch ist, gegen die Angst vor dem Tod (und die psychische Symptomatik) vorzugehen, dieser allerdings nicht wirksam ist. \(\textit {Background:}\) The findings of previous studies suggest that death anxiety is an important factor for the development of mental disorders. Especially, terror management theory assumes that human beings use 2 different strategies to prevent death anxiety: (1) they try to increase "self-worth"; (2) they uphold the values of their culture. \(\textit {Patients and Methods:}\) Within the framework of this prospective study, 56 outpatients under psychotherapy (29 females, age 42.8 years, SD 13.8), mainly with depressive disorders, were investigated by interviews/surveys concerning death anxiety (BOFRETTA) as well as religiosity, among other things. \(\textit {Results:}\) Death anxiety was significantly correlated with the severity of psychic symptomatology (BDI), neuroticism (NEO-FFI), and upholding of cultural values (LeBe). As expected, there was a significant negative relationship between self-worth and death anxiety. This was not observed regarding other parameters, such as sense of life, religiosity, and spirituality. \(\textit {Discussion and Conclusions:}\) Death anxiety seems to play an important role in the development and continuation of mental problems. An important protective factor seems to be self-worth. It is assumed that upholding of cultural values is an unconscious attempt to reduce death anxiety and mental symptomatology; however, this is not effective.

Background: Open-door policies in psychiatry are discussed as a means to improve the treatment of involuntarily committed patients in various aspects. Current research on open-door policies focuses mainly on objective effects, such as the number of coercive interventions or serious incidents. The aim of the present study was to investigate more subjective perceptions of different psychiatric inpatient settings with different door policies by analyzing ward atmosphere and patient satisfaction. Methods: Quantitative data on the ward atmosphere using the Essen Climate Evaluation Scale (EssenCES) and on patient satisfaction (ZUF-8) were obtained from involuntarily committed patients (n = 81) in three psychiatric hospitals with different ward settings and door policies (open, facultative locked, locked). Furthermore, qualitative interviews with each of 15 patients, nurses, and psychiatrists were conducted in one psychiatric hospital with a facultative locked ward comparing treatment in an open vs. a locked setting. Results: Involuntarily committed patients rated the EssenCES’ subscale “Experienced Safety” higher in an open setting compared with a facultative locked and a locked setting. The subscale “Therapeutic Hold” was rated higher in an open setting than a locked setting. Regarding the safety experienced from a mental health professionals’ perspective, the qualitative interviews further revealed advantages and disadvantages of door locking in specific situations, such as short-term de-escalation vs. increased tension. Patient satisfaction did not differ between the hospitals but correlated weakly with the EssenCES’ subscale “Therapeutic Hold.” Conclusion: Important aspects of the ward atmosphere seem to be improved in an open vs. a locked setting, whereas patient satisfaction does not seem to be influenced by the door status in the specific population of patients under involuntary commitment. The ward atmosphere turned out to be more sensitive to differences between psychiatric inpatient settings with different door policies. It can contribute to a broader assessment by including subjective perceptions by those who are affected directly by involuntary commitments. Regarding patient satisfaction under involuntary commitment, further research is needed to clarify both the relevance of the concept and its appropriate measurement.

\(\textbf {Background:}\) Open-door policies in psychiatry are discussed as a means to improve the treatment of involuntarily committed patients in various aspects. Current research on open-door policies focuses mainly on objective effects, such as the number of coercive interventions or serious incidents. The aim of the present study was to investigate more subjective perceptions of different psychiatric inpatient settings with different door policies by analyzing ward atmosphere and patient satisfaction. \(\textbf {Methods:}\) Quantitative data on the ward atmosphere using the Essen Climate Evaluation Scale (EssenCES) and on patient satisfaction (ZUF-8) were obtained from involuntarily committed patients (\(\it n\) = 81) in three psychiatric hospitals with different ward settings and door policies (open, facultative locked, locked). Furthermore, qualitative interviews with each of 15 patients, nurses, and psychiatrists were conducted in one psychiatric hospital with a facultative locked ward comparing treatment in an open vs. a locked setting. \(\textbf {Results:}\) Involuntarily committed patients rated the EssenCES’ subscale "Experienced Safety" higher in an open setting compared with a facultative locked and a locked setting. The subscale "Therapeutic Hold" was rated higher in an open setting than a locked setting. Regarding the safety experienced from a mental health professionals’ perspective, the qualitative interviews further revealed advantages and disadvantages of door locking in specific situations, such as short-term de-escalation vs. increased tension. Patient satisfaction did not differ between the hospitals but correlated weakly with the EssenCES’ subscale "Therapeutic Hold". \(\textbf {Conclusion:}\) Important aspects of the ward atmosphere seem to be improved in an open vs. a locked setting, whereas patient satisfaction does not seem to be influenced by the door status in the specific population of patients under involuntary commitment. The ward atmosphere turned out to be more sensitive to differences between psychiatric inpatient settings with different door policies. It can contribute to a broader assessment by including subjective perceptions by those who are affected directly by involuntary commitments. Regarding patient satisfaction under involuntary commitment, further research is needed to clarify both the relevance of the concept and its appropriate measurement.

\(\bf Background:\) Given the lethal severity of amyotrophic lateral sclerosis (ALS), the aim of this study was to illuminate the coherence of depression and death anxiety in both ALS patients and caregivers and in how far patients and caregivers are influenced by the mindset of their respective counterpart. \(\bf Methods:\) 30 couples of patients (mean age 60.57; 13 women, 17 men) and primary caregivers (mean age 57.33; 16 women, 14 men) were included into the study. Death anxiety was assessed using the newly developed BOFRETTA scale, depression via Beck Depression Inventory, anxiety by means of State Trait Anxiety Inventory and caregivers' exertion using the Caregiver Strain Index. Patients' impairment was assessed with the ALS functional rating scale. \(\bf Results:\) We found that while death anxiety was related to depression in both patients and caregivers, death anxiety was related to anxiety only in patients. Caregiver strain correlated with both caregiver‘s depression and anxiety. Moreover, patients' and caregivers’ depression, anxiety and death anxiety correlated to the ones of their counterpart. \(\bf Conclusion:\) These results suggest that despite little depressive symptoms in ALS patients the fatal prognosis of the disease takes into account, depression and death anxiety influence each other and might be addressed together in pharmacological and especially psychotherapeutic interventions to the benefit of the patient. Medical professionals should not forget to offer sufficient support to caregivers tending patients affected by depression and death anxiety as they are likely to mirror their patient's feelings.

An interdisciplinary research perspective is developed concerning the question of how we understand others’ emotions and how reliable our judgment about others’ emotion can be. After an outline of the theoretical background of emotions, we briefly discuss the importance of prior experiences and context information for the recognition of emotions. To clarify this role, we describe a study design, utilizing emotional expressions and context information while controlling for prior experiences and the actual emotional situation to systematically approach these questions.

Impaired neural synchronization is a hallmark of psychotic conditions such as schizophrenia. It has been proposed that schizophrenia-related cognitive deficits are caused by an unbalance of reciprocal inhibitory and stimulatory signaling. This supposedly leads to decreased power of induced gamma oscillations during the performance of cognitive tasks. In light of this hypothesis an efficient antipsychotic treatment should modify the connectivity and synchronization of local neural circuits. To address this issue, we investigated a model of hippocampal neuronal networks \(\textit {in vitro}\). Inhibitory and excitatory innervation of GABAergic and glutamatergic neurons was quantified using immunocytochemical markers and an automated routine to estimate network connectivity. The first generation (FGA) and second generation (SGA) antipsychotic drugs haloperidol and olanzapine, respectively, differentially modified the density of synaptic inputs. Based on the observed synapse density modifications, we developed a computational model that reliably predicted distinct changes in network activity patterns. The results of computational modeling were confirmed by spontaneous network activity measurements using the multiple electrode array (MEA) technique. When the cultures were treated with olanzapine, overall activity and synchronization were increased, whereas haloperidol had the opposite effect. We conclude that FGAs and SGAs differentially affect the balance between inhibition and excitation in hippocampal networks.

Prenatal immune activation has been associated with increased risk of developing schizophrenia. The polyinosinic-polycytidylic acid (Poly(I:C)) mouse model replicates some of the endophenotype characteristic of this disorder but the social deficits observed in schizophrenia patients have not been well studied in this model. Therefore we aimed to investigate social behavior, in particular emotional contagion for pain, in this mouse model. We injected pregnant mouse dams with Poly(I:C) or saline (control) on gestation day 9 (GD9) and we evaluated their offspring in the pre-pulse inhibition (PPI) test at age 50–55 days old to confirm the reliability of our model. Mice were then evaluated in an emotional contagion test immediately followed by the light/dark test to explore post-test anxiety-like behavior at 10 weeks of age. In the emotional contagion test, an observer (prenatally exposed to Poly(I:C) or to saline) witnessed a familiar wild-type (WT) mouse (demonstrator) receiving electric foot shocks. Our results replicate the sensory gating impairments in the Poly(I:C) offspring but we only observed minor group differences in the social tasks. One of the differences we found was that demonstrators deposited fewer feces in the presence of control observers than of observers prenatally exposed to Poly(I:C), which we suggest could be due to the observers’ behavior. We discuss the findings in the context of age, sex and day of prenatal injection, suggesting that Poly(I:C) on GD9 may be a valuable tool to assess other symptoms or symptom clusters of schizophrenia but perhaps not comprising the social domain.

Additional file 1. Web appendix.

Zusammenfassung Fragestellung: Durch Anwendung der OPD sollten Hinweise und Hypothesen im Hinblick auf eine genauere Risikoeinschatzung und praventive Psychotherapie bei Patienten mit Prodromalzustand gewonnen werden. Methode: 20 Probanden im schizophrenen Prodromalstadium, sechs psychoseferne und 14 psychosenahe, sowie zehn Patienten mit paranoider Schizophrenie als Referenzgruppe, wurden mit Hilfe der ersten vier OPD-Achsen untersucht. Ergebnisse: Beide Gruppen unterschieden sich auf allen vier Achsen wesentlich voneinander. Die Prodromalprobanden schienen wesentlich bessere Therapievoraussetzungen zu bieten, nahmen ihre Interaktionspartner einschlieslich der Untersucher als weniger aversiv wahr und induzierten weniger distanziertes Verhalten der Untersucher als die schizophrenen Patienten. In beiden Prodromal-Untergruppen waren Selbstwertkonflikte prominent. Allerdings zeigten die psychosefernen Probanden gegenuber den psychosenahen weniger Autonomie-Abhangigkeitskonflikte und eine besser integrierte S...

Alterations in reward and punishment processing have been reported in adults suffering from long-term cannabis use. However, previous findings regarding the chronic effects of cannabis on reward and punishment processing have been inconsistent. In the present study, we used functional magnetic resonance imaging (fMRI) to reveal the neural correlates of reward and punishment processing in long-term cannabis users (\(\it n\) = 15) and in healthy control subjects (\(\it n\) = 15) with no history of drug abuse. For this purpose, we used the well-established Monetary Incentive Delay (MID) task, a reliable experimental paradigm that allows the differentiation between anticipatory and consummatory aspects of reward and punishment processing. Regarding the gain anticipation period, no significant group differences were observed. In the left caudate and the left inferior frontal gyrus, cannabis users were – in contrast to healthy controls – not able to differentiate between the conditions feedback of reward and control. In addition, cannabis users showed stronger activations in the left caudate and the bilateral inferior frontal gyrus following feedback of no punishment as compared to healthy controls. We interpreted these deficits in dorsal striatal functioning as altered stimulus-reward or action-contingent learning in cannabis users. In addition, the enhanced lateral prefrontal activation in cannabis users that is related to non-punishing feedback may reflect a deficit in emotion regulation or cognitive reappraisal in these subjects.

Background: Bipolar disorders (BD) are among the most severe mental disorders with first clinical signs and symptoms frequently appearing in adolescence and early adulthood. The long latency in clinical diagnosis (and subsequent adequate treatment) adversely affects the course of disease, effectiveness of interventions and health-related quality of life, and increases the economic burden of BD. Despite uncertainties about risk constellations and symptomatology in the early stages of potentially developing BD, many adolescents and young adults seek help, and most of them suffer substantially from symptoms already leading to impairments in psychosocial functioning in school, training, at work and in their social relationships. We aimed to identify subjects at risk of developing BD and investigate the efficacy and safety of early specific cognitive-behavioural psychotherapy (CBT) in this subpopulation. Methods/Design: EarlyCBT is a randomised controlled multi-centre clinical trial to evaluate the efficacy and safety of early specific CBT, including stress management and problem solving strategies, with elements of mindfulness-based therapy (MBT) versus unstructured group meetings for 14 weeks each and follow-up until week 78. Participants are recruited at seven university hospitals throughout Germany, which provide in-and outpatient care (including early recognition centres) for psychiatric patients. Subjects at high risk must be 15 to 30 years old and meet the combination of specified affective symptomatology, reduction of psychosocial functioning, and family history for (schizo) affective disorders. Primary efficacy endpoints are differences in psychosocial functioning and defined affective symptomatology at 14 weeks between groups. Secondary endpoints include the above mentioned endpoints at 7, 24, 52 and 78 weeks and the change within groups compared to baseline; perception of, reaction to and coping with stress; and conversion to full BD. Discussion: To our knowledge, this is the first study to evaluate early specific CBT in subjects at high risk for BD. Structured diagnostic interviews are used to map the risk status and development of disease. With our study, the level of evidence for the treatment of those young patients will be significantly raised.

Humans have evolved strong preferences for equity and fairness. Neuroimaging studies suggest that punishing unfairness is associated with the activation of a neural network comprising the anterior cingulate cortex, anterior insula, the ventral striatum, and the dorsolateral prefrontal cortex (DLPFC). Here, we report the neuronal correlates of retribution and "forgiveness" in a scenario, in which individuals first acted as a recipient in an Ultimatum Game, and subsequently assumed the position of a proposer in a Dictator Game played against the same opponents as in the Ultimatum Game. Most subjects responded in a tit-for-tat fashion, which was accompanied by activation of the ventral striatum, corroborating previous findings that punishing unfair behaviour has a rewarding connotation. Subjects distinguished between the human opponent and computer condition by activation of the ventromedial PFC in the human condition, indicative of mentalising. A substantial number of subjects did not retaliate. Neurally, this "forgiveness" behaviour was associated with the activation of the right (and to a lesser degree left) DLPFC, a region that serves as a cognitive control region and thus may be involved in inhibiting emotional responses against unfairness.

Suicide is the most important incident in psychiatric disorders. Psychological pain and empathy to pain involves a neural network that involves the anterior cingulate cortex (ACC) and the anterior insula (AI). At the neuronal level, little is known about how complex emotions such as shame, guilt, self-derogation and social isolation, all of which feature suicidal behavior, are represented in the brain. Based on the observation that the ACC and the AI contain a large spindle-shaped cell type, referred to as von Economo neuron (VEN), which has dramatically increased in density during human evolution, and on growing evidence that VENs play a role in the pathophysiology of various neuropsychiatric disorders, including autism, psychosis and dementia, we examined the density of VENs in the ACC of suicide victims. The density of VENs was determined using cresyl violet-stained sections of the ACC of 39 individuals with psychosis (20 cases with schizophrenia, 19 with bipolar disorder). Nine subjects had died from suicide. Twenty specimen were available from the right, 19 from the left ACC. The density of VENs was significantly greater in the ACC of suicide victims with psychotic disorders compared with psychotic individuals who died from other causes. This effect was restricted to the right ACC. VEN density in the ACC seems to be increased in suicide victims with psychosis. This finding may support the assumption that VEN have a special role in emotion processing and self-evaluation, including negative self-appraisal.

This paper provides the rationale and design of the European Prediction of Psychosis Study (EPOS), the first European prospective transnational field study of the prodrome and moderating risk/resilience factors of psychosis. As different health systems provide different structures of care, prevention programmes will only be successfully implemented and sustained system-wide, if they can be adapted to the system's special opportunities and needs. EPOS will provide a sound data base for a future evidence-based prevention of psychosis. Data on the recruitment of subjects and on the distribution of the four clinical criteria for an at-risk mental state for psychosis are given

OBJECTIVES: Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients. METHODS: A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models. RESULTS: BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment. CONCLUSIONS: The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype. peerReviewed

Georg Juckel,1 Andrea de Bartolomeis,2 Philip Gorwood,3 Sergey Mosolov,4 Luca Pani,5 Alessandro Rossi,6 Julio Sanjuan7 1Department of Psychiatry, LWL-University Hospital, Ruhr-University Bochum, Bochum, Germany; 2Laboratory of Molecular Psychiatry and Unit of Treatment Resistant Psychosis, University School of Medicine of Naples Federico II, Napoli, Italy; 3Groupe Hospitalier Sainte-Anne (CMME), Paris-Descartes University, Paris, France; 4Moscow Research Institute of Psychiatry, Moscow, Russia; 5Institute of Translational Pharmacology, Italian National Research Council, Rome, Italy; 6Università de L’Aquila, L’Aquila, Italy; 7Clinic Hospital, Spanish Mental Health Network (CIBERSAM), University of Valencia, Valencia, Spain Introduction: Prompt administration of antipsychotic treatment that is adhered to is essential for the optimal treatment of schizophrenia. Many patients have benefited from the advent of second-generation antipsychotics, which can offer good symptomatic control with reduced incidence of extrapyramidal symptoms, although with higher risk of metabolic side effects. It is unsurprising that accounts as to whether first- and second-generation antipsychotics differ in their efficacy vary, since treatment effectiveness is a broad notion and difficult to define. Objectives: Numerous factors may be used to gauge treatment effectiveness and, while it has largely been defined in terms of improvements in four domains (symptoms of disease, treatment burden, disease burden, and health and wellness), the real-world clinical utility of this consensus is unclear. Therefore, this article aims to provide a framework that can aid psychiatrists in making assessments about treatment effectiveness. Methods and results: A panel of 12 psychiatrists and psychopharmacologists convened to develop and propose an accessible and globally-applicable framework for assessing the effectiveness of antipsychotic treatments in patients with schizophrenia. Following presentation of a preliminary proposal to a wider group of psychiatrists from across Europe, it was refined into a framework comprising five domains: symptomatic remission and retention of treatment; affective symptoms; cognitive functioning; treatment satisfaction; and personal and social functioning – each of which is discussed in this article. Conclusions: This article provides a framework that can aid psychiatrists in making assessments about treatment effectiveness. It is anticipated that the framework outlined here may contribute to improving clinical practice through the promotion of a patient-centered approach to the assessment of treatment effectiveness, using five specified domains, in patients with schizophrenia. Keywords: antipsychotic, assessment scales, functioning, mental illness, satisfaction