soulspace: Integrated youth mental health care in Berlin, Germany-An introduction to the program and a description of its users.

AIM: A substantial gap between young people's need for mental health care services and their actual access to such services led worldwide organizations (e.g., the WHO) to recommend the implementation of early intervention programs and youth mental health services. Some countries around the world have established structures to meet this recommendation. In this paper, we describe soulspace as the first integrated youth mental health service for young people aged between 15 and 35 years in Berlin, Germany. METHODS: We introduce soulspace as easily accessible mental health care for young people, and we characterize soulspace along the lines of the internationally established eight key principles of integrated youth mental health services (Killackey, et al., 2020, World Economic Forum). Soulspace is a cooperation between clinical outpatient units of psychiatric clinics for adolescents and young adults as well as a community-based counselling service. It provides initial contact, counselling, diagnostics, and treatment. RESULTS: Our analyses of the pathways to soulspace and the characteristics of the soulspace users suggest that the low threshold is a facilitator to help finding for young people in comparison to more conventional early intervention models. That is, having transferred the early intervention center in a youth-facing counselling service as was done in soulspace seems to have reduced the threshold to seek help for families and for young people in need for support. CONCLUSIONS: In summary, with soulspace, an easily accessible mental health care service was established that integrates counselling and specialized psychiatric treatment if needed.

Prediction of estimated risk for bipolar disorder using machine learning and structural MRI features.

BACKGROUND: Individuals with bipolar disorder are commonly correctly diagnosed a decade after symptom onset. Machine learning techniques may aid in early recognition and reduce the disease burden. As both individuals at risk and those with a manifest disease display structural brain markers, structural magnetic resonance imaging may provide relevant classification features. METHODS: Following a pre-registered protocol, we trained linear support vector machine (SVM) to classify individuals according to their estimated risk for bipolar disorder using regional cortical thickness of help-seeking individuals from seven study sites (N = 276). We estimated the risk using three state-of-the-art assessment instruments (BPSS-P, BARS, EPIbipolar). RESULTS: For BPSS-P, SVM achieved a fair performance of Cohen's κ of 0.235 (95% CI 0.11-0.361) and a balanced accuracy of 63.1% (95% CI 55.9-70.3) in the 10-fold cross-validation. In the leave-one-site-out cross-validation, the model performed with a Cohen's κ of 0.128 (95% CI -0.069 to 0.325) and a balanced accuracy of 56.2% (95% CI 44.6-67.8). BARS and EPIbipolar could not be predicted. In post hoc analyses, regional surface area, subcortical volumes as well as hyperparameter optimization did not improve the performance. CONCLUSIONS: Individuals at risk for bipolar disorder, as assessed by BPSS-P, display brain structural alterations that can be detected using machine learning. The achieved performance is comparable to previous studies which attempted to classify patients with manifest disease and healthy controls. Unlike previous studies of bipolar risk, our multicenter design permitted a leave-one-site-out cross-validation. Whole-brain cortical thickness seems to be superior to other structural brain features.

Young people at risk for developing bipolar disorder: Two-year findings from the multicenter prospective, naturalistic Early-BipoLife study.

Early identification and intervention of individuals with an increased risk for bipolar disorder (BD) may improve the course of illness and prevent long­term consequences. Early-BipoLife, a multicenter, prospective, naturalistic study, examined risk factors of BD beyond family history in participants aged 15-35 years. At baseline, positively screened help-seeking participants (screenBD at-risk) were recruited at Early Detection Centers and in- and outpatient depression and attention-deficit/hyperactivity disorder (ADHD) settings, references (Ref) drawn from a representative cohort. Participants reported sociodemographics and medical history and were repeatedly examined regarding psychopathology and the course of risk factors. N = 1,083 screenBD at-risk and n = 172 Ref were eligible for baseline assessment. Within the first two years, n = 31 screenBD at-risk (2.9 %) and none of Ref developed a manifest BD. The cumulative transition risk was 0.0028 at the end of multistep assessment, 0.0169 at 12 and 0.0317 at 24 months (p = 0.021). The transition rate with a BD family history was 6.0 %, 4.7 % in the Early Phase Inventory for bipolar disorders (EPIbipolar), 6.6 % in the Bipolar Prodrome Interview and Symptom Scale-Prospective (BPSS-FP) and 3.2 % with extended Bipolar At-Risk - BARS criteria). In comparison to help-seeking young patients from psychosis detection services, transition rates in screenBD at-risk participants were lower. The findings of Early-BipoLife underscore the importance of considering risk factors beyond family history in order to improved early detection and interventions to prevent/ameliorate related impairment in the course of BD. Large long-term cohort studies are crucial to understand the developmental pathways and long-term course of BD, especially in people at- risk.

Linguistic findings in persons with schizophrenia-a review of the current literature.

Introduction: Alterations of verbalized thought occur frequently in psychotic disorders. We characterize linguistic findings in individuals with schizophrenia based on the current literature, including findings relevant for differential and early diagnosis. Methods: Review of literature published via PubMed search between January 2010 and May 2022. Results: A total of 143 articles were included. In persons with schizophrenia, language-related alterations can occur at all linguistic levels. Differentiating from findings in persons with affective disorders, typical symptoms in those with schizophrenia mainly include so-called "poverty of speech," reduced word and sentence production, impaired processing of complex syntax, pragmatic language deficits as well as reduced semantic verbal fluency. At the at-risk state, "poverty of content," pragmatic difficulties and reduced verbal fluency could be of predictive value. Discussion: The current results support multilevel alterations of the language system in persons with schizophrenia. Creative expressions of psychotic experiences are frequently found but are not in the focus of this review. Clinical examinations of linguistic alterations can support differential diagnostics and early detection. Computational methods (Natural Language Processing) may improve the precision of corresponding diagnostics. The relations between language-related and other symptoms can improve diagnostics.

Machine Learning Prediction of Estimated Risk for Bipolar Disorders Using Hippocampal Subfield and Amygdala Nuclei Volumes.

The pathophysiology of bipolar disorder (BD) remains mostly unclear. Yet, a valid biomarker is necessary to improve upon the early detection of this serious disorder. Patients with manifest BD display reduced volumes of the hippocampal subfields and amygdala nuclei. In this pre-registered analysis, we used structural MRI (n = 271, 7 sites) to compare volumes of hippocampus, amygdala and their subfields/nuclei between help-seeking subjects divided into risk groups for BD as estimated by BPSS-P, BARS and EPIbipolar. We performed between-group comparisons using linear mixed effects models for all three risk assessment tools. Additionally, we aimed to differentiate the risk groups using a linear support vector machine. We found no significant volume differences between the risk groups for all limbic structures during the main analysis. However, the SVM could still classify subjects at risk according to BPSS-P criteria with a balanced accuracy of 66.90% (95% CI 59.2-74.6) for 10-fold cross-validation and 61.9% (95% CI 52.0-71.9) for leave-one-site-out. Structural alterations of the hippocampus and amygdala may not be as pronounced in young people at risk; nonetheless, machine learning can predict the estimated risk for BD above chance. This suggests that neural changes may not merely be a consequence of BD and may have prognostic clinical value.

Feasibility and efficacy of an acceptance and mindfulness-based group intervention for young people with early psychosis (Feel-Good group).

Background: Over the last decade, researchers have sought for alternative interventions that have better treatment effects than Cognitive Behavioral Therapy (CBT) when treating psychotic symptoms. Mindfulness-based interventions have been a proposed alternative to CBT, yet research regarding its feasibility, acceptance and effectiveness is lacking when treating individuals with early psychosis in inpatient settings. Objective: Before conducting a large-scale randomized-controlled trial (RCT), this pilot study evaluated the feasibility and the potential efficacy of a mindfulness-based inpatient group intervention that targets emotion regulation in patients with early psychosis, and thus indirectly improving psychotic symptoms. Methods: A pre-post study was performed. Thirty-six patients with early psychosis treated at the specialized inpatient treatment "Frühinterventions- und Therapiezentrum; FRITZ" (early intervention and therapy center) received eight group therapy sessions. Assessments were performed at baseline, after 8 weeks post treatment and at follow-up after 16 weeks. Results: Rates of patients who participated in the study suggests that a mindfulness-based group therapy is highly accepted and feasible for patients with early psychosis being treated in an inpatient ward. Friedman analyses revealed significant changes in the primary outcomes of emotional goal attainment (Goal 1: W = 0.79; Goal 2: W = 0.71) and psychotic symptoms (PANSS-T: W = 0.74). Significant, albeit small, effect sizes were found in patients' self-perception of emotion regulation skills (ERSQ: W = 0.23). Discussion: We found favorable findings regarding the feasibility and acceptance of the Feel-Good mindfulness-based intervention. Results of the study provide a basis for an estimation of an adequate sample size for a fully powered RCT that needs to be conducted to test whether Feel-Good is effective in the inpatient treatment of psychotic symptoms for individuals with early psychosis. Clinical trial registration: [https://clinicaltrials.gov/ct2/show/NCT04592042], identifier [NCT04592042].

Specialized inpatient treatment for young people with early psychosis: acute-treatment and 12-month results.

The objective of the study was to investigate the development of clinical outcomes of young people with early psychosis in a specialized inpatient treatment and assess the feasibility of such an intervention in an inpatient setting. The study was a prospective cohort study of patients with early psychosis treated at the specialized inpatient treatment "Fühinterventions-und Therapiezentrum, FRITZ" (early intervention and therapy center) in Berlin, Germany. The primary outcomes were attitudes towards psychiatric medication and patient satisfaction with treatment after 6 weeks. Secondary outcomes were clinical symptoms, functioning, remission, recovery, all-cause treatment discontinuation, and rehospitalisation at 6 and 12 months after inpatient treatment. We recruited 95 inpatients with early psychosis. Attitudes towards psychiatric medication (Δ6weeks = 3.00, d6weeks = 0.55; Δ6mo = 2.15, d6mo = 0.35; Δ12mo = 3.03, d12mo = 0.52) and patient satisfaction (Δ6weeks = 0.21, d6weeks = 0.40; Δ6mo = 0.32, d6mo = 0.43; Δ12mo = 0.13, d12mo = 0.17) changed with medium effect sizes at six weeks up to a 6- and 12-month follow-up. Clinical outcomes changed significantly with medium-to-large-effect sizes over 12 months CGIΔ12mo = 1.64, d12mo = -1.12; PANSS totalΔ12mo = 20.10, d12mo = -0.76; GAFΔ12mo = 19.58, d12mo = 1.25). The all-cause treatment discontinuation rate was 13.69% (n = 13) at a 6-month and 35.79% (n = 34) at a 12-month follow-up. The rehospitalization rate was 30.53% (n = 29) at a 6-month and 43.16% (n = 41) at a 12-month follow-up. Patients with specialized inpatient treatment for early psychosis showed improvements in attitude towards psychiatric medication, patient satisfaction, symptoms, and functioning for up to 12 months.Trial registration: DRKS00024351, 2021/02/11 retrospectively registered.

Individuals at increased risk for development of bipolar disorder display structural alterations similar to people with manifest disease.

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.

Clinical Risk Constellations for the Development of Bipolar Disorders.

The early recognition of psychiatric disorders has been a focus of research in the last decades and has led to improvements in clinical care, especially in the area of early psychosis. Like non-affective psychosis, bipolar disorders are often diagnosed with a delay that can lead to long periods of untreated illness and impact long-term outcomes. This article presents the rationale for early recognition in bipolar disorder and presents the current evidence for the identification of risk factors, their assessment and validity in predicting the onset of bipolar disorder.

Early detection of bipolar disorders and treatment recommendations for help-seeking adolescents and young adults: Findings of the Early Detection and Intervention Center Dresden.

BACKGROUND: Early identification and intervention of individuals with risk factors for or subtle prodromal symptoms of bipolar disorders (BD) may improve the illness course and prevent adverse long-term consequences. METHODS: We examined sociodemographic, clinical and psychopathological characteristics of help-seeking adolescents and young adults who consulted the Early Detection and Intervention Center Dresden at the University of Dresden (Germany) and presented with or without pre-defined at-risk criteria for BD. The standardized diagnostic procedure for all help-seeking youth included a comprehensive psychiatric history and a structured clinical interview. When BD at-risk state was suspected, early detection instruments (EPIbipolar, BPSS-FP) were applied. Treatment recommendations were formulated in multi-professional case conferences. RESULTS: Out of 890 help-seeking persons between 05/2009 and 04/2018, 582 (65%) completed the diagnostic process. Of these, 24 (4%) had manifest BD and 125 (21%) fulfilled at-risk BD criteria (age = 23.9 ± 0.6 years, female = 62%). Of the pre-defined main risk factors, family history for BD was reported in 22% of the at-risk persons, (hypo-)mania risk state in 44%, and increasing cyclothymic mood swings with increased activity in 48%. The most common secondary risk factors were decreased psychosocial functioning (78%), lifetime diagnosis of depressive disorder (67%) and specific sleep/circadian rhythm disturbances (59%). Substance use was very common in subjects at-risk for BD (cannabis = 50%, alcohol = 33%) and highest in patients with BD (cannabis = 75%, alcohol = 40%). Psychiatric treatment history, including psychopharmacological therapy, was similar between the groups, while treatment recommendations differed, with more advice for psychotherapy and antidepressants in the at-risk group with a lifetime diagnosis of depression and more advice for specialized BD treatment including mood stabilizers in patients with BD. CONCLUSION: This analysis on the phenomenology of different BD at-risk stages suggests that early detection of individuals presenting with suggested risk factors for the development of BD is feasible in help-seeking young people. Future research should further develop/test stage-specific prevention and early targeted intervention approaches that were described in a naturalistic setting.

The Patient, Investigator, Nurse, Carer Questionnaire (PINC-Q): a cross-sectional, retrospective, non-interventional study exploring the impact of less frequent medication administration with paliperidone palmitate 3-monthly as maintenance treatment for schizophrenia.

BACKGROUND: To understand the implications of switching from paliperidone palmitate 1-monthly (PP1M) to paliperidone palmitate 3-monthly (PP3M) treatment of schizophrenia from the perspective of four key stakeholders: patients, physicians, nurses and carers. METHODS: This was a cross-sectional, retrospective, non-interventional study comprising a one-time questionnaire (PINC-Q) for adult patients (aged ≥18 years) with schizophrenia (International Classification of Diseases; ICD-10) and their physician, nurse and carer. Questionnaires were developed in association with patient and carer advocacy groups (GAMIAN and EUFAMI) and following an advisory board formed of psychiatrists and nurses. The degree of alignment between stakeholders was also examined. RESULTS: Responses were received from a total of 224 evaluable patients. For most patients (88.4%), responses were received from at least two other stakeholders. Patients were moderately ill with mild-to-moderate lack of insight and had received PP1M for a mean (standard deviation [SD]) of 23.9 (21.28) months before switching to PP3M (duration mean [SD] 12.8 [3.72] months). The most frequently reported reasons to switch from PP1M to PP3M were 'to live life as normally as possible' and 'patient convenience'. Over 79% of responses within each stakeholder group stated that PP3M helped the patients, with increased patient activity and social involvement, improved frequency and quality of physician-patient and nurse-patient communication and decreased perceived stigma. CONCLUSIONS: The results of this study add to the increasing body of evidence supporting the benefits of PP3M in a population of patients with schizophrenia representative of real-world clinical practice.

Treatment Goals for Patients with Schizophrenia - A Narrative Review of Physician and Patient Perspectives.

INTRODUCTION: There are many possible treatment goals for patients with schizophrenia. Two major perspectives on treatment goals are the patient's and the physician's perspective. Patient-centered treatment mandates that an individual patient's treatment goals are taken into account when treatment is planned. In this narrative review, we address the commonalities and differences of the patient's and physician's perspectives. METHODS: We searched for literature on treatment goals for patients with schizophrenia from the last 10 years. RESULTS: Fifty-two relevant records were identified, 4 of which directly compare patient's and physician's perspectives. Two further articles used the same set of goals to ask patients or physicians for their assessment. DISCUSSION: Agreement between patients and physicians regarding valuation of treatment goals was high. However, physicians tended to put more emphasis on the classical "textbook" goals of symptom resolution and functioning, while patients stressed well-being and quality of life more. Results on treatment goals from patients are difficult to generalize, since recruiting representative patient samples is challenging and patient subgroups may have differing priorities.

The relationship between cannabis use and cognition in people diagnosed with first-episode psychosis.

Cannabis use is highly prevalent among young people diagnosed with first-episode psychosis (FEP), however, its impact on cognition is still unclear. The aim of the present study was to examine the association of cannabis use with cognition in people diagnosed with FEP. We extended previous research findings by operationalising the comorbid cannabis use, considering recency of cannabis use and use of other illicit substances and including people with a broad spectrum of psychotic diagnoses. A total of 89 people diagnosed with FEP were interviewed about their history of substance use and completed a cognitive test battery assessing verbal memory, verbal fluency and attention. Sixty-one participants were lifetime cannabis users (CU; ≥three times per week for ≥four weeks; 68.5%) and 28 were cannabis non-users (CNU; 31.5%). CU were significantly more likely to be male and exhibited significantly more positive symptoms than CNU. In contrast, CNU displayed significantly more negative symptoms than CU. There were no differences between CU and CNU on neurocognitive tasks of verbal memory, verbal fluency and attention. In conclusion, there was no indication that cannabis use was associated with cognitive impairments in people diagnosed with FEP.

Improving early recognition and intervention in people at increased risk for the development of bipolar disorder: study protocol of a prospective-longitudinal, naturalistic cohort study (Early-BipoLife).

BACKGROUND: Bipolar disorders (BD) belong to the most severe mental disorders, characterized by an early onset and recurrent, severe episodes or a chronic course with poor psychosocial functioning in a proportion of patients. Many patients with BD experience substantial symptomatology months or even years before full BD manifestation. Adequate diagnosis and treatment is often delayed, which is associated with a worse outcome. This study aims to prospectively evaluate and improve early recognition and intervention strategies for persons at-risk for BD. METHODS: Early-BipoLife is a prospective-longitudinal cohort study of 1419 participants (aged 15-35 years) with at least five waves of assessment over a period of at least 2 years (baseline, 6, 12, 18 and 24 months). A research consortium of ten university and teaching hospitals across Germany conducts this study. The following risk groups (RGs) were recruited: RG I: help-seeking youth and young adults consulting early recognition centres/facilities presenting ≥ 1 of the proposed risk factors for BD, RG II: in-/outpatients with unipolar depressive syndrome, and RG III: in-/outpatients with attention-deficit/hyperactivity disorder (ADHD). The reference cohort was selected from the German representative IMAGEN cohort. Over the study period, the natural course of risk and resilience factors, early symptoms of BD and changes of symptom severity (including conversion to manifest BD) are observed. Psychometric properties of recently developed, structured instruments on potential risk factors for conversion to BD and subsyndromal symptomatology (Bipolar Prodrome Symptom Scale, Bipolar at-risk criteria, EPIbipolar) and biomarkers that potentially improve prediction are investigated. Moreover, actual treatment recommendations are monitored in the participating specialized services and compared to recently postulated clinical categorization and treatment guidance in the field of early BD. DISCUSSION: Findings from this study will contribute to an improved knowledge about the natural course of BD, from the onset of first noticeable symptoms (precursors) to fully developed BD, and about mechanisms of conversion from subthreshold to manifest BD. Moreover, these generated data will provide information for the development of evidence-based guidelines for early-targeted detection and preventive intervention for people at risk for BD.

[Early Intervention in Schizophrenia - an Update]. / Frühintervention bei Schizophrenie ­ ein Update.

In Germany, psychoses are still diagnosed too late. The average duration of untreated psychosis is (DUP) one year. Early intervention should, therefore, be given higher priority. The shorter the duration of the DUP, the higher the probability of permanent recovery and a better long-term prognosis. Public education work and specialised early detection centres with low-threshold access can improve care and thus the prospects of patients, mostly young, and already in the early phase of the disease. In addition to anti-psychotic therapy, evidence-based psychotherapeutic procedures, family and peer work, as well as accompanying offers are necessary to support patients individually in being or remaining reintegrated into the labour market ("Individual Placement and Support", IPS). While in some countries, such as Denmark and Australia, the possibility of early intervention is already part of standard care, Germany has not yet gone beyond model projects. Changing this must be one of the main objectives for the coming years. With this review, the authors would therefore like to encourage further thinking and action.

Prevalence of Prediabetes and Diabetes Mellitus Type II in Bipolar Disorder.

INTRODUCTION: Bipolar disorder (BD) is characterized by recurrent episodes of depression and mania and affects up to 2% of the population worldwide. Patients suffering from bipolar disorder have a reduced life expectancy of up to 10 years. The increased mortality might be due to a higher rate of somatic diseases, especially cardiovascular diseases. There is however also evidence for an increased rate of diabetes mellitus in BD, but the reported prevalence rates vary by large. MATERIAL AND METHODS: 85 bipolar disorder patients were recruited in the framework of the BiDi study (Prevalence and clinical features of patients with Bipolar Disorder at High Risk for Type 2 Diabetes (T2D), at prediabetic state and with manifest T2D) in Dresden and Würzburg. T2D and prediabetes were diagnosed measuring HBA1c and an oral glucose tolerance test (oGTT), which at present is the gold standard in diagnosing T2D. The BD sample was compared to an age-, sex- and BMI-matched control population (n = 850) from the Study of Health in Pomerania cohort (SHIP Trend Cohort). RESULTS: Patients suffering from BD had a T2D prevalence of 7%, which was not significantly different from the control group (6%). Fasting glucose and impaired glucose tolerance were, contrary to our hypothesis, more often pathological in controls than in BD patients. Nondiabetic and diabetic bipolar patients significantly differed in age, BMI, number of depressive episodes, and disease duration. DISCUSSION: When controlled for BMI, in our study there was no significantly increased rate of T2D in BD. We thus suggest that overweight and obesity might be mediating the association between BD and diabetes. Underlying causes could be shared risk genes, medication effects, and lifestyle factors associated with depressive episodes. As the latter two can be modified, attention should be paid to weight changes in BD by monitoring and taking adequate measures to prevent the alarming loss of life years in BD patients.

[Patients' Work-Related Participation Impairments and Need for Support in Day Hospital and Inpatient Psychiatric Treatment]. / Arbeitsbezogene Teilhabebeeinträchtigungen und Unterstützungsbedarf von Patienten in der (teil-)stationären psychiatrischen Versorgung.

OBJECTIVE: Approximately 80 % of patients in psychiatric treatment are significant impaired in participation work and are excluded from the labor market. METHOD: Survey of 176 patients in day hospital and inpatient psychiatric treatment regarding work-related participation impairments, need for support in competitive employment, education or study and actually received support. RESULTS: Data of 90 patients were available. 63 % of patients indicated a need for support in work-related participation, 53 % of them would participate in a job coaching. 49 % of the patients were addressed on the topic of work. Regardless of the need for support, only 1/5 of patients received concrete help. There is a strong need for support for young adults (77 %) and first-admission patients (73 %). CONCLUSION: There is a high but unmet need for support in managing work-related participation impairment. Routine needs assessment and the implementation of evidence-based methods could improve work-related inclusion.

Efficacy of cognitive-behavioral group therapy in patients at risk for serious mental illness presenting with subthreshold bipolar symptoms: Results from a prespecified interim analysis of a multicenter, randomized, controlled study.

OBJECTIVE: Most patients with bipolar disorders (BD) exhibit prodromal symptoms before a first (hypo)manic episode. Patients with clinically significant symptoms fulfilling at-risk criteria for serious mental illness (SMI) require effective and safe treatment. Cognitive-behavioral psychotherapy (CBT) has shown promising results in early stages of BD and in patients at high risk for psychosis. We aimed to investigate whether group CBT can improve symptoms and functional deficits in young patients at risk for SMI presenting with subthreshold bipolar symptoms. METHOD: In a multicenter, randomized, controlled trial, patients at clinical risk for SMI presenting with subthreshold bipolar symptoms aged 15-30 years were randomized to 14 weeks of at-risk for BD-specific group CBT or unstructured group meetings. Primary efficacy endpoints were differences in affective symptomatology and psychosocial functioning at 14 weeks. At-risk status was defined as a combination of subthreshold bipolar symptomatology, reduction of psychosocial functioning and a family history for (schizo)affective disorders. A prespecified interim analysis was conducted at 75% of the targeted sample. RESULTS: Of 128 screened participants, 75 were randomized to group CBT (n = 38, completers = 65.8%) vs unstructured group meetings (n = 37, completers = 78.4%). Affective symptomatology and psychosocial functioning improved significantly at week 14 (P < .001) and during 6 months (P < .001) in both groups, without significant between-group differences. Findings are limited by the interim character of the analysis, the use of not fully validated early detection interviews, a newly adapted intervention manual, and the substantial drop-outs. CONCLUSIONS: Results suggest that young patients at-risk for SMI presenting with subthreshold bipolar symptoms benefit from early group sessions. The degree of specificity and psychotherapeutic interaction needed requires clarification.

Acute and Long-term Memantine Add-on Treatment to Risperidone Improves Cognitive Dysfunction in Patients with Acute and Chronic Schizophrenia.

INTRODUCTION: Patients with schizophrenia are mainly characterized by negative symptoms and cognitive dysfunction. In this proof-of-concept study we tested effects on cognition and negative symptoms of a 6- or 24-week memantine add-on treatment to risperidone in patients with acute or chronic schizophrenia. MATERIALS AND METHODS: Patients with an acute episode of schizophrenia (n=11) and predominating positive symptoms were randomized to a 6-week add-on treatment with memantine (10 mg twice a day) versus placebo and patients with chronic schizophrenia (n=13) and negative symptoms were randomized to a 24-week add-on treatment with memantine (10 mg twice a day) versus placebo. All patients received antipsychotic medication with risperidone (2-8 mg/day). Psychopathological changes were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and after 2, 4, 6, 12, and 24 weeks. Cognitive function was measured at baseline, after 6 weeks, and 24 weeks. RESULTS: Patients with acute schizophrenia who received add-on treatment with memantine showed a significantly higher performance in attention intensity (p=0.043), problem-solving (p=0.043), verbal learning (p=0.050), and flexibility (p=0.049). Patients with chronic schizophrenia showed a significantly higher immediate memory in the memantine group compared to the placebo group (p=0.033) and a significantly greater reduction of the PANSS sum score if compared to the placebo group. DISCUSSIONS: Our study gives further evidence that memantine add-on treatment to risperidone may have neuroprotective effects and improve cognitive function in patients with schizophrenia. ClinicalTrials.gov Number: NCT00148590 and NCT00148616.