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Background: Impairments of social cognition are considered core features of schizophrenia and are established predictors of social functioning. However, affective aspects of social cognition including empathy have far less been studied than its cognitive dimensions. The role of empathy in the development of schizophrenia remains largely elusive., Methods: Emotional and cognitive empathy were investigated in large sample of 120 individuals at Clinical High Risk of Psychosis (CHR-P) and compared with 50 patients with schizophrenia and 50 healthy controls. A behavioral empathy assessment, the Multifaceted Empathy Test, was implemented, and associations of empathy with cognition, social functioning, and symptoms were determined., Results: Our findings demonstrated significant reductions of emotional empathy in individuals at CHR-P, while cognitive empathy appeared intact. Only individuals with schizophrenia showed significantly reduced scores of cognitive empathy compared to healthy controls and individuals at CHR-P. Individuals at CHR-P were characterized by significantly lower scores of emotional empathy and unspecific arousal for both positive and negative affective valences compared to matched healthy controls and patients with schizophrenia. Results also indicated a correlation of lower scores of emotional empathy and arousal with higher scores of prodromal symptoms., Conclusion: Findings suggest that the tendency to 'feel with' an interaction partner is reduced in individuals at CHR-P. Altered emotional reactivity may represent an additional, early vulnerability marker, even if cognitive mentalizing is grossly unimpaired in the prodromal stage. Different mechanisms might contribute to reductions of cognitive and emotional empathy in different stages of non-affective psychotic disorders and should be further explored., (© 2020 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Patients with schizophrenia suffer from stigma and discrimination due to their illness. Yet it is not well examined how experiences of stigma and discrimination express at the early illness stage and how they develop subsequently. Therefore, clinical and psycho-social correlates of stigma experiences and perceived stigma are analyzed in patients with first-episode schizophrenia over the course of 1 year after their first in-patient treatment. Questionnaire data assessed within the multi-centre-RCT "First-Episode Study" of the German Research Network on Schizophrenia were analyzed. Patients with first-episode schizophrenia were assessed 8 weeks after their first in-patient treatment (post-acute assessment) and 1 year later. N = 48 (post-acute) and N = 24 (1-year follow-up) patients provided questionnaire data appropriate for analyses, with N = 12 dyads. These data included burden due to stigma experiences (B-STE), perceived stigma (PDDQ), clinical (PANSS, CDSS, CGI, GAF, SAS) and psycho-social factors (LQLP, FSNK-self-esteem, KK-Scale). Cross-lag-correlation models showed a causal relation between stigma experiences (post-acute) and reduced self-esteem after 1 year. Multiple regression models revealed different models for experienced and perceived stigma. Factors associated with higher stigma experiences were older age, worse clinical global impression, better social adjustment, lower self-esteem, and the belief that illness is not driven by chance or fate. The different associations between psycho-social factors and stigma experiences and perceived stigma demonstrate the complexity of this inter-relationship. The results have practical implications for psycho-educational and other therapeutic interventions addressing stigma coping. Since the sample was small and selective, replication studies are needed.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a promising augmentation treatment for schizophrenia, however there are few controlled studies of rTMS augmentation of clozapine., Methods: Using data from the 'rTMS for the Treatment of Negative Symptoms in Schizophrenia' (RESIS) trial we examined the impact of rTMS on PANSS total, general, positive and negative symptoms among participants on clozapine. rTMS was applied to the left dorsolateral prefrontal cortex (DLPFC) for five treatment sessions/week for 3-weeks as augmentation for patients with a predominant negative syndrome of schizophrenia, as rated on PANSS., Results: 26 participants from the RESIS trial were on clozapine, receiving active (N=12) or sham (N=14) rTMS treatment. In our Linear Mixed Model (LMM) analysis, time×group interactions were significant in the PANSS positive subscale (p=0.003) (not being the corresponding behavioral output for DLPFC stimulation), the PANSS general subscale (p<0.001), the PANSS total scale (p=0.015), but not the PANSS negative subscale (p=0.301) (primary endpoint of the RESIS trial), when all PANSS measurements from screening to day 105 were included. Descriptive data suggests that in the active group the improvement was more pronounced compared to the sham rTMS group., Conclusions: In this largest available clozapine cohort, active rTMS may be more effective than sham rTMS when added to clozapine for positive and total psychotic symptoms. These findings should be interpreted with caution given this is a secondary analysis with a limited number of participants., (Copyright © 2019. Published by Elsevier B.V.)

Repetitive transcranial magnetic stimulation (rTMS) applied to the left frontal lobe is discussed to be a promising add-on treatment for negative symptoms in schizophrenia. The Positive and Negative Syndrome Scale (PANSS) has been used as outcome parameter in several previous rTMS trials, but studies focusing on PANSS factor analyses are lacking. For this purpose, we used the available PANSS data of the 'rTMS for the Treatment of Negative Symptoms in Schizophrenia' (RESIS) trial to calculate different literature-based PANSS factors and to re-evaluate the impact of rTMS on negative symptoms in this trial. In an exploratory re-analysis of published data from the RESIS study (Wobrock et al. 2015), we tested the impact of rTMS applied to the left dorsolateral prefrontal cortex on two PANSS factors for negative symptoms in psychotic disorders as well as on a PANSS five-factor consensus model intending to show that active rTMS treatment improves PANSS negative symptom subscores. In accordance to the original analysis, all PANSS factors showed an improvement over time in the active and, to a considerable extent, also in the sham rTMS group. However, comparing the data before and directly after the rTMS intervention, the PANSS excitement factor improved in the active rTMS group significantly more than in the sham group, but this finding did not persist if follow-up data were taken into account. These additional analyses extend the previously reported RESIS trial results showing unspecific improvements in the PANSS positive subscale in the active rTMS group. Our PANSS factor-based approach to investigate the impact of prefrontal rTMS on different negative symptom domains confirmed no overall beneficial effect of the active compared to sham rTMS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In the development of the International Classsification of Disorders (ICD-11), the World Health Organisation (WHO) has used a systematic approach with a focus on the utility of the revised classification criteria. For all major groups of mental and behavioural disorders working groups were set up, and these reviewed the scientific evidence and developed suggestions for revised classification criteria. These initial proposals, then submitted to public consultation and review, resulted in updated proposals. The chapter title for the primary psychotic disorders will be "Schizophrenia and other primary psychotic disorders". The clinical subtypes of schizophrenia will be substituted by symptom specifiers, which are applicable to all primary psychotic disorders. The role of Schneider's first-rank symptoms will be deemphasized. Course specifiers will be introduced and will be compatible with the U.S.-American classification system for mental disorders (Diagnostic and Statistical Manual, 5th revision, DSM-5). The group of Acute and Transient Psychotic Disorders will be more clearly differentiated from schizophrenia. Currently, field trials are under way both in clinical and internet-based settings to test the utility of the revised classification criteria. In early 2018, the final classification criteria of ICD-11 should be available., Competing Interests: Die Autoren erklären, dass sie innerhalb der letzten drei Jahre ein Autorenhonorar von Servier International für einen Überblicksartikel erhalten haben (J.Z.)., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: In Germany, several quality indicators have been proposed for the measurement of quality of mental healthcare. Some of these quality indicators have been tested in feasibility studies. The German Association for Psychiatry and Psychotherapy (DGPPN) established the "Task Force Quality Indicators (QI)" that, based on previous experience in the development and pilot testing of indicators, considered the further development and practical realization of QI for schizophrenia., Aim: The aim was to select a set of QI for schizophrenia that can also be applied to other diagnoses or used in generic measurements. Another goal was to focus on high feasibility of indicators., Methods: In a multistage selection process, the DGPPN Task Force selected QI that focus on essential quality aspects from an inventory of 161 existing QI developed by national and international research groups. Indicators were adapted in consultation with the "trialogic forum" of the DGPPN., Results: The DGPPN proposes the following ten indicators for quality measurement in mental healthcare for schizophrenia: QI1 Long-term treatment/Monitoring of side effects, QI2 Seclusion and restraint, QI3 Number of suicides, QI4 Psychoeducational-oriented intervention for significant others, QI5 Timely beginning of outpatient treatment after discharge from inpatient treatment, QI6 Aggression management - inpatient treatment, QI7 Diagnostic procedures/Physical examination, QI8 Antipsychotic polypharmacy, QI9 Rehabilitation/Vocational rehabilitation, QI10 Diagnostic procedures/Psychosocial functioning., Discussion: Most of our proposed QI have to be measured by means of additional data documentation. Based on prior experience in the pilot testing of QI, the DGPPN estimates that the additional efforts in data documentation would be manageable, but have to be refinanced. The indicators will be tested in feasibility studies in different mental healthcare hospitals in Germany.

Significant changes of schizophrenia patients during inpatient treatment were evalutaed and compared to established outcome criteria. The concept of reliable and clinically significant change methods was applied to three hundred and ninety-six patients suffering from a schizophrenia spectrum disorder. First, information on whether or not the change of the patient's condition is sufficient in order to declare that it is beyond a measurement error or random effect (= reliable change) was evaluated and in a second step it was observed if the reliable change was clinically meaningful (= clinically significant change). Different Positive and Negative Syndrome Scale for Schizophrenia (PANSS) thresholds were applied to define the clinically significant change (40, 45 and 50 points). These changes were then compared to established outcome criteria such as response and remission. Seventy-nine of the 396 patients (20%) showed a reliable improvement of symptoms, whereas 70% improved without achieving a reliable change of their condition. Of the 79 patients achieving a reliable change during treatment 8-15% concurrently showed a clinically significant change depending on the respective PANSS threshold. In contrast, 56% of the patients achieved response and 60% were in remission at discharge when applying established outcome criteria. Our results showed that a rather small number of schizophrenia patients were found to reliably change during inpatient treatment, with even less patients achieving a clinically significant change. The concept of reliable and clinically significant changes revealed to be a lot more stringent than today's established outcome criteria and should be critically evaluated regarding its use in schizophrenia patients., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: Patients with mental illnesses, especially with schizophrenia, suffer from stigma and discrimination. In addition, the stigma is a barrier to recognising and treating patients with first-episode psychosis; however, a self-rating instrument that assesses the general burden due to stigma experiences is still lacking., Material and Methods: A total of N = 48 patients with first-episode schizophrenia who were participants in the multicenter first-episode (long-term) study within the German Research Network on Schizophrenia, completed a newly developed self-rating questionnaire to assess the burden due to stigma experiences (B-STE). The following variables were analyzed as possible correlates: psychopathology (CGI, PANSS, CDSS and HAM-D), global functioning (GAF), social adjustment (SAS), self-esteem (FSKN), as well as quality of life (LQLP), subjective well-being under neuroleptic treatment (SWN) and anticipated stigma (PDDQ)., Results: Of the participants 25 % showed an increased burden due to stigma experiences, which correlated with a lower quality of life, lower subjective well-being under neuroleptic treatment, lower self-esteem and higher anticipated stigma. The results indicate that patients rated higher on the CGI scale who are at the same time better socially adjusted (SAS), are more intensely affected by the burden due to stigma experiences., Conclusion: The short self-rating instrument burden due to stigma experiences (B-STE) can help to identify patients who might benefit from therapeutic or educational interventions to support coping with stigma experiences.

Objective: Investigate whether treatment response in people at clinical high risk of psychosis (CHR) is predicted by their cognitive performance., Method: 128 CHR outpatients were randomized into two treatment groups, one receiving integrated psychological intervention (IPI), including psychoeducation, the other receiving supportive counselling (SC) for 12 months. Multiple regression analysis was used to identify neurocognitive predictors of treatment response in a subgroup of n = 105, measured by symptomatic and functional improvement at 1-year follow-up., Results: In the IPI, treatment response was associated with performance of executive control and processing speed (R² = 0.27, p = 0.002). In both treatment groups, performance of working memory/attention was a significant predictor (IPI: R² = 0.15, p = 0.039, SC: R² = 0.19, p = 0.012)., Conclusion: Cognitive performance is associated with treatment response in CHR people. The enhancement of cognitive performance is a useful target of early intervention., (© Georg Thieme Verlag KG Stuttgart · New York.)

The aim of this study was to evaluate residual symptoms in patients achieving remission according to the consensus criteria and to analyze their potential influence on the patient's outcome one year after discharge. In total, 399 patients suffering from a schizophrenia spectrum disorder were evaluated within a naturalistic study. Remission status was examined using the consensus criteria. Residual symptoms were defined as any symptom present at the time-point of remission following analogous analyses performed in depressed patients. Therefore, a PANSS item with a symptom severity of >1 (= at least borderline mentally ill) was defined to be a residual symptom. Remitters with and without residual symptoms were compared regarding psychopathology, functioning and side effects. In total, 236 patients (59%) were remitters at discharge with 94% of them suffering from at least one residual symptom. The most common residual symptoms were blunted affect (49%), conceptual disorganization (42%) and social withdrawal (40%). A significant association was found between the presence of residual symptoms and the severity of side effects (p < 0.0001) and functioning (p = 0.0003) at discharge as well as between residual symptoms and the risk of relapse and chance of remission one year after discharge. Residual symptoms were highly prevalent in remitted schizophrenia inpatients following the suggested definition. Most residual symptoms were persistent baseline symptoms suggesting an ongoing illness severity. Also, the necessity to re-evaluate the consensus criteria questioning the status of remission in these patients is also pointed out.

Background: Aim was to examine depressive symptoms in acutely ill schizophrenia patients on a single symptom basis and to evaluate their relationship with positive, negative and general psychopathological symptoms., Methods: Two hundred and seventy-eight patients suffering from a schizophrenia spectrum disorder were analysed within a naturalistic study by the German Research Network on Schizophrenia. Using the Calgary Depression Scale for Schizophrenia (CDSS) depressive symptoms were examined and the Positive and Negative Syndrome Scale (PANSS) was applied to assess positive, negative and general symptoms. Correlation and factor analyses were calculated to detect the underlying structure and relationship of the patient's symptoms., Results: The most prevalent depressive symptoms identified were depressed mood (80%), observed depression (62%) and hopelessness (54%). Thirty-nine percent of the patients suffered from depressive symptoms when applying the recommended cut-off of a CDSS total score of >6 points at admission. Negligible correlations were found between depressive and positive symptoms as well as most PANSS negative and global symptoms despite items on depression, guilt and social withdrawal. The factor analysis revealed that the factor loading with the PANSS negative items accounted for most of the data variance followed by a factor with positive symptoms and three depression-associated factors., Limitations: The naturalistic study design does not allow a sufficient control of study results for the effect of different pharmacological treatments possibly influencing the appearance of depressive symptoms., Conclusion: Results suggest that depressive symptoms measured with the CDSS are a discrete symptom domain with only partial overlap with positive or negative symptoms., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objective: Facial affect recognition, a basic building block of social cognition, is often impaired in schizophrenia. Poor facial affect recognition is closely related to poor functional outcome; however, neither social cognitive impairments nor functional outcome are sufficiently improved by antipsychotic drug treatment alone. Adjunctive repetitive transcranial magnetic stimulation (rTMS) has been shown to enhance cognitive functioning in both healthy individuals and in people with neuropsychiatric disorders and to ameliorate clinical symptoms in psychiatric disorders, but its effects on social cognitive impairments in schizophrenia have not yet been studied. Therefore, we evaluated the effects of sham-controlled rTMS on facial affect recognition in patients with chronic schizophrenia., Method: Inpatients (N = 36) on stable antipsychotic treatment were randomly assigned to double-blind high-frequency (10 Hz) rTMS or sham stimulation for a total of ten sessions over two weeks. In the verum group, each session consisted of 10 000 stimuli (20 trains of 5 s) applied over the left dorsolateral prefrontal cortex at 110% of motor threshold. Facial affect recognition was assessed before (T0) and after (T1) the ten sessions., Results: Facial affect recognition improved significantly more after rTMS (accuracy change: mean = 8.9%, SD = 6.0%) than after sham stimulation (mean = 1.6%, SD = 3.5; Cohen's d = 1.45). There was no correlation with clinical improvement., Conclusion: Our results indicate that prefrontal 10 Hz rTMS stimulation may help to ameliorate impaired facial affect recognition in schizophrenia., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The diagnosis of schizophrenia includes "positive" and "negative" symptoms. These titles were developed to respectively reflect if the symptoms are additions to normal experiences, such as delusions and hallucinations, or if they refer to the absence or the loss of normal emotional function or behavior. This paper describes the history of the negative symptom concept, from its origins up to the considerations for the DSM-5, including the steps that produced the current conceptualizations. The DSM-5 only includes deficits in emotional expression and avolition as negative symptoms, which can be assessed from interview information. Factor analyses show they encompass most other negative symptom items. In addition to using these negative symptoms in a categorical manner to make a diagnosis, the DSM-5 has quantitative severity ratings of the negative symptoms, along with ratings of delusions, cognitive symptoms, motor symptoms, disorganization, depression and mania. With this approach, the different symptom domains, including negative symptoms, can be measured and tracked over time. Another change in the DSM-5 is the dropping of the schizophrenia subtypes that have been included in earlier volumes, as they were not useful in treatment decisions or prognosis. An intended outcome of these changes in DSM-5 is for clinicians to directly treat the individual psychopathological domains of the disorder for optimizing individual outcomes. Finally, this paper includes descriptions of the negative symptom items from over a dozen different scales., (© 2013 Published by Elsevier B.V. and ECNP.)

Objective: Despite the availability of effective long-term treatment strategies in schizophrenia, relapse is still common. Relapse prevention is one of the major treatment objectives, because relapse represents burden and costs for patients, their environment, and society and seems to increase illness progression at the biological level. Valid predictors for relapse are urgently needed to enable more individualized recommendations and treatment decisions to be made., Methods: Mainly recent evidence regarding predictors and early warning signs of relapse in schizophrenia was reviewed. In addition, data from the first-episode (long-term) study (FES; Gaebel et al., 2007, 2011) performed within the German Research Network on Schizophrenia were analyzed., Results: On the basis of FES data, premorbid adjustment, residual symptoms and some side effects are significant predictors. Although a broad spectrum of potential parameters has been investigated in several other studies, only a few and rather general valid predictors were identified consistently. Data of the FES also indicated that predictive power could be enhanced by considering interacting conjunctions, as suggested by the Vulnerability-Stress-Coping model. Prospective studies, however, are rare. In addition, prodromal symptoms as course-related characteristics likewise investigated in the FES add substantially to early recognition of relapse and may serve as early warning signs, but prognosis nevertheless remains a challenge., Conclusions: Comprehensive and well-designed studies are needed to identify and confirm valid predictors for relapse in schizophrenia. In this respect, broadly accepted and specifically defined criteria for relapse would greatly facilitate comparison of results across studies., (© 2013 Elsevier B.V. All rights reserved.)

Despite advances in the treatment of schizophrenia over the past half-century, the illness is frequently associated with a poor outcome. This is principally related to the late identification and intervention in the course of the illness by which time patients have experienced a substantial amount of socio-occupational decline that can be difficult to reverse. The emphasis has therefore shifted to defining psychosis-risk syndromes and evaluating treatments that can prevent transition to psychosis in these ultra-high risk groups. To consider the appropriateness of adding psychosis risk syndrome to our diagnostic nomenclature, the psychotic disorders work group extensively reviewed all available data, consulted a range of experts, and carefully considered the variety of expert and public comments on the topic. It was clear that reliable methods were available to define a syndrome characterized by sub-threshold psychotic symptoms (in severity or duration) and which was associated with a very significant increase in the risk of development of a full-fledged psychotic disorder (schizophrenia spectrum, psychotic mood disorder, and other psychotic disorders) within the next year. At the same time, the majority of individuals with "attenuated psychotic symptoms" had one or more other current psychiatric comorbid conditions (usually mood or anxiety disorders, substance use disorder; Fusar-Poli 2012) and exhibited a range of psychiatric outcomes other than conversion to psychosis (significant proportions either fully recover or develop some other psychiatric disorder, with a minority developing a psychotic disorder). Although the reliability of the diagnosis is well established in academic and research settings, it was found to be less so in community and other clinical settings. Furthermore, the nosological relationship of attenuated psychosis syndrome (APS) to schizotypal personality disorder and other psychiatric conditions was unclear. Further study will hopefully resolve these questions. The work group decided to recommend the inclusion of attenuated psychosis syndrome as a category in the appendix (Section 3) of DSM-5 as a condition for further study., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Unlabelled: Studies and meta-analyses investigating the influence of substance use disorder (SUD) (substance abuse or dependence) on psychopathology and neurocognitive function in schizophrenia patients have revealed controversial results. Most studies did only have small samples and did not focus exclusively on first-episode schizophrenia patients., Method: In a post-hoc analysis of the European First Episode Schizophrenia Trial (EUFEST) psychopathology and cognitive performances of patients with (FE-SUD, N=119, consisting of N=88 patients with persisting SUD at baseline and N=31 patients with previous SUD) and without SUD (FE-non-SUD, N=204) were compared at baseline and 6 months follow-up. Neurocognitive assessment included the Rey Auditory Verbal Learning Test (RAVLT); Trail Making Tests A and B (TMT), Purdue Pegboard and Digit-Symbol Coding., Results: In total 31.1% of patients reported SUD, and 22.2% of patients used cannabis. There were no significant differences between patients with and without SUD concerning PANSS scores, extrapyramidal motor symptoms or neurocognitive measures except better performance in psychomotor speed (TMT-A, p=0.033, Cohen's d=0.26) in patients with SUD at 6 months follow-up. Interestingly, SUD patients with ongoing substance use at follow-up showed elevated positive symptoms (PANSS positive score, p=0.008, Cohen's d=0.84) compared to those who abstained. PANSS scores at baseline were increased in patients with an onset of SUD before the age of 16 years. In addition we found a correlation between longer duration of cannabis use and higher cognitive performance as well as reduced symptom improvement and more extrapyramidal motor symptoms in patients with higher frequency of cannabis consumption., Conclusions: FE-SUD and FE-non-SUD show similar psychopathology and neuropsychological performances at baseline and during the first 6 months of antipsychotic treatment., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Against the background of the growing evidence that the patient's functioning significantly influences the course and outcome of schizophrenia, the aims of this analysis were to examine what proportion of patients achieve functional outcome criteria after 1 year, and to identify clinical and sociodemographic predictive factors for functional remission. Patients with the diagnosis of schizophrenia who were treated as inpatients at the beginning of the study were examined within a naturalistic follow-up trial. The present study reports on the time frame from admission to discharge of an inpatient treatment period and the 1-year follow-up assessment. The Global Assessment of Functioning (GAF) Scale and Social and Occupational Functioning Assessment Scale (SOFAS) were evaluated with respect to functional outcome, whereas Positive and Negative Syndrome Scale (PANSS) scores were rated as psychopathological outcome measures. Functional remission thresholds were defined according to a GAF score of ≥61 points and a SOFAS score ≥61 points. Symptomatic remission criteria were applied according to the remission criteria of the Schizophrenia Working Group. The Strauss-Carpenter Prognostic Scale (SCPS), the Phillips Premorbid Adjustment Scale, medical history, sociodemographic and psychopathologic parameters were evaluated in order to find valuable predictors for functional remission. One year after discharge from inpatient treatment, 211 out of 474 patients were available for analysis according to both rating scales used to assess functional remission (GAF and SOFAS). Forty-seven percent of patients fulfilled criteria for functional remission (GAF and SOFAS) at discharge and 51% of patients at the 1-year follow-up visit. With regard to symptomatic remission criteria, the corresponding remitter rates were 61% of patients at discharge and 54% at the 1-year follow-up visit. Forty-two percent of patients fulfilled both remission criteria at discharge and 37% at the 1-year follow-up visit. A significant association was found between functional and symptomatic remission at discharge and at the 1-year follow-up visit. The strongest predictors for functional remission at the 1-year follow-up visit were: a higher SCPS total score at admission, a lower number of previous hospitalizations, a status of employment, lower scores in all PANSS subscales at discharge, a better premorbid social adjustment, the occurrence of a first psychotic episode, a younger age, a lower PANSS negative subscore at admission, a status of being an early responder, a shorter duration of inpatient treatment, a later age of onset, and female gender., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: To date, research has identified distinct antipsychotic response trajectories yet focussing on data from randomized-controlled trials (RCTs). Therefore, the heterogeneity of response in "real-world" schizophrenia patients is still unknown., Methods: Antipsychotic response was evaluated in 399 patients suffering from a schizophrenia spectrum disorder within a naturalistic multicenter study of the Competence Network on Schizophrenia using latent class regression. Baseline and illness-related variables were compared between the different trajectory classes as well as currently proposed outcome definitions (early improvement, response, remission) using univariate tests. In order to predict the trajectory group membership classification and regression tree analysis were furthermore performed., Results: Five distinct trajectories of antipsychotic response were identified: Class 1 (15%) showing an early and considerable improvement, Class 2 (14%) incorporating patients with the greatest response to treatment, Class 3 (34%) again showing an early improvement to treatment yet with a slightly lower degree of improvement, Class 4 (22%) featuring patients gradually responding to treatment, and Class 5 (15%) with the poorest antipsychotic response. Fewer depressive symptoms at admission, better functioning, a shorter duration of illness and less previous hospitalizations were found to be significant predictors of good response. No considerable differences were found comparing the present results to the previous trajectory analyses deriving from RCTs., Conclusion: Our results underline the heterogeneous course of response independent of the study or treatment design suggesting that the diversity in schizophrenia response and outcome is determined primarily by different pathophysiological underpinnings., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Remission and recovery are major outcome goals in schizophrenia yet their predictors have not been studied in detail. Therefore, 186 patients were examined regarding remission and recovery including their potential sociodemographic and clinical predictors 1 year after discharge. Remission was defined according to the consensus remission criteria and recovery following the definition by Liberman et al. (2002). Of the 186 patients 54% achieved remission and 26% recovery at the 1-year follow-up. The remission status at discharge was found to significantly influence remission and recovery at follow-up. A higher SOFAS score (P = 0.0002) as well as a positive attitude towards treatment at discharge (P = 0.0038) were identified to be significant predictors of remission at 1-year follow-up. Having a job (P = <0.0001) and being without pharmacological treatment at follow-up (P = 0.0113) were found to be significantly predictive of recovery. Our results underline the need to implement more specific treatment strategies to improve long-term outcome.

Objective: To evaluate depressive symptoms regarding their association with the acute outcome in first-episode schizophrenia comparing risperidone and haloperidol., Method: A total of 274 patients were analysed within a double-blind randomized controlled trial and treated with risperidone or haloperidol. The patients were grouped according to their baseline HAMD-21 total score in a "depressed" (HAMD-21 ≥16) or "non-depressed" (HAMD-21 <16) patient subgroup. PANSS, HAMD-21, GAF, SOFAS and AIMS ratings were performed. Early response was defined as an initial 20% reduction of the PANSS total score from admission to week 2, response as an at least 50% reduction of the PANSS total score from admission to discharge and remission according to the consensus criteria., Results: A total of 124 patients were classified as depressive at baseline with 22 patients still being depressive at discharge. The depressed and non-depressed patients did not significantly differ regarding the treatment with risperidone and haloperidol (P = 0.2270). The depressive patients suffered from significantly more suicidal tendencies (P = 0.0165), had significantly less insight into their illness (P = 0.0152) and featured significantly worse functioning (P = 0.0066). Patients with depressive symptoms achieved remission significantly less often than non-depressed patients., Conclusion: The importance of a specific and adequate treatment of depressive symptoms is highlighted.

Objective: Relapse and its predictors were examined among patients with schizophrenia in the year after hospital discharge., Methods: The sample included 200 patients with schizophrenia participating in a German multicenter study. Relapse was defined as a worsening of psychopathological symptoms or rehospitalization in the year after hospital discharge. Predictors examined were variables related to course of illness and to response and remission at discharge., Results: Fifty-two percent of participants had a relapse. Patients whose symptoms were not in remission at discharge were more likely to have a relapse, as were those who had more severe symptoms and more side effects at discharge. Those who experienced a relapse were less likely to be taking a second-generation antipsychotic at discharge, less likely to have a positive attitude toward treatment adherence, and less likely to be employed., Conclusions: The high rate of relapse among patients with schizophrenia highlights the need to improve current treatment strategies.

Background: Young people with self-experienced cognitive thought and perception deficits (basic symptoms) may present with an early initial prodromal state (EIPS) of psychosis in which most of the disability and neurobiological deficits of schizophrenia have not yet occurred., Aims: To investigate the effects of an integrated psychological intervention (IPI), combining individual cognitive-behavioural therapy, group skills training, cognitive remediation and multifamily psychoeducation, on the prevention of psychosis in the EIPS., Method: A randomised controlled, multicentre, parallel group trial of 12 months of IPI v. supportive counselling (trial registration number: NCT00204087). Primary outcome was progression to psychosis at 12- and 24-month follow-up., Results: A total of 128 help-seeking out-patients in an EIPS were randomised. Integrated psychological intervention was superior to supportive counselling in preventing progression to psychosis at 12-month follow-up (3.2% v. 16.9%; P = 0.008) and at 24-month follow-up (6.3% v. 20.0%; P = 0.019)., Conclusions: Integrated psychological intervention appears effective in delaying the onset of psychosis over a 24-month time period in people in an EIPS.

In August 2002 the Japanese Society of Psychiatry and Neurology decided to rename the Japanese expression for schizophrenia from Sêshin Bunretsu Byô to Tôgô Shicchô Shô. Currently the psychiatric classification systems ICD-10 and DSM-IV are under revision. Against this background the Japanese process of renaming a psychiatric disorder is of high interest as far as the clinical, social and cultural implications of the new name are concerned.The authors give an overview of the Japanese process of renaming schizophrenia. Its background and realization are explained and the expectations of Japanese physicians, patients and their families related to the new name are analysed. Furthermore, its effects are evaluated. The aim of the paper is to clarify in how far the Japanese example may serve as a model for evaluating the possible implications that a renaming or nosological redefinition of schizophrenia might have in the course of the revision process of ICD 10 and DSM IV.

Integrative models of the etiopathogesnesis of psychotic disorders are needed since a wealth of information from such diverse fields as neurobiology, psychology, and the social sciences is currently changing the concepts of mental disorders. Several approaches to integrate these streams of information into coherent concepts of psychosis are feasible and will need to be assessed in future experimental studies. Common to these concepts are the notion of psychotic disorders as brain disorders and a polythetic approach in that it is increasingly realized that a multitude of interindividually partially different pathogenetic factors interact in individual persons in a complex fashion resulting in the clinical symptoms of psychosis.

Impairments in neuropsychological functioning have been described in subjects clinically at high risk for psychosis, but the specific cognitive deficits in different clinical high-risk groups remain to be elucidated. The German Research Network on Schizophrenia employs a heuristic 2-stage model: a putatively late prodromal state (LPS), characterized by the onset of attenuated positive or brief psychotic symptoms, and an early prodromal state (EPS), mainly characterized by the presence of basic symptoms, which are predictive for psychosis within the next 10 years. A total of 205 subjects met the criteria for either an EPS or an LPS of psychosis and were assessed with a comprehensive neuropsychological test battery. Neurocognitive profiles of high-risk groups were compared with data of 87 healthy controls comparable with regard to gender, age, and premorbid verbal IQ. Patients in the LPS were impaired in all neurocognitive domains (memory/learning, executive control/processing speed, and working memory) examined, with memory being the worst. Deficits were less pronounced in patients in the EPS, with a specific deficit in the executive control/processing speed domain. Consistent with a progressive neurodevelopmental disorder, some cognitive abilities were already impaired in patients in the EPS, followed by further deterioration in the LPS. Specifically, deficits in executive control functioning were related to the presence of basic symptoms, indicating a vulnerability for psychosis. Memory deficits were associated with the onset of psychotic symptoms indicating further disease progression in the trajectory to psychosis and, thus, may be useful in predicting psychosis and targeting early intervention.

Background: Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being., Method: The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome., Results: Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission., Conclusions: Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Objective: To examine depressive symptoms, their course during treatment, and influence on outcome., Method: Weekly Calgary Depression Scale for Schizophrenia ratings were performed in 249 inpatients with schizophrenia. Early response was defined as a 20% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia from admission to week 2, response as a 50% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) from admission to discharge and remission according to the consensus criteria., Results: Thirty six per cent of the patients were depressed at admission, with 23% of them still being depressed at discharge. Depressed patients scored significantly higher on the PANSS negative and general psychopathology subscore, featured more impairments in subjective well-being (P < 0.0001) and functioning (P < 0.0001). They suffered from more suicidality (P = 0.0021), and had greater insight into their illness (P = 0.0105). No significant differences were found regarding early response, response, and remission., Conclusion: Patients with depressive symptoms should be monitored closely, given the burden of negative symptoms, their impairments in well-being and functioning and the threat of suicidality., (© 2010 John Wiley & Sons A/S.)

Objective: After acute treatment of the first illness episode in schizophrenia, antipsychotic maintenance treatment is recommended for at least 1 year. Evidence for the optimal subsequent treatment is still scarce. Targeted intermittent treatment was found to be less effective than continuous treatment at preventing relapse in multiple episode patients; however, a post hoc analysis of our own data from a previous study suggested comparable efficacy of the 2 treatment approaches in first-episode patients. The current study was therefore designed to compare prospectively the relapse preventive efficacy of further maintenance treatment and targeted intermittent treatment in patients with ICD-10-diagnosed first-episode schizophrenia., Method: A randomized controlled trial was conducted within the German Research Network on Schizophrenia. Entry screening took place between November 2000 and May 2004. After 1 year of antipsychotic maintenance treatment, stable first-episode patients were randomly assigned to 12 months of further maintenance treatment or stepwise drug discontinuation and targeted intermittent treatment. In case of prodromal symptoms of an impending relapse, patients in both groups received early drug intervention, guided by a decision algorithm. The primary outcome measure was relapse (increase in the Positive and Negative Syndrome Scale positive score > 10, Clinical Global Impressions-Change score ≥ 6, and decrease in Global Assessment of Functioning score > 20 between 2 visits)., Results: Of 96 first-episode patients, only 44 were eligible for the assigned treatment (maintenance treatment, n = 23; intermittent treatment, n = 21). The rates of relapse (19% vs 0%; P = .04) and deterioration (up to 57% vs 4%; P < .001) were significantly higher in the intermittent treatment group than in the maintenance treatment group, but quality-of-life scores were comparable. Intermittent treatment patients received a significantly lower amount of antipsychotics (in haloperidol equivalents; P < .001) and tended to show fewer side effects, particularly extrapyramidal side effects., Conclusions: Maintenance treatment is more effective than targeted intermittent treatment in preventing relapse, even in stable first-episode patients after 1 year of maintenance treatment, and should be the preferred treatment option. However, about 50% of patients remain stable at a significantly lower drug dose and show fewer side effects, and a substantial proportion refuse maintenance treatment. Alternative long-term treatment strategies, including targeted intermittent treatment, should therefore be provided in individual cases., Trial Registration: clinicaltrials.gov Identifier: NCT00159120., (© Copyright 2011 Physicians Postgraduate Press, Inc.)

Background: Recently, a role of the transcription factor 4 (TCF4) gene in schizophrenia has been reported in a large genome-wide association study. It has been hypothesized that TCF4 affects normal brain development and TCF4 has been related to different forms of neurodevelopmental disorders. Schizophrenia patients exhibit strong impairments of verbal declarative memory (VDM) functions. Thus, we hypothesized that the disease-associated C allele of the rs9960767 polymorphism of the TCF4 gene led to impaired VDM functioning in schizophrenia patients., Method: The TCF4 variant was genotyped in 401 schizophrenia patients. VDM functioning was measured using the Rey Auditory Verbal Learning Test (RAVLT)., Results: Carriers of the C allele were less impaired in recognition compared to those carrying the AA genotype (13.76 vs. 13.06; p = 0.049). Moreover, a trend toward higher scores in patients with the risk allele was found for delayed recall (10.24 vs. 9.41; p = 0.088). The TCF4 genotype did not influence intelligence or RAVLT immediate recall or total verbal learning., Conclusion: VDM function is influenced by the TCF4 gene in schizophrenia patients. However, the elevated risk for schizophrenia is not conferred by TCF4-mediated VDM impairment., (Copyright © 2011 S. Karger AG, Basel.)

Objectives: To examine quality of life and subjective well-being as predictors of symptomatic treatment outcome., Methods: Biweekly PANSS ratings were performed in 285 inpatients with schizophrenia spectrum disorders within a multicenter trial by the German Research Network on Schizophrenia. Quality of life and subjective well-being were assessed using the Medical Outcomes Study-Short Form 36-Item Health Survey (SF-36), the Subjective Well-being Under Neuroleptic Treatment Scale (SWN-K) and the Adjective Mood Scale (AMS). Response was defined as an initial 20% PANSS total score reduction and remission according to the consensus criteria. Correlation analysis, logistic regression and CART-analysis were performed., Results: In total, 81% of the sample achieved symptom response and 48% symptom remission. The statistical analyses revealed early improvement within the first two treatment weeks in the SWN-K scale to be a significant predictor for symptomatic response. Concerning symptomatic remission the SF-36 and SWN-K baseline scores as well as SWN-K early improvement showed significant predictive value., Conclusions: These results highlight the importance of the patient's self-perception and especially of early improvement of quality of life and subjective well-being for symptomatic treatment outcome.

Sustained attention as measured by the Continuous Performance Test (CPT) has proved a valuable endophenotype for schizophrenia. Recently pharmacological studies suggested a role of the serotonin (5-HT) 3 receptor in schizophrenia. The 5-HT3 receptors are the only ligand-gated ion channels within the 5-HT receptor family. Applying an endophenotype approach, we investigated a potential impact of the genes of the 5-HT3A and 5-HT3B subunits as well as the novel 5-HT3C, 5-HT3D, and 5-HT3E subunits on CPT performance in subjects with schizophrenia. The study included 196 patients with schizophrenia, 113 of their parents, and 205 healthy controls recruited from community registers. Sustained attention was assessed with the Continuous Performance Test-Identical Pairs (CPT-IP). Assessing functional and coding variants of the 5-HT3 receptor subunit genes, we found the GG genotype of the 5-HT3E subunit gene (rs7627615; Thr86Ala) to be associated with better attentional capacities in subjects with schizophrenia and healthy controls. This study provides additional evidence for a role of the serotonergic system and the 5-HT3 receptor in schizophrenia., (2010 Elsevier B.V. and ECNP. All rights reserved.)

Unlabelled: We conducted a randomized, sham-controlled repetitive transcranial magnetic stimulation (rTMS) study in chronic schizophrenia in-patients (n=35) to evaluate the therapeutic efficacy of 10 Hz stimulation. Patients, who were on stable antipsychotic treatment, were randomly assigned to the active or sham condition. In the active rTMS group, ten sessions with a total of 10,000 stimuli were applied over the left dorsolateral prefrontal cortex at 110% of motor threshold. The sham group received corresponding sham stimulation. Clinical improvement was measured by the Clinical Global Impression scale (primary outcome measure), the Global Assessment of Functioning Scale (GAF) and the Positive and Negative Symptom Scale (PANSS; secondary outcome measures). Between-group comparisons revealed no significant differences in clinical outcome variables. Only a subgroup of patients with pronounced negative symptoms developed some clinical improvement as indicated by significant changes in the GAF-scale. Besides there is some evidence for a more favourable clinical outcome within this subgroup after rTMS in the CGI-S and PANSS negative scale, too. In line with earlier investigations, our results suggest a moderate - potentially clinically relevant - treatment effect of prefrontal 10 Hz rTMS stimulation in chronic patients. However, in our study this beneficial effect was restricted to subjects with pronounced negative symptoms., Clinical Trial Registration Information: ClinicalTrial.gov Identifier: NCT00169689, http://www.clinicaltrials.gov., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Effectiveness has become more and more important as a comprehensive outcome measure for (long-term) treatment in schizophrenia. Early predictors to identify patients at a high risk for not succeeding the initiated treatment would be very useful. Discontinuation of the initiated treatment was used as criterion for effectiveness and patients' drug attitude was shown to be predictive for non-adherence or discontinuation of long-term treatment in schizophrenia. Accordingly, the predictive validity of the Drug Attitude Inventory (DAI) for effectiveness should be evaluated. Based on a sub-sample of patients from the EUFEST study for whom DAI assessments were available significant predictors for effectiveness as measured by discontinuation of initiated treatment were identified based on a logistic and a Cox-regression analysis. A Receiver-Operating Characteristic- (ROC-) analysis was conducted for the DAI, prognostic / diagnostic parameters (sensitivity, specificity) were calculated and a cut-off value suggested. In a sample of 228 first-episode patients, the DAI score was the most powerful predictor for effectiveness (p<0.001) besides two other significant predictors (PANSS-positive score and sexual side effects). The ROC-analysis revealed an area under the curve of 0.64 (p<0.001). The suggested cut-off point of about 20 yielded a sensitivity of 70-75% and a specificity of 40-45%. Study results indicate that the Drug Attitude Inventory, filled in by patients early in treatment seems to be a valid predictor for effectiveness as measured by discontinuation of the initiated treatment. DAI scores could also serve as an (differential) indicator for the need of enhanced treatment monitoring. These findings have to be validated in other (first-episode) samples., (2010 Elsevier B.V. and ECNP. All rights reserved.)

Objective: Purpose was to assess suicidality before and at the time of admission in patients with schizophrenia and compare outcome differences., Method: Biweekly PANSS (Positive and Negative Syndrome Scale), HAMD (Hamilton Depression Rating Scale) and UKU (Udvalg for Klinske Undersogelser Side Effect Rating Scale) ratings were evaluated in 339 in-patients with schizophrenic spectrum disorders. Response was defined as an initial 20% PANSS total score reduction at discharge, remission was defined according to the proposed consensus criteria by the Remission in Schizophrenia Working Group., Results: Suicidal patients (22%) scored significantly higher on the PANSS negative subscore, PANSS insight item and HAMD total score at admission and at discharge. They developed significantly more side effects. No differences were found concerning response and remission between the two patient subgroups., Conclusion: Despite receiving significantly more antidepressants the suicidal patients suffered from significantly more depressive symptoms up to discharge, yet without differing regarding response and remission.

This study investigated gender differences in facial expression as a reaction to various emotional stimuli in two groups of schizophrenia patients. The first group consisted of hospitalized patients (22 men and 13 women) who were tested at three points in time. The second group consisted of outpatients (21 men, 8 women) who were tested at two points in time. In addition, the facial behaviour of two control groups was investigated (17 men and 12 women; 18 men and 14 women, respectively). Facial activity was videotaped, whilst participants watched emotion-eliciting video clips and participated in an emotion-inducing interview, and measured using the Facial Action Coding System. In agreement with our expectations, schizophrenia patients showed significantly less facial activity overall than healthy control participants. Contrary to expectations, however, female patients did not display more facial activity compared to male schizophrenia patients. This finding contrasts with those of healthy participants in previous studies where women tended to show more facial activity than men. It was further expected that in non-psychotic patients (i.e. outpatients), gender differences would be more clearly apparent and female schizophrenia patients would show considerably more facial activity than male patients, with findings more or less comparable to the gender differences found in healthy controls. However, no significant interaction was found between patient group (in- vs. outpatients) and gender. The different explanations for these findings are considered in this study.

Background: Purpose of the present study was to assess the attitude towards adherence at discharge and to verify its predictability using anamnestic and sociodemographic variables, factors influencing clinical treatment as well as the medical treatment applied., Methods: Attitude towards adherence was evaluated in 369 inpatients with schizophrenic spectrum disorders within a naturalistic multicenter trial using the Compliance Rating Scale (CRS) by Kemp. Biweekly ratings of the PANSS, UKU and the Subjective Well-being under Neuroleptic Treatment Scale (SWN-K) were applied. Logistic regression and CART analyses were used to determine significant predictor variables for the attitude towards adherence at discharge., Results: Sixty-seven percent of the patients were rated to have an attitude of active participation and moderate participation (=positive attitude towards adherence) and 33% of the patients to have an attitude of passive acceptance, occasional or permanent reluctance towards treatment as well as refusing treatment (=negative attitude towards adherence). A significant correlation was found between patients with a positive attitude towards adherence and course of all PANSS subscales. Statistical analyses revealed a reduction in PANSS general psychopathology subscore, employment status, greater illness insight and treatment with atypical antipsychotics to be significantly predictive for a positive attitude towards adherence at discharge., Conclusions: The importance of an adequate antipsychotic treatment as a precondition for a favourable adherence attitude and the need to incorporate adherence-focused psychotherapy and psychoeducation into daily clinical practice are highlighted.

Background: To assess criteria and to identify predictive factors for functional outcome. The criteria should cover all domains proposed by the Remission in Schizophrenia Working Group., Method: PANSS ratings were used to evaluate the symptomatic treatment outcome of 262 inpatients with schizophrenia spectrum disorders within a naturalistic multicenter trial. Functional remission was defined as a GAF score >61 (Global Assessment of Functioning Scale), SOFAS score >61 (Social and Occupational Functioning Scale) and a SF-36 mental health subscore >40 (Medical Outcomes Study-Short Form Health Survey). Multivariate logistic regression and CART analyses were used to determine valid clinical and sociodemographic predictors., Results: In total, 52 patients (20%) fulfilled the criteria for functional remission, 125 patients (48%) achieved symptomatic resolution and when criteria for functional remission and symptomatic resolution were combined 33 patients (13%) achieved complete remission. Younger age, employment, a shorter duration of illness, a shorter length of current episode, less suicidality, and a lower PANSS negative and global subscore at admission were predictive of functional remission. The regression model showed a predictive value of more than 80%., Conclusions: A significant association was found between functional remission and symptomatic resolution, indicating reasonable validity of the proposed definition for functional outcome. The revealed predictors for functional treatment outcome emphasize the need for psychosocial and vocational rehabilitation in schizophrenic patients.

Objective: Standardized consensus criteria for remission in schizophrenia were recently proposed. The present study applied the symptom-severity component of these criteria to a sample of inpatients in order to determine the rates of remission during inpatient treatment and to explore predictors of remission., Method: A total of 288 inpatients from a multi-centre follow-up programme who fulfilled ICD-10 criteria for schizophrenia were included in the present analyses. PANSS ratings at admission and at discharge from hospitalization were used to examine remission status. Clinical and sociodemographic variables at admission were tested for their ability to predict remission at discharge., Results: In total, 55% of the sample achieved symptom remission during inpatient treatment; 84% percent showed remission with respect to 'reality distortion', 85% with respect to 'disorganization' and only 65% with respect to 'negative symptoms'. Logistic regression analysis revealed that the global functioning (GAF) in the year before admission, the total score of the Strauss-Carpenter Prognostic Scale and the PANSS negative subscore at admission were predictive for symptom remission. The regression model showed a predictive value of about 70% and explained 36% of the observed variance., Conclusion: The results highlight the impact of negative symptoms for the course and treatment response of schizophrenic illness.

Social cognition has become a high priority area for the study of schizophrenia. However, despite developments in this area, progress remains limited by inconsistent terminology and differences in the way social cognition is measured. To address these obstacles, a consensus-building meeting on social cognition in schizophrenia was held at the National Institute of Mental Health in March 2006. Agreement was reached on several points, including definitions of terms, the significance of social cognition for schizophrenia research, and suggestions for future research directions. The importance of translational interdisciplinary research teams was emphasized. The current article presents a summary of these discussions.

The aim of the present study was to examine the relevance of depressive symptoms during an acute schizophrenic episode for the prediction of treatment response. Two hundred inpatients who fulfilled DSM-IV criteria for schizophrenia or schizophreniform disorders were assessed at hospital admission and after 6 weeks of inpatient treatment using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Rating Scale for Depression (HAM-D). Depressive symptoms showed positive correlations with both positive and negative symptoms at admission and after 6 weeks, and decreased during 6 weeks of treatment. Pronounced depressive symptoms (HAM-D score> or =16) were found in 28% of the sample at admission and in 9% after 6 weeks of treatment. Depressive symptoms at admission predicted a greater improvement of positive and negative symptoms over 6 weeks of treatment, but also more, rather than fewer remaining symptoms after 6 weeks. Both results, however, lost statistical significance when analyses were controlled for the influence of positive and negative symptoms at admission. Therefore, the hypothesis that depressive symptoms are predictive of a favorable treatment response was not supported by the present study.

Objectives: In 2001, the World Psychiatric Association's global antistigma-program "Fighting stigma and discrimination because of schizophrenia--Open the Doors" was initiated in Germany. Several measures to tackle the stigma in certain target populations have been proven successful, but the effectiveness of the program on the general population level has not yet been examined., Methods: Before the start of a number of antistigma interventions in 2001, a professional survey institute was commissioned to conduct a representative telephone survey in 6 German cities (N=7225). The cities were chosen with respect to the implementation of antistigma programs (Düsseldorf, Munich), awareness programs (Bonn, Cologne; with the aim to enhance early recognition of schizophrenia), and none of the programs (Berlin, Essen). A panel design follow-up survey (N=4622) was conducted in 2004. Stereotypes, beliefs and attitudes about schizophrenia and social distance--i.e. the distance between different groups of society--towards people with schizophrenia, and the knowledge of antistigma projects were assessed., Results: Overall, social distance decreased significantly between 2001 and 2004 (p=0.001). At the city level, this effect was only significant in those cities where antistigma projects were implemented (p<0.001), although the observed attitude changes were small. In cities with antistigma projects, social distance primarily decreased in the social distance subscale "transient social relations" (p<0.001), but not in the subscale "closer social relations". Both subcales did not change significantly in cities without antistigma projects., Discussion: The present study provides limited evidence for the efficacy of antistigma interventions on the population level in Germany. Further research is needed to separate direct effects of antistigma interventions from more general, indirect influences on social distance.

Objective: Second-generation antipsychotics (SGAs) have proven superior to first-generation antipsychotics regarding relapse prevention, mainly in multiple-episode patients. Practice guidelines recommend SGAs as first-line treatment particularly in first-episode patients, although evidence for this group is still limited. Accordingly, the hypothesis of whether 1-year relapse rate in first-episode schizophrenia under maintenance treatment with risperidone is lower compared to haloperidol in low dose was tested., Method: Between November 2000 and May 2004, 1372 patients had been screened for eligibility in the inpatient facilities of 13 German psychiatric university hospitals. 159 remitted patients were enrolled after treatment of an acute first episode of schizophrenia according to ICD-10 F20 criteria. In the randomized controlled trial, double-blind antipsychotic treatment with risperidone or haloperidol was maintained in a targeted dose of 2 to 4 mg/day for 1 year. 151 patients were eligible for analysis. For 127 patients, this was a continuation trial after 8 weeks of randomized, double-blind, acute treatment with the same drugs; 24 patients were additionally randomly assigned after open acute treatment., Results: With both antipsychotics (risperidone, N = 77; haloperidol, N = 74), no relapse evolved. Additionally, according to 2 post hoc defined measures of "marked clinical deterioration," significant differences occurred neither in the 2 respective deterioration rates (risperidone = 9%/23%; haloperidol = 8%/22%) nor in time until deterioration. Both antipsychotics were equally effective regarding significant symptom reduction and improvement in quality of life. Extrapyramidal symptoms were slightly higher with haloperidol. The overall dropout rate of 68%, however, was not significantly different between the 2 drug groups., Conclusion: Against the background of an overall favorable outcome, the hypothesized difference between risperidone and low-dose haloperidol regarding relapse prevention could not be supported for this sample of patients with first-episode schizophrenia. Possible design-related reasons for this finding are discussed. With regard to the high dropout rate, special programs are needed to keep schizophrenia patients who are in their early acute and postacute illness course in effective and safe treatment., Clinical Trials Registration: ClinicalTrials.gov identifier: NCT00159081.

After recovering from a first episode in schizophrenia, relapse prevention is a major objective and long-term treatment is indicated. Due to empirical findings regarding relapse preventive efficacy of antipsychotics, guidelines recommend maintenance neuroleptic treatment, which however is not feasible for all patients. Both under maintenance treatment and drug withdrawal, doctors and patients try to anticipate a reexacerbation by means of early signs of relapse in order to intervene as early as possible. Prodromal symptoms are supposed to be such early indicators, although empirical evidence is not uniform. In order to prepare a new research program, data from an earlier study were reanalyzed to examine the relapse predictive validity of prodromal symptoms. 339 outpatients observed prospectively for 2 years under different long-term treatment strategies were included in this analysis resulting in a total amount of 5861 observations/visits. Several prognostic parameters were computed regarding relationship between clinical state (relapse yes/no) and the occurrence of prodromal symptoms the immediate visit before. As to the results, none of the 22 single prodromal symptoms exceeded a sensitivity of 40%, with specificities ranging from 69% to 95%. An overall prodrome score led to a sensitivity of 72%, however specificity declined to 38%. The performed logistic regression analyses including other potential predictors (psychopathology, clinical change etc.) yielded other relevant 'early signs'. It is concluded that the relapse predictive validity of prodromal symptoms has to be enhanced e.g. by supplement of other clinical parameters with predictive potential or by closer monitoring.

Background: In several German cities various programmes and initiatives have been conducted during recent years aimed at reducing the stigma attached to mental illness, especially schizophrenia. So far only single interventions in specific target groups have been evaluated but not their effectiveness in the general population., Methods: Two representative telephone surveys with repeated measurements were conducted in six German cities (n 7,225/4,622). Social distance towards people with schizophrenia and knowledge of antistigma projects were assessed., Results: Between 2001 and 2004 the social distance toward persons with schizophrenia decreased in the general population. Persons familiar with antistigma projects or who lived in cities with such projects showed lower social distance., Conclusions: For the first time evidence has been found that antistigma interventions are successful in reducing the stigma attached to schizophrenia in the general population.

Objective: The aim was to investigate the hypothesis that patients with first episode schizophrenic disorders have a more favorable treatment response than those with multiple episodes., Method: A total of 400 inpatients from an ongoing multi-centre, follow-up program who fulfilled ICD-10 criteria for schizophrenic disorders (F2) were assessed at admission to and discharge from hospital using the Positive and Negative Syndrome Scale (PANSS)., Results: At admission, first episode patients (n = 121) showed higher levels of positive symptoms (PANSS positive subscore) and lower ones of negative symptoms (PANSS negative subscore) than multiple episode patients (n = 279), whereas the global disease severity (PANSS total score) was comparable. Analyses of covariance revealed that treatment response (adjusted symptom levels at discharge) was more favorable in first-episode patients, with respect to both positive and negative symptoms., Conclusion: The results are compatible with the hypothesis that treatment response becomes less favorable during the course of schizophrenic illness. This finding might be associated with progressive neurobiological alterations.

Public relations activities of the German Research Network on Schizophrenia (GRNS) have shown that there is a demand for more information about schizophrenia disorder. This confirms international research findings that relatives of schizophrenia patients are particularly in need of information and support. In response, the GRNS has maintained a telephone hotline since 2001. The hotline is manned by clinical experts, psychiatrists, or psychologists once a week. The telephone calls are documented in a systematic manner. From 2001 to 2003, 3,909 calls were registered. This volume exceeds the limit of the hotline's resources. The telephone hotline is mainly used by relatives of psychotic patients. Most questions relate to the symptoms of schizophrenia and pharmaceutical treatment. The need for emotional support is also a high motivational factor for dialing the hotline number. The telephone hotline seems to be a worthwhile addition to the already existing crisis telephones and should be maintained even after public funding of the network expires.

Rationale: Short- and long-term compliance to prescribed antipsychotic drugs is of particular concern in regard to medication choice and treatment outcome in the care of psychotic disorders., Objective: We evaluated patient-related and treatment-related factors associated with medication compliance in inpatients with a diagnosis of schizophrenia, schizoaffective disorder, or other psychotic disorder., Methods: Within a naturalistic study in seven psychiatric hospitals, individuals with a psychotic disorder were assessed weekly on mental state, social functioning, side effects, and medication compliance. Logistic regression analyses were computed to assess patient and clinical predictors of medication compliance., Results: We found a significant association between medication compliance and substance abuse (OR 0.52, CI 0.32-0.85), involuntary admission (OR 0.60, CI 0.41-0.89), history of aggressive behavior (OR 0.57, CI 0.38-0.85), and no school graduation (OR 0.59, CI 0.41-0.86). Individuals with pronounced paranoid or negative symptoms were also less compliant in taking their prescribed medication. There was no association between the initial inpatient antipsychotic medication regime and patients' compliance. Individuals who switched from a typical to an atypical antipsychotic drug were more compliant than those with their typical antipsychotic drug maintained. Those with higher medication compliance showed significantly greater improvement of their psychiatric symptoms during the inpatient stay., Conclusion: Patient-related in addition to disease-related factors may strongly influence medication compliance. Besides more compliance with atypicals supposed by the literature, there may be a higher propensity for atypical drugs to be prescribed to those assumed to be more compliant.

Objective: To investigate influencing factors for lay perception of mental illness severity and their effects on the stigma of mental illness., Method: Selective review including attitude surveys assessing social distance towards different diagnostic labels, and attitudes towards treatment professions, treatment strategies, and psychopharmacotherapy., Results: Lays differentiate in their attitudes towards people with mental illness according to the given diagnostic label, the involved treatment professions or institutions, the applied treatment methods, and the perceived psychosocial disability., Conclusion: Beside perceived treatment intensity and diagnostic label, the perception of social disability of mentally ill people accounts for a differentiated stigma. The question arises how anti-stigma-programmes can include the topic of social disability into their messages without risking to strengthen the stigma of mental illness.