What happens with schizophrenia patients after their discharge from hospital? Results on outcome and treatment from a "real-world" 2-year follow-up trial.

Aim of the study was to examine the course of schizophrenia patients within 2 years after discharge. Within a multicenter study of the German Competence Network on Schizophrenia, patients suffering from a schizophrenia spectrum disorder were examined regarding their psychopathological improvement, tolerability, and the treatment regime applied during hospitalization and a 2-year follow-up period. Response, remission, the level of everyday functioning, and relapse were furthermore evaluated during the follow-up period using established definitions for these outcome domains. The psychopharmacological treatment was specifically evaluated in terms of a potential association with relapse. 149 patients were available for analysis, with 65% of the patients being in response, 52% in symptomatic remission, and 64% having a satisfiable everyday functioning 2 years after their discharge from hospital. Despite these favorable outcome rates, 63% of the patients suffered from a relapse within the 2-year follow-up period with 86% of these patients being rehospitalized. Discharge non-responder and non-remitter were twice as likely to relapse during follow-up. A significant decrease of side-effects was observed with negligible rates of extrapyramidal side-effects, sedation, and weight gain during follow-up. Patients receiving treatment with atypical antipsychotics were found to have the lowest risk to relapse (p < 0.0001). The results highlight the natural and unsteady course of schizophrenia in most patients underlining the need to develop more specific treatment strategies ensuring ongoing stability and preventing relapse.

Antisaccade and prosaccade eye movements in individuals clinically at risk for psychosis: comparison with first-episode schizophrenia and prediction of conversion.

Saccadic eye movements are well-described markers of cerebral function and have been widely studied in schizophrenia spectrum populations. However, less is known about saccades in individuals clinically at risk for schizophrenia. Therefore, we studied individuals in an at-risk mental state (ARMS) (N = 160), patients in their first episode of schizophrenia (N = 32) and healthy controls (N = 75). N = 88 ARMS participants showed an early at-risk mental state (E-ARMS), defined by cognitive-perceptive basic symptoms (COPER) or a combination of risk and loss of function, whereas N = 72 were in a late at-risk mental state (L-ARMS), defined by attenuated psychotic symptoms or brief limited intermittent psychotic symptoms. We examined prosaccades, reflecting overt attentional shifts, and antisaccades, measuring inhibitory control, as well as their relationship as an indicator of the interplay of bottom-up and top-down influences. L-ARMS but not E-ARMS participants had increased antisaccade latencies compared to controls. First-episode patients had higher antisaccade error rates compared to E-ARMS participants and controls, and increased latencies compared to all other groups. Prosaccade latencies did not differ between groups. We observed the expected negative correlation between prosaccade latency and antisaccade error rate, indicating that individuals with shorter prosaccade latencies made more antisaccade errors. The magnitude of the association did not differ between groups. No saccadic measure predicted conversion to psychosis within 2 years. These findings confirm the existence of antisaccade impairments in patients with schizophrenia and provide evidence that volitional response generation in the antisaccade task may be affected even before onset of clinically overt psychosis.

Stigma experiences and perceived stigma in patients with first-episode schizophrenia in the course of 1 year after their first in-patient treatment.

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.

[Social Anxiety in individuals with clinical high-risk state for psychosis]. / Soziale Ängste im klinischen Hochrisikostadium für Psychosen.

In recent years an increased comorbidity of schizophrenic disorders with anxiety disorders has been reported. Thus, among patients with a disorder from the schizophrenia spectrum, a general anxiety disorder was found in 38.3 % of patients, with 14.9 % of these with social phobia (SP). Especially social anxiety (SA) is of particular importance because it is often associated with depression and can contribute to psychosocial disabilities in patients with psychosis.Anxiety disorders already seem to occur prior to the first psychotic manifestation in the clinical high-risk state (CHR). Therefore, the questions arise as to whether this comorbidity is also dominated by SP in this patient group and, if so, what its consequences are on early detection and prevention of psychotic disorders. To clarify these questions, the present paper provides a systematic review of all published studies on social anxiety (SA) in the CHR.A total of 124 studies were included comprising 1702 CHR individuals, 445 healthy controls, 67 relatives / siblings of patients with psychotic disorders and 95 patients with a psychosis. In the most meaningful study, anxiety disorders were generally highly significant in CHR individuals (51 %) compared to control subjects from the normal population (4 %). Among those with anxiety disorders, 14.4 % suffered from SP compared to 0.36 % in normal controls and thus SP was almost as frequent as the prevalence of this type of anxiety disorders in the schizophrenic spectrum (14.9 %). Also, the degree of SA in CHR individuals (SIAS score = 34.4, SD = 6.11) (SIAS-Score = 22.1, SD = 8.7), measured with the Social Interaction and Anxiety Scale (SIAS) in 9 studies, was almost as high as in psychotic patients (SIAS score = 35.0, SD = 9.56) and healthy controls (SIAS score = 14.,6; SD = 7,28). This degree of SA was also related to the attenuated psychotic symptomatology of the CHR individuals. However, the only study investigating the relationship between SA and a possible transition to a first psychotic manifestation did not reveal any predictive power. The feared psychosocial loss of function, which is already present in CHR, seems to be connected not only to the strong SA, but also to the similarly frequent comorbid depressive disorders.Moreover, one study has already provided some evidence that it is promising to address the SA as well as functional impairments in the CHR through newly developed specialized cognitive behavioural therapies.

Course of clinical high-risk states for psychosis beyond conversion.

BACKGROUND: The main focus of research on clinical high-risk states for psychosis (CHR) has been the development of algorithms to predict psychosis. Consequently, other outcomes have been neglected, and little is known about the long-term diagnostic and functional outcome among those not converting to psychosis. METHODS: In a naturalistic study, incidence, persistence, and remission rates of CHR states according to symptomatic ultra-high risk or cognitive disturbances criteria were investigated in 160 of 246 outpatients of an early detection of psychoses service (21.1% CHR negative and 78.9% CHR positive at baseline) who had not converted to psychosis within follow-up (median 53.7 months, range 13.9-123.7 months). RESULTS: Remission rate of CHR status was 43.3% of all 194 CHR-positive cases, including converters, or 72.4% if only the 116 non-converters were considered, persistence rate was 27.6%, and new occurrence rate in initially CHR-negative patients was 9.1%. At follow-up, 54.5% of the non-converters met criteria of at least one Axis-I diagnosis, mainly affective and anxiety disorders, and had functional problems. The severity of risk at baseline was not associated with a higher presence of Axis-I diagnosis at follow-up. CONCLUSIONS: During follow-up, CHR symptoms remitted in one-third of initially CHR-positive patients, while almost 10% met CHR criteria newly in CHR-negative adults presenting at early detection services. The presence of CHR criteria seems to maintain the risk for lower functioning and mental disorders, particularly for affective disorders. Thus, therapeutic efforts targeting CHR patients should also focus on the current mental disorders as well as social and role functions to improve the long-term outcome.

Validity of remission and recovery criteria for schizophrenia and major depression: comparison of the results of two one-year follow-up naturalistic studies.

The objective of the present study was the application and comparison of common remission and recovery criteria between patients with the diagnosis of schizophrenia and major depressive disorder (MDD) under inclusion of other outcome parameters. Patients with schizophrenia and MDD who were treated as inpatients at the beginning of the study were examined within two naturalistic follow-up trials from admission to discharge of an inpatient treatment period and the one-year follow-up assessment. PANSS criteria of the Remission in Schizophrenia Working Group (RSWG) for schizophrenia and HAMD criteria of the ACNP Task Force in MDD for depressive patients as well as the Clinical Global Impression-Severity Scale (CGI-S) were applied as symptomatic outcome measures additionally to functional outcome parameters. Data of 153 schizophrenia patients and 231 patients with a MDD episode have been included in the analysis. More depressive than schizophrenia patients reached a threshold score of ≤3 on the CGI-S, indicating symptomatic remission at discharge and at the one-year follow-up. In contrast similar proportions of patients reaching symptomatic remission at discharge from inpatient treatment and at the one-year follow-up in the schizophrenia and in the MDD group were found when disease-related consensus criteria (RSWG vs. ACNP Task Force) were used. Functional remission and recovery rates were significantly lower in schizophrenia than in depressive patients at the one-year follow-up visit. Common outcome criteria for remission and recovery in schizophrenia and major depression were not directly comparable. However, our results indicated a significantly poorer outcome in schizophrenia than in depressive patients according to terms of remission and recovery.

Add-on Antidepressants in the Naturalistic Treatment of Schizophrenia Spectrum Disorder - When, Who, and How?

The aim of this study was to evaluate antidepressant add-on treatment within the acute treatment of schizophrenia spectrum disorder patients. Antidepressant add-on was evaluated in 365 patients within a naturalistic multicenter study. Patients with/without antidepressant add-on were compared regarding clinical and treatment-related variables, response and remission, and remission of depressive and negative symptoms. The efficacy of antidepressant add-on treatment was furthermore analyzed applying marginal structure models. Twenty-three percent of the patients received antidepressant add-on for a mean duration of 50.28 (33.42) days. Patients with the diagnosis of a schizoaffective disorder, multiple illness episodes, and a longer duration of their illness as well as those with significantly fewer baseline positive symptoms, more negative and depressive symptoms, more side effects, and less subjective well-being were augmented with antidepressants. At discharge no significant effect of antidepressant add-on treatment was observed in terms of a 25% improvement (p=0.2623), a 50% improvement (p=0.3946), remission (p=0.0552), or remission of depressive (p=0.6336) and negative symptoms (p=0.8756). Also, when analyzing marginal structure models considering the diagnostic subgroups, no significant effect was found. Add-on with antidepressants is common. A final recommendation in terms of this strategy's efficacy cannot be given.

Restricted attention to social cues in schizophrenia patients.

Deficits of psychosocial functioning are a robust finding in schizophrenia. Research on social cognition may open a new avenue for the development of effective interventions. As a correlate of social perceptive information processing deficits, schizophrenia patients (SZP) show deviant gaze behavior (GB) while viewing emotional faces. As understanding of a social environment requires gathering complex social information, our study aimed at investigating the gaze behavior of SZP related to social interactions and its impact on the level of social and role functioning. GB of 32 SZP and 37 healthy control individuals (HCI) was investigated with a high-resolution eye tracker during an unguided viewing of 12 complex pictures of social interaction scenes. Regarding whole pictures, SZP showed a shorter scanpath length, fewer fixations and a shorter mean distance between fixations. Furthermore, SZP exhibited fewer and shorter fixations on faces, but not on the socially informative bodies nor on the background, suggesting a cue-specific abnormality. Logistic regression with bootstrapping yielded a model including two GB parameters; a subsequent ROC curve analysis indicated an excellent ability of group discrimination (AUC .85). Face-related GB aberrations correlated with lower social and role functioning and with delusional thinking, but not with negative symptoms. Training of spontaneous integration of face-related social information seems promising to enable a holistic perception of social information, which may in turn improve social and role functioning. The observed ability to discriminate SZP from HCI warrants further research on the predictive validity of GB in psychosis risk prediction.

Depression predicts persistence of paranoia in clinical high-risk patients to psychosis: results of the EPOS project.

BACKGROUND: The link between depression and paranoia has long been discussed in psychiatric literature. Because the causality of this association is difficult to study in patients with full-blown psychosis, we aimed to investigate how clinical depression relates to the presence and occurrence of paranoid symptoms in clinical high-risk (CHR) patients. METHODS: In all, 245 young help-seeking CHR patients were assessed for suspiciousness and paranoid symptoms with the structured interview for prodromal syndromes at baseline, 9- and 18-month follow-up. At baseline, clinical diagnoses were assessed by the Structured Clinical Interview for DSM-IV, childhood adversities by the Trauma and Distress Scale, trait-like suspiciousness by the Schizotypal Personality Questionnaire, and anxiety and depressiveness by the Positive and Negative Syndrome Scale. RESULTS: At baseline, 54.3% of CHR patients reported at least moderate paranoid symptoms. At 9- and 18-month follow-ups, the corresponding figures were 28.3 and 24.4%. Depressive, obsessive-compulsive and somatoform disorders, emotional and sexual abuse, and anxiety and suspiciousness associated with paranoid symptoms. In multivariate modelling, depressive and obsessive-compulsive disorders, sexual abuse, and anxiety predicted persistence of paranoid symptoms. CONCLUSION: Depressive disorder was one of the major clinical factors predicting persistence of paranoid symptoms in CHR patients. In addition, obsessive-compulsive disorder, childhood sexual abuse, and anxiety associated with paranoia. Effective pharmacological and psychotherapeutic treatment of these disorders and anxiety may reduce paranoid symptoms in CHR patients.

What are residual symptoms in schizophrenia spectrum disorder? Clinical description and 1-year persistence within a naturalistic trial.

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.

Duration of unspecific prodromal and clinical high risk states, and early help-seeking in first-admission psychosis patients.

PURPOSE: Prevention of psychosis requires both presence of clinical high risk (CHR) criteria and early help-seeking. Previous retrospective studies of the duration of untreated illness (i.e. prodrome plus psychosis) did not distinguish between prodromal states with and without CHR symptoms. Therefore, we examined the occurrence of CHR symptoms and first help-seeking, thereby considering effects of age at illness-onset. METHODS: Adult patients first admitted for psychosis (n = 126) were retrospectively assessed for early course of illness and characteristics of first help-seeking. RESULTS: One-hundred and nine patients reported a prodrome, 58 with CHR symptoms. In patients with an early illness-onset before age 18 (n = 45), duration of both illness and psychosis were elongated, and CHR symptoms more frequent (68.9 vs. 33.3 %) compared to those with adult illness-onset. Only 29 patients reported help-seeking in the prodrome; this was mainly self-initiated, especially in patients with an early illness-onset. After the onset of first psychotic symptoms, help-seeking was mainly initiated by others. State- and age-independently, mental health professionals were the main first point-of-call (54.0 %). CONCLUSIONS: Adult first-admission psychosis patients with an early, insidious onset of symptoms before age 18 were more likely to recall CHR symptoms as part of their prodrome. According to current psychosis-risk criteria, these CHR symptoms, in principle, would have allowed the early detection of psychosis. Furthermore, compared to patients with an adult illness-onset, patients with an early illness-onset were also more likely to seek help on their own account. Thus, future awareness strategies to improve CHR detection might be primarily related to young persons and self-perceived subtle symptoms.

Prediction and prevention of psychosis: current progress and future tasks.

Prevention of psychoses has been intensively investigated within the past two decades, and particularly, prediction has been much advanced. Depending on the applied risk indicators, current criteria are associated with average, yet significantly heterogeneous transition rates of ≥30 % within 3 years, further increasing with longer follow-up periods. Risk stratification offers a promising approach to advance current prediction as it can help to reduce heterogeneity of transition rates and to identify subgroups with specific needs and response patterns, enabling a targeted intervention. It may also be suitable to improve risk enrichment. Current results suggest the future implementation of multi-step risk algorithms combining sensitive risk detection by cognitive basic symptoms (COGDIS) and ultra-high-risk (UHR) criteria with additional individual risk estimation by a prognostic index that relies on further predictors such as additional clinical indicators, functional impairment, neurocognitive deficits, and EEG and structural MRI abnormalities, but also considers resilience factors. Simply combining COGDIS and UHR criteria in a second step of risk stratification produced already a 4-year hazard rate of 0.66. With regard to prevention, two recent meta-analyses demonstrated that preventive measures enable a reduction in 12-month transition rates by 54-56 % with most favorable numbers needed to treat of 9-10. Unfortunately, psychosocial functioning, another important target of preventive efforts, did not improve. However, these results are based on a relatively small number of trials; and more methodologically sound studies and a stronger consideration of individual profiles of clinical needs by modular intervention programs are required.

Fatty acid ethanolamide levels are altered in borderline personality and complex posttraumatic stress disorders.

Borderline personality (BPD) and complex posttraumatic stress disorders (PTSD) are both powerfully associated with the experience of interpersonal violence during childhood and adolescence. The disorders frequently co-occur and often result in pervasive problems in, e.g., emotion regulation and altered pain perception, where the endocannabinoid system is deeply involved. We hypothesize an endocannabinoid role in both disorders. We investigated serum levels of the endocannabinoids anandamide and 2-arachidonoylglycerol and related fatty acid ethanolamides (FAEs) in BPD, PTSD, and controls. Significant alterations were found for both endocannabinoids in BPD and for the FAE oleoylethanolamide in PTSD suggesting a respective link to both disorders.