Efficacy of Integrated Social Cognitive Remediation vs. Neurocognitive Remediation in Improving Functional Outcome in Schizophrenia: Concept and Design of a Multicenter, Single-Blind RCT (The ISST Study)

Background: Although clinically effective treatment is available for schizophrenia, recovery often is still hampered by persistent poor psychosocial functioning, which in turn is limited by impairments in neurocognition, social cognition, and social behavioral skills. Although cognitive remediation has shown general efficacy in improving cognition and social functioning, effects still need to be improved and replicated in appropriately powered, methodologically rigorous randomized controlled trials (RCTs). Existing evidence indicates that effects can most likely be optimized by combining treatment approaches to simultaneously address both social cognitive and social behavioral processes. Objectives: To assess whether Integrated Social Cognitive and Behavioral Skill Therapy (ISST) ismore efficacious in improving functional outcome in schizophrenia than the active control treatment Neurocognitive Remediation Therapy (NCRT). Methods: The present study is a multicenter, prospective, rater-blinded, two-arm RCT being conducted at six academic study sites in Germany. A sample of 180 at least partly remitted patients with schizophrenia are randomly assigned to either ISST or NCRT. ISST is a compensatory, strategy-based program that targets social cognitive processes and social behavioral skills. NCRT comprisesmainly drill and practice-oriented neurocognitive training. Both treatments consist of 18 sessions over 6 months, and participants are subsequently followed up for another 6 months. The primary outcome is all-cause discontinuation over the 12-month study period; psychosocial functioning, quality of life, neurocognitive and social cognitive performance, and clinical symptoms are assessed as secondary outcomes at baseline before randomization (V1), at the end of the six-month treatment period (V6), and at the six-month follow-up (V12). Discussion: This RCT is part of the German Enhancing Schizophrenia Prevention and Recovery through Innovative Treatments (ESPRIT) research network, which aims at using innovative treatments to enhance prevention and recovery in patients with schizophrenia. Because this study is one of the largest and methodologically most rigorous RCTs on the efficacy of cognitive remediation approaches in schizophrenia, it will not only help to identify the optimal treatment options for improving psychosocial functioning and thus recovery in patients but also allow conclusions to be drawn about factors influencing and mediating the effects of cognitive remediation in these patients

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

Prediction of Psychosis by Mismatch Negativity

BACKGROUND: To develop risk-adapted prevention of psychosis, an accurate estimation of the individual risk of psychosis at a given time is needed. Inclusion of biological parameters into multilevel prediction models is thought to improve predictive accuracy of models on the basis of clinical variables. To this aim, mismatch negativity (MMN) was investigated in a sample clinically at high risk, comparing individuals with and without subsequent conversion to psychosis. METHODS: At baseline, an auditory oddball paradigm was used in 62 subjects meeting criteria of a late risk at-state who remained antipsychotic-naive throughout the study. Median follow-up period was 32 months (minimum of 24 months in nonconverters, n = 37). Repeated-measures analysis of covariance was employed to analyze the MMN recorded at frontocentral electrodes; additional comparisons with healthy controls (HC, n = 67) and first-episode schizophrenia patients (FES, n = 33) were performed. Predictive value was evaluated by a Cox regression model. RESULTS: Compared with nonconverters, duration MMN in converters (n = 25) showed significantly reduced amplitudes across the six frontocentral electrodes; the same applied in comparison with HC, but not FES, whereas the duration MMN in in nonconverters was comparable to HC and larger than in FES. A prognostic score was calculated based on a Cox regression model and stratified into two risk classes, which showed significantly different survival curves. CONCLUSIONS: Our findings demonstrate the duration MMN is significantly reduced in at-risk subjects converting to first-episode psychosis compared with nonconverters and may contribute not only to the prediction of conversion but also to a more individualized risk estimation and thus risk-adapted prevention

Feasibility of six-month outpatient cognitive remediation in schizophrenia: Experience from the randomized controlled integrated social cognition and social skills therapy study

Patients with schizophrenia often have cognitive impairments that contribute to diminished psychosocial functioning. Cognitive remediation therapy (CRT) has proven efficacy and is recommended by evidence-based treatment guidelines. Important moderators of efficacy include integration of CRT into a psychiatric rehabilitation concept and patient attendance at a sufficient number of therapy sessions. These conditions can probably best be met in an outpatient setting; however, outpatient treatment is prone to higher rates of treatment discontinuation and outpatient settings are not as well protected as inpatient ones and less closely supervised.The present study investigated the feasibility of outpatient CRT in schizophrenia over a six-month period. Adherence to scheduled sessions and safety parameters were assessed in 177 patients with schizophrenia randomly assigned to one of two matched CRT programs.Results showed that 58.8 % of participants completed the CRT (>80 % of scheduled sessions) and 72.9 % completed at least half the sessions. Predictor analysis revealed a high verbal intelligence quotient as favorable for good adherence, but this factor had only low general predictive power. During the six-month treatment phase, serious adverse events occurred in 15.8 % (28/177) of the patients, which is a comparable rate to that reported in the literature.Our findings support the feasibility of six-month outpatient CRT in schizophrenia in terms of adherence to scheduled sessions and safety. Trial registration number: NCT02678858, DRKS00010033

Can quantitative EEG measures predict clinical outcome in subjects at Clinical High Risk for psychosis? A prospective multicenter study

BACKGROUND Prediction studies in subjects at Clinical High Risk (CHR) for psychosis are hampered by a high proportion of uncertain outcomes. We therefore investigated whether quantitative EEG (QEEG) parameters can contribute to an improved identification of CHR subjects with a later conversion to psychosis. METHODS This investigation was a project within the European Prediction of Psychosis Study (EPOS), a prospective multicenter, naturalistic field study with an 18-month follow-up period. QEEG spectral power and alpha peak frequencies (APF) were determined in 113 CHR subjects. The primary outcome measure was conversion to psychosis. RESULTS Cox regression yielded a model including frontal theta (HR=1.82; [95% CI 1.00-3.32]) and delta (HR=2.60; [95% CI 1.30-5.20]) power, and occipital-parietal APF (HR=.52; [95% CI .35-.80]) as predictors of conversion to psychosis. The resulting equation enabled the development of a prognostic index with three risk classes (hazard rate 0.057 to 0.81). CONCLUSIONS Power in theta and delta ranges and APF contribute to the short-term prediction of psychosis and enable a further stratification of risk in CHR samples. Combined with (other) clinical ratings, EEG parameters may therefore be a useful tool for individualized risk estimation and, consequently, targeted prevention