The relationship between empathy, theory of mind and facial affect recognition in schizophrenia patients.

Although impairments in social cognition are a core feature in schizophrenia, the relationship between its subcomponents is less clear. Nineteen schizophrenia patients and 20 matched healthy controls were tested for emotion recognition, and for the cognitive and affective subcomponents of empathy and theory of mind (ToM). Patients scored significantly worse than controls on cognitive empathy and both subcomponents of ToM. Group differences disappeared for cognitive empathy and affective ToM when emotion recognition was included as a covariate. Our results indicate that emotion recognition is an important factor involved in the deficits on higher levels of social cognition in schizophrenia.

Oxytocin reactivity to an emotional challenge paradigm and its relation to social-cognitive functions in healthy volunteers.

The neuropeptide oxytocin (OT) is known to be an important modulator of social cognition. It has been shown that lower OT plasma concentrations are linked to impairments in social cognition. Studies have also shown that intranasal OT may enhance social-cognitive abilities in healthy subjects. We hypothesize that, besides baseline OT concentrations, the reactivity of the OT system may have an important role in social-cognitive functioning of individuals. In the present study, we explored if an emotional challenge paradigm is suitable to elicit OT release into plasma to make the reactivity of the OT system measurable. Therefore, 20 healthy male volunteers watched an emotional film clip, showing another person in pain during a severe dentist's treatment, while blood draws were conducted pre and post challenge. OT concentrations in plasma were measured by ELISA after solid phase extraction from plasma. OT plasma concentrations at baseline were significantly negatively correlated to an empathetic rating of our film clip and to measures of emotional empathy for positive and negative emotions, whereas the difference between post-challenge value and baseline was significantly positively correlated with the latter measures. Our data thus show that a short emotional video can be successfully employed as a challenge paradigm for eliciting an increase of peripheral OT in healthy male subjects. Calculating the relative OT change post- vs. pre-challenge may give a measure of OT reactivity. The combination of low peripheral OT at baseline with high OT reactivity may be a psychoendocrine trait that is linked to higher emotional functioning.

Facial affect recognition performance and event-related potentials in violent and non-violent schizophrenia patients.

We investigated whether male inpatients with schizophrenia and a history of hands-on violent offences (forensic schizophrenic, FOS) are more impaired in emotion recognition than matched schizophrenia patients without any history of violence (general psychiatric schizophrenic, GPS). This should become apparent in performance in psychometry and in scalp event-related brain potentials (ERPs) evoked by pictures of facial affect. FOS and GPS (each n = 19) were matched concerning age, intelligence, comorbid addiction, medication and illness duration. FOS revealed significantly poorer affect recognition (AR) performance, especially of neutral and fear stimuli. Analysis of ERPs revealed a significant interaction of hemisphere, electrode position and group of the N250 component. Post hoc analysis of group effect showed significantly larger amplitudes in FOS at FC3. These results support the hypothesis that in FOS emotional faces are more salient and evoke higher arousal. Larger impairment in AR performance combined with higher salience and arousal may contribute to the occurrence of violent acts in schizophrenia patients.

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) is more 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 comprises mainly 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. Trial Registration: ClinicalTrials.gov NCT02678858, German Study Register DRKS 00010033.

Effects of abstinence on brain morphology in alcoholism: a MRI study.

Chronic alcohol abuse leads to morphological changes of the brain. We investigated if these volumetric changes are reversible after a period of abstinence. For this reason 41 male and 15 female alcohol patients underwent MRI-scanning after in-patient detoxification (baseline) entering alcoholism treatment programs, and between 6 and 9 months later (follow-up), in a phase of convalescence. Additionally, 29 male and 16 female control subjects were examined. The MRI-scans were delineated and the resulting regions of interest, volumes of lateral ventricles and prefrontal lobes were expressed relatively to total brain volume. Compared to control subjects alcohol patients showed bilaterally decreased prefrontal lobes (11% reduction) and increased lateral ventricles (up to 42% enlargement). The extent of the ventricular increase was depending on patient's additional psychiatric diagnosis, showing smaller lateral ventricles in patients with additional personality disorder. While at follow-up the size of prefrontal lobes remained unchanged, volumes of the lateral ventricles decreased (5-6% reduction) in alcohol patients with abstinence and improved drinking behavior, especially in patients that underwent only one detoxification. The extent of the ventricular enlargement correlated with the elevation of alcohol related laboratory measures (mean corpuscular volume, gamma-glutamyl transpeptidase). In conclusion this study confirms the hypothesis that alcoholism causes brain damages that are partially reversible. It should be analyzed in further studies with larger sample sizes, if complete brain regeneration is possible maintaining abstinence over a longer period.

Cognitive behavioural treatment of negative symptoms in schizophrenia patients: study design of the TONES study, feasibility and safety of treatment.

Currently, there are no convincing treatment strategies for negative symptoms of schizophrenia. On this background, we are conducting the treatment of negative symptoms (TONES) study which addresses the question whether cognitive behavioural therapy (CBT) is efficacious for the reduction of negative symptoms in schizophrenia. The present paper aims at presenting the design of the clinical trial of the study as well as the treatment concept. Further, we investigate the feasibility and the safety of our study treatment. The TONES study is a multicentric, prospective, single-blind, randomised, and controlled trial (RCT). The clinical trial compares CBT (test condition) and cognitive remediation (CR; control condition) with respect to the efficacy in reducing negative symptoms. In order to systematically assess aspects of adherence and feasibility therapists filled in session reports after each session. The safety analysis is performed using the sequential method of Whitehead (The design and analysis of sequential clinical trials, Ellis Horwood, Chichester, 1983). We were able to conduct a systematic recruitment and to include a sample of N = 198 patients which is characterised by negative symptoms of medium severity. The majority of patients accepted the format of a 50-min treatment session. The manualised treatment content seemed to be adequate and the cooperation between patients and therapists was excellent or adequate in approximately 80% of the treatment sessions. Of the 15 severe adverse events 10 occurred in the CBT and 5 in the CR. This difference between the groups was not significant. The study presented here is presumably the first high quality RCT which evaluates CBT with negative symptoms as primary endpoint. On the background of the data presented we conclude that CBT for the reduction of negative symptoms is feasible and can be conducted safely.

Social cognition intervention in schizophrenia: Description of the training of affect recognition program - Indian version.

Social cognition refers to mental operations involved in processing of social cues and includes the domains of emotion processing, Theory of Mind (ToM), social perception, social knowledge and attributional bias. Significant deficits in ToM, emotion perception and social perception have been demonstrated in schizophrenia which can have an impact on socio-occupational functioning. Intervention modules for social cognition have demonstrated moderate effect sizes for improving emotion identification and discrimination. We describe the Indian version of the Training of Affect Recognition (TAR) program and a pilot study to demonstrate the feasibility of administering this intervention program in the Indian population. We also discuss the cultural sensibilities in adopting an intervention program for the Indian setting. To the best of our knowledge this is the first intervention program for social cognition for use in persons with schizophrenia in India.

Remediation of impairments in facial affect recognition in schizophrenia: efficacy and specificity of a new training program.

OBJECTIVE: Schizophrenia patients often exhibit impairments in facial affect recognition which contribute to their poor social functioning. These impairments are stable in the course of the disorder and seem not to be affected by conventional treatment. The present study investigates the efficacy and specificity of a new training program for the remediation of such impairments. METHOD: A newly developed training program tackling affect recognition (TAR) was compared with a cognitive remediation training program (CRT) and treatment as usual (TAU) within a randomized three group pre-post design in n=77 post-acute schizophrenia patients. The TAR is a computer-aided 12-session program focussing on facial affect recognition, whereas the CRT aims to improve attention, memory and executive functioning. Facial affect recognition, face recognition, and neurocognitive performance were assessed before (T0) and after (T1) the six week training phase. During the training period all patients received antipsychotic medication. RESULTS: Patients under TAR significantly improved in facial affect recognition, with recognition performance after training approaching the level of healthy controls from former studies. Patients under CRT and those without special training (TAU) did not improve in affect recognition, though patients under CRT improved in verbal memory functions. CONCLUSION: According to these results, remediation of disturbed facial affect recognition in schizophrenia patients is possible, but not achievable with a traditional cognitive rehabilitation program such as the CRT. Instead, functional specialized remediation programs such as the newly developed TAR are a more suitable option.

Training of Affect Recognition impacts electrophysiological correlates of facial affect recognition in schizophrenia: Analyses of fixation-locked potentials.

OBJECTIVES: Training of Affect Recognition (TAR) is a useful approach to restoring cognitive function in schizophrenic patients. Along with improving visual exploration of faces and altering central information processing in relevant brain areas, TAR attenuates impairments in facial affect recognition. In the present study, we investigate the effects of TAR on early electrophysiological correlates of facial affect recognition in schizophrenia. METHODS: The study population comprised 12 schizophrenic patients and 14 healthy controls. In each individual, we carried out EEG, concomitant measurements of scanning eye movements and fixation-based low resolution electromagnetic tomography (sLORETA) analyses of brain electric activity. All analyses were performed at baseline and after participation in TAR. RESULTS: In patients, brain activation patterns significantly changed after completing the TAR. Functional improvements were particularly pronounced in the superior parietal and inferior parietal lobes, where trained patients showed a larger increase in activation than untrained healthy controls. CONCLUSIONS: The TAR activates compensatory brain processes involved in the perception, attention and evaluation of emotional stimuli. This may underlie the established behavioral effects of the TAR in schizophrenic patients, which include improvements in facial affect recognition and alterations of visual exploration strategies.

First vs multiple episode schizophrenia: two-year outcome of intermittent and maintenance medication strategies.

Results of studies on intermittent neuroleptic treatment strategies in first episode (FE) schizophrenia have not been published. Aims of the present study were to elucidate the comparative efficacy of prodrome-based neuroleptic intervention in first vs multiple episode (ME) schizophrenia. As to the methods, three randomly assigned open neuroleptic treatment strategies were compared over 2 years in 363 schizophrenic outpatients (115 FE, 248 ME; ICD-9, RDC): maintenance medication vs two intermittent medication strategies (prodrome-based intervention and crisis intervention). Concerning relapse prevention, the results demonstrate that ME patients seemed to profit most from maintenance medication compared to both intermittent treatments, whereas FE patients did equally well under maintenance medication and prodrome-based intervention treatment. Psychopathology, social adjustment, subjective well-being, and side-effects after two years did not differ significantly between the FE and ME patients irrespective of treatment strategy. Concerning treatment adherence, FE patients complied better with prodrome-based intervention than with maintenance medication. Cumulative neuroleptic dosage was lowest in FE patients under intermittent treatment. In conclusion, maintenance medication is the best strategy for relapse prevention in ME patients. In FE patients, prodrome-based intermittent intervention seems to be equivalent or even better with respect to compliance and dosage applied.

Remediation of facial affect recognition impairments in patients with schizophrenia: a new training program.

Impairments in facial affect recognition are trait-like characteristics in schizophrenia and might contribute to poor social functioning. A special Training of Affect Recognition program was developed, which shows a good feasibility and promising treatment effects. The specificity of these effects can now be demonstrated in a control group design.

Effects of Training of Affect Recognition on the recognition and visual exploration of emotional faces in schizophrenia.

BACKGROUND: Schizophrenia patients have impairments in facial affect recognition and display scanpath abnormalities during the visual exploration of faces. These abnormalities are characterized by fewer fixations on salient feature areas and longer fixation durations. The present study investigated whether social-cognitive remediation not only improves performance in facial affect recognition but also normalizes patients' gaze behavior while looking at faces. METHODS: Within a 2 × 2-design (group × time), 16 schizophrenia patients and 16 healthy controls performed a facial affect recognition task with concomitant infrared oculography at baseline (T0) and after six weeks (T1). Between the measurements, patients completed the Training of Affect Recognition (TAR) program. The influence of the training on facial affect recognition (percent of correct answers) and gaze behavior (number and mean duration of fixations into salient or non-salient facial areas) was assessed. RESULTS: In line with former studies, at baseline patients showed poorer facial affect recognition than controls and aberrant scanpaths, and after TAR facial affect recognition was improved. Concomitant with improvements in performance, the number of fixations in feature areas ('mouth') increased while fixations in non-feature areas ('white space') decreased. However, the change in fixation behavior did not correlate with the improvement in performance. CONCLUSIONS: After TAR, patients pay more attention to facial areas that contain information about a displayed emotion. Although this may contribute to the improved performance, the lack of a statistical correlation implies that this factor is not sufficient to explain the underlying mechanism of the treatment effect.

Training of affect recognition in schizophrenia patients with violent offences: behavioral treatment effects and electrophysiological correlates.

Violent offenders with schizophrenia have a particularly poor performance level in facial affect recognition. Nineteen male schizophrenia patients, who had been committed to psychiatric hospital detention because of violent offences and lack of criminal responsibility, were recruited to receive the Training of Affect Recognition (TAR). Performance in the Pictures of Facial Affect (PFA)-test and event-related potentials (ERPs) were registered in a pre-post-treatment design. TAR was feasible with a very high treatment effect (Cohen's d = 1.88), which persisted for 2 months post-treatment. ERPs remained unchanged post- vs. pre-treatment, while low resolution brain electromagnetic tomography (LORETA) revealed activation decreases in left-hemispheric parietal-temporal-occipital regions at 172 msec and activation increases in right dorsolateral prefrontal cortex and anterior cingulate at 250 msec. Possibly, violent offenders with schizophrenia are particularly amenable to TAR because of a high level of dysfunction at baseline. Post- vs. pre-treatment changes of neural activity (LORETA) may mirror a gain of efficiency in structural face decoding and a shift towards a more reflective mode of emotional face decoding, relying on increased frontal brain activity. Functional magnetic resonance imaging (BOLD-fMRI) -data from another study further supports this notion. TAR treatment might enable subjects with schizophrenia and a disposition to violence to reach a higher degree of deliberation of their reactive behavior to facial affect stimuli.

Social-cognitive remediation in schizophrenia: generalization of effects of the Training of Affect Recognition (TAR).

In the last decade, several social cognitive remediation programs have been developed for use in schizophrenia. Though existing evidence indicates that such programs can improve social cognition, which is essential for successful social functioning, it remains unclear whether the improvements generalize to social cognitive domains not primarily addressed by the intervention and whether the improved test performance transfers into everyday social functioning. The present study investigated whether, beyond its known effects on facial affect recognition, the Training of Affect Recognition (TAR) has effects on prosodic affect recognition, theory of mind (ToM) performance, social competence in a role-play task, and more general social and occupational functioning. Thirty-eight inpatients with a diagnosis of schizophrenia or schizoaffective disorder were randomly assigned to 6 weeks of treatment with the TAR--primarily targeted at facial affect recognition-or Cognitive Remediation Training (CRT)--primarily targeted at neurocognition. Intention-to-treat analyses found significantly larger pre-post improvements with TAR than with CRT in prosodic affect recognition, ToM, and social competence and a trend effect in global social functioning. However, the effects on ToM and social competence were no longer significant in the smaller group of patients who completed treatment according to protocol. Results suggest that TAR effects generalize to other social cognitive domains not primarily addressed. TAR may also enhance social skills and social functioning, although this has to be confirmed. Results are discussed with regard to the need to improve functional outcome in schizophrenia against the background of current evidence from other social cognitive remediation approaches.

The effects of combined acamprosate and integrative behaviour therapy in the outpatient treatment of alcohol dependence: a randomized controlled trial.

AIMS: The aim of this randomized, controlled, multisite trial was to evaluate the efficacy of combined treatment with integrative behaviour therapy (IBT) and acamprosate on drinking behaviour in detoxified alcohol-dependent patients. METHODS: A total of 371 patients were randomized to one of the three treatment conditions: IBT plus acamprosate, IBT plus placebo, or supportive counselling ('treatment as usual', TAU) plus acamprosate. The main outcome was success rate, i.e., rate of abstinence plus improvement according to the criteria of Feuerlein and Küfner (1989), at the end of the six-month treatment phase and at the subsequent six-month follow-up. Drinking status was validated by blood parameters (CDT, GGT, and MCV). Data were analyzed by an intent-to-treat model and missing data were classified as relapse. RESULTS: The success rates at the end of treatment under both TAU plus acamprosate (37.7%) and IBT plus placebo (48%) almost reached the levels derived from the literature. However, adding acamprosate to IBT did not result in the expected increase in success rate (IBT plus acamprosate: 47.6%), and success rates did not differ significantly between groups. Similarly, there was no significant difference between treatment success rates at follow-up. CONCLUSION: The results suggest that the combination of acamprosate and IBT is not more effective than treatment with either IBT or acamprosate alone. However, the two acamprosate conditions differed in success rate by about 10%, which might constitute a clinically relevant though statistically non-significant effect.

Training of affect recognition in schizophrenia: Neurobiological correlates.

Recently, a standardized program for training of affect recognition (TAR) was developed which has demonstrated efficacy and specificity with respect to behavioral performance. The effects of the TAR on the cerebral correlates were evaluated using repeated fMRI event-related measurements in a group of schizophrenia patients (n=10) before and after TAR treatment six weeks apart. A second patient group without training (n=10, treatment as usual, TAU) as well as healthy subjects (n=10) were investigated at equivalent time points. Schizophrenia patients were shown to be differentially impaired in the identification of the emotional aspects of facial expressions (but not age discrimination) when compared with healthy participants. A specific improvement in the increased number of correct identifications was observed in trained patients only. In parallel, an increase in activation was noted in the left middle and superior occipital lobe, the right inferior and superior parietal cortex, and the inferior frontal cortex bilaterally in TAR patients compared to the TAU group. These activation changes in TAR patients correlated with their behavioral improvement, further corroborating the positive effect of training. Specific training effects are seen to correspond with cerebral effects, probably reflecting a more efficient use of attentional, perceptual, or cognitive strategies.