Andreas Wittorf

Negative Symptoms of Schizophrenia as Primary Target of Cognitive Behavioral Therapy: Results of the Randomized Clinical TONES Study

Clinical studies on cognitive behavioral therapy (CBT) that include schizophrenia patients primarily on the basis of negative symptoms are uncommon. However, those studies are necessary to assess the efficacy of CBT on negative symptoms. This article first gives an overview of CBT on negative symptoms and discusses the methodological problems of selecting an adequate control group. Furthermore, the article describes a clinical study (the TONES-Study, ISRCTN 25455020), which aims to investigate whether CBT is specifically efficacious for the reduction of negative symptoms. This multicenter randomized clinical trial comparing CBT with cognitive remediation (CR) for control of nonspecific effects is depicted in detail. In our trial, schizophrenia patients (n = 198) participated in manualized individual outpatient treatments. Primary outcome is the negative syndrome assessed with the positive and negative syndrome scale, analyzed with multilevel linear mixed models. Patients in both groups moderately improved regarding the primary endpoint. However, against expectation, there was no difference between the groups after treatment in the intention to treat as well as in the per-protocol analysis. In conclusion, psychotherapeutic intervention may be useful for the reduction of negative symptoms. However, there is no indication for specific effects of CBT compared with CR.

Is impaired set-shifting a feature of ''pure'' anorexia nervosa? Investigating the role of depression in set-shifting ability in anorexia nervosa and unipolar depression

Impaired set-shifting has been reported in patients with anorexia nervosa (AN) and in patients with affective disorders, including major depression. Due to the prevalent comorbidity of major depression in AN, this study aimed to examine the role of depression in set-shifting ability. Fifteen patients with AN without a current comorbid depression, 20 patients with unipolar depression (UD) and 35 healthy control participants were assessed using the Trail Making Test (TMT), the Wisconsin Card Sorting Test (WCST) and a Parametric Go/No-Go Test (PGNG). Set-shifting ability was intact in patients with AN without a comorbid depression. However, patients with UD performed significantly poorer in all three tasks compared to AN patients and in the TMT compared to healthy control participants. In both patient groups, set-shifting ability was moderately negatively correlated with severity of depressive symptoms, but was unrelated to BMI and severity of eating disorder symptoms in AN patients. Our results suggest a pivotal role of comorbidity for neuropsychological functioning in AN. Impairments of set-shifting ability in AN patients may have been overrated and may partly be due to comorbid depressive disorders in investigated patients.

Collaboration in outpatient antipsychotic drug treatment: analysis of potentially influencing factors.

Knowledge of factors relevant for medication adherence and patient collaboration is still limited. Our study aims at exploring the contribution of a variety of factors to collaboration in outpatients with schizophrenia and schizoaffective disorder. We obtained self-rated and observer-rated data from 108 outpatients during an interview 6 months after hospital discharge. The compliance rating scale (CRS) classified 76% of the patients as collaborative. Factors related to the patient, illness, treatment, and social environment were analysed in two-step explorative correlation and regression analyses in order to determine their relative contribution to collaboration. Only trust in medication and lack of insight were associated with collaboration, and they accounted for 38% of the variance. Neither medication side effects nor neuropsychological functioning correlated with collaboration. The conceptualisation of medication adherence is complex, and there are a number of unresolved methodological problems. The data indicate that illness and treatment-related subjective attitudes may be more relevant than side effects, cognitive functioning or any sociodemographic variable.

Change mechanisms in psychotherapy: Multiperspective assessment and relation to outcome

Abstract The study aimed at constructing a reliable and valid post-session questionnaire measuring general change mechanisms of psychotherapy with correspondent versions for patient and therapist perspectives. Therefore, 253 inpatients in early, middle, and late stages of psychotherapy completed the newly developed Scale for the Multiperspective Assessment of General Change Mechanisms in Psychotherapy (SACiP) and diverse outcome measures. The psychometric qualities of the SACiP were excellent as shown by (a) exploratory factor analyses on patient and therapist ratings, (b) confirmatory factor analyses on later measuring times, and (c) high internal consistencies. Supporting construct validity, the SACiP predicted outcome, as shown by correlational analyses and mixed effects modeling. Patient evaluations of change mechanisms were better predictors of outcome than the corresponding therapist evaluations.

Does the cognitive dispute of psychotic symptoms do harm to the therapeutic alliance

We examined whether the cognitive dispute of psychotic symptoms has a negative impact on the course of the therapeutic alliance. Sixty-seven patients with persistent psychotic symptoms received either cognitive behavioral therapy (CBT) or supportive therapy. Questionnaire-based alliance ratings were repeatedly obtained throughout the course of therapy. Patient and therapist alliance ratings were examined separately. Data analyses comprised repeated measurement analyses of variance and cluster analytic procedures. Neither patient nor therapist alliance ratings showed a differential course throughout the treatments. This was despite the implementation of disputing strategies in later stages of CBT. Irrespective of the treatment condition a cluster with a positive alliance rating and a cluster with a poorer rating were found for therapist and patient ratings, respectively. Baseline symptoms and insight differentiated between the types of clusters. In conclusion, CBT-specific interventions that challenge psychotic symptoms do not necessarily negatively influence the course of the alliance.

Adverse effects of cognitive behavioral therapy and cognitive remediation in schizophrenia: results of the treatment of negative symptoms study.

Abstract This study examined the frequency and extent of detrimental effects of cognitive behavioral therapy (CBT) for psychosis. In a randomized clinical trial, we investigated the efficacy of CBT for the reduction of negative symptoms as compared with cognitive remediation (CR) in schizophrenia patients (n = 198). Safety was addressed through assessment of severe adverse events (SAEs), which were defined as suicides, suicide attempts, suicidal crises, and severe symptom exacerbations over a period of 12 months after inclusion in the study. Monthly assessments with Positive and Negative Syndrome Scale and Scale for the Assessment of Negative Symptoms allowed for the analysis of symptom increases during the treatment. There were no suicides in the trial. SAEs were observed in 10 CBT and 5 CR patients. Increases in negative symptoms occurred in 64 CBT and 58 CR patients. These differences were not significant. The maximum increase in negative symptoms under treatment, as compared with the baseline, was equal to an effect size of −0.66 in CBT patients and −0.77 in CR patients. Thus, the SAE rate was comparable between both interventions and was relatively low, given the severity of the psychotic disorder. Therapists should be aware of a subgroup of patients who show symptom increases with large effect sizes and might require more intensive care.

Cognitive behavioural therapy versus supportive therapy for persistent positive symptoms in psychotic disorders: The POSITIVE Study, a multicenter, prospective, single-blind, randomised controlled clinical trial

BackgroundIt has been demonstrated that cognitive behavioural therapy (CBT) has a moderate effect on symptom reduction and on general well being of patients suffering from psychosis. However, questions regarding the specific efficacy of CBT, the treatment safety, the cost-effectiveness, and the moderators and mediators of treatment effects are still a major issue. The major objective of this trial is to investigate whether CBT is specifically efficacious in reducing positive symptoms when compared with non-specific supportive therapy (ST) which does not implement CBT-techniques but provides comparable therapeutic attention.Methods/DesignThe POSITIVE study is a multicenter, prospective, single-blind, parallel group, randomised clinical trial, comparing CBT and ST with respect to the efficacy in reducing positive symptoms in psychotic disorders. CBT as well as ST consist of 20 sessions altogether, 165 participants receiving CBT and 165 participants receiving ST. Major methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, analysis by intention to treat, data management using remote data entry, measures of quality assurance (e.g. on-site monitoring with source data verification, regular query process), advanced statistical analysis, manualized treatment, checks of adherence and competence of therapists.Research relating the psychotherapy process with outcome, neurobiological research addressing basic questions of delusion formation using fMRI and neuropsychological assessment and treatment research investigating adaptations of CBT for adolescents is combined in this network. Problems of transfer into routine clinical care will be identified and addressed by a project focusing on cost efficiency.DiscussionThis clinical trial is part of efforts to intensify psychotherapy research in the field of psychosis in Germany, to contribute to the international discussion on psychotherapy in psychotic disorders, and to help implement psychotherapy in routine care. Furthermore, the study will allow drawing conclusions about the mediators of treatment effects of CBT of psychotic disorders.Trial RegistrationCurrent Controlled Trials ISRCTN29242879

The Individual Therapy Process Questionnaire: Development and Validation of a Revised Measure to Evaluate General Change Mechanisms in Psychotherapy

There is a dearth of measures specifically designed to assess empirically validated mechanisms of therapeutic change. To fill in this research gap, the aim of the current study was to develop a measure that covers a large variety of empirically validated mechanisms of change with corresponding versions for the patient and therapist. To develop an instrument that is based on several important change process frameworks, we combined two established change mechanisms instruments: the Scale for the Multiperspective Assessment of General Change Mechanisms in Psychotherapy (SACiP) and the Scale of the Therapeutic Alliance-Revised (STA-R). In our study, 457 psychosomatic inpatients completed the SACiP and the STA-R and diverse outcome measures in early, middle and late stages of psychotherapy. Data analyses were conducted using factor analyses and multilevel modelling. The psychometric properties of the resulting Individual Therapy Process Questionnaire were generally good to excellent, as demonstrated by (a) exploratory factor analyses on both patient and therapist ratings, (b) CFA on later measuring times, (c) high internal consistencies and (d) significant outcome predictive effects. The parallel forms of the ITPQ deliver opportunities to compare the patient and therapist perspectives for a broader range of facets of change mechanisms than was hitherto possible. Consequently, the measure can be applied in future research to more specifically analyse different change mechanism profiles in session-to-session development and outcome prediction. Key Practitioner Message This article describes the development of an instrument that measures general mechanisms of change in psychotherapy from both the patient and therapist perspectives. Post-session item ratings from both the patient and therapist can be used as feedback to optimize therapeutic processes. We provide a detailed discussion of measures developed to evaluate therapeutic change mechanisms.

Neurocognitive effects of atypical and conventional antipsychotic drugs in schizophrenia: A naturalistic 6-month follow-up study

The present study aimed to assess the neurocognitive effects of atypical and conventional antipsychotic drugs on neurocognition under naturalistic treatment conditions. Eighty-two patients with schizophrenia underwent a comprehensive neuropsychological assessment both at baseline during inpatient treatment and 6 months after discharge from hospital (follow-up). From this sample, we selected two subgroups of patients, which had either a continuous atypical (n=33) or conventional (n=16) antipsychotic medication. Twenty-seven out of 40 healthy controls were also retested to control for practice effects. Both patient groups showed a moderate and significant improvement in global cognitive functioning. The repeated measurement ANOVAs revealed no differential treatment effects for all neuropsychological domains. These results remained after controlling for potential confounders between groups. Administering antipsychotic medications in an individually optimized manner seems to have the potential to improve some aspects of neurocognition in schizophrenia, regardless of the kind of antipsychotic medication.

Specificity of jumping to conclusions and attributional biases: A comparison between patients with schizophrenia, depression, and anorexia nervosa

Introduction. The knowledge of the specificity of cognitive biases in psychiatric disorders is important in order to develop disorder-specific cognitive models and therapies. This cross-sectional study aimed to investigate the specificity of jumping to conclusions (JTC) and attributional biases (AB) for patients with schizophrenia. Methods. Twenty patients with paranoid schizophrenia were compared with patients with depression (n=20) and with anorexia nervosa (n=15) and nonclinical controls (n=55). All participants were administered a modified version of the beads task (JTC), a revised German version of the Internal, Personal, and Situational Attributions Questionnaire (AB), and several symptom and neurocognitive measures. Results. The proportion of patients with JTC bias in the schizophrenia group was, at the descriptive level, higher than in the depression and the anorexia groups. Regarding AB, the schizophrenia group showed a significantly stronger externalising but not personalising bias than the clinical control groups. Neither JTC nor attributional biases were significantly associated with delusions in general or persecutory delusion. Conclusions. We found evidence for the specificity of an externalising bias for paranoid schizophrenia. Concerning JTC bias the evidence was less clear. Whether the modification of those biases through psychological interventions would have an effect on psychopathology should be investigated in the context of clinical trials.