Gerhard Buchkremer

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.

German research network on schizophrenia-bridging the gap between research and care.

Abstract.The German Research Network on Schizophrenia (GRNS) is a nationwide network of presently 16 psychiatric university departments, 14 state and district hospitals, as well as six local networks of psychiatric practices and general practitioners, which are collaborating in about 25 interrelated, multicentre projects on schizophrenia research. The GRNS aims to intensify collaboration and knowledge exchange between leading research institutions and qualified routine care facilities, both within (horizontal network) and between (vertical network) the two levels of research and care, in order to create the scientific preconditions for optimization of care in patients with schizophrenia. With respect to illness development, the network is organized into two main “Project Networks” (PN). Whereas PN I targets the implementation of early detection and early intervention strategies, PN II aims at optimization of acute and long-term treatment, especially in first-episode patients. PN II also includes projects aiming at improvement of rehabilitation, particularly in patients with residual symptoms. Furthermore, there is a “Special Network” on molecular and pharmaco-genetics. Several more general projects address fighting stigma and discrimination, health care economy, continuing medical education, quality assurance, and methodology. The network is mainly funded by the German Ministry for Research spanning a period of 5 years.

Psychoeducational training for schizophrenic patients: background, procedure and empirical findings.

As neuroleptic therapy alone still fails to other effective relapse prevention in schizophrenic patients, psychoeducational therapeutic approaches have been developed as an additional aid for patients and their families. This article details the central characteristics of these approaches. A psychoeducational group program for schizophrenic outpatients, the efficacy of which was investigated within the scope of a German controlled intervention study on 191 patients, is also presented. The article describes in detail the methods used and the therapeutic objectives, reporting on changes in the attitudes of patients to their medication. At the end of the training program, patients who had attended regularly showed significantly better medication compliance and were more reserved with respect to their medication self-management. After 1 year the positive effects had diminished. However, booster sessions or participation of the psychiatrist in charge as group therapist would have had longer lasting effects.

A genotype-controlled analysis of plasma dopamine β-hydroxylase in healthy and alcoholic subjects: evidence for alcohol-related differences in noradrenergic function

BACKGROUND Norepinephrine and dopamine mediate important aspects of alcoholism and alcohol withdrawal. Dopamine-beta-hydroxylase (DbetaH) converts dopamine to norepinephrine. A recent study demonstrated a strong association between variance in plasma DbetaH activity and a novel polymorphism (DBH-1021C-->T) at the structural locus (DBH) encoding DbetaH protein. METHODS Our study investigated whether the DBH-1021C-->T polymorphism and plasma DbetaH activity were associated with alcoholism or with delirium tremens (DT) during alcohol withdrawal by analyzing 207 German alcoholic and 102 healthy control subjects. We also examined the influence of the polymorphism on enzyme activity. RESULTS Mean (+SD) plasma DbetaH activity measured in alcoholic subjects abstinent was significantly lower than that observed in control (27.7 + 16.7 vs. 35.6 + 18.8; p =.01). It did not differ between subjects with DT during withdrawal and subjects with mild withdrawal symptoms. The T allele of the DBH-1021C-->T polymorphism was significantly associated with lower plasma DbetaH activity. None of the alleles or genotypes were associated with alcoholism or DT. CONCLUSIONS The data indicate that the alcoholism-related reduction in plasma DbetaH activity is independent of genotype at DBH-1021C-->T and replicate the finding that DBH-1021C-->T is strongly associated with plasma DbetaH activity in a native Western European population.

Long-term effects of a psychoeducational psychotherapeutic intervention for schizophrenic outpatients and their key-persons--results of a five-year follow-up.

Abstract The study examines long-term effects on rehospitalization rates of a psychoeducationally and cognitive-behaviorally oriented intervention for schizophrenic outpatients and their key-persons. 191 patients and their key-persons were allocated by random into four different treatment groups and one control group. Five years after completion of treatment 126 patients were reexamined by interviews or case notes. The rate of patients experiencing psychiatric rehospitalization during the follow-up was assessed in each respective treatment group. Concerning rehospitalization rates there was no significant difference between controls (n = 35) and patients of the four treatment groups (n = 91). There were, however, fewer rehospitalized patients in the group with combined psychoeducational and cognitive treatment, including key-person counselling (42%), than in the control group (69%). Regarding the overall functioning, the patients in this treatment group did slightly better than those in the control group. These results are in accordance with the findings of comparable studies.

Short-term treatment with risperidone or haloperidol in first-episode schizophrenia: 8-week results of a randomized controlled trial within the German Research Network on Schizophrenia

Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics, and to be more sensitive to developing extrapyramidal side-effects. The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol. Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms. Patients were randomly assigned under double-blind conditions to receive risperidone (n=143) or haloperidol (n=146) for 8 wk. The primary efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom Scale (PANSS) negative score between treatment groups; secondary efficacy criteria were changes on the PANSS total score and other PANSS subscores, and several other measures of psychopathology and general functioning. The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of extrapyramidal side-effects measured with the Simpson-Angus Scale (SAS) compared between treatment groups. The main hypothesis was that risperidone would be superior in terms of improving negative symptoms and lowering the risk of extrapyramidal symptoms. Secondary tolerability criteria were the other extrapyramidal symptoms, measured with the Hillside Akathisia Scale (HAS) and the Abnormal Involuntary Movement Scale (AIMS). The average mean daily doses were 3.8 mg (s.d.=1.5) for risperidone and 3.7 mg (s.d.=1.5) for haloperidol. There were similar, significant improvements in both treatment groups in the primary and secondary efficacy criteria. At week 8 nearly all scores of extrapyramidal side-effects indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with risperidone [SAS: risperidone 36.5% of patients; haloperidol 51.5% of patients; likelihood ratio test, chi2(1)=7.8, p=0.005]. There were significantly fewer drop-outs [risperidone n=55, drop-out rate=38.5%; haloperidol n=79, drop-out rate=54.1%, chi2(1)=7.1, p=0.009] and a longer non-discontinuation time [risperidone: average of 50.8 d to drop-out; haloperidol: average of 44.0 d to drop-out; log rank test, chi2(1)=6.4, p=0.011] in the risperidone group. Risperidone and haloperidol appear to be equally effective in treating negative and other symptoms of first-episode schizophrenia. Risperidone has better extrapyramidal tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients.

Autoantibody reactivity in serum of patients with major depression, schizophrenia and healthy controls

The present study assessed 25 patients with unipolar major depression and 34 patients with schizophrenia along with 50 healthy, non-psychiatric controls for the presence of serum antinuclear (ANA), smooth muscle (SMA), anti-endothelial (AEA), anti-sarcolemma (ASA), thyroid gland (TGA) and parietal cell (PCA) antibodies. In the group of patients with major depression, the frequency of elevated ANA, TGA and PCA was significantly higher than in the control group. In addition, the group of patients with schizophrenia significantly more often showed increased levels of ANA and SMA than the control group of healthy volunteers. When the two psychiatric groups were compared, PCA serum titers in major depression and SMA values in schizophrenia were significantly more frequently elevated, whereas values of AEA and ASA showed no difference. These results point towards the existence of an unspecific (auto) immune disposition or reaction in at least a subgroup of patients with major depression and schizophrenia.

German research network on schizophrenia

Abstract.The German Research Network on Schizophrenia (GRNS) is a nationwide network of presently 16 psychiatric university departments, 14 state and district hospitals, as well as six local networks of psychiatric practices and general practitioners, which are collaborating in about 25 interrelated, multicentre projects on schizophrenia research. The GRNS aims to intensify collaboration and knowledge exchange between leading research institutions and qualified routine care facilities, both within (horizontal network) and between (vertical network) the two levels of research and care, in order to create the scientific preconditions for optimization of care in patients with schizophrenia. With respect to illness development, the network is organized into two main “Project Networks” (PN). Whereas PN I targets the implementation of early detection and early intervention strategies, PN II aims at optimization of acute and long-term treatment, especially in first-episode patients. PN II also includes projects aiming at improvement of rehabilitation, particularly in patients with residual symptoms. Furthermore, there is a “Special Network” on molecular and pharmaco-genetics. Several more general projects address fighting stigma and discrimination, health care economy, continuing medical education, quality assurance, and methodology. The network is mainly funded by the German Ministry for Research spanning a period of 5 years.

Sustained improvement of obsessive–compulsive disorder by deep brain stimulation in a woman with residual schizophrenia

Co-occurrence of obsessive–compulsive disorder (OCD) and schizophrenia is not rare (Eisen et al., 1997). Given that the obsessional content is not related to psychotic subject matter, both disorders can be regarded as delimitable diagnostic entities (Bottas et al., 2005). Recently, a number of case reports and small case series have demonstrated that deep brain stimulation (DBS) targeting the fronto-striato-thalamic circuit can have beneficial effects on OCD (Abelson et al., 2005; Greenberg et al., 2006; Sturm et al., 2003). DBS treatment of patients with current or past psychotic disorders has not yet been reported. Here, we present a comprehensive clinical evaluation of a woman with intractable OCD and residual symptoms of schizophrenia that were treated with unilateral DBS of the right nucleus accumbens (NAc), including neuropsychological long-term follow-up, neurophysiological measurements and functional brain imaging. This 51-yr-old right-handed woman suffered from a severely disabling, chronic and intractable form of OCD with excessive hand washing, cleaning, rearrangement of objects and compulsory praying [Yale–Brown Obsessive Compulsive Scale (YBOCS) score 32/40, 1 month prior to treatment]. Psychosocial functioning as measured by the GAF (Global Assessment of Functioning) scale was severely impaired (31/100). The symptoms started during childhood and accumulated during her early twenties. Obsession consisted of preoccupation with thoughts about guilt and purgation. Later in the course of the disease, psychotic symptoms (delusions, hallucinations, disorganized behaviour) meeting DSM-IV criteria for schizophrenia occurred transiently. The remaining presence of a few odd beliefs, minor paranoid ideation and disorganized behaviour in an attenuated form that were unrelated to the obsessions and compulsions led to the diagnosis of residual schizophrenia according to DSM-IV using SCID (Structured Clinical …

Differential therapy effects of psychoeducational psychotherapy for schizophrenic patients – results of a 2-year follow-up

Abstract There is increasing evidence of the efficacy and effectiveness of psychosocial interventions in schizophrenic patients. However, little research has been done on differential therapy effects. In a prospective, randomized clinical trial we carried out psychoeducational medication management training, cognitive psychotherapy, and key-person counseling. The patients of the control group participated in structured free-time activities for control of therapeutic commitment. Data from a total of 156 schizophrenic patients (DSM-III-R, no first-admissions) were available at 2-year follow-up. We analyzed in this study whether there are differential therapy effects of these interventions, depending on patient characteristics at baseline. There was a significant statistical interaction between treatment condition (specific/non-specific) and prognosis with respect to treatment outcome. Patients with a favorable prognosis and better social functioning had a better course under the specific treatment but a less favorable outcome in the non-specifically treated control group. These results suggest that more vulnerable patients are not sufficiently capable of learning and using coping strategies for relapse prevention. We need to learn more about differential indications for psychosocial treatment.