[Concept and results of the German Research Network on Schizophrenia]. / Konzept und Ergebnisse des Kompetenznetzes Schizophrenie.

BACKGROUND: The German Research Network on Schizophrenia (GRNS) was funded by the Federal Ministry of Education and Research (BMBF) from 1999 to 2011. The aim was to obtain a better horizontal and vertical networking of German research and care facilities on schizophrenia, in order to investigate open research questions, to transfer the results into clinical practice and improve care and quality of life in patients with schizophrenia. OBJECTIVES/METHODS: This paper describes the concept and operations of the GRNS as well as its results on the basis of selected research projects. RESULTS: The GRNS comprised about 25 clinical trials of high practical relevance, which were closely interrelated regarding content, methodology and organization. The trials primarily served the development and evaluation of new and established diagnostic and therapeutic approaches, the assessment of the status quo of clinical care, as well as its improvements, together with the investigation of basic scientific questions. Many substantial results to highly relevant issues were obtained, which led or will lead to an improvement in mental health care. CONCLUSIONS: Quantitative and qualitative evaluation parameters, such as scientific publications and obtaining additional grants, as well as promotion of young scientists, public relations activities, congress activities and the foundation of a European Schizophrenia Association, document the successful work of the network. Successful funding requests will allow us to continue cooperative schizophrenia research in Germany as initiated by the GRNS, without necessarily always binding these activities formally to the GRNS.

[12 years of competence network schizophrenia: results and perspectives]. / 12 Jahre Kompetenznetz Schizophrenie: Ergebnisse und Perspektiven.

The German Research Network on Schizophrenia (GRNS) was funded by the Federal Ministry of Education and Research (BMBF) from 1999 to 2011. The objectives and the structure of the network with its horizontal and vertical networking of German research and care facilities served for the scientific investigation of open research questions for schizophrenia, and the transfer of the results into clinical practice. In this paper, the functioning and results of the GRNS are described on the basis of selected research projects. Quantitative and qualitative evaluation parameters such as scientific publications and additional external funds, as well as promotion of young scientists, public relations activities, congress activities and foundation of an European Schizophrenia Association demonstrate the successful work of the network. As a final point, the funding programme of the BMBF is critically evaluated using the example of the GRNS and future funding prospects are outlined.

Evaluation of a cognitive behaviourally oriented service for relapse prevention in schizophrenia.

OBJECTIVE: There is little work demonstrating the effectiveness of cognitive behaviourally oriented interventions in routine service settings. This pragmatic trial is designed to test the impact of a group treatment service on relapse rates under the conditions of routine health care. METHOD: A total of 169 schizophrenia patients were randomly allocated either to a comprehensive cognitive behaviourally oriented service (CBOS) or to treatment as usual (TAU). The primary outcome is the time until the first relapse after discharge from hospital. Relapse was defined as an increase in positive or negative symptoms as assessed with the Positive and Negative Syndrome Scale. Survival analysis has been conducted up to the 6-month assessment. RESULTS: The mean time to relapse after discharge from hospital in the CBOS group was significantly longer than in the TAU group (log rank test, P = 0.033). This was due to less exacerbations regarding negative symptoms in the CBOS condition (log rank test, P = 0.014). The number of social contacts was improved in the CBOS group only. CONCLUSION: The CBOS intervention appears to be beneficial in reducing early negative symptom exacerbations.

[New developments in psychotherapy for schizophrenic psychoses]. / Neue Entwicklungen in der Psychotherapie schizophrener Psychosen.

There already exists sufficient evidence of the efficacy of psychotherapeutic interventions, in particular cognitive behavioral therapy, for symptom reduction and relapse prevention. Evidence-based treatment guidelines recommend this approach for routine care. An increasing number of randomized clinical trials and research on active elements of treatment characterize this field. This paper presents research and clinical implications. Treatment strategies for reducing positive and negative symptoms, which represent an innovative field of research, are presented and discussed in terms of efficacy, treatment principles, and possible future developments.

Frontal brain asymmetry as a biological substrate of emotions in patients with panic disorders.

BACKGROUND: Right frontal hemisphere activation, as indicated by reduced frontal alpha amplitude, seems to represent activation of an avoidance-withdrawal system and seems to be associated with negative emotions. Since patients with panic disorder are characterized by both negative emotions and avoidance-withdrawal behavior, we expected them to show greater right than left frontal hemisphere activation. METHODS: Spontaneous electroencephalography was recorded from the left and right frontal and parietal scalp regions of 23 patients with panic disorder patients without a diagnosis of depression and from 25 healthy control participants during the following conditions: rest, confrontation with neutral, panic-relevant, anxiety-relevant but panic-irrelevant, or anxiety-irrelevant but emotionally relevant stimuli, and performance of a motor task. Their emotional state during these conditions was assessed by the Self-Assessment Manikin. RESULTS: In patients with panic disorders, there were asymmetries in frontal hemisphere activation during resting phases and when confronted with anxiety-relevant stimuli. Their right frontal alpha power was significantly decreased compared with the left, while control participants did not show frontal brain asymmetry during these phases. There was no frontal brain asymmetry when patients observed an emotionally neutral picture or performed a motor task. Under these conditions, left and right frontal hemisphere alpha activation of patients with panic disorder and healthy participants were comparable. CONCLUSIONS: These data support the hypothesis that patients with panic disorder are characterized by greater activation of a right frontal avoidance-withdrawal system in negatively valenced situations. The findings are interpreted as biological evidence for a disturbed cortical processing in patients with panic disorder.

Behavioral and neurophysiological evidence for altered processing of anxiety-related words in panic disorder.

Body-related and nonsomatic words were presented tachistoscopically to 15 panic patients and 15 healthy controls at each participant's threshold for correctly identifying 50% of neutral words. Behavioral (proportion of words correctly recognized) and electrocortical (event-related brain potentials [ERPs]) measures were registered. Panic patients recognized more body-related than nonsomatic words, and body-related as compared with nonsomatic words elicited, in these patients, significantly larger P300 amplitudes and enhanced positive slow waves (600 to 800 ms after stimulus presentation). In healthy controls, the number of correct recognized words and the ERPs were not differentially affected by the 2 word types. These results are grossly consistent with cognitive models of panic disorders, assuming that certain bodily sensation are perceived and processed in an affective manner that differentiates panic patients from healthy controls.

Left prefrontal activation predicts therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) in major depression.

There is evidence that repetitive transcranial magnetic stimulation (rTMS) applied to the prefrontal cortex has antidepressive properties. In the present study we evaluated the clinical status and the hemodynamic responses during mental work in the prefrontal cortex before therapeutic rTMS. Twelve patients diagnosed with major depression (DSM-IV) were randomized in a sham-controlled cross-over treatment protocol of 4 weeks' duration consisting of two periods of 5 days with rTMS separated by 9 days of no stimulation. rTMS (10 Hz) was applied to the left dorsolateral prefrontal cortex. Hemodynamic changes in the prefrontal cortex during mental work were evaluated by multi-site near-infrared spectroscopy (NIRS). Scores on the Hamilton Depression Rating Scale (HAMD) decreased significantly by -5.4 points after 5 days of active stimulation, whereas it did not change (+1.6 points) after sham stimulation. Absence of a task-related increase of total hemoglobin concentrations at the stimulation site (P<0.005), but not at other locations, before the first active rTMS significantly predicted the clinical response to active rTMS. Clinical benefits of rTMS are predicted by low local hemodynamic responses and support the idea of activation-dependent targeting of rTMS location.

The dopamine D2 receptor (DRD2) gene-a genetic risk factor in heavy smoking?

Indications of a genetic predisposition to nicotine dependence have been derived from numerous epidemiological data and from individual genetic studies suggesting the involvement of the dopaminergic D2 receptor. Previous association studies defined the TaqlA polymorphism as a risk factor for addiction, in particular for alcoholism and tobacco dependence. Results of investigations into this polymorphism in 110 severely addicted smokers and a control group of 60 population-matched German non-smokers did not support these findings. However, our results indicate an association between the DRD2-Fokl-1 allele and the onset and intensity of smoking.

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.

Combination of behavioral smoking cessation with transdermal nicotine substitution.

Effects of a transdermal nicotine substitution on psychological smoking cessation were investigated in a double-blind prospective study. 131 smokers were randomly assigned to three treatment conditions: All smokers underwent nine weeks of self-controlled smoking cessation. During six weeks one group was additionally treated with nicotine patches continuously releasing nicotine through the skin into the blood circuit. The second group received placebo patches; while the third group was treated with behavioral training alone. Treatment effects were measured by daily cigarette consumption. Nicotine-treated subjects reached significantly higher abstinence rates during and at the end of treatment than both placebo- and control-subjects: 69% in the nicotine condition, 51.2% and 44.4% under placebo and control conditions respectively. Effects are influenced by initial cigarette consumption, with the light smokers benefitting most from the nicotine patch. Self-assessments suggest an aversive effect of transdermal nicotine on cigarette taste. Our results, although not yet verified by long-term observations, demonstrate that transdermal nicotine substitution significantly enhances the effectiveness of behavioral smoking cessation methods.

Emotional family atmosphere and relapse: investigations on the role of relapse definition, duration of illness and resignation of relatives.

An analysis of existing studies on the expressed emotion (EE) concept shows that the predictive validity of the EE index depends on the definition of relapse. Whilst symptomatic relapses are recorded in patients from high-EE families, about 3 times as often as in patients from low-EE families, a comparison of hospitalization rates reveals a difference of only approximately 1.5 times. In the Münster Families Study, a prospective intervention study to evaluate the therapeutic impact of relatives' groups, the predictive value of the familial emotional atmosphere could be measured in a prospective design. Ninety-nine DSMIII Schizophrenics, 72 male, 27 female, mean age 27 (SD 6.6), mean duration of illness 5.5 (SD 4.3) were followed up. In the first eighteen months patients from high-EE- families had a risk of rehospitalisation approximately 1.5 (p < 0.05). Further analysis showed that relapse rates among patients from high-EE and low-EE families were roughly the same for patients with a duration of illness of less than 4.5 years but were significantly different after a longer duration (p = 0.019). Besides a high EE rating, resignation of relatives was also a significant (p = 0.000) predictor of rehospitalisation for high and - even more - low EE families. Possible causes of these findings and therapeutic consequences are discussed.

Electroconvulsive therapy: a review on indications, methods, risks and medication.

This paper reviews and presents data of practical impact for those administering electroconvulsive therapy (ECT). In the first section, physical and physiological aspects of the stimulus as well as methods of stimulation are discussed. The second section deals with indications for ECT, efficacy and treatment modalities such as seizure duration, treatment frequency and total number of ECT applications. The last section is devoted to side effects, risks, comedication and comorbidity.

Expressed emotion in an 8 year follow-up.

This study addresses the questions if and for which patients expressed emotion (EE) has a predictive validity in an 8 year follow-up study and if this is dependent on the residential form, especially on patients and relatives living together. Eight years after a baseline examination (Camberwell Family Interviews [CFI], global assessment scale [GAS], symptom score) 69 of 99 patients were reexamined. The number and duration of rehospitalizations as well as the symptom and GAS scores were recorded. These was no difference between outcome of high and low EE patients with a duration of illness of less than 4.5 years and for those living with partners. Patients from high EE parents with a longer duration of illness (> 4.5 years) at the outset of the study were significantly more often and longer in hospital. They had significantly higher symptom and GAS scores at the outset of the study and after 8 years. The EE effect was equal in the first and second 4 years of the follow-up and was independent from patients and parents living together. The results emphasize the significance of the EE index as a long-term predictor for the course of schizophrenic illness. The independence of the prediction from living together is an argument against a simple causal interpretation of the connection between EE and the course of schizophrenia.

The impact of therapeutic relatives' groups on the course of illness of schizophrenic patients.

This study considers the question of whether relapse rates among schizophrenic patients can be reduced by means of relatives' groups. In a randomized, controlled intervention study, two therapeutic strategies (therapeutic relatives' groups, initiated relatives' self-help groups) were compared with each other and with a control group. Interventions were confined to the relatives, with the patients continuing their standard treatment. The study involved 151 relatives of 99 chronic DSMIII schizophrenics. Data were collected before and after a 1-year intervention phase and in a 2-year follow-up. No difference existed between the groups with respect to rehospitalization data. However, numerous differences recorded in the psychopathological findings and in living and working circumstances suggest that therapeutic work with relatives is of clinically significant benefit.

Psychiatrists meet on the web: the chance for a virtual congress. Results and experiences from the First International Internet Congress on Psychiatry 1997.

From December 1-31, 1997, the Department of Psychiatry and Psychotherapy in co-operation with the Department of Information Technology, University of Tübingen, Germany, organised the first virtual congress on psychiatry in the Internet. The congress was aimed at facilitating exchange of results of psychiatric studies and ideas and at stimulating discussion among interested colleagues. Almost 100 participants from 17 countries on four continents took part in this event. Sixteen contributions were presented and discussed. The problems and opportunities of this medium in the organisation and running of congresses are presented and discussed. The experience gained in this congress suggests that the Internet will find increasing use as a medium for medical congresses within the next few years.

Antinuclear antibodies in schizophrenia and major depressive disorder - a lasting puzzle.

Sera from patients with major depressive disorder and paranoid schizophrenia were screened for antinuclear antibodies (antigens: ds-DNA, ENA, histone H3) and circulating immune complexes (CIC-Cq1) by ELISA. Controls were healthy blood donors. Only a few of the patients' sera were positive for anti-ds-DNA and anti-ENA antibodies. There was no significant result. In paranoid schizophrenia 20.5% of sera were positive for antibodies against histone H3. In the case of CIC-Cql, 7% of the patients with major depressive disorder and 11 % of those with paranoid schizophrenia were positive. Controls showed positive sera in 39%. This study disagrees with former studies which could demonstrate a series of antinuclear antibodies in mental disorders. In the case of antihistone antibodies, the present results could indicate an autoimmune process in a subgroup of schizophrenic patients.

Efficiency of multimodal smoking cessation therapy combining transdermal nicotine substitution with behavioral therapy.

Effects of smoking cessation treatment combining transdermal nicotine substitution with behavioral therapy were investigated in three studies. A total of 535 smokers underwent 9 weeks of behavioral self-control treatment. For 7 weeks, groups with transdermal nicotine substitution received in addition nicotine patches that continuously released nicotine through the skin into the circulatory system. The effects of treatment were measured by daily cigarette consumption. Subjects additionally treated with transdermal nicotine substitution reached significantly higher abstinence rates by the end of treatment and during the follow-up period than control subjects. The results thus indicate enhanced therapeutic effectiveness of transdermal nicotine substitution.

The effect of different dosages of a transdermal nicotine substitution system on the success rate of smoking cessation therapy.

The effectiveness of different nicotine dosages on abstinence rates was investigated in a smoking cessation study. One hundred smokers underwent nine weeks of self-controlled treatment based on behavioral principles. The overall group was divided into two subgroups randomized according to sex, cigarette consumption and age. The first group (n = 51) was given a nicotine dose adapted to daily cigarette consumption. The second group (n = 49) was given a standardized dose. There was, unexpectedly, no difference between the two groups in respect to short-term abstinence rates. These results suggest that standardized dosage is preferred to individually adapted dosage.

Contact allergies induced by TTS-treatment.

The efficiency of a nicotine-containing transdermal therapeutic system (TTS) was investigated in a clinical study, the purpose of which was to help 183 heavy smokers give up their addiction by systematic and continuous nicotine application and simultaneous behavioral therapy. During the treatment period, 53% of the patients complained of pruritus and 39% developed erythemas that were almost exclusively confined to those areas where the patches had been applied. However, most symptoms appeared only in slight or moderate forms. In contrast to irritative cutireactions, 6 patients developed a genuine contact allergy (type IV, delayed type reaction) which proved in 5 cases to be induced by the nicotine contained in the patches. Presumably TTS-treatment may induce contact allergies to pharmaceutic agents, as has already been described in other observations on allergies to haptens.

[Experiences of schizophrenic patients in ambulatory care with oral neuroleptics--baseline for psychoeducational interventions]. / Erfahrungen ambulanter schizophrener Patienten mit oralen Neuroleptika--Befundbasis für psychoedukative Interventionen.

In the run-up to a prospective intervention study to assist the preparation of psychoeducational therapeutic measures, schizophrenic out-patients were questioned on their experiences with two oral neuroleptics, Clozapine and Perazine. The two drugs, which are known to have similar side effects, find equal acceptance among patients. Subjective attitudes to medication and general evaluations of drug therapy are extremely positive. Numerous patients had already modified their neuroleptic dosage on their own initiative, in most cases discontinuing their medication but in some cases increasing or reducing the dose. These experiences can be used in designing a psychoeducational intervention directed towards individual needs.