[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.

Response and remission of subjective well-being in patients suffering from schizophrenia spectrum disorders.

BACKGROUND: Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being. METHOD: The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome. RESULTS: Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission. CONCLUSIONS: Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.

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.

Early improvement as a predictor of remission and response in schizophrenia: Results from a naturalistic study.

OBJECTIVE: To examine the predictive validity of early improvement in a naturalistic sample of inpatients and to identify the criterion that best defines early improvement. METHODS: Two hundred and forty-seven inpatients who fulfilled ICD-10 criteria for schizophrenia were assessed with the Positive And Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the recently proposed consensus criteria, response as a reduction of at least 40% in the PANNS total score from admission to discharge. RESULTS: Receiver operating characteristic (ROC) analyses showed that early improvement (reduction of the PANSS total score within the first 2 weeks of treatment) predicts remission (AUC=0.659) and response (AUC=0.737) at discharge. A 20% reduction in the PANSS total score within the first 2 weeks was the most accurate cut-off for the prediction of remission (total accuracy: 65%; sensitivity: 53%; specificity: 76%), and a 30% reduction the most accurate cut-off for the prediction of response (total accuracy: 76%; sensitivity: 47%; specificity: 90%). CONCLUSION: The findings of clinical drug trials that early improvement is a predictor of subsequent treatment response were replicated in a naturalistic sample. Further studies should examine whether patients without early improvement benefit from an early change of antipsychotic medication.

[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.

Standardized remission criteria in schizophrenia: descriptive validity and comparability with previously used outcome measures.

INTRODUCTION: Standardized consensus criteria for remission in schizophrenia were recently proposed. As yet, the validity of these criteria and their comparability with previously used outcome measures are unclear. METHODS: The symptom-severity component of the proposed remission criteria was applied to 288 inpatients who fulfilled the ICD-10 criteria for schizophrenia. Global functioning and psychopathological symptoms were assessed using GAF, PANSS, SANS, HAM-D and CDSS. RESULTS: When patients with symptom remission at discharge from hospitalization (n=158, 54.9%) were compared to those without symptom remission, significant differences were found with respect to the global functioning (GAF) and all observed psychopathological symptom dimensions. The percentage agreement with previously used outcome measures ranged between 52.6 and 80.0%, the kappa values between 0.120 and 0.594. A moderate accordance (kappa value: 0.495) was found with a Clinical Global Impression (CGI) severity score of three or less. DISCUSSION: The results indicate a high descriptive validity of the symptom-severity component of the proposed remission definition. However, the new criteria differ partially from previously used outcome measures. This aspect should be considered in the interpretation of clinical trials.

Increase of BDNF serum concentration during donepezil treatment of patients with early Alzheimer's disease.

Alzheimer's disease (AD) can be treated with inhibitors of the enzyme acetylcholinesterase (AChE). Recent pre-clinical and clinical studies gave evidence that AChE-inhibitors have neuroprotective effects and thereby a disease-modifying potential. The mechanism of this action is still discussed. In an animal model oral administration of an AChE-inhibitor lead to an increase of brain derived neurotrophic factor (BDNF) in hippocampus and cortex. Recent studies have found a decrease of BDNF in the serum and brain of AD patients with potentially consecutive lack of neurotrophic support and contribution to progressive neurodegeneration. BDNF serum concentrations were assessed by ELISA in 19 AD patients and 20 age-matched healthy controls at baseline and in the AD patients after 15 months of treatment with donepezil 10 mg per day (one patient received just 5 mg). Before treatment with donepezil we found in AD significantly decreased BDNF serum concentrations (19.2 +/- 3.7 ng/ml) as compared to healthy controls (23.2 +/- 6.0 ng/ml, P = 0.015). After 15 months of treatment the BDNF serum concentration increased significantly in the AD patients (23.6 +/- 7.0 ng/ml, P = 0.001) showing no more difference to the healthy controls (P = 0.882). The results of the present study confirm data of prior investigations that a down-regulation of BDNF in serum and brain of AD patients seems to begin with the first clinical symptoms and to be persistent. A treatment with the AChE-inhibitor donepezil is accompanied with an increase of BDNF serum concentration in AD patients reaching the level of healthy controls. Thus, up-regulation of BDNF might be part of a neuroprotective effect of AChE-inhibitors. The molecular mechanism of this potentially disease-modifying mechanism of action of donepezil should be clarified.

Gender specific correlations of adrenal gland size and body fat distribution: a whole body MRI study.

OBJECTIVE: The aim of this study was to investigate the gender specific correlations of stress related tissues [adrenal gland volume (AV), visceral fat] and alimentary dependent fat compartments with cortisol concentrations in healthy male and female subjects. METHODS: Fourteen men and 13 women were examined. Fat compartments [whole body fat, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT)] were determined using whole body MRI. Adrenal gland volume was assessed by a 3D MR data set. The salivary cortisol was determined at 9 AM and 4 PM. RESULTS: Men had significantly more visceral fat and less subcutaneous fat than women. Adrenal gland size correlated significantly with the visceral and subcutaneous fat in women (r=0.7, p=0.008), but not in men (r=0.2, p=0.4). There was a negative correlation between the decrease of cortisol between 9 AM and 4 PM with VAT (r=-0.451, p=0.027) in the whole group. DISCUSSION: The high correlation between the adrenal gland volume and VAT in women underlines the link between hypothalamic-pituitary-adrenal (HPA) axis, stress, and circadian cortisol rhythm, respectively, and an increased abdominal fat volume. The lack of correlation between visceral fat and adrenal volume in men points to an additional influence of sex hormones.

[A pilot project with clowns in psychiatric clinics]. / Clowns in der Psychiatrie? Ein Pilotprojekt.

BACKGROUND: This project examines whether visits of specially trained clinic clowns, as established in pediatrics, would also be useful in psychiatry. METHODS: We describe the effects of a 6-week phase with one clown visit per week in a ward for acutely ill geriatric patients. The patients and medical team were also questioned about their attitudes towards the clowns. RESULTS: We found more positive attitudes in patients after this phase. CONCLUSIONS: We interpret this result as an indication of positive effects and sufficient reason to initiate similar projects in the future.

[Evidence-based psychotherapy of schizophrenic disorders]. / Evidenzbasierte Psychotherapie schizophrener Störungen.

In the past, treatment of schizophrenic disorders was limited to pharmacotherapy. Psychotherapy was not regarded as evidence-based. A number of randomised clinical trials have led to a different perspective during the last two decades. This paper highlights and discusses evidence-based strategies. In particular, cognitive behavioural therapy and family intervention have recently been recommended in evidence-based treatment guidelines. Additionally, psychoeducation and social skills training showed treatment effects. Psychotherapeutic treatment requires an individual case concept. Neuropsychological testing for cognitive deficits should be included in comprehensive assessment in order to avoid overstimulation and optimise rehabilitation. Major treatment goals are to reduce persistent symptoms and relapse rates.

Stage-dependent BDNF serum concentrations in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive decline and loss of neurons in specific brain regions. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain. To our knowledge, the present pilot study assessed for the first time BDNF serum and CSF concentrations in 30 patients with different stages of AD in comparison to 10 age-matched non-demendet controls. AD patients were divided in two groups according to their MMSE score: Group 1 (n = 15) in early stages with MMSE scores >or=21 (mean of 25.5) and Group 2 (n = 15) with more severe stages of dementia with MMSE scores <21 (mean of 13.3). As main results, we found in patients with early stages of probable AD significantly increased BDNF serum concentrations as compared to more severe stages of AD (p < 0.0001) and age-matched healthy controls (p = 0.028). BDNF serum values in all AD patients correlated significantly with MMSE scores (r = 0.486; p < 0.0001). Levels of BDNF were below the detection limit of the assay in unconcentrated CSF samples of AD patients and non-demendet controls.In summary, BDNF serum values are increased in early stages of Alzheimer's disease, which may reflect a compensatory repair mechanism in early neurodegeneration and could also contribute to increased degradation of beta-amyloid (Abeta). During the course of the disease, BDNF is decreasing, which correlates with the severity of dementia. The decrease of BDNF may constitute a lack of trophic support with an increase of Abeta accumulation and thus contribute to progressive degeneration of specific regions in the AD-affected brain. BDNF should be further evaluated as a candidate marker for clinical diagnosis and therapeutic monitoring in Alzheimer's disease.

CADASIL: underdiagnosed in psychiatric patients?

OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is exclusively related to symptoms of the central nervous system. Retrospectively in up to 15% the initial presentation is psychiatric disturbances. In these cases the diagnosis often is delayed or missed. METHOD: Two cases of CADASIL diagnosed in a psychiatric hospital are presented. RESULTS: Both patients were admitted to the gerontopsychiatric department (one because of a suicidal attempt and a depressive episode, the other because of cognitive decline and progressive personal neglect). Brain magnetic resonance imaging (MRI) showed severe leukoencephalopathy in the absence of cardiovascular risk factors. In both cases, diagnosis of CADASIL was made by the identification of specific granular osmiophilic material in skin biopsies. CONCLUSION: Brain MRI should be performed in all cases of late onset of severe psychiatric symptoms. CADASIL should be considered as a possible differential diagnosis whenever a marked leukoencephalopathy is detectable. Diagnosis can be verified by taking a skin biopsy or by specific genetic testing.

Diminished production of proinflammatory cytokines in patients with Alzheimer's disease.

Cerebral inflammation as well as systemic immunological alterations have been reported in Alzheimer's disease (AD). We examined the production of the proinflammatory cytokines interleukin-6, interleukin-12, interferon-gamma, and tumor necrosis factor-alpha in whole blood cell cultures of AD patients and age-matched controls. The production of all measured cytokines after mitogen stimulation is significantly decreased in the AD group compared to controls. The results reflect an attenuated secretory activity of monocytes/macrophages, but also of T-helper cells. The data sustain the assumption that a systemic, possibly age-related alteration of immune mechanisms may play a pathogenetic role in the development of AD.

[Depression in Hashimoto's encephalopathy. Successful treatment of a severe depressive episode with a glucocorticoid as an add-on therapy]. / Depression bei Hashimoto-Enzephalopathie. Erfolgreiche Behandlung einer schweren depressiven Episode mit einem Kortikosteroid als Add-on-Therapie.

Characteristic clinical findings of Hashimoto's encephalopathy (HE) are stroke-like episodes, epileptic seizures, myoclonus, psychosis, and progressive cognitive impairment. Diagnosis of HE is supported by elevated antithyroid antibodies, an abnormal EEG, and by good response to steroids. We report on a 74-year-old female patient with a severe depressive episode who showed no treatment response to citalopram 40 mg/day and venlafaxine 150 mg/day. Diagnostic examination revealed an abnormal EEG, elevated thyroid peroxidase antibodies (TPO-Ab), and older postinflammatory changes in thyroidal sonography. We diagnosed a depression in HE and began treatment with prednisolone 70 mg/day with stepwise dose reduction, continuing treatment with venlafaxine 150 mg/day. Within 4 weeks of treatment, the severe depressive episode disappeared as well as abnormal EEG. In addition, serum values of TPO-Ab decreased. In HE, depressive symptoms can possibly be seen in a subgroup of patients or in the early course of the disease. Diagnosis of HE should be included in diagnostic procedures in cases of therapy-refractory depression because of a good response of HE to steroids.

[Dementia as a primary symptom in late onset multiple sclerosis. Case series and review of the literature]. / Demenz als Erstsymptom bei spät beginnender Multipler Sklerose. Fallserie mit Literaturübersicht.

Cognitive impairment is meanwhile accepted as a well-known symptomatology affecting up to 60% of the patients even in the early disease course of multiple sclerosis (MS). After a longer duration the development of dementia is not unusual. However, cognitive dysfunction as the primary or only manifestation of MS is thought to be rare. We report on four elderly patients referred to the memory clinic of our psychiatric university hospital because of beginning dementia. All of them were found to have evidence of a chronic inflammatory CNS process compatible with the diagnosis of MS. At the beginning of their symptomatology all patients were older than 60 years . Just in one case, progressive gait disturbances beginning after cognitive decline contributed to restriction in the activities of daily living. Data of 239 cases of the literature were reviewed and revealed motor disturbances as the main initial symptom and often a primary progressive course with unfavourable prognosis in late onset MS. Until now dementia as the primary symptomatology has not been described in patients older than 60 years. Possibly MS as a differential diagnosis in dementia as well as cognitive impairment as an initial symptom of MS is under-recognized.

[Alzheimer's disease with secondary Parkinson's syndrome. Case report of a patient with dementia and Parkinson's syndrome after long-term occupational exposure to insecticides, herbicides, and pesticides]. / Präsenile Demenz vom Alzheimer-Typ mit sekundärem Parkinson-Syndrom. Falldarstellung eines Patienten mit Demenz und Parkinson-Syndrom nach jahrelanger nebenberuflicher Insektizid-, Herbizid- und Pestizidexposition.

This case report describes long-term occupational exposure to agricultural insecticides, herbicides, and pesticides as possible environmental risk factors of Alzheimer's disease (AD) and Parkinson's syndrome in a 59-year-old man. Initially the patient complained about disturbances in concentration, mnestic deficits, and problems finding words. In the further course of the disease, he developed Parkinson's syndrome with predominant hypokinesia and rigor in addition to mild-to-moderate dementia. Low levels of beta-amyloid 1-42 were found in the CSF. Electroencephalography showed left frontotemporal theta waves. Cranial MRI revealed general brain atrophy with a maximum biparietally. In cerebral positron emission tomography, general hypometabolism was found with maxima biparietally and left frontally. The possible differential diagnosis of AD and Parkinson's syndrome is discussed.

[Neuroleptics--psychotherapy--psychiatric social work. In schizophrenia help is needed from many sides]. / Neuroleptika--Psychotherapie--sozialpsychiatrische Begleitung. Bei Schizophrenie muss Hilfe von vielen Seiten kommen.

Schizophrenic disorders require a complex, multidimensional treatment strategy. Throughout the entire course of the illness, psychopharmacologic, psychotherapeutic and psychosocial therapeutic measures must be integrated within an overall management plan. Although treatment planning should be orientated to the needs and expectations of the patient, current therapeutic guidelines must also be taken into account. Management decisions are based on such central questions as the patient's ability to cope with the requirements of daily life, or the attitude to the illness of the patient and family members. Inpatient treatment concepts include, in addition to pharmacotherapy, a cognitive-behavioral therapeutic program. In the outpatient setting, the question as to supportive rehabilitation measures and social integration aids needs to be dealt with.

[Effects of autogenic training in elderly patients]. / Effekte von Autogenem Training bei Alteren.

Autogenic training (AT) is a widely available relaxation method with beneficial outcome on physiological and psychological functioning. In our study, we wanted to test the effects of an AT course in cognitively impaired, frail elderly. After a 3 month waiting period (control), AT courses (intervention) of 3 months duration were offered in 2 nursing homes. Thirty-two frail elderly took part in the study, 24 of them had a psychiatric diagnosis (mean age 82.1 +/- 7.2 years, CAMCOG 75.5 +/- 15.7, MMSE 23.3 +/- 4.3, HAMD 10.0 +/- 3.6, NOSGER 57.2 +/- 18.4, AT-SYM 32.9 +/- 17.6 points). Eight participants dropped out during the waiting period, 8 during the course. From the 16 participants, 15 (94%) were able to learn the AT according to subjective, 9 (54%) according to objective criteria. The ability to practice the AT successfully correlated with the CAMCOG (p = 0.001) and the NOSGER (p = 0.01) score. Participants with a dementia syndrome had major difficulties, whereas age, depressiveness, and number of complaints (AT-SYM) had no influence on the ability to learn the AT. There was no intervention effect, measured with the HAMD, NOSGER, AT-SYM and MMSE. In the pre-post comparison of training sessions, a significant improvement in general well being was found (p < 0.001). Mentally impaired, frail elderly participants are able to learn the AT. Cognitive impairment is disadvantageous for a successful participation.

[Cerebral toxocariasis: a rare cause of cognitive disorders. A contribution to differential dementia diagnosis]. / Zerebrale Toxokariasis: seltene Ursache kognitiver Störungen. Ein Beitrag zur Differenzialdiagnostik der Demenz.

We report on a 65-year-old woman with depressive symptoms and cognitive deficits confirmed by psychometric tests. Routine blood tests, serology, EEG, and cranial computed tomography (CCT) being normal, the CSF revealed an eosinophilic reaction and a positive antibody titre against Toxocara canis. After treatment with two oral courses of albendazole, the eosinophils had disappeared, whereas the antibody titre had increased. One year later, the patient's cognitive symptoms had improved, and new antibodies against toxocara were seen in the peripheral blood. This increase in antibodies represents an expected immunological reaction to the increased exposition to toxocara antigen under effective therapy. The infection might go back to the patient's youth, when she was a shepherd for several years and in close contact to dogs. A review of the literature did not yield other reports of toxocara infections leading to cognitive or other psychiatric symptoms. Taking the toxocara infection as the cause of this patient's cognitive defects, we propose that lumbar punction becomes part of the diagnostic standard in differential diagnosis of dementia.