Michaela Jänner

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.

Detection of changed regional cerebral blood flow in mild cognitive impairment and early Alzheimer's dementia by perfusion-weighted magnetic resonance imaging

The utility of perfusion-weighted magnetic resonance imaging (PW-MRI) for detecting changes in regional cerebral blood flow (rCBF) in patients with mild cognitive impairment (MCI) and early Alzheimers disease (AD) was evaluated. Thirteen cognitively normal (CN) elderly subjects, 35 mostly amnestic MCI subjects and 20 subjects with mild probable AD were enrolled. During i.v. injection of gadopentetate dimeglumine, a dynamic T2*-weighted single-shot EPI sequence was conducted using a 1.5-T scanner. Frontobasal (FROB), temporoparietal (TPAR), mesiotemporal (MTMP), anterior and posterior cingular (ACING, PCING), amygdala (AMYG), thalamus and cerebellar brain regions were studied. rCBF was computed from regional cerebral blood volume and arterial input function and normalised to white matter. Images were analysed by manually placed regions of interest using anatomical coregistration. Significant decreases of rCBF were detected in MCI vs. CN in MTMP (-23%), AMYG (-20%) and ACING (-15%) with no further decline in mild AD. In PCING hypoperfusion (-10%) was confined to AD. These hypoperfusional changes are a possible correlate of localised impairment of CNS function. In FROB no perfusion changes were observed between diagnostic groups, but hyperperfusion was observed in mild dementia stages, possibly reflecting functional compensatory mechanisms. These data suggest that PW-MRI detects specific changes in rCBF not only in AD, but also in amnestic MCI, a disorder suggested to largely represent a pre-dementia stage of AD. This method may thus be useful in both research and clinical applications to detect early functional brain changes in the pathogenesis of dementias.

Die Elektrokrampftherapie in psychiatrischen Kliniken der Bundesrepublik Deutschland 1995

ZusammenfassungEs wurde eine Umfrage unter 451 bundesdeutschen Kliniken im Jahr 1995 zur Anwendung der Elektrokrampftherapie (EKT) durchgeführt, die Vergleichsdaten zu 2 Umfragen aus den Jahren 1977 und 1985 und Informationen aus den neuen Bundesländern erbringen sollte. Die EKT steht als therapeutisches Verfahren grundsätzlich nicht mehr zur Diskussion. Die Anwendungshäufigkeit hat sich in den knapp 20 Jahren zwischen der ersten und dieser Studie insgesamt deutlich erhöht. Die Verteilung der Standorte der Kliniken, die häufig die EKT anwenden, ist ungleich über das Gebiet der BRD verteilt. Hauptindikationen für die EKT sind febrile Katatonie/febriler Stupor und depressiver Stupor. Depressionen werden als Indikation angeführt bei Psychopharmaka-Resistenz/-Unverträglichkeit. Die Modi der Vorbereitung und Durchführung entsprechen den Standards. Die Einstellungen der leitenden Ärzte zur EKT wurden eruiert und mit Daten einer Umfrage aus dem Jahre 1985 verglichen. Die positiven Stellungnahmen zur EKT sind richtungsgleich sind, fallen 1995 aber pointierter aus. Insgesamt zeigt sich, daß die EKT als Therapieverfahren innerhalb der leitenden Ärzteschaft sehr positiv gesehen wird; die Koppelung an eine enge Indikation gilt allgemein als Voraussetzung. Von dieser grundsätzlichen Einstellung ist die tatsächliche Anwendung der EKT nur bedingt abhängig, soziale Faktoren wie z.B. Haltung der Mitarbeiterschaft, politische Einstellung und Stereotypien der Bevölkerung beeinflussen die Anwendung in Richtung Zurückhaltung bzw. Nichtanwendung oftmals mehr.SummaryA total of 451 German psychiatric hospitals were asked in 1995 about their use of electroconvulsive therapy (ECT). As ECT nowadays is well accepted as a therapeutic tool, we wanted to compare our data with data collected in former inquiries in 1977 and 1985 and to acquire information from the new German States. Since 1977, the use of ECT has evidently increased. The psychiatric hospitals that often use ECT are for scattered throughout the whole country. ECT is mainly indicated for febrile catatonia/febrile stupor and depressive stupor, not for schizophrenia. ECT is applied especially when depressive patients are resistant or intolerant of psychopharmacotherapy. The preparation and application correspond to the standards. One focus in the present study was the attitudes of the managing directors towards ECT. Data were collected by open questionnaires. When these data were compared with data from a standardized inquiry of 1985, a similar trend was found regarding positive statements about ECT. Statements are emphasized even more when using open questionnaires. If there is a strong indication for ECT, the basic attitudes of the managing directors toward ECT are very positive. However, its application is in fact much more influenced by social factors than by indication because of negative attitudes by colleagues and nursing staff and political and stereotypic thinking of the general population.

Blood biomarkers of osteoporosis in mild cognitive impairment and Alzheimer’s disease

Previous studies revealed some comorbidity of Alzheimer’s disease and osteoporosis not only for advanced disease, but also for the incipient conditions cognitive decline and decline of bone mineral density. To detect comorbidity with osteoporosis at a subclinical level, we studied concentrations of biochemical osteoporosis markers in blood plasma of subjects with mild cognitive impairment and mild Alzheimer’s disease compared to subjects with primary osteoporosis and age-matched cognitively normal controls in an explorative approach. Regarding disease-spanning molecular pathology we also studied osteoprotegerin, a decoy receptor of RANKL and TRAIL. Equally increased C-terminal collagen fragments, marking bone catabolism, were seen in osteoporosis and Alzheimer’s disease (+68%) versus controls. Osteocalcin, marking bone remodelling and anabolism, was concomitantly increased in osteoporosis (+63%), as a trend, and significantly in Alzheimer’s disease (+76%). Osteoprotegerin was unchanged between patient groups and controls. 25 (OH) vitamin D plasma levels were low normal and of equal amount in all groups except for the osteoporosis group. These results point to increased bone catabolism and concomitant remodelling/anabolism unrelated to vitamin D state in mild Alzheimer’s disease, but not in mild cognitive impairment. This corroborates previous findings of comorbidity of Alzheimer’s disease with osteoporosis in the early disease course at the level of biochemical blood markers. Regarding osteoprotegerin, previously reported plasma level increases in Alzheimer’s disease were not observed in this study, which does not rule out subtle changes to be detected in larger samples or the possibility that other components of osteoprotegerin pathways are affected in Alzheimer’s disease.

The relation of regional cerebral perfusion and atrophy in mild cognitive impairment (MCI) and early Alzheimer's dementia

The spatial and temporal relations between regional cerebral blood flow (rCBF) and brain volume (rVOL) changes in incipient and early Alzheimers dementia (AD) are not fully understood. The participants comprised 30 subjects with mild cognitive impairment (MCI) and 15 with mild AD who were examined using structural and perfusion-weighted magnetic resonance imaging (MRI) at 1.5 Tesla. Hippocampus and amygdala volumes were measured by manual volumetry. A region-of-interest co-localisation method was used to calculate rCBF values. DNA samples were genotyped for apolipoprotein E (APO E). In comparisons of AD with MCI, rCBF was reduced in the posterior cingulum only, while profound rVOL reductions occurred in both right and left amygdala and in the right hippocampus, and as a trend, in the left hippocampus. Brain volumes of the hippocampus and the amygdala were uncorrelated with the respective rCBF variables in both MCI and AD. Hippocampal but not amygdalar volumes were associated with presence of one or two APOE epsilon4 alleles in MCI and mild AD, while there was no association of APOE epsilon4 allele with rCBF. These data support earlier indications that rCBF and rVOL changes are at least partly dissociated in the early pathogenesis of AD and heterogeneously associated with the APOE risk allele. The data also support the concept of functional compensatory brain activation and the diaschisis hypothesis as relevant in incipient and early AD.

Externe Qualitätssicherung der stationären Behandlung schizophrener Patienten Ergebnisse einer multizentrischen Studie

ZusammenfassungIn einem vom BMG geförderten 2-jährigen Projekt wurde anhand von insgesamt 1042 Behandlungsfällen an 4 psychiatrischen Kliniken unterschiedlicher Struktur in Nordrhein-Westfalen die Voraussetzung für eine externe Qualitätssicherung mit Hilfe der Tracer-Diagnose Schizophrenie geschaffen und durchgeführt. Ziele waren die Evaluation eines Erhebungsinstrumentariums, die Entwicklung von Qualitätsindikatoren und der Aufbau eines Rückmeldesystems zur Optimierung des internen Qualitätsmanagements. Anhand der erhobenen Daten ist es auf wissenschaftlich-statistischer Basis gelungen, Qualitätsindikatoren und eine vergleichende Art der Rückmeldung zu entwickeln, die neben Ergebnisvariablen auch Struktur-, Patienten- und Prozessvariablen beinhaltet. Diese Qualitätsprofile bilden einen wesentlichen Ausgangspunkt für krankheitsspezifische Problemanalysen im Rahmen eines internen Qualitätsmanagements.SummaryDue to legal regulations, external quality assurance is mandatory in Germany. Supported by the German Health Ministry (BMG),we present the results of a multicenter study in four hospitals with different structures on 1042 inpatients with the trace diagnosis of schizophrenia (ICD 10). We defined disease-specific indicators of structure, process, and outcome quality, developed an assessment instrument, and implemented a feedback system for quality comparison. The resulting quality profiles are useful as a starting point for internal quality management.

Prodromal States in Schizophrenia

The vulnerability-stress-coping (VSC) model is the most influential heuristic concept in understanding the course of schizophrenia, whose prodromal status still offers unsolved conceptual and methodological issues. Improved knowledge about the prodromal phase would provide a better understanding of the developing psychopathology and psychophysiology of schizophrenia and could also be of predictive value to attune therapeutic actions to the course of the illness more precisely. To shed more light on the characteristics of prodromal states, data from a German multicenter study on intermittent versus maintenance neuroleptic long-term treatment in schizophrenia (ANI study) were reanalyzed with respect to the prevalence and profile, nature, time course, and predictive value of prodromal symptoms in impending relapse. The results demonstrate that prodromes are a category of symptoms on their own, but they share variance with other symptom domains. Treatment side effects, psychotic symptoms, dysphoric mood, and social dysfunction are all associated with prodromal states--the direction of this association, however, is still to be clarified. Prodromal symptoms are also related to the neuroleptic treatment strategy and its relapse-preventive efficacy--findings that underscore neuroleptic maintenance medication in preventing both overt and subthreshold psychotic morbidity in schizophrenia.

A novel MRI-biomarker candidate for Alzheimer's disease composed of regional brain volume and perfusion variables.

Background:  Earlier evidence indicates that regional cerebral volume (rVOL) and blood flow (rCBF) variables carry independent information on incipient and early Alzheimer’s disease (AD) and combining these modalities may increase discriminant performance. We compared single variables and combinations regarding their power for optimizing diagnostic accuracy.

PATIENTENVERFUGUNGEN UND BEVOLLMACHTIGUNGEN IN GESUNDHEITLICHEN ANGELEGENHEITEN ALTERER PSYCHISCH KRANKER MENSCHEN

ZusammenfassungDie Patientenverfügung und die Bevollmächtigung in gesundheitlichen Angelegenheiten sind zwei in ihrer rechtlichen Verbindlichkeit gegenwärtig noch ungeklärte Instrumente, mit denen eine Person über den Zeitpunkt eines krankheitsbedingten Verlustes ihrer Einwilligungsfähigkeit hinaus Einfluß auf sie betreffende medizinische Entscheidungen nehmen kann. Im klinischen Alltag diagnostischer und therapeutischer Maßnahmen, aber auch bei der Durchführung von Forschungsvorhaben sind solche Schriftstücke für die Ermittlung des Willens bei einwilligungsunfähigen Patienten im Rahmen von Entscheidungen über die Vornahme oder das Aussetzen medizinischer Interventionen sehr bedeutsam. In einer nichtrepräsentativen Fragebogenerhebung bei 206 psychisch kranken älteren Personen in stationärer psychiatrischer Behandlung ergab sich, daß die Mehrzahl der Befragten (62,7%) die Erstellung derartiger Dokumente grundsätzlich befürwortet. Dabei lagen bereits bei 5,4% aller interviewten Personen Dokumente in schriftlich gefaßter Form vor. Immerhin lehnten aber rund ein Viertel der Befragten die Erstellung dieser Dokumente als nicht sinnvoll ab, während sich 12,5% weder dafür noch dagegen entscheiden konnten. Das Alter der Patienten bei Befragung, das Geschlecht und die zum Zeitpunkt der Untersuchung bestehende Erkrankung waren mit dem Zustimmungsverhalten nicht verknüpft. Lediglich ein hoher Ausbildungsstand war mit der Befürwortung von Patientenverfügungen assoziiert. Die durchgeführte Untersuchung zeigt, daß in einer relativ großen Stichprobe von älteren Personen mit einer psychischen Erkrankung die Erstellung von Patientenverfügungen und gewillkürten Stellvertretungen mehrheitlich befürwortet wird. Die Studie weist auch darauf hin, daß eine intensivere Aufklärung in der Bevölkerung über die Möglichkeiten erforderlich scheint, auf welche Weise in schriftlicher Form Vorkehrungen für den Zeitpunkt des Verlustes der eigenen Einwilligungsfähigkeit in bezug auf medizinische Entscheidungen getroffen werden können.SummaryIn clinical practice and in research projects the presence of an advance directive or an appointment of a health-care proxy may substantially contribute to decisions of diagnostic and therapeutic interventions, if a person has lost his ability to consent. A special questionnaire was given to a non representative sample of 206 elderly inpatients suffering from different psychiatric disorders. The majority of these patients (57%) supported the necessity of such instruments. In a further 5,4% of the interviewees written documents, either advance directive or determination of a health-care proxy, were already present. However, 25% of the interviewed patients did not approve of the usefulness of these instruments and 12,5% answered that they were not able to give any decision. Among the interviewed patients, age, gender and the psychiatric disorder present were not associated with approval or refusal. However, higher education was related to the approval of advance directives.This study demonstrates that in a relatively large sample of elderly patients with psychiatric disorders approval of an advance directive and a determination of a health-care proxy is present in a substantial majority. The results suggest that there is urgent need for more intensive information of elderly people about these documents. This could contribute to a decision process about medical interventions in incapacitated persons which is in accordance with their former will.

Estrogen receptor beta polymorphisms and cognitive performance in women: associations and modifications by genetic and environmental influences

Genetic and environmental risk factors contribute to the pathogenesis of Alzheimer’s dementia. Besides known genetic risk factors like the apolipoprotein (APO) Eε4 allele, single nuclear polymorphisms (SNPs) of the estrogen receptors (ESRs) are candidate genetic risk factors, while air pollution represents an environmental risk factor for dementia. Effects of these risk factors and their interaction were investigated in the SALIA cohort of 834 non-demented elderly women. Cognitive function was assessed by the CERAD-plus test battery. Air pollution was estimated by land use regression (LUR) models. Genotyping was carried out for nine ESR1 and ESR2 SNPs and two ApoE SNPs. Carriers of minor ESR2 alleles showed significantly reduced cognitive performance in the CERAD total score with most pronounced deficits in semantic memory (rs1256062, rs10144225, and rs2274705) and executive function (rs1256062). The minor allele effects of ESR2 were stronger in carriers of APOEε4 for the cognitive domain ‘executive function’ (p value of interaction 0.023 for rs1256062). The investigated ESR1 SNPs were not associated with cognition. Furthermore, we found a significant gene–environment interaction between the ESR2 SNP rs1256062 and air pollution on cognition. Carriers of two major alleles of rs1256062 were more susceptible for an air pollution-induced decrease in performance of ‘figure copying’ than carriers of minor alleles (p value of interaction, e.g., 0.031 for PM2.5). In conclusion, ESR2 but not ESR1 minor alleles were associated with lower cognitive performance in elderly women with an indication of a gene–gene interaction with APOEε4. We also found indications for gene–environment interactions of ESR2 with traffic-related air pollution exposure on cognitive performance.