Depression als eine Störung der Stressregulation : Die Rolle von HPA-Achse, Serotonin-Transporter-Polymorphismus 5-HTTLPR und Hippocampusvolumen für die Depressionsentstehung und das Ansprechen auf die antidepressive Therapie

Einleitung: Depressive Störungen gelten schon lange als stressassoziierte Störungen, die vor dem Hinter-grund einer Vulnerabilität, bedingt durch genetische Faktoren und frühkindliche Lernerfahrungen, beim Erleben von Stress ausbrechen. Die Erforschung der biologischen Korrelate und Ursachen dieser stressbe-zogenen Störung hat in den letzten Jahren große Fortschritte gemacht. Metaanalysen belegen beispielswei-se die Assoziation des Serotonin-Transporter-Polymorphismus (5-HTTLPR) mit depressiven Störungen und der mit Depression assoziierten Persönlichkeitseigenschaft Neurotizismus. Das Konzept der Endophänotypisierung nimmt an, dass psychische Störungen „neurobiologisch bedingt bzw. verursacht“ sind. Eine Dysfunktion der Hypothalamus-Hypophysen-Nebennierenrinden-Achse (HPA-Achse) und eine reduzierte Serotoninfunktion an den Thrombozyten werden als erfolgversprechende Endophänotypen an-gesehen. Ebenfalls ist der Hippocampus, welcher der neurotoxischen Wirkung der Glukokortikoide unter-liegt, eine wichtige Hirnstruktur im Zusammenhang mit depressiven Störungen. Methode: Es wurden 220 unipolar depressive Patienten und 203 gesunden Kontrollpersonen hinsichtlich der Ausprägung der biologischen Parameter HPA-Achsen-Aktivität, 5-HTTLPR und Hippocampusvolumen verglichen. Neben der Untersuchung des Zusammenhangs der biologischen Parameter untereinander wie z.B. der postulierten erhöhten Cortisolresponse von S-Allel Trägern des 5-HTTLPR, wurde auch die prädiktive Rolle der drei biologischen Parameter für das Ansprechen auf die fünfwöchige stationäre antidepressive Therapie untersucht. Eingesetzt wurden der Dex/CRH-Test zur Erhebung der Cortisolreaktivität und eine MRT-Untersuchung zur Vermessung des Hippocampusvolumens. Des Weiteren wurden Morgen-Speichelcortisoldaten erhoben und die Genetikvariante 5-HTTLPR typisiert. Ergebnisse: Erwartungsgemäß waren zwei der biologischen Faktoren im Patienten-Kontrollpersonen-Vergleich mit Depression assoziiert. Depressive Männer, besonders diejenigen mit mehreren depressiven Episoden, zeigten einen höheren Cortisolspiegel im Dex/CRH-Test im Vergleich zu Kontrollpersonen. Ein verkleinertes hippocampales Volumen depressiver Patienten mit der ersten und depressiver Patienten mit mehreren depressiven Episoden konnte für den 1,5-Tesla-Scanner im Vergleich zu Kontrollpersonen belegt werden, was auf die Rolle eines verkleinerten Hippocampusvolumens in der Depressionsentstehung hindeutet. Bezüglich der Interaktion biologischer Parameter wurde eine Assoziation des S-Allels mit er-höhten Neurotizismuswerten in der Kontrollstichprobe für Männer und eine erhöhte Cortisol-Antwort im Dex/CRH-Test bei allen depressiven Patienten gefunden. Zusätzlich bestand eine positive Korrelation der Cortisolwerte mit den Neurotizismuswerten. Die depressive Symptomatik besserte sich im Therapieverlauf und korrelierte dabei in der gesamten Patientenstichprobe auf Trendniveau sowohl mit den Cortisolwerten im Dex/CRH-Test als auch mit den basalen Cortisolwerten, was die Theorie stützt, dass eine Nor-malisierung der HPA-Achsen-Hyperreagibilität mit der Besserung der depressiven Symptomatik assoziiert ist. Die Cortisolwerte nach einwöchiger Behandlung und die initiale Cortisolbesserung innerhalb der ersten Woche nach der stationären Aufnahme waren allerdings nicht mit der Besserung der depressiven Symptomatik nach der fünfwöchigen Therapie assoziiert. Einen prädiktiven Wert konnte somit einem einzelnen Dex/CRH-Test zu Beginn der Behandlung nicht zugeordnet werden. Der 5-HTTLPR hatte einen Einfluss auf das Therapieansprechen, wobei sich Träger des SS-Genotyps am schlechtesten besserten. Im Gegensatz zur aktuellen Studienlage konnten wir die Theorie zur Assoziation eines größeren Hippocampusvolumens und einem besseren Therapieansprechen nicht stützen. Schlussfolgerungen: Auf der Suche nach genetischen Varianten und Endophänotypen der Depression er-wiesen sich die hier untersuchten Parameter Hippocampusvolumen, 5-HTTLPR und Cortisol als vielver-sprechende Kandidaten. Weitere Studien zum 5-HTTLPR scheinen erfolgversprechend zu sein, da die vorliegende Arbeit Einflüsse des 5-HTTLPR auf Neurotizismuswerte, Cortisolwerte und die Besserung der depressiven Symptomatik unter antidepressiver Therapie belegen konnten

Novel Schizophrenia Risk Gene TCF4 Influences Verbal Learning and Memory Functioning in Schizophrenia Patients

Background: Recently, a role of the transcription factor 4 (TCF4) gene in schizophrenia has been reported in a large genome-wide association study. It has been hypothesized that TCF4 affects normal brain development and TCF4 has been related to different forms of neurodevelopmental disorders. Schizophrenia patients exhibit strong impairments of verbal declarative memory (VDM) functions. Thus, we hypothesized that the disease-associated C allele of the rs9960767 polymorphism of the TCF4 gene led to impaired VDM functioning in schizophrenia patients. Method: The TCF4 variant was genotyped in 401 schizophrenia patients. VDM functioning was measured using the Rey Auditory Verbal Learning Test (RAVLT). Results: Carriers of the C allele were less impaired in recognition compared to those carrying the AA genotype (13.76 vs. 13.06; p = 0.049). Moreover, a trend toward higher scores in patients with the risk allele was found for delayed recall (10.24 vs. 9.41; p = 0.088). The TCF4 genotype did not influence intelligence or RAVLT immediate recall or total verbal learning. Conclusion: VDM function is influenced by the TCF4 gene in schizophrenia patients. However, the elevated risk for schizophrenia is not conferred by TCF4-mediated VDM impairment. Copyright (C) 2011 S. Karger AG, Base

DAOA/G72 predicts the progression of prodromal syndromes to first episode psychosis

The genetic factors determining the progression of prodromal syndromes to first episode schizophrenia have remained enigmatic to date. In a unique prospective multicentre trial, we assessed whether variants at the d-amino acid oxidase activator (DAOA)/G72 locus influence progression to psychosis. Young subjects with a prodromal syndrome were observed prospectively for up to 2 years to assess the incidence of progression to schizophrenia or first episode psychosis. Of the 82 probands with a prodromal syndrome, 21 probands experienced progression to psychosis within the observation period. Assessment of nine common variants in the DAOA/G72 locus yielded two variants with the predictive value for symptom progression: all four probands with the rs1341402 CC genotype developed psychosis compared with 17 out of 78 probands with the TT or CT genotypes (χ2 = 12.348; df = 2; p = 0.002). The relative risk for progression to psychosis was significantly increased in the CC genotype: RR = 4.588 (95% CI = 2.175–4.588). Similarly, for rs778294, 50% of probands with the AA genotype, but only 22% of probands with a GG or GA genotype progressed to psychosis (χ2 = 7.027; df = 2; p = 0.030). Moreover, haplotype analysis revealed a susceptibility haplotype for progression to psychosis. This is one of the first studies to identify a specific genetic factor for the progression of prodromal syndromes to schizophrenia, and further underscores the importance of the DAOA/G72 gene for schizophrenia

GrassPlot - a database of multi-scale plant diversity in Palaearctic grasslands

GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board

Investigating antecedents and stage-specific effects of customer integration intensity on new product success

This cross-sectional study specifically examines the antecedents and performance consequences of customer integration intensity for B2C industries. In line with this focus, we extend the notion of market-oriented management by explicitly considering the role of customers and retailers as two distinct facets of the market intelligence perspective. Moreover, for new product development in B2C industries, research says little about when customers should be integrated during the new product development process. First, data from 205 firms and evidence from a validation study of 175 firms indicate that customer integration intensity in new goods development positively affects overall new product success. Further, the results show that companies can foster the intensity of customer integration by emphasising both retailer and customer orientation and by establishing an incentive system that comprises new product development-specific components. Second, additional cross-sectional data from 171 firms show that managers need to integrate customers intensively in the development and launch stage and less in the ideation stage for the successful development of new goods. </jats:p

Pricing New Service for Consumer Acceptance: The Influence of Consumer Characteristics and Expectations?

In order to shed more light upon the effect of pricing for the successful launch of service innovations (SIs), we investigate the effect of a high versus low launch price on perceived price fairness and, ultimately, adoption intention and two potential moderators. In a experiment we find that the negative effect of a high versus a low launch price on price fairness is moderated by consumer innovativeness and expected future price reduction. Furthermore, we find price fairness to mediate the pricing strategy-adoption intention relationship. Results help managers to better design pricing strategies for SIs

Pricing Service Innovations: The Influence of Consumer Characteristics and Expectations?

Research has highlighted the importance of the pricing strategy for the successful launch of innovations. Still, pricing service innovations (SIs) is a major challenge for managers. Despite the relative absence of appropriate price comparators in the case of SIs, price fairness is the key link between a new service’s launch price and adoption intention. Consumers’ future price expectations and consumer innovativeness are two potential moderators of the negative effect of new service launch price on perceived price fairness. In an between - subject design experiment (N=123) we find that the negative effect of a high versus a low launch price on perceived price fairness is moderated by consumer innovativeness and expected future price reduction. Furthermore, we find price fairness to mediate the pricing strategy - adoption intention relationship. Results provide valuable insights regarding consumer reaction to launch prices for SIs and help managers to better design pricing strategies for SIs

Pricing Service Innovations: The Influence of Consumer Characteristics and Expectations?

Research has highlighted the importance of the pricing strategy for the successful launch of innovations. Still, pricing service innovations (SIs) is a major challenge for managers. Despite the relative absence of appropriate price comparators in the case of SIs, price fairness is the key link between a new service’s launch price and adoption intention. Consumers’ future price expectations and consumer innovativeness are two potential moderators of the negative effect of new service launch price on perceived price fairness. In an between - subject design experiment (N=123) we find that the negative effect of a high versus a low launch price on perceived price fairness is moderated by consumer innovativeness and expected future price reduction. Furthermore, we find price fairness to mediate the pricing strategy - adoption intention relationship. Results provide valuable insights regarding consumer reaction to launch prices for SIs and help managers to better design pricing strategies for SIs