Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.

Individuals at risk for psychosis experienced a marked impairment of sQoL across all domains. This was evident even in the early state, showed no significant further deterioration during the late state and was predominantly explained by non-specific symptoms.

Background: One reason for the decision to delay the introduction of an Attenuated Psychosis Syndrome in the main text of the fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders was the concern that attenuated psychotic symptoms (APS) might in fact be common features in adolescents and young adults from the general population of no psychopathological significance in themselves. This concern was based on reports of high prevalence rates of psychotic-like experiences (PLEs) in the general population and the assumption that PLEs are a good estimate of APS. Although the criterion validity of self-reported PLEs had already been studied with respect to clinician-rated psychotic symptoms and found insufficient, it had been argued that PLEs might in fact be more comparable with mild, subclinical expressions of psychotic symptoms and, therefore, with APS. The present paper is the first to specifically study this assumption. Sampling and Methods: The sample consisted of 123 persons seeking help at a service for the early detection of psychosis, of whom 54 had an at-risk mental state or psychosis, 55 had a nonpsychotic mental disorder and 14 had no full-blown mental disorder. PLEs were assessed with the Peters Delusion Inventory and the revised Launay-Slade Hallucination Scale, and psychotic symptoms and APS were assessed with the Structured Interview for Prodromal Syndromes. Results: At a level of agreement between the presence of any PLE (in 98.4% of patients) and any APS (in 40.7%) just exceeding chance (κ = 0.022), the criterion validity of PLEs for APS was insufficient. Even if additional qualifiers (high agreement or distress, preoccupation and conviction) were considered, PLEs (in 52.8%) still tended to significantly overestimate APS, and agreement was only fair (κ = 0.340). Furthermore, the group effect on PLE prevalence was, at most, moderate (Cramer's V = 0.382). Conclusions: The prevalence of APS cannot be deduced from studies of PLEs. Thus, the high population prevalence rate of PLEs does not allow the conclusion that APS are common features of no pathological significance and would lack clinical validity as an Attenuated Psychosis Syndrome in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. Rather, the population prevalence rate of APS has to be assumed to be largely unknown at present but is likely lower than indicated by epidemiological studies of PLEs. Therefore, dedicated studies are warranted, in which APS are assessed in a way that equates to their clinical evaluation.

Die Behandlung der psychotischen Syndrome hat in den letzten Dekaden erhebliche Fortschritte gemacht. Dennoch unterliegen vor allem die schizophrenen Psychosen hinsichtlich Verlauf und Ausgang deutlichen individuellen Schwankungen. In Deutschland etwa stellt die Schizophrenie die mit Abstand wichtigste einzelne Ursache für Erwerbsunfähigkeit in der Altersgruppe unter 40 Jahren dar [1]. Die Angehörigen sind in ihrer Lebensführung und Gesundheit ebenfalls erheblich belastet, zumal auch sie einer Stigmatisierung seitens der Gesellschaft unterliegen. In gesundheitsökonomischer Hinsicht schließlich entstehen jedes Jahr hohe direkte und indirekte Kosten. Entwicklung des Präventionskonzepts Der Gedanke, dass wesentliche Erfolge bei der Bekämpfung vor allem der schizophrenen Psychosen durch eine erfolgreiche Prävention erreicht werden können, ist in der psychiatrischen Literatur seit Langem immer wieder vorgetragen worden und mittlerweile hat das Ziel der Prävention psychischer Störungen Eingang in die nationalen und internationalen gesundheitspolitischen Programme gefunden. Bezogen auf die Psychosen wurden international vor allem seit Mitte der 90er-Jahre erhebliche Anstrengungen unternommen, um dieses Ziel zu erreichen. Wesentlich für diese intensive Forschungstätigkeit waren zum einen methodische Weiterentwicklungen im Bereich der psychiatrischen Präventionsforschung, die es zumindest theoretisch erlaubten, in überschaubaren Zeiträumen Aussagen über die prädiktive Validität bestimmter Kriterien bzw. die präventiven Effekte bestimmter Maßnahmen zu treffen. Zum anderen trat ein von der somatischen Medizin ausgehender Paradigmenwechsel von einem an klaren Ursache-Wirkungs-Beziehungen orientierten, deterministischen zu einem auf Risikofaktoren basierenden, probabilistischen Präventionskonzept ein [2]. Dieser Paradigmenwechsel reflektierte das gewachsene Wissen um die multifaktorielle Genese komplexer Erkrankungen. Indizierte Prävention Basierend auf diesen Erkenntnissen werden eine universelle, selektive und indizierte Prävention unterschieden, die alle wie das ältere Konzept der Primär-prävention die Senkung der Inzidenz einer Erkrankung zum Gegenstand haben. Das für die psychischen Stö-rungen weiterentwickelte Konzept der indizierten Prä-vention ermöglichte die Entwicklung von Kriterien, die auch klinisch manifeste Anzeichen (z. B. einen Leis-

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