Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia.

Rare copy number variants (CNVs) have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large (>500-kilobase) CNVs at several loci, including microdeletions at 1q21.1 (ref. 2), 3q29 (ref. 3), 15q13.3 (ref. 2) and 22q11.2 (ref. 4) and microduplication at 16p11.2 (ref. 5). However, these CNVs collectively account for a small fraction (2-4%) of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 (0.35%) patients versus 2 of 7,431 (0.03%) controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs.

Psychopathology in the 21st century.

OBJECTIVES: The present publication sets out to evaluate the position of psychopathology in the 21st century and should also serve as a basis for defining the framework for the future tasks of the WFSBP Task Force. METHODS: Review of publications on the various approaches of psychopathology in general and of different tasks, theories and tools of psychopathology approaches in particular. RESULTS: The main tasks of psychopathology are, to record and describe experiential and behavioral abnormalities in their intersubjective context, to explain their origin from an objective scientific perspective, and to attempt to understand them from the subjective perspective of the patient. In order to provide stable fundaments for the work in clinical and scientific psychiatry all three components are indispensable. CONCLUSIONS: The future of psychiatry hence lies in the hands of a type of psychopathology that we will call Integrative Psychopathology. The main tasks of psychopathology can only be pursued in close cooperation with other branches of science interested in studying psychiatric issues. Whereas contemporary psychopathology must lay the foundations for that cooperation, Integrative Psychopathology must be complemented by further advancements in Theoretical Psychopathology, so as to enable conceptual new developments, which can then be fruitful for cooperative research and psychiatric clinical practice.

Antipsicóticos atípicos / Atypical antipsychotics

Los antipsicóticos atípicos han representado un aporte para el tratamiento de las psicosis, particularmente de la esquizofrenia. En este artículo se discute el concepto de antipsicótico y se revisan las características clínicas y farmacológicas de estos medicamentos. El concepto de atipicidad puede ser considerado desde un punto de vista clínico o farmacológico. Desde el punto de vista clínico implica efectividad sobre los síntomas positivos, negativos, afectivos y cognitivos de la esquizofrenia, además de menores afectos colaterales. Desde el punto de vista farmacológico implica una acción diferencial sobre distintos receptores cerebrales. En la segunda parte del artículo se revisan las características clínica y farmacológicas de la clozapina, risperidona, olanzapina, quetiapina, amisulprida, ziprasidona, zotepina, loxapina y otros antipsicóticos en etapas avanzadas de investigación