Lovestone Simon, Killick Richard, Di Forti Marta, Murray Robin
Departments of Psychological Medicine and Neuroscience Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK.
Trends Neurosci. 2007 Apr;30(4):142-9. doi: 10.1016/j.tins.2007.02.002. Epub 2007 Feb 26.
Converging evidence suggests that the regulation of glycogen synthase kinase 3 (GSK-3) might be important in schizophrenia. Atypical and typical antipsychotic drugs alter GSK-3 activity, as do drugs that induce psychosis. GSK-3 regulatory pathways are altered in schizophrenia, and many of the genes associated with schizophrenia directly or indirectly regulate GSK-3 activity. We propose a variant on the neurodevelopment and dopamine hypotheses of schizophrenia, whereby (i) an early dysfunction in GSK-3 regulation has neurodevelopmental consequences that predispose to disease and (ii) dysfunction in GSK-3 regulation in the adult brain alters dopamine signalling events, causing psychotic symptoms and cognitive dysfunction. If, as we suggest, GSK-3 regulation is crucial to schizophrenia, the Wnt and insulin signalling pathways become targets for therapy.
越来越多的证据表明，糖原合酶激酶3（GSK-3）的调节在精神分裂症中可能很重要。非典型和典型抗精神病药物会改变GSK-3的活性，诱导精神病的药物也是如此。精神分裂症中GSK-3调节通路发生改变，许多与精神分裂症相关的基因直接或间接调节GSK-3的活性。我们提出了一种精神分裂症神经发育和多巴胺假说的变体，即（i）GSK-3调节的早期功能障碍具有神经发育后果，易患疾病，（ii）成人大脑GSK-3调节功能障碍会改变多巴胺信号事件，导致精神病症状和认知功能障碍。如果正如我们所建议的，GSK-3调节对精神分裂症至关重要，那么Wnt和胰岛素信号通路就成为治疗靶点。
