Section of Psychiatry Laboratory of Molecular Psychiatry and Unit of Treatment Resistant Psychosis, Department of Neuroscience, Reproductive Science and Odontostomatology, University Medical School of Naples "Federico II", Naples, Italy.
Section of Psychiatry Laboratory of Molecular Psychiatry and Unit of Treatment Resistant Psychosis, Department of Neuroscience, Reproductive Science and Odontostomatology, University Medical School of Naples "Federico II", Naples, Italy.
Neurosci Biobehav Rev. 2019 Dec;107:795-827. doi: 10.1016/j.neubiorev.2019.08.019. Epub 2019 Aug 25.
There is a growing interest in new molecular targets for antipsychotic therapy. Multiple signal transduction systems have been recently implicated in the pathophysiology of schizophrenia. However, the weight of each specific mechanism remains controversial. A need for a more vigorous approach to the pharmacotherapy of schizophrenia arises from the bedside: about 30-40% of patients do not respond to antipsychotic therapy. Postsynaptic Density (PSD) proteins have recently attracted attention for their role in signal transduction modulation and for their potential implication in psychosis and cognition. The involvement of PSD in the pathophysiology of schizophrenia is supported by post mortem studies, preclinical animal models, modulation by antipsychotics, and association of PSD genes with schizophrenia in GWAS. Taken together, these studies underline the role of PSD modulation, its effects on striatal function and its relationship with motor, executive- and cognitive-like functions suggesting a potential role of PSD proteins as a l target of novel intervention in the treatment of refractory psychosis.
人们对新型抗精神病治疗的分子靶点越来越感兴趣。多个信号转导系统最近被牵涉到精神分裂症的病理生理学中。然而，每种特定机制的重要性仍存在争议。从临床角度来看，需要更积极地治疗精神分裂症：大约 30-40%的患者对抗精神病治疗没有反应。突触后密度（PSD）蛋白因其在信号转导调节中的作用及其在精神病和认知中的潜在作用而引起关注。PSD 参与精神分裂症的病理生理学得到了尸检研究、临床前动物模型、抗精神病药物的调节以及 PSD 基因与 GWAS 中精神分裂症的关联的支持。综上所述，这些研究强调了 PSD 调节的作用、对纹状体功能的影响以及与运动、执行和认知样功能的关系，提示 PSD 蛋白作为新型干预难治性精神病治疗的潜在靶点。
