Weidenauer Ana, Bauer Martin, Sauerzopf Ulrich, Bartova Lucie, Praschak-Rieder Nicole, Sitte Harald H, Kasper Siegfried, Willeit Matthäus
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria (Drs Weidenauer, Bauer, Sauerzopf, Bartova, Praschak-Rieder, Kasper, and Willeit); Department of Clinical Pharmacology (Dr Bauer), and Institute of Pharmacology, Medical University of Vienna, Austria (Dr Sitte).
Int J Neuropsychopharmacol. 2016 Dec 31;20(1):1-10. doi: 10.1093/ijnp/pyw081. Print 2017 Jan.
Sensitization is defined as a process whereby repeated intermittent exposure to a given stimulus results in an enhanced response at subsequent exposures. Next to robust findings of an increased dopamine synthesis capacity in schizophrenia, empirical data and neuroimaging studies support the notion that the mesolimbic dopamine system of patients with schizophrenia is more reactive compared with healthy controls. These studies led to the conceptualization of schizophrenia as a state of endogenous sensitization, as stronger behavioral response and increased dopamine release after amphetamine administration or exposure to stress have been observed in patients with schizophrenia. These findings have also been integrated into the neurodevelopmental model of the disorder, which assumes that vulnerable neuronal circuits undergo progressive changes during puberty and young adulthood that lead to manifest psychosis. Rodent and human studies have made an attempt to identify the exact mechanisms of sensitization of the dopaminergic system and its association with psychosis. Doing so, several epigenetic and molecular alterations associated with dopamine release, neuroplasticity, and cellular energy metabolism have been discovered. Future research aims at targeting these key proteins associated with sensitization in schizophrenia to enhance the knowledge of the pathophysiology of the illness and pave the way for an improved treatment or even prevention of this severe psychiatric disorder.
致敏作用被定义为一个过程，即反复间歇性接触特定刺激会导致后续接触时反应增强。除了在精神分裂症中多巴胺合成能力增加的有力发现外，实证数据和神经影像学研究支持这样一种观点，即与健康对照相比，精神分裂症患者的中脑边缘多巴胺系统反应性更强。这些研究导致将精神分裂症概念化为一种内源性致敏状态，因为在精神分裂症患者中观察到，服用安非他命或暴露于应激后，行为反应更强且多巴胺释放增加。这些发现也已被纳入该疾病的神经发育模型，该模型假设脆弱的神经回路在青春期和成年早期会经历渐进性变化，从而导致明显的精神病症状。啮齿动物和人类研究已尝试确定多巴胺能系统致敏的确切机制及其与精神病的关联。通过这样做，已经发现了一些与多巴胺释放、神经可塑性和细胞能量代谢相关的表观遗传和分子改变。未来的研究旨在针对与精神分裂症致敏相关的这些关键蛋白质，以增进对该疾病病理生理学的了解，并为改善这种严重精神疾病的治疗甚至预防铺平道路。
