Inta Dragos, Lima-Ojeda Juan M, Gass Peter, Fusar-Poli Paolo
Department of Psychiatry and Psychotherapy, Central Institute for Mental Health Mannheim, University of Heidelberg, J 5, 68159 Mannheim, Germany.
Recent Pat CNS Drug Discov. 2012 Dec;7(3):236-42. doi: 10.2174/157488912803251998.
Schizophrenia is most likely a neurodevelopmental disorder with a characteristic delayed onset of symptoms occurring usually during transition from adolescence to adulthood. Recent studies revealed that both genetic and environmental risk factors for the disease disturb not only embryonic, but also postnatal neurogenesis, possible contributing to neurochemical alterations associated with schizophrenia. Several recent patents proposed therapeutic interventions in schizophrenia by increasing postnatal neurogenesis. It remains, however, unclear, how such pro-neurogenic interventions could ameliorate alterations in neurotransmitter systems associated with the disease, such as the dopamine system. Here we review these patents in the context of the existent data about postnatal neurogenesis in the subventricular zone in rodents and primates. We discuss also in light of a recently proposed theoretical model the possible relevance of disturbed neurogenesis for the dopamine system, focusing on the dopamine receptors associated with neurogenesis, the D3 receptors, and a D3-expressing structure derived from the subventricular zone, the Islands of Calleja. Finally, we discuss these findings in the light of molecular imaging studies in early schizophrenia.
精神分裂症很可能是一种神经发育障碍，其特征是症状通常在从青春期向成年期过渡期间延迟出现。最近的研究表明，该疾病的遗传和环境风险因素不仅会干扰胚胎期神经发生，还会干扰出生后神经发生，这可能导致与精神分裂症相关的神经化学改变。最近的几项专利提出了通过增加出生后神经发生来治疗精神分裂症的干预措施。然而，目前尚不清楚这种促进神经发生的干预措施如何改善与该疾病相关的神经递质系统的改变，例如多巴胺系统。在此，我们结合关于啮齿动物和灵长类动物脑室下区出生后神经发生的现有数据来综述这些专利。我们还根据最近提出的理论模型，讨论神经发生紊乱与多巴胺系统的可能相关性，重点关注与神经发生相关的多巴胺受体、D3受体以及源自脑室下区的表达D3的结构——Calleja岛。最后，我们根据早期精神分裂症的分子影像学研究来讨论这些发现。
