Roberts Rosalinda C
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, PO Box 21247, Baltimore, MD 21228, USA.
Schizophr Bull. 2007 Jan;33(1):11-5. doi: 10.1093/schbul/sbl063. Epub 2006 Nov 30.
The disrupted in schizophrenia 1 (DISC1) gene has been linked to schizophrenia and other serious mental illnesses in multiple pedigrees. This article will review the neurobiology of DISC1 in normal developing and adult brain and the putative role of the mutant form in major mental illness, particularly schizophrenia. The initial genetic finding of an association between DISC1 and schizophrenia in a Scottish population has now been replicated in Finnish, American, Japanese, and Taiwanese populations. DISC1 is present throughout the brain of a variety of species during development and adulthood, including many of the brain regions known to be abnormal in schizophrenia, such as the prefrontal cortex, hippocampus, and thalamus. The functions of DISC1 in the developing brain include neuronal migration, neurite outgrowth, and neurite extension. In the adult, DISC1 has been identified in multiple populations of neurons and in structures associated with synaptic function, suggesting that one of its adult functions may be synaptic plasticity. DISC1 is associated with numerous cognitive functions that are abnormal in schizophrenia. Converging evidence from cell culture, mice mutants, postmortem brain, and genetics implicates mutant DISC1 in the pathophysiology of schizophrenia and other mental illnesses.
精神分裂症相关1（DISC1）基因已在多个家系中与精神分裂症及其他严重精神疾病相关联。本文将综述DISC1在正常发育大脑和成年大脑中的神经生物学，以及该突变形式在主要精神疾病，尤其是精神分裂症中的假定作用。最初在苏格兰人群中发现的DISC1与精神分裂症之间的关联，现已在芬兰、美国、日本和台湾人群中得到重复验证。在发育和成年期，DISC1存在于多种物种的整个大脑中，包括许多已知在精神分裂症中异常的脑区，如前额叶皮质、海马体和丘脑。DISC1在发育中的大脑中的功能包括神经元迁移、神经突生长和神经突延伸。在成年期，DISC1已在多个神经元群体和与突触功能相关的结构中被鉴定出来，这表明其成年期功能之一可能是突触可塑性。DISC1与精神分裂症中异常的众多认知功能相关。来自细胞培养、小鼠突变体、死后大脑和遗传学的越来越多的证据表明，突变的DISC1参与了精神分裂症和其他精神疾病的病理生理学过程。
