Schizophrenia Research Laboratory, Schizophrenia Research Institute Sydney, NSW, Australia ; Neuroscience Research Australia Sydney, NSW, Australia ; School of Psychiatry, University of New South Wales Sydney, NSW, Australia.
Front Cell Neurosci. 2013 May 15;7:60. doi: 10.3389/fncel.2013.00060. eCollection 2013.
The schizophrenia brain is differentiated from the normal brain by subtle changes, with significant overlap in measures between normal and disease states. For the past 25 years, schizophrenia has increasingly been considered a neurodevelopmental disorder. This frame of reference challenges biological researchers to consider how pathological changes identified in adult brain tissue can be accounted for by aberrant developmental processes occurring during fetal, childhood, or adolescent periods. To place schizophrenia neuropathology in a neurodevelopmental context requires solid, scrutinized evidence of changes occurring during normal development of the human brain, particularly in the cortex; however, too often data on normative developmental change are selectively referenced. This paper focuses on the development of the prefrontal cortex and charts major molecular, cellular, and behavioral events on a similar time line. We first consider the time at which human cognitive abilities such as selective attention, working memory, and inhibitory control mature, emphasizing that attainment of full adult potential is a process requiring decades. We review the timing of neurogenesis, neuronal migration, white matter changes (myelination), and synapse development. We consider how molecular changes in neurotransmitter signaling pathways are altered throughout life and how they may be concomitant with cellular and cognitive changes. We end with a consideration of how the response to drugs of abuse changes with age. We conclude that the concepts around the timing of cortical neuronal migration, interneuron maturation, and synaptic regression in humans may need revision and include greater emphasis on the protracted and dynamic changes occurring in adolescence. Updating our current understanding of post-natal neurodevelopment should aid researchers in interpreting gray matter changes and derailed neurodevelopmental processes that could underlie emergence of psychosis.
精神分裂症大脑与正常大脑的区别在于细微的变化，正常状态和疾病状态下的测量值有很大的重叠。在过去的 25 年中，精神分裂症越来越被认为是一种神经发育障碍。这种参考框架促使生物研究人员考虑如何解释在胎儿、儿童或青少年时期发生的异常发育过程中，在成人脑组织中发现的病理性变化。要将精神分裂症神经病理学置于神经发育的背景下，需要有坚实的、经过严格审查的证据来证明人类大脑正常发育过程中发生的变化，特别是在皮层中；然而，关于正常发育变化的数据往往是有选择性地引用的。本文重点关注前额叶皮层的发育，并绘制了人类大脑皮层发育主要分子、细胞和行为事件的相似时间线。我们首先考虑人类认知能力（如选择性注意、工作记忆和抑制控制）成熟的时间，强调达到完全成人潜力是一个需要几十年的过程。我们回顾了神经发生、神经元迁移、白质变化（髓鞘形成）和突触发育的时间。我们考虑了神经递质信号通路中的分子变化是如何在整个生命过程中发生变化的，以及它们如何与细胞和认知变化同时发生。最后，我们考虑了滥用药物的反应随年龄的变化。我们得出结论，关于人类皮质神经元迁移、中间神经元成熟和突触退化时间的概念可能需要修订，并更加重视青少年时期发生的漫长而动态的变化。更新我们对产后神经发育的理解应该有助于研究人员解释灰质变化和脱轨的神经发育过程，这些过程可能是精神病出现的基础。
