A Case for Thalamic Mechanisms of Schizophrenia: Perspective From Modeling 22q11.2 Deletion Syndrome.
A Case for Thalamic Mechanisms of Schizophrenia: Perspective From Modeling 22q11.2 Deletion Syndrome.
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DOI：
10.3389/fncir.2021.769969
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发表时间：
2021
影响因子：
3.5
通讯作者：
Zakharenko SS
中科院分区：
文献类型：
--
作者：
Jiang Y;Patton MH;Zakharenko SS
精神分裂症是一种严重的慢性精神疾病，影响着全世界数百万人的生活。这种疾病的特征是一系列症状，从认知缺陷到社交退缩，再到幻觉。尽管经过数十年的研究，我们对这种疾病的神经生物学，特别是精神分裂症症状背后的神经回路的理解仍然处于早期阶段。因此，治疗的发展仍然停滞不前，总体预后很差。改善精神分裂症治疗的主要障碍是其多病因、多基因病因，这是难以建模的。临床观察和罕见但明确定义的基因组病变的临床前模型的出现，这些病变赋予精神分裂症的实质性风险（例如，22q11.2微缺失）突出了丘脑在疾病中的作用。在这里，我们回顾了精神分裂症的分子，细胞和电路研究结果的文献，并讨论了该领域的领先理论，指出丘脑内的异常是精神分裂症的潜在致病机制。我们认为，突触功能障碍和振荡异常的神经回路涉及的预测和丘脑内，重点是丘脑皮质回路，可能是精神分裂症的精神病（和可能的其他）症状的基础。
Schizophrenia is a severe, chronic psychiatric disorder that devastates the lives of millions of people worldwide. The disease is characterized by a constellation of symptoms, ranging from cognitive deficits, to social withdrawal, to hallucinations. Despite decades of research, our understanding of the neurobiology of the disease, specifically the neural circuits underlying schizophrenia symptoms, is still in the early stages. Consequently, the development of therapies continues to be stagnant, and overall prognosis is poor. The main obstacle to improving the treatment of schizophrenia is its multicausal, polygenic etiology, which is difficult to model. Clinical observations and the emergence of preclinical models of rare but well-defined genomic lesions that confer substantial risk of schizophrenia (e.g., 22q11.2 microdeletion) have highlighted the role of the thalamus in the disease. Here we review the literature on the molecular, cellular, and circuitry findings in schizophrenia and discuss the leading theories in the field, which point to abnormalities within the thalamus as potential pathogenic mechanisms of schizophrenia. We posit that synaptic dysfunction and oscillatory abnormalities in neural circuits involving projections from and within the thalamus, with a focus on the thalamocortical circuits, may underlie the psychotic (and possibly other) symptoms of schizophrenia.
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