Lysosomal Diseases and Neuropsychiatry: Opportunities to Rebalance the Mind
Lysosomal Diseases and Neuropsychiatry: Opportunities to Rebalance the Mind
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DOI：
10.3389/fmolb.2020.00177
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发表时间：
2020-08-26
影响因子：
5
通讯作者：
Cox, Timothy M.
中科院分区：
文献类型：
--
作者：
Cox, Timothy M.
大脑是精神的生理器官，但迄今为止，从神经生物学的角度来理解精神疾病的努力还没有成功。精神障碍（焦虑、抑郁、双相情感障碍和精神分裂症）影响着大约五分之一的人口，并在人类科学的前沿提出了几乎无穷无尽的社会挑战。功能神经成像和大规模遗传学方面的巨大技术进步，尚未带来对精神疾病的精细分子理解的前景，超出了对脑代谢的早期解剖学描述。然而，在正电子发射断层扫描中使用复杂的放射配体进行密集的临床表型和定量代谢研究，始终倾向于神经生物学方法。这一观点遵循了医学中一个熟悉的格言，用Arthur Koestler的话来恰当地概括：“大自然在对人类进行毫无意义的实验时是慷慨的。”迄今为止，神经精神病学的研究在很大程度上忽略了罕见的遗传疾病，但大脑实验室中特定成分的紊乱为机制探索提供了丰富的机会。异常的精神行为是许多先天代谢错误的特征，尽管每一种紊乱都代表着它自己的宇宙，但我们正处在理解的门槛上，因为当代遗传学和细胞生物学提供了丰富的材料来研究精神错乱这个令人不安的谜题。进一步的发展涉及对确定的分子靶点起作用的孤儿药：这些药物代表了以以前不可能的方式研究与罕见疾病相关的精神现象发病机制的新方法。在这里，我们介绍精神分裂症的前沿及其与晚发性泰-萨克斯病的强烈联系作为一个范例来探索。
The brain is the physical organ of the mind but efforts to understand mental illness within a neurobiological context have hitherto been unavailing. Mental disorders (anxiety, depression, bipolar disorder, and schizophrenia) affect about one fifth of the population and present an almost endless societal challenge at the frontier of human sciences. Prodigious technological advances in functional neuroimaging and large-scale genetics have not yet delivered the prospect of refined molecular understanding of mental illness beyond early anatomical descriptions of brain metabolism. However, intensive clinical phenotyping and quantitative metabolic studies using sophisticated radio-ligands in positron-emission tomography, persistently favor the neurobiological approach. ThisPerspectivepursues a familiar maxim in Medicine, aptly summarized in the words of Arthur Koestler: "Nature is generous in her senseless experiments on mankind." Hitherto, studies in neuropsychiatry have largely ignored rare genetic disorders but derangements of specific components within the cerebral laboratory offer rich opportunities for mechanistic exploration. Aberrant psychic behavior is characteristic of many inborn errors of metabolism and although each disorder represents a universe of its own, we are at a threshold for understanding, since contemporary genetics and cell biology furnish abundant materials to take on the perturbing enigma of mental derangement. A further development relates to orphan drugs with actions on defined molecular targets: these represent new ways to study the pathogenesis of psychiatric phenomena associated with rare diseases and in a manner not formerly possible. Here we introduce the frontier of schizophrenia and its strong association with late-onset Tay-Sachs disease as a paradigm to explore.