New drug targets in psychiatry: Neurobiological considerations in the genomics era
New drug targets in psychiatry: Neurobiological considerations in the genomics era
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DOI：
10.1016/j.neubiorev.2022.104763
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发表时间：
2022-07-04
影响因子：
8.2
通讯作者：
Tunbridge，Elizabeth M.
中科院分区：
文献类型：
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作者：
Harrison，Paul J.;Mould，Arne;Tunbridge，Elizabeth M.
经过一段时间的退出，制药公司已经开始重新投资于神经精神疾病，因为我们对这些疾病的理解有所提高，部分是受到基因组研究的刺激。然而，将这些信息转化为疾病见解并最终转化为可处理的治疗靶点是一个重大挑战。在这里，我们考虑如何集成不同的信息源来指导这一过程。我们回顾了如何利用神经生物学的理解来推进前基因组时代确定的治疗候选者，以儿茶酚- o -甲基转移酶（COMT）为例。然后，我们将其与第一个全基因组重要的精神分裂症基因znf804a进行对比，并从这些和其他例子中吸取一些教训。我们强调，至少在短期内，有正交神经生物学支持的潜在靶点的翻译可能比仅依赖基因组信息的翻译更直接和有效。虽然我们在这里关注的是来自精神分裂症基因组研究的信息，但这些观点广泛适用于主要精神疾病及其症状。
After a period of withdrawal, pharmaceutical companies have begun to reinvest in neuropsychiatric disorders, due to improvements in our understanding of these disorders, stimulated in part by genomic studies. However, translating this information into disease insights and ultimately into tractable therapeutic targets is a major challenge. Here we consider how different sources of information might be integrated to guide this process. We review how an understanding of neurobiology has been used to advance therapeutic candidates identified in the pre-genomic era, using catechol-O-methyltransferase (COMT) as an exemplar. We then contrast withZNF804A, the first genome-wide significant schizophrenia gene, and draw on some of the lessons that these and other examples provide. We highlight that, at least in the short term, the translation of potential targets for which there is orthogonal neurobiological support is likely to be more straightforward and productive than that those relying solely on genomic information. Although we focus here on information from genomic studies of schizophrenia, the points are broadly applicable across major psychiatric disorders and their symptoms.