Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures.
Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures.
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DOI：
10.1038/s41398-023-02716-8
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发表时间：
2024-01-10
影响因子：
6.8
通讯作者：
Hahn, Margaret K.
中科院分区：
文献类型：
--
作者：
Lee, Jiwon;Xue, Xiangning;Au, Emily;Mcintyre, William B.;Asgariroozbehani, Roshanak;Panganiban, Kristoffer;Tseng, George C.;Papoulias, Maria;Smith, Emily;Monteiro, Jonathan;Shah, Divia;Maksyutynska, Kateryna;Cavalier, Samantha;Radoncic, Emril;Prasad, Femin;Agarwal, Sri Mahavir;Mccullumsmith, Robert;Freyberg, Zachary;Logan, Ryan W.;Hahn, Margaret K.
抗精神病药（AP）初治的首发精神病（FEP）患者表现出早期精神障碍，包括胰岛素抵抗和前驱糖尿病。因此，代谢失调可能是精神病谱系障碍（PSD）固有的，独立于AP的代谢作用。然而，PSD和血糖异常状态之间重叠的潜在生物学途径仍有待确定。使用转录组数据集的荟萃分析方法，我们调查了AP-初治FEP患者是否与非精神病性早期精神障碍个体共享重叠的基因表达特征。我们荟萃分析了AP初治FEP患者和非精神病性早期精神障碍受试者的外周转录组数据集，以确定共同的基因表达特征。共同的签名经历了途径富集分析，然后通过基于网络的细胞签名的综合库（iLINCS）用于鉴定潜在的新药理学化合物。我们的检索结果得到了5项AP初治FEP研究和4项符合纳入标准的早期发育不良研究。我们发现，AP-幼稚FEP和非精神病患者表现出早期精神障碍共享221个共同的签名，这是丰富的内质网应激和异常脑能量相关的途径。九种FDA批准的药物被确定为潜在的药物治疗，其中抗糖尿病二甲双胍，2型糖尿病的一线治疗，有证据表明可以减轻PSD的代谢功能障碍。综上所述，我们的研究结果支持共同的基因表达变化和生物学途径与PSD血糖异常疾病。这些数据表明，PSD的病理生物学重叠，并可能导致功能障碍。最后，我们发现二甲双胍可能是一种潜在的治疗PSD固有的早期代谢功能障碍。
Antipsychotic (AP)-naive first-episode psychosis (FEP) patients display early dysglycemia, including insulin resistance and prediabetes. Metabolic dysregulation may therefore be intrinsic to psychosis spectrum disorders (PSDs), independent of the metabolic effects of APs. However, the potential biological pathways that overlap between PSDs and dysglycemic states remain to be identified. Using meta-analytic approaches of transcriptomic datasets, we investigated whether AP-naive FEP patients share overlapping gene expression signatures with non-psychiatrically ill early dysglycemia individuals. We meta-analyzed peripheral transcriptomic datasets of AP-naive FEP patients and non-psychiatrically ill early dysglycemia subjects to identify common gene expression signatures. Common signatures underwent pathway enrichment analysis and were then used to identify potential new pharmacological compounds via Integrative Library of Integrated Network-Based Cellular Signatures (iLINCS). Our search results yielded 5 AP-naive FEP studies and 4 early dysglycemia studies which met inclusion criteria. We discovered that AP-naive FEP and non-psychiatrically ill subjects exhibiting early dysglycemia shared 221 common signatures, which were enriched for pathways related to endoplasmic reticulum stress and abnormal brain energetics. Nine FDA-approved drugs were identified as potential drug treatments, of which the antidiabetic metformin, the first-line treatment for type 2 diabetes, has evidence to attenuate metabolic dysfunction in PSDs. Taken together, our findings support shared gene expression changes and biological pathways associating PSDs with dysglycemic disorders. These data suggest that the pathobiology of PSDs overlaps and potentially contributes to dysglycemia. Finally, we find that metformin may be a potential treatment for early metabolic dysfunction intrinsic to PSDs.
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影响因子：
5.6
作者：
González-García I;García-Cáceres C
通讯作者：
García-Cáceres C
DOI：
10.1002/ajmg.b.32271
发表时间：
2014-12-01
影响因子：
2.8
作者：
Cheng, Dan;Zhang, Kan;Xue, Zheng
通讯作者：
Xue, Zheng
影响因子：
7.7
作者：
Lee TW;Kwon H;Zong H;Yamada E;Vatish M;Pessin JE;Bastie CC
通讯作者：
Bastie CC
影响因子：
64.5
作者：
García-Cáceres C;Quarta C;Varela L;Gao Y;Gruber T;Legutko B;Jastroch M;Johansson P;Ninkovic J;Yi CX;Le Thuc O;Szigeti-Buck K;Cai W;Meyer CW;Pfluger PT;Fernandez AM;Luquet S;Woods SC;Torres-Alemán I;Kahn CR;Götz M;Horvath TL;Tschöp MH
通讯作者：
Tschöp MH
影响因子：
6.1
作者：
Feng Nan;Ma Xiaowei;Guo Xiaohui
通讯作者：
Guo Xiaohui