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早期生活逆境削弱了抑郁、超重成年人对吡格列酮的反应。

Early life adversity blunts responses to pioglitazone in depressed, overweight adults.

机构信息

Stanford University, Department of Psychiatry and Behavioral Sciences, United States.

Stanford University, Department of Psychiatry and Behavioral Sciences, United States.

出版信息

Eur Psychiatry. 2019 Jan;55:4-9. doi: 10.1016/j.eurpsy.2018.09.009. Epub 2018 Oct 29.

DOI:10.1016/j.eurpsy.2018.09.009
PMID:30384111
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6309647/
Abstract

PURPOSE

Early life adversity is associated with both metabolic impairment and depression in adulthood, as well as with poorer responses to antidepressant medications. It is not yet known whether individual differences in sensitivity to antidiabetic medications could also be related to early life adversity. We examined whether a history of early life adversity affected the observed changes in metabolic function and depressive symptoms in a randomized trial of pioglitazone for augmentation of standard treatments for depression.

PURPOSE

Early life adversity is associated with both metabolic impairment and depression in adulthood, as well as with poorer responses to antidepressant medications. It is not yet known whether individual differences in sensitivity to antidiabetic medications could also be related to early life adversity. We examined whether a history of early life adversity affected the observed changes in metabolic function and depressive symptoms in a randomized trial of pioglitazone for augmentation of standard treatments for depression.

FINDINGS

We found that early life adversity significantly impaired the metabolic response to pioglitazone. Effects on depressive symptoms did not reach significance, but nonetheless suggested that pioglitazone could mitigate the depressant effects of childhood adversity, only among those insulin resistant at baseline.

CONCLUSIONS

We conclude that a history of early life adversity may impair the body's ability to respond to insulin sensitizing pharmacotherapy, and furthermore that its contribution to resistant depression may function in part via the generation of an insulin resistant phenotype.

摘要

目的

早期生活逆境与成年期的代谢损伤和抑郁有关,也与抗抑郁药物的反应较差有关。目前尚不清楚个体对降糖药物的敏感性差异是否也与早期生活逆境有关。我们在一项针对吡格列酮增强抗抑郁标准治疗的随机试验中,研究了早期生活逆境史是否会影响代谢功能和抑郁症状的观察到的变化。

发现

我们发现,早期生活逆境显著损害了吡格列酮的代谢反应。对抑郁症状的影响没有达到显著水平,但表明吡格列酮可以减轻童年逆境的抑郁作用,仅在基线时胰岛素抵抗的人群中。

结论

我们得出结论,早期生活逆境史可能会损害身体对胰岛素增敏药物治疗的反应能力,此外,它对抵抗性抑郁症的贡献可能部分通过产生胰岛素抵抗表型来发挥作用。

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The antidepressant-like effects of pioglitazone in a chronic mild stress mouse model are associated with PPARγ-mediated alteration of microglial activation phenotypes.吡格列酮在慢性轻度应激小鼠模型中的抗抑郁样作用与PPARγ介导的小胶质细胞激活表型改变有关。
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Telomere length as a predictor of response to Pioglitazone in patients with unremitted depression: a preliminary study.
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Psychiatry Res. 2015 Dec 30;230(3):846-52. doi: 10.1016/j.psychres.2015.10.013. Epub 2015 Oct 22.
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