Treatment of the psychiatric problems associated with fragile X syndrome.
Treatment of the psychiatric problems associated with fragile X syndrome.
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DOI：
10.1097/yco.0000000000000131
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发表时间：
2015-03
影响因子：
6.9
通讯作者：
Polussa J
中科院分区：
文献类型：
--
作者：
Hagerman RJ;Polussa J
这项工作回顾了最近关于脆性X综合征（FXS）治疗的研究，FXS是智力残疾和自闭症谱系障碍最常见的遗传原因。表型包括与感觉过度觉醒、多动和注意力问题相关的焦虑，这些问题与注意力缺陷多动障碍和社交缺陷一致，导致60%的男孩和25%的女孩患有FXS的自闭症谱系障碍。针对FXS的多种靶向治疗已经挽救了fmr 1敲除小鼠的表型，但很少对FXS患者有益。代谢型谷氨酸受体5拮抗剂福尔斯的失败紧随阿巴氯芬在自闭症或FXS儿童和成人中的疗效失败之后。与此相反，二甲胺四环素在FXS儿童中的疗效已在对照试验中得到证实。米诺环素降低FXS中异常升高的基质金属蛋白酶9水平。阿坎酸和洛伐他汀在FXS的开放标签试验中获益。当与行为和/或教育干预相结合时，生命的前5年可能是最有效的干预时间。米诺环素、阿坎酸、洛伐他汀和舍曲林是目前可用于治疗FXS儿童的药物，并已显示出获益。联合使用药物和行为干预可能对治疗FXS最有效。
This work reviews recent research regarding treatment of fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism spectrum disorder. The phenotype includes anxiety linked to sensory hyperarousal, hyperactivity, and attentional problems consistent with attention deficit hyperactivity disorder and social deficits leading to autism spectrum disorder in 60% of boys and 25% of girls with FXS. Multiple targeted treatments for FXS have rescued the phenotype of the fmr1 knockout mouse, but few have been beneficial to patients with FXS. The failure of the metabotropic glutamate receptor 5 antagonists falls on the heels of the failure of Arbaclofen’s efficacy in children and adults with autism or FXS. In contrast, efficacy has been demonstrated in a controlled trial of minocycline in children with FXS. Minocycline lowers the abnormally elevated levels of matrix metalloproteinase 9 in FXS. Acamprosate and lovastatin have been beneficial in open-label trials in FXS. The first 5 years of life may be the most efficacious time for intervention when combined with behavioral and/or educational interventions. Minocycline, acamprosate, lovastatin, and sertraline are treatments that can be currently prescribed and have shown benefit in children with FXS. Use of combined medical and behavioral interventions will likely be most efficacious for the treatment of FXS.