Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD
Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD
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DOI：
10.1007/s00213-014-3837-2
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发表时间：
2015-06-01
影响因子：
3.4
通讯作者：
Rubia, Katya
中科院分区：
文献类型：
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作者：
Chantiluke, Kaylita;Barrett, Nadia;Rubia, Katya
注意缺陷多动障碍(ADHD)和自闭症谱系障碍(ASD)经常并存，在运动反应抑制时既有表现也有脑功能障碍。5-羟色胺激动剂调节运动反应抑制，并在这两种疾病中显示出积极的行为效应。因此，我们使用功能磁共振成像(FMRI)来研究这两种疾病中迄今未知的共有和特定于疾病的抑制性脑功能障碍，以及单剂量选择性5-羟色胺再摄取抑制剂氟西汀的影响。年龄匹配的ADHD男孩(18例)、ASD患者(19例)和健康对照组(25例)在一项测量运动抑制的停止任务中与fMRI进行了比较。在双盲、安慰剂对照的随机设计中，患者接受了两次扫描，要么是急性剂量的氟西汀，要么是安慰剂。患者体内的重复测量分析评估了药物效果。为了测试大脑功能障碍的潜在正常化效果，研究人员将每种药物状态下的患者与对照组进行了比较。与对照组相比，在安慰剂组，自闭症男孩的左侧和右侧下额叶皮质(IFC)表现为过度激活，而ADHD男孩的眼眶前额皮质(OFC)和基底节表现出特定的异常激活不足。在氟西汀作用下，由于氟西汀对这些激活的反向作用，前额叶功能障碍不再被观察到：氟西汀下调ASD的IFC和OFC的激活，但上调ADHD的IFC和OFC的激活。研究结果表明，氟西汀通过反向作用恢复这两种疾病的额叶功能障碍，下调ASD的异常增加的额叶激活，上调ADHD的异常降低的额叶激活，潜在地反映了这两种疾病的反向基线5-羟色胺水平。
Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are often comorbid and have both performance and brain dysfunctions during motor response inhibition. Serotonin agonists modulate motor response inhibition and have shown positive behavioural effects in both disorders.We therefore used functional magnetic resonance imaging (fMRI) to investigate the so far unknown shared and disorder-specific inhibitory brain dysfunctions in these two disorders, as well as the effects of a single dose of the selective serotonin reuptake inhibitor fluoxetine.Age-matched boys with ADHD (18), ASD (19) and healthy controls (25) were compared with fMRI during a stop task measuring motor inhibition. Patients were scanned twice, under either an acute dose of fluoxetine or placebo in a double-blind, placebo-controlled randomised design. Repeated measures analyses within patients assessed drug effects. To test for potential normalisation effects of brain dysfunctions, patients under each drug condition were compared to controls.Under placebo, relative to controls, ASD boys showed overactivation in left and right inferior frontal cortex (IFC), while ADHD boys showed disorder-specific underactivation in orbitofrontal cortex (OFC) and basal ganglia. Under fluoxetine, the prefrontal dysfunctions were no longer observed, due to inverse effects of fluoxetine on these activations: fluoxetine downregulated IFC and OFC activation in ASD but upregulated them in ADHD.The findings show that fluoxetine normalises frontal lobe dysfunctions in both disorders via inverse effects, downregulating abnormally increased frontal activation in ASD and upregulating abnormally decreased frontal activation in ADHD, potentially reflecting inverse baseline serotonin levels in both disorders.