Chantiluke Kaylita, Barrett Nadia, Giampietro Vincent, Santosh Paramala, Brammer Michael, Simmons Andrew, Murphy Declan G, Rubia Katya
Department of Child and Adolescent Psychiatry/MRC Center for Social, Genetic and Developmental Psychiatry (SGDP), Institute of Psychiatry, King's College London, 16 De Crespigny Park, PO46, London, SE5 8AF, UK.
Psychopharmacology (Berl). 2015 Jun;232(12):2071-82. doi: 10.1007/s00213-014-3837-2. Epub 2014 Dec 24.
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.
注意缺陷多动障碍（ADHD）和自闭症谱系障碍（ASD）常常共病，在运动反应抑制过程中均存在行为表现和大脑功能障碍。血清素激动剂可调节运动反应抑制，且已在这两种障碍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）来研究这两种障碍中迄今未知的共同和特定于障碍的抑制性大脑功能障碍，以及单剂量选择性血清素再摄取抑制剂氟西汀的作用。
在一项测量运动抑制的停止任务期间，对年龄匹配的患有ADHD的男孩（18名）、ASD的男孩（19名）和健康对照者（25名）进行fMRI比较。患者在双盲、安慰剂对照随机设计下，接受氟西汀急性剂量或安慰剂扫描两次。患者内部的重复测量分析评估药物效果。为了测试大脑功能障碍的潜在正常化效应，将每种药物条件下的患者与对照者进行比较。
在安慰剂条件下，相对于对照者，ASD男孩在左右额下回皮质（IFC）表现出过度激活，而ADHD男孩在眶额皮质（OFC）和基底神经节表现出特定于障碍的激活不足。在氟西汀条件下，由于氟西汀对这些激活的相反作用，前额叶功能障碍不再被观察到：氟西汀下调了ASD中IFC和OFC的激活，但上调了ADHD中的激活。
研究结果表明，氟西汀通过相反作用使两种障碍中的额叶功能障碍正常化，下调ASD中异常增加的额叶激活，并上调ADHD中异常减少的额叶激活，这可能反映了两种障碍中相反的基线血清素水平。
