對派醋甲酯不同反應之注意力不足過動症個案的腦部結構差異

Abstract

前言：注意力不足過動症（Attention-Deficit Hyperactivity Disorder, ADHD）是最常見的神經發育障礙症之一，具有長期功能障礙，其核心症狀可透過派醋甲酯（methylphenidate）緩解。然而，多達30％的ADHD患者對派醋甲酯的反應不佳。因此，本研究擬了解ADHD患者對派醋甲酯治療是否有良好反應的腦部神經解剖結構差異，以促進對ADHD與藥物機制之暸解。 方法：使用自然觀察設計，我們招募了79名過去未曾接受過任何精神藥物治療且沒有其他主要精神疾病共病的ADHD個案。在結構核磁造影掃描後，參與者在門診的依照臨床判斷開始methylphenidate治療。經由回顧性病歷研究，基於臨床症狀整體改善量表（Clinical Global Impression-Improvement, CGI-I）將參與者分為兩組（藥物良好反應組和藥物有限反應組）。我們使用體素的形態分析法（Voxel-based morphometry）比較這兩組之間的全腦區域灰質體積的差異。之後進一步使用紋狀體遮罩和預設模式網絡（default mode network, DMN）遮罩來進行局部區域分析。此外，我們也對提取感興趣的紋狀體區域(Region of Interest, ROI)來進行事後分析。 結果：根據CGI-I評分，有63位個案在藥物良好反應組中，16位在藥物有限反應組。使用無母數的影像分析方式，相對於不良反應組，全腦分析顯示左側殼核(putamen)的灰質體積較大，良好反應組的楔前葉(precuneus)區域體積較小。然後，我們進一步使用紋狀體遮罩和預設模式網絡遮罩來比較兩組體積之差異，兩者之間呈現統計顯著之差異。進一步使用的事後ROI分析顯示，與藥物有限反應者相比，良好的反應者具有更大的左殼核體積與較小的楔前葉體積。 結論：與先前關於methylphenidate機制的影像研究一致，我們的結果顯示紋狀體灰質體積和楔前葉體積在ADHD患者的治療反應中扮演關鍵的角色

Objective: Attention-Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders with long-term functional impairment. Methylphenidate has been approved for treating ADHD. However, up to 30% of ADHD individuals show poor responses to methylphenidate. Little is known about the imaging biomarker to predict the methylphenidate treatment response. Thus, this study aimed to characterize neuroanatomical differences between ADHD individuals with and without good responses to methylphenidate. Methods: Using a naturalistic observation design, we assessed 79 drug-naive patients with ADHD, who were not comorbid with any other major mental disorders using a psychiatric interview, and structural MRI (T1-weighted) scans. After assessments, these patients started methylphenidate treatment per clinical guidelines in the outpatient clinics. The participants were divided into two subgroups (good- and poor-response group) based on the scoring of the Clinical Global Impression – Improvement Scale (CGI-I) by a child psychiatrist through a retrospective chart review of the medical record of a senior child psychiatrist, who treated these patients. Voxel-based morphometry (VBM) was used to contrast differences in whole-brain regional gray matter volume between these two subgroups. Besides, we also implemented small-volume corrections using the striatal and default-mode network (DMN) mask for the VBM. Post-hoc analyses extracting the volumes of striatal and precuneus regions of interest (ROIs) were also performed. Results: There were 63 and 16 patients in the good-response and poor-response groups, respectively, based on the CGI-I score. Using the Statistical NonParametric Mapping, the whole-brain analysis showed a larger gray matter volume in the left putamen and smaller volume of precuneus area in the good-response group, relative to the poor-response group. Then, we identified a significant group difference by using small-volume correction based on the striatal mask and DMN mask. Further post-hoc ROI analyses also showed that good responders had a larger volume of the left putamen and smaller volume of the precuneus compared to poor responders. Conclusions: Consistent with the prior imaging reports investigating methylphenidate mechanisms, our results suggest regional striatal and precuneus gray matter volume play a critical role in mediating treatment responses in individuals with ADHD.