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注意力缺陷多动障碍

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注意力缺陷多动障碍(ADHD)
attention deficit hyperactivity disorder
同义词注意力缺失症、注意力缺陷过动症、过度活跃症、hyperkinetic disorder (ICD-10)
注意力缺陷多动障碍的常见症状
注意力缺陷多动障碍的常见症状
症状容易分心英语attentional shift(难以把专注力放对地方)、过度的活动、 难以控制行为和冲动[1][2]
常见始发于6 - 12岁左右[3][4]
病程多于6个月[3]
类型特殊性发育障碍, 多动障碍[*], distractibility[*]
肇因尚不明确[5]
诊断方法根据症状并排除其他可能的致病原因。[1]
相似疾病或共病品行障碍对立反抗症学习障碍躁郁症[6]自闭症谱系睡眠障碍[7]焦虑症[7]忧郁症[7]
治疗心理治疗、改变生活方式、药物[1]
药物中枢神经刺激剂阿托莫西汀胍法辛英语guanfacine[8][9]
患病率5,110万(2015年)[10]
分类和外部资源
医学专科精神医学儿童与青少年精神医学
ICD-116A05
ICD-10F90.0
OMIM143465、608903、608904、608905、608906、612311、612312
DiseasesDB6158
MedlinePlus001551
eMedicine289350912633
Patient UK英语Patient UKattention-deficit-hyperactivity-disorder-pro 注意力缺陷多动障碍(ADHD)
attention deficit hyperactivity disorder
“ADHD”的各地常用译名
中国大陆注意力缺陷多动障碍
台湾注意力不足过动症
香港专注力失调/过度活跃症
澳门专注力失调/过度活跃症
日本注意欠陥・多动性障害
大韩民国注意力缺乏过多行动障碍
注意力缺乏 过剩行动 综合征
越南𦇒乱增动减注意

注意力缺陷多动障碍(英语:attention deficit hyperactivity disorder,缩写为ADHD),又称注意力缺失症(英语:attention deficit disorder,缩写为ADD),是神经发展障碍精神疾患[11][12]。它的特性是难以专注、过度活跃、做事不考虑后果等等。除此之外,还有不合年纪的行为,有注意力缺失的个体也可能表现出情绪调节困难或执行功能方面的问题[1][13]。对于诊断来说,症状应在患者12岁之前出现、持续超过六个月、至少发生于两种情境下(如学校、家中、休闲活动等)[3][4]。儿童患者注意力不集中的问题可能导致学习成绩不佳[1],此外,此病症也跟其他心智障碍或药物滥用有关[14]。虽然此病症(特别是在现代社会中)会造成一些“障碍”,但很多过动症者会对他们感兴趣或认为有价值的任务保持持续的专注,此状况被称为过度专注[15][16]

尽管此病症在小孩与青年的范围中被大量的研究以及诊断,多数的例子中,仍然找不到精确的病因,他们认为基因的原因占了75%,在怀孕期间尼古丁的接触也可能是一个导致病因的外部风险,似乎跟自律以及家庭风格没有关系[17]。依照《精神疾病诊断与统计手册》第四版(DSM-IV)的判据,约有5–7%的儿童确诊[13][18],若依照《世界通用疾病分类手册》第十版ICD-10的判据,则有1–2%确诊[19]。2015年估计全球有5110万人受到注意力缺陷多动障碍的影响[10]。患病率主要会受到诊断方式及判断基准不同所影响[20],男孩确诊的比例是女孩的二倍以上[13],不过因为女孩的症状和男孩不同,因此常被忽略[21][22][23]。儿童期诊断到的注意力缺陷多动障碍,约到30–50%会持续到成年,成年人约有2–5%会有成人注意力缺陷多动障碍[24][25][26]。在成人注意力缺陷多动障碍中,过动的情形可能会被“内在的不安宁”所取代[27]。ADHD的症状可能不太容易和其他疾病的症状区分,也不太容易区分正常范围的活力充沛以及过动的分界点在哪里[4]

建议治疗的方法依国家不同而有所差异,一般都会以心理治疗、生活方式调整以及药物,这三种中的一种或多种方式来进行治疗[1]。英国的医学指南建议针对儿童,只有在症状严重时,才建议使用药物为第一线的疗法,若儿童拒绝接受心理治疗,或是接受治疗后进展不大,需考虑用药物进行治疗,若针对成人,药物为第一线的治疗方式[28]。加拿大及美国则是建议第一线的治疗应该是合并药物治疗及行为治疗,只有一些学龄前的儿童例外[29][30]。在所有的医学指南中,都不建议针对学龄前的儿童用兴奋剂作为第一线的治疗方式[28][30]。用兴奋剂治疗,在前十四个月的疗效有研究数据可供佐证,不过不确定长期使用的疗效[31][32][33]。患有ADHD的成人可能会发展出应对方法英语Coping_(psychology),来处理症状造成的部分或所有影响[34]

18世纪起的医学文献中就有描述过类似注意力缺陷多动障碍的症状[35]。自1970年起,就有出现有关注意力缺陷多动障碍疾病本身、其诊断及治疗方式的争议[36],争议和临床医师、教师、政策订定者、家长及媒体有关。争议焦点包括ADHD的病因,以及是否要用兴奋剂来治疗ADHD[37]。目前大部分的医疗人员都接受ADHD是儿童及成人的遗传性疾病,科学界的争议点则是在其诊断方式及治疗方式[38][39][40]。此疾病在1980年至1987年的正式名称是注意力缺失症(attention-deficit disorder,简称ADD),在更早期的名称是儿童过度活跃的反应(hyperkinetic reaction of childhood)[41][42]

名称[编辑]

注意力缺陷多动障碍也译作注意力不集中/过动症(英语:Attention Deficit/Hyperactivity Disorder,简称AD/HD)、过度活跃症(英语:Hyperkinetic Disorder;于ICD 10中的名称),俗称有多动症、多动障碍及大雄·胖虎综合征(日本)等。此病患的儿童习称过动儿,也有医疗人士建议改称为心动儿[43][44]

症状及体征[编辑]

ADHD的症状[45]
专注力失调 过动-冲动
  • 很难注意事情的细节
  • 不容易专注在一件事情上
  • 不容易针对事物或是活动进行规划组织
  • 会遗忘一些需要的物品
  • 在日常活动中比较健忘
  • 注意力持续时间较短,较容易分心
  • 不容易处理较具结构性的学校功课
  • 难以完成繁琐或需要花时间的任务
  • 没办法好好坐着
  • 在座位上坐立不安、动来动去
  • 会在不适当的时间点离开座位
  • 从事具风险性的事物,不太考虑后果
  • 时常处于活跃状态、精力充沛、停不下来
  • 说话的频率及时间会比其他人要多
  • 问题未说完就抢着说答案
  • 不容易轮流等候
  • 在对话中常常插嘴或是打断别人说话

注意力缺陷多动障碍的常见情形有不专心、过动(在成人则会以不安来表现)、破坏行为及冲动[46][47]。在人际关系及学业上都容易出现问题[46],不过其症状不容易定义,因为很难介定一般情形下的不专心、过动及冲动会到什么程度,到什么情形下才需要介入治疗[48]

依照《精神疾病诊断与统计手册》(DSM)第五版(DSM-5)的定义,注意力缺陷多动障碍的症状需出现超过六个月,或是其情形要比同年龄的要明显很多[13],而且其症状已造成至少二个情境(例如社交、学校/工作、家庭)的问题[13],这些条件需在12岁以前就出现[13],若是17岁以下的,在专注力失调或是过动/冲动上的症状,至少需要有五项符合[13]

子类型[编辑]

注意力缺陷多动障碍可分为三个子类型[13][48]:

若是以注意力不足(专注力失调)为主的儿童或青少年,会有以下大部分甚至全部的症状,且非由其他医学疾病或药物直接造成[13][49]

  • 容易分心、粗心、忘记事情、且经常从一件事情切换至另一件事情。
  • 很难持续专注在同一件事情上。
  • 除非进行自身有兴趣的事务,不然进行几分钟后就觉得无聊。
  • 难以对组织(规划)事情、完成一个任务保持专注。
  • 很难完成回家作业,或是如期缴交,常会遗失一些要完成作业或是其他活动需要的东西(例如铅笔、玩具、作业等)*
  • 当别人在和患者说话时,似乎没有在听对方说话。
  • 作白日梦、很感到困惑、动作缓慢。
  • 不容易像其他非注意力缺陷多动障碍患者一样,快速且准确的处理信息。
  • 难以遵从指示
  • 不容易认知细节,常忽略细节。

若是以过动为主的儿童或青少年,会有以下大部分甚至全部的症状且非由其他医学疾病或药物直接造成[13][49]

  • 常常烦躁及坐立不安
  • 不停地讲话
  • 四处东奔西跑、碰触或玩弄视野内的任一或每一个物体。
  • 难以在上课时间、吃饭时间、做功课的时间乖乖坐好。
  • 不停的动来动去。
  • 不容易进行安静的活动或是工作。
  • 没有耐心
  • 脱口说出不恰当的话语、毫无掩饰地流露内心的想法,且行事不顾后果。
  • 难耐在游戏中因轮流所产生的等待时间。
  • 经常打断他人的对话或活动。

若注意力缺陷多动障碍患者的症状符合上述二类,则属于合并型的注意力缺陷多动障碍。

ADHD的女性比较不会有过动及冲动的症状,比较会有注意力不集中及分心的症状[50]。注意力缺陷多动障碍中有关过动的症状,可能会随着年龄增长而渐渐消退,而转变为青少年及成人阶段的“内在不安宁”[24]

注意力缺陷多动障碍的儿童、青少年及成年比较容易有社交技巧英语social skills上的问题,例如社交互动、发展友谊及建立友谊。有半数的注意力缺陷多动障碍患者曾受到同侪社会排斥的情形,而没有注意力缺陷多动障碍的人被社会排斥的比例约为10%至15%。患有注意力缺陷多动障碍的人比较不容易处理口语及非语言的讯息,比较容易在社交互动上有负面的影响,也比较容易在对话时离题、忽略到一些社交的信息、也比较不容易学习社交技能[51]

注意力缺陷多动障碍的儿童比较常有不容易控制情绪的问题[52],其写字英语handwriting能力也比较弱[53],在语言、说话及运动上的发展都比较晚[54][55]。虽然注意力缺陷多动障碍会造成许多的不便,不过若注意力缺陷多动障碍的儿童针对有兴趣的主题及事物,其专注力持续时间和其他儿童相当,甚至比其他儿童要好[16]

可能有关的疾病[编辑]

在注意力缺陷多动障碍患者中,大约会有三分之二的概率会伴随其他的疾病或特征[16]。常见的共病或特征如下:

  • 癫痫[56]
  • 妥瑞症[56]
  • 自闭症谱系(ASD):此疾病会影响社交技巧、沟通能力,也会出现固定兴趣和重复行为[56]
  • 在注意力缺陷多动障碍患者中,较常出现有焦虑症的情形[57]
  • 间歇性暴怒英语Intermittent explosive disorder[13]
  • 在注意力缺陷多动障碍的儿童中,有20%至30%有学习障碍的情形。学习障碍可能包括发展障碍、语言障碍以及学习技巧的障碍[58]。注意力缺陷多动障碍本身不是一种学习障碍,不过常常会造成其他学业上的困难[58]
  • 强迫症(OCD)常和注意力缺陷多动障碍一起出现,其中也有许多相同的特征[59]
  • 智能障碍[13]
  • 反应性依附疾患英语Reactive attachment disorder[13]
  • 物质使用疾患。注意力缺陷多动障碍的儿童及成人在物质滥用上的风险较高[24]。最常见的是酒或是大麻[24]。物质使用疾患的原因可能和注意力缺陷多动障碍造成的大脑回馈酬赏回路英语reward pathway改变有关[24]。若注意力缺陷多动障碍和物质使用疾患一起出现,这会让注意力缺陷多动障碍的评估及治疗更加困难。如果ADHD合并“严重的”物质滥用问题,基于往后衍生的风险大小之考量,会优先治疗物质滥用问题[60][61]
  • 睡眠障碍常和ADHD一起出现。这也可能是治疗ADHD的副作用。对于注意力缺陷多动障碍的儿童而言,失眠是最常见的睡眠障碍,一般会用行为疗法来进行治疗[62][63]。 ADHD患者常伴随着不容易入睡的问题,而他们也会睡的比较熟,因此早上不容易起床[64],有时会针对不容易入睡的儿童用褪黑素治疗[65]
  • ADHD的患者约有50%有对立反抗症(ODD),有20%有行为规范障碍(CD)[66],其特性是反社会的行为,例如心态固执、有攻击性、常常闹脾气英语temper tantrums、说谎和偷窃等[59]。若有对立反抗症或行为规范障碍的ADHD患者,长大成人后出现反社会人格障碍的概率约有一半[67]。根据脑部造影,可确认ADHD和行为规范障碍是两种不同的疾病[68]
  • 有关注意力的原发型疾病,其症状是注意力不佳,不容易专注,也不容易维持清醒。这类儿童常会坐立不安、打呵欠及伸展身体,这些动作看似过动,但其实是为了让自己维持警觉以及有活力的状态[69]
  • 迟缓的认知速率英语Sluggish cognitive tempo(SCT)是许多症状的总称,其中不少症状可能也包括了注意力不足的问题。在ADHD的病例中,不论其子类型如何,有30%至50%符合这些症状[70]
  • 刻板的惯性动作症英语Stereotypic movement disorder[13]
  • 情感障碍(特别是躁郁症重度抑郁症)。诊断患有混合子类型ADHD的男孩较容易有情感障碍[57]。有ADHD的成人有时也会有躁郁症,需要很仔细的评估来诊断及治疗这两种疾病[71]
  • 注意力缺陷多动障碍的患者较常有不宁腿综合征,一般是因为缺铁性贫血所造成[72][73]。不过不宁腿综合征也可能是注意力缺陷多动障碍症状的一部分,因此需要进行详细的诊断,区分不宁腿综合征和注意力缺陷多动障碍[74]
  • 注意力缺陷多动障碍的患者出现夜遗尿的风险较高[75]

有一个2016年的系统回顾发现注意力缺陷多动障碍和肥胖、哮喘及睡眠障碍有有着直接的关联,和乳糜泻偏头痛也有一些关系[76]。不过同一年的另一篇系统回顾认为注意力缺陷多动障碍和乳糜泻没有明确关系[77]

智力[编辑]

有研究发现患有注意力缺陷多动障碍的人其智商(IQ)测试的结果会比没有注意力缺陷多动障碍的人要低[78],不过有关此研究结果的重要性,目前仍有争议,因为很难区分影响是因为ADHD的症状(例如分心)所造成还是ADHD本身对于智力有影响[78]

有一份成人ADHD的研究指出有关ADHD患者在智力上的差异,没有统计上的意义,也可以用其他相关的疾病来解释[79]

有一份最新的研究报告指出,智能障碍的病患罹患ADHD的概率相比其他人较为提高;而若亲属中有人为智能障碍者的话,家族中其他成员罹患ADHD的概率(相比于亲属中没有智能障碍者)也较高。根据拟和模型的分析,造成这种情况的原因有91%的可能性与基因有关。[80]

诊断[编辑]

注意力缺陷多动障碍的诊断是根据患者的行为和心理发展的评鉴并且排除毒品、药物的影响、或其他生理或心理的可能造成类似ADHD症状的因素而成。[60]诊断过程通常会将病例的父母意见及师长意见列入考量。[4] 大多数的诊断都是因为病例的教师首先对于孩子的健康提出关切,经转介后而成。[81] 注意力缺陷多动障碍的症状可能会被认为是人类个性光谱的极端或是其中一环而已。[82] 对于ADHD的药物反应结果,无法就此确认诊断或排除诊断。迄今为止ADHD与非ADHD病患脑部构造的差异方面,学界尚未达成一致结论,因此脑部造影只被用于对于复杂的人脑进一步的研究,尚未能应用于诊断ADHD。[83]使用量化脑波英语quantitative electroencephalography (QEEG) 诊断ADHD是学界中正在研究的领域之一,然而迄今为止,脑波经过量化后的数值与ADHD之间的关系仍然不明。[84][85]

注意力缺陷多动障碍又可细分为以下三种类型:注意力不足(专注力失调)为主型、过动-冲动为主型、或注意力不足(专注力失调)且过动-冲动的混合型。[86]过动,即为“过度”活跃。过度两字意味着活跃的程度已经对生活造成不良的影响。[87]即便病例并无上述注意力缺陷多动障碍的所有特征,他仍有可能是ADHD患者,有无全部特征牵涉到是否有其他共病存在且治疗的主要目的在于协助患者避免缺点并发扬优点。成人及儿童青少年的注意力缺陷多动障碍的诊断依据《精神疾病诊断与统计手册》的标准、患者的历史经历(病例史)[86]、门诊病人的主诉、症状学、发展史、家族史、共病、生理评估、心理测验(例如:工作记忆、执行功能:计划与决策等、视觉记忆、空间记忆、理智等等[5])及各种医师评估后认为需要进一步的检查等。[7][88][5]

ADHD隶属于神经发育所致之精神疾患[12][24]。 除此之外,ADHD也隶属于紊乱行为综合征英语disruptive behavior disorder,同样隶属于紊乱行为综合征的心理疾病有:对立反抗症品行障碍、和反社会人格障碍[89]。ADHD的诊断并不暗指任何一个神经系统疾病英语neurological disorder[90]

医师在诊断过程中必须衡量病例的焦虑忧郁程度、及对立反抗症品行障碍、及学习语言障碍。其他需要考量的问题包括:其他神经发育障碍、抽动综合征、和睡眠呼吸暂停[91]

自我评量表,例如:ADHD 评量表英语ADHD rating scaleVanderbilt ADHD诊断评量表英语Vanderbilt ADHD diagnostic rating scale会在诊断和评估ADHD的过程中使用。[92]

病因学[编辑]

ADHD患者的脑部与非ADHD患者(Typically developing controls)的脑部造影显示的大脑发育成熟度的差异[93][94]

迄今为止,注意力缺陷多动障碍是儿童精神病学,获得最多且最深入研究的领域,然而绝大多数ADHD的确切成因目前并没有定论[95],最有可能是基因、环境和社会等因素相互作用导致。[96][97][98][99]

有些病例的成因可能与脑部的疾病感染和脑部创伤有关。[96][97][98]根据研究统计,注意力缺陷多动障碍具有相当高的遗传率。[96][97]除了基因外,一些环境及社会因子也可能是注意力缺陷多动障碍的致病因素。[100][101][90]

基因遗传[编辑]

双生子研究指出此疾病常常是遗传得来的,占了所有案例的75%[90][102][103]。若一儿童的兄弟姊妹中有患有ADHD,其自己身罹患ADHD的概率,是兄弟姊妹都没有ADHD的儿童的三至四倍[104]。一般也认为基因因素会决定ADHD的症状是否会持续到成年[105]

一般来说,ADHD和许多基因有关,特别是和会影响多巴胺神经传导的基因有关[106][107]。和多巴胺有关的有多巴胺转运体(DAT)、多巴胺受体D4(DRD4)、多巴胺受体D5英语DRD5痕量胺相关受体1英语TAAR1单胺氧化酶A英语MAOA儿茶酚-O-甲基转移酶(COMT)及多巴胺β羟化酶(DBH)[107][108][109],其他和ADHD有关的有血清素转运体(SERT)、HTR1B英语HTR1BSNAP25英语SNAP25GRIN2A英语GRIN2AADRA2A英语ADRA2ATPH2英语TPH2脑源性神经营养因子(BDNF)[106][107]。有一种常见的Latrophilin 3英语Latrophilin 3基因变异,估计造成9%的ADHD,若有这种变异时,会对兴奋剂药物格外有反应[110]DRD4 7R变体基因会增强多巴胺造成的抑制作用,也和ADHD有关。DRD4受体是G蛋白偶联受体,会抑制腺苷酸环化酶。DRD4-7R变异会造成许多行为上的表型,包括反映了注意力分散的ADHD症状[111]

演化也可能是造成ADHD高比率的原因,特别是男性过动以及冲动的倾向[112],有人曾提出假说,认为女性比较容易被会冒险的男性所吸引,因此增加了基因库中爱好冲动及冒险的基因的比率[113]。其他人则认为这种倾向有助于男性面对有压力或是危险的环境(例如更有冲劲,从事探索行为)[112][113]。在特定情境下,ADHD倾向虽然对个体是有害的,但是对群体是有益的[112][113][114]。ADHD虽然对个体可能不利,但其高比例以及异质性也有利于群体的生殖健康,并且可以增加基因库的多样性,对群体有益[114]。在特定环境下,ADHD也可能对个体有利,例如对捕食者的反应更快,以及较好的狩猎技巧英语Hunter vs. farmer hypothesis[115]

患有唐氏综合征的人比较容易患有ADHD[116]

环境因素[编辑]

除了基因外,一些环境因子也可能是注意力缺陷多动障碍的致病因素[117]。例如:在怀孕期间摄取酒精可能导致胎儿酒精谱系障碍,可能包括了注意力缺陷多动障碍,或是有类似症状[118]。暴露在特定有毒物质,例如:多氯联苯等,可能会产生类似注意力缺陷多动障碍的中毒症状[17][119]。暴露在磷酸酯的杀虫剂毒死蜱烷基磷酸酯英语Alkyl phosphate中,也可能会增加患病的风险,不过此一论点尚未受到广泛认可[120]。在怀孕过程中吸烟,将不利于胚胎的脑部神经发育,并将增加罹患注意力缺陷多动障碍的概率[17][121]

新生儿极度早产体重过轻、极端疏于照料、遭受凌虐、缺乏社会的互动也会增加ADHD的风险[17][122]。母亲在怀孕期间、儿童在出生时或成长初期遭受一些疾病的感染都可能提高致病率(例如麻疹、, 带状疱疹英语Varicella zoster virus脑炎风疹EV71等)[123]。长时间于妊娠期间使用对对乙酰氨基酚与孩子出生后带有ADHD,有统计上的相关性[124][125]创伤性脑损伤的儿童中,后来至少有30%有ADHD的症状[126],其中约有5%是因为脑部损伤[127]

一些研究发现,人工食用色素防腐剂可能与少部分儿童出现类似ADHD的症状,或者是与ADHD的流行率增加有关[17][128],但是这些研究的证据力薄弱,而且可能只适用于有食物敏感的孩子[128][129][130]英国欧洲联盟已针对这些疑虑发布相关食品管理措施[131]。对于某些食物的食物过敏食物不耐症,可能会恶化少数孩子既有的ADHD症状[132]

截至2018年11月,研究并不支持注意力缺陷多动障碍是因为摄取过多的精致糖、看太多电视、教养方式英语parenting、贫穷或家庭吵吵闹闹所造成,不过这些可能会让一些注意力缺陷多动障碍的症状更加恶化[47]

社会[编辑]

有些情形下,ADHD的患者不是其自身的问题,而是反映了家庭机能不全或是教育系统的不足[133]。也有一种情形,诊断出ADHD表示其他人对其课业期待的增加,因为在一些国家,诊断是一种让家长取得更多对小孩经济及教育支持的方式[127]。一般有经历过暴力或是情感虐待的儿童比较容易出现ADHD的行为[90]

ADHD的社会建构理论英语social construct theory of ADHD认为评断正常及异常的标准是社会建构的(是由社会中的所有人建立并且使其有效的,特别是医生、病患、家长、教师等),然后再主观的评估及判断要使用哪一种判据,以及有多少人会因此受到影响[134]。他们认为这是依DSM-IV标准诊断到的ADHD人数会是由ICD-10标准所诊断人数三至四倍的原因[23]汤玛士·非典是ADHD社会建构理论的支持者,他认为ADHD是“发明出来的,之后取了这个名字”[135]

班上里年龄最小的儿童比较容易诊断为ADHD,原因可能是他们的发展本来就比其他年龄略长几个月到一年的同学要晚一些[136][137][138],在许多国家都有出现这种情形[138],他们使用ADHD药物的比例也是其他同学的两倍左右[139]

病理生理学[编辑]

ADHD的左前额叶通常与控制组(非ADHD患者)显著不同[140][141]

注意力缺陷多动障碍被认为是肇因于部分脑内的神经传导物质系统的损伤(特别是与多巴胺和去甲肾上腺素有关的神经传导系统),进而对患者的脑部执行功能产生不良的影响[142][140]。多巴胺与去甲肾上腺素的脑内神经传导物质通道系统英语Neural_pathway大多起源自脑内的腹侧被盖区蓝斑核,并由此投射至不同的脑区且管理许多认知的流程(与认知功能相关的处理流程)。[142][143]特别是那些投射至前额叶和纹状体脑内多巴胺神经传导通道系统英语dopaminergic pathway脑内去甲肾上腺素通道系统/蓝斑核系统。它们主要的工作就是负责调节执行功能(认知和行为的功能与管理)、动机酬赏/报偿的感受能力、和运动神经的功能[注 1][142][140][143]以上是目前已知在注意力缺陷多动障碍的病理生理学中扮演主要角色的几条脑内神经传导物质通道系统。也已经有人提议强化对于注意力缺陷多动障碍更全面的概观以及更多可能与之相关的脑内神经传导物质通道系统之探究。[140][144][145]

而研究也发现,注意力缺陷多动障碍是由一种发生于脑前额叶遗传性的多巴胺新陈代谢失常引致。更近期的研究认为去甲肾上腺素新陈代谢亦会对病情有所影响 [146] [147] [148]

截至2019年8月底,已知ADHD也与 血清素传导系统英语serotonin pathways(5hydroxytryptamine [5-HT])、 乙酰胆碱传导系统英语acetylcholine pathways(ACH)、阿片类传导系统英语opioid pathways、和谷氨酸传导系统英语glutamate pathways(GLU)的失调有关。[149][150][151]

治疗[编辑]

注意力缺陷多动障碍的治疗方式包括心理治疗行为治疗及药物,也有可能是用几种方式一起进行。治疗对病症会有长期的改善,但是无法完全根除病症的影响[152]。药物包括有兴奋剂、阿托莫西汀肾上腺素受体α2英语alpha-2 adrenergic receptor拮抗剂,有时也会包括抗抑郁药物[57][153]。若时无法专注在长期奖励上的人,有许多的正增强方式可以提升其工作表现[154]。ADHD药物中的兴奋剂也可以提升患者的毅力及工作表现[140][154]

行为治疗[编辑]

有关行为治疗在ADHD上的应用,有许多良好的实证,若是针对学龄前,或是症状轻微的病患,一般会建议用行为治疗为第一线的疗法[155][156]。心理疗法包括有心理教育行为治疗认知行为疗法(CBT)、人际取向心理治疗家庭治疗英语family therapy、学校介入、社交技巧训练、行为方面的同侪介入、机构培训[157]父母管理训练[90]。父母管理训练可以改善包括反对行为以及不合常规行为在内的一些行为问题[158]。心理疗法也包括神经反馈英语neurofeedback训练[159],目前还不清楚是否有效[160]

有关家庭治疗的效果,目前还很少足够品质的证据可以佐证。目前证据认为家庭治疗的效果类似群体照顾(community care),效果比安慰剂要好[161]。有许多注意力缺陷多动障碍支持组织可以提供相关信息,并且协助家庭适应ADHD的情形[162]

有关社交技巧的训练、行为调整以及药物的对病患的好处可能有限。要减少后续心理及精神问题(例如重度抑郁症犯罪、学校学习失败、物质使用疾患)的主要因素是和没有从事偏差行为的人建立友谊[163]

规律的体能锻炼,特别是有氧运动,对于患有ADHD的儿童及成人而言也是有效的附加疗法英语adjunct therapy,特别是配合兴奋剂药物治疗时更是如此,不过针对改善症状,最理想的运动种类及强度还不清楚[164][165][166]。长期规律有氧运动对ADHD患者的好处是提升行为及运动能力、提升管控功能(包括专注、抑制控制、计划等)、较快的信息处理速度,记忆力也会比较好[164][165][166]。家长及教师针对ADHD儿童规律有氧运动对行为及以社交-情绪上的改善有:全身整体机能较佳、减少ADHD症状、自尊感较好、减少焦虑及抑郁的程度、较少身体症状、课业成绩及教室行为较佳,社交行为也有改善[164]。若在有使用兴奋剂治疗时进行运动,会增加兴奋剂药物对执行功能的影响[164],一般认为运动的短期效果是因为运动时大脑突触多巴胺和去甲肾上腺素浓度的增加所造成[164]

药物[编辑]

针对注意力缺陷多动障碍,可以用中枢神经刺激剂(也称为兴奋剂)药物进行治疗[167][168][已过时],对于症状至少会有一些效果,短期而言,约有80%会有效果[37][169][168]。家长及教师反应哌甲酯比较可以改善其症状[37][170],中枢神经刺激剂也可以减少ADHD儿童意外事故的风险[171]。针对ADHD的中枢神经刺激剂药物除了哌甲酯外,还有苯丙胺甲基苯丙胺等。

针对ADHD的非中枢神经刺激剂药物有许多种,包括阿托莫西汀安非他酮胍法辛英语guanfacine可乐定,这些可以作为主要药物治疗,或是配合中枢神经刺激剂药物一起使用[167][172]。目前有关各药物之间的比较,还没有说服力足够的研究结果可以佐证,不过在副作用上似乎差不多[173]。中枢神经刺激剂药物比较可以提升课业表现,阿托莫西汀则无此效果[174]。阿托莫西汀比较不会有成瘾问题,因此若有娱乐性药物或是强迫性药物使用风险的人,比较建议使用阿托莫西汀[24]。有关药物对社交行为上的影响,目前的数据也还不充份[173]。截至2015年6月年 (2015年6月-Missing required parameter 1=month!),还没有完全确定ADHD药物的长期影响[175][176]核磁共振成像 研究推测长期用苯丙胺哌甲酯治疗,会减少因为ADHD造成的大脑功能及结构异常[177][178][179]。2018年的文献回顾发现若考虑短期效果,哌甲酯对儿童最有效,苯丙胺对成人最有效[180]

什么情形要用胍法辛英语guanfacine治疗会依国家而不同,英国国家健康照护专业组织英语National Institute for Health and Care Excellence(NICE)针对成人是第一线药物,若针对儿童,只建议在病情严重时才使用,而大部分美国的医学指南会建议可以针对各年龄层使用[29]。针对学龄前的儿童,一般不建议用药物治疗[90][181]。若治疗用的中枢神经刺激剂剂量不足,可能会有没有药效的情形[182],这尤其常出现在青少年及成人身上,因为核可的剂量是针对学龄儿童的,因此有些医疗人员会依体重或是依其他因素给药[183][184][185]

一般而言,在正常治疗剂量的哌甲酯及中枢神经刺激剂是安全的,不过有其副作用以及禁忌症[167]。若哌甲酯给儿童及青少年使用,有研究发现这和一些严重或不严重的有害副作用有关,不过证据品质还不充份[186]。若针对儿童开立这类药物,需仔细的监测儿童的情形[186]。若ADHD的中枢神经刺激剂严重过量,可能会和兴奋性精神病英语stimulant psychosis或是狂躁的症状[187]。若是治疗用的剂量,出现类似情形的概率非常低,只有0.1%,会在开始用中枢神经刺激剂药物治疗后的前几周出现[187][188][189],若也使用抗精神病药,可以有效缓解急性苯丙胺精神病的症状[187],若长期治疗,需要定期的监测[190]。兴奋剂的药物治疗需要定期停药,评估是否还需要用药、减少发育迟缓的情形,并且减低抗药性[191][192]。若是长期使用超过ADHD治疗剂量的兴奋剂药物滥用,一般会和成瘾物质依赖有关[193][194]。不过未治疗的ADHD,会提高物质滥用以及行为规范障碍的风险[193]。兴奋剂药物的使用,可能可以降低风险,但也有可能没有此效果[24][175][193]。还不清楚怀孕时服用这些药物是否安全[195]

饮食[编辑]

饮食的调整可能对少部分的ADHD儿童有帮助[196]。一份2013年的统合分析针对有ADHD症状,而且有补充游离脂肪酸或是减少食用有人工色素食品的儿童的相关研究发现,只有不到三分之一的儿童在症状上有改善[129]。这方面的助益有可能只是对有食物敏感的儿童有帮助,也有可能是因为这些儿童同时也在接受ADHD的治疗[129]。这些文献也指出目前已有的证据无法支持减少食用特定食物来治疗ADHD的疗法[129]。2014年发表的文献也发现排除饮食在治疗ADHD上的成效有限[132]。另一篇2016年文献回顾指出,根据研究结果,“无麸质饮食在未来成为ADHD的标准疗法”之概率是微乎其微[77]

2017的文献回顾指出有一些排除饮食的方式对于非常小,无法用药的幼童,以及对药物没有反应的患者可能有用,不过不鼓励用补充游离脂肪酸或是减少食用有人工色素食品作为ADHD的正规治疗方式[197] 。长期铁、镁及碘等矿物质的不足可能可以让ADHD的症状加剧[198],也有少数证据指出组织内含量过低和ADHD有关[199]。不过除非证实有锌不足英语zinc deficiency的情形(目前多半是发展中国家才会有锌不足的情形),一般不建议用锌补充剂英语zinc supplementation治疗[200]。不过若锌矿物质和苯丙胺类药物同时使用的话,可以减低苯丙胺药物的最小有效剂量,也就是可以服用较少的药物而达到相同的效果[201]。另有证据指出Ω-3脂肪酸对于病情会有些许的改善,不过不建议取代医学治疗[202][203]

流行病学[编辑]

注意力缺陷多动障碍各子类型的比例分布(紫色为混合型;蓝色为注意力缺陷为主型;粉红色为过动—冲动为主型)[204][205]

注意力缺陷多动障碍是童年阶段最常见的发育疾患[206]。根据2015年发表的研究,依照DSM-III, DSM-III-R及DSM-IV的标准,国际ADHD流行率中位数,儿童为6-8%[207][18]。若使用ICD-10的标准,同年龄儿童的流行率则为1–2% [19]

美国的成人注意力缺陷多动障碍的流行率为4-5%[208][209]。根据《找回专注力:成人ADHD全方位自助手册》,成人ADHD在台湾的流行率推估为3-4%[96]:24-25。ADHD是全球性的[210][211][212][213]。世界各地ADHD流行率的差异主要是因为世界各地使用的ADHD诊断方法不同。[214] 若使用相同的诊断方法,则世界各地所得出的ADHD流行率将介于伯仲之间。[215]

在亚洲,台湾[216][217]、日本[218]、韩国[219]、越南[220]、中国大陆[221]港澳[222][223]等地的未成年之ADHD流行率均介于6-8%之间。

英国和美国的ADHD诊断率和治疗率自1970年代起逐年增加至今[224]。学界的共识认为这个现象是因为诊断方法的变迁[224]以及人们逐渐愿意利用药物来治疗ADHD所致[19],并非ADHD的流行率真的增加了。[214][225]

学界共识认为,2013年起,DSM的版本从DSM 4TR 推进到 DSM 5 会使得ADHD的诊断数增加(特别是成人注意力缺陷多动障碍的诊断数) [226]

历史[编辑]

关于ADHD治疗、诊断标准及流行率的时间轴 (英文)

1798年时苏格兰医师亚历山大·克里奇顿英语Alexander Crichton在其著作《对精神紊乱的性质和起源的探究》(An inquiry into the nature and origin of mental derangement)中提到了精神不安[227][228],1902年,英国儿科医生George Still英语George Frederic Still首次描述一项与注意力缺陷多动障碍近似的病征[229][224]

不同的时期,描述注意力缺陷多动障碍的名词也有所不同:在1952年的DSM-I称为微细脑功能失常,在1968年的DSM-II则称为儿童活动亢进,在1980年的DSM-III称为注意力不足症(可能伴随过动,也可能没有)英文为 attention-deficit disorder (ADD) with or without hyperactivity[224],在1987年的DSM-III-R更名为注意力缺陷多动障碍,在1994年的DSM-IV将注意力缺陷多动障碍分为注意力散涣主导型英语Attention deficit hyperactivity disorder predominantly inattentive、活动量过多型以及混合型[230],在2013年的DSM-5仍延用此一分类[13]。其他的名词有在1930年代使用的微细脑创伤[231],但因为不少病童都没有发觉有受过任何创伤,因此后来改名为微细脑功能失常。

1937年时,神经刺激剂开始用在注意力缺陷多动障碍的治疗[232]。1934年时美国许可将安非他命用在注意力缺陷多动障碍治疗,是美国第一个许可的苯丙胺类药物[233],1950年代开始使用哌甲酯(商品名称为利他林),1970年代则开始使用对映异构右旋苯丙胺[224]

预后[编辑]

孩童的ADHD有30–50%的概率持续到其成人时期,[234][235][236] 那些持续被ADHD影响的成人可能会在成长过程中发展出一些技巧弥补部分ADHD的症状。[34] 带有ADHD的儿童与青少年相较于不带有ADHD的儿童与青少年,有较高的风险发生意外受伤等事故。[171]

ADHD药物能改善(非治愈)患者在生活中许多方面的功能性损伤(functional impairment ;可理解为应对能力的损伤)和生活品质英语Quality of life (healthcare)(例如:发生意外事故的风险)。但是ADHD患者的学习障碍和执行功能缺损(例如时间管理、生活秩序以及组织能力[237])等症状,即便在服用ADHD药物后,这些症状的改善程度极其有限或几乎没有效果。[238]

考科蓝协作组织于2015年发表的系统性文献回顾指出,虽然中枢神经刺激剂不会令服用者产生严重的副作用,但他们较常出现失眠、食欲不振等较为轻微、影响较轻的副作用,并衍生出长期预后的不确定因素,因此未来的研究重点将会聚焦于探讨解决前述的副作用的方法。与此同时,未来亦需要深入地研究“非药物治疗方式”以及可能的“非药物治疗方式”之随机对照试验[239][240]

迄今为止,对于ADHD的长期追踪调查主要都是小规模的,代表性有限。唯一规模较大也较具有代表性的美国卫生及公共服务部MTA(多模式治疗)研究发现,那些曾在1990年代参加MTA的儿童ADHD,六到八年后进入青春期,他们在许多方面的应对能力,取决于他们小时候治疗前呈现的症状、共病、疾病的严重度以及治疗后对于MTA四种治疗模式的任意一种模式的契合度高低等因素。[241]

当MTA追踪这些受试者长达十六年,直到受试者的平均年龄到达25岁的时候,发现这些患者生活中各领域的应对能力取决于ADHD的症状是否持续到成年、ADHD的症状严重度、和共病等因素。[242][243][244]

社会与文化[编辑]

美国电影电视演员伊丽莎·杜什库鼓励大众认识ADHD[245]

注意力缺陷多动障碍患者常被错误认为“只是懒惰或缺乏意志力”、“诊断只不过是用来为患者们的问题找借口罢了”等。有ADHD患童因长期遭到霸凌,于独处时结束生命。[246][247][248]台湾医师的研究发现,在台湾,注意力缺陷多动障碍患者具有显著较高的“因伤致死”概率,起因来自:自杀意外谋杀[249]

一些家庭对过度活跃症认识不深,不了解、误解为弱智、低能,大部分会选择以暴易暴的方法解决问题。有些会选择送去智能庇护所,因为专业人员不懂得审查过度活跃症与智障无关,患者会被送去孤儿院、保良局及儿童之家。

许多国家或地区都程度不等的在“精神医疗及心理卫生”方面遭遇资源不足以面对现实所需的情况。[250][251][252]以美国为例,美国精神医疗环境即便先进且持续进步中,然而注意力缺陷多动障碍患者接受行为治疗的比例仍被当地学者专家认为仍然太低。 [252] 2017年美国政府拨出一亿美金用于支持儿童与青少年常见精神疾病的研究:如何提供自闭症者更好的治疗、其他儿童心理精神疾病(包括ADHD在内)的病理学生理学等。[253]

治疗方式的争议[编辑]

自1970年代开始,注意力缺陷多动障碍疾病本身、其诊断及医疗在欧美就已经是有争议性的议题。争议和临床医师、教师、政策订定者、家长及媒体有关。世界卫生组织也认可治疗ADHD儿童时,先进行非药物治疗再进行药物治疗的作法[254][255],但各观点对注意力缺陷多动障碍的认知差异很大。

有的观点认为注意力缺陷多动障碍是正常行为的范围内,也有的假定注意力缺陷多动障碍是一种遗传疾病。其他有关注意力缺陷多动障碍的争议包括对儿童用(合理剂量的)中枢神经刺激剂(俗称兴奋剂)药物进行治疗、诊断的方式,以及是否有过度诊断英语Overdiagnosis的情形。有些宗教对治疗方式也会有不同的认知,例如公民人权委员会山达基在1969年成立的反精神医学团体)曾在1980年代提出反对使用利他林的运动,目前该组织的立场仍是不主张用中枢神经刺激剂处方治疗ADHD[256]

中国大陆、香港[编辑]

目前注意力缺陷多动障碍的治疗策略(涵盖药物及非药物治疗)已成为中国大陆的相关医学指南 [257],中国大陆的多动症关爱协会指出:“中国大陆对‘注意力缺陷多动障碍’的诊断、治疗尚不规范,家长的认知亦不够全面,导致社会上仍有很多不科学的治疗方式和训练方法在被家长们使用。”

香港特别行政区则遇到特教需求的识别及轮流服务的等候时间过长、资源及服务不足、教师人手不足及培训有待改善、医校社合作不顺畅以及政府未有整体支援特教学生的政策蓝图及愿景的问题。目前正在推动特殊教育进行立法,以全面保障特殊教育需要学生的权利。[251]另外,香港的一项问卷调查发现,有特殊教育需要的学生受欺凌的比率极高,在小学环境下有33%遭受欺凌,在中学环境下有47%。而于国际学生能力评估计划的调查亦显示,香港中学生遭到欺凌的比率为32.3%。即使家长们想寻求协助亦因资源问题,大部分服务需要自费,而基层家长较为难以负担。另外,亦有社工指出服务缺乏系统整理,而大部分学校都缺乏动机正面处理事件[258]

备注[编辑]

  1. ^ 台湾儿童与青少年精神科医师高淑芬在其著作《找回专注力:成人ADHD全方位自助手册》提到,虽然“过动-冲动型”和“混合型”的ADHD从小就非常好动,坐不住,老是跑跑跳跳、追逐打闹,精力无穷,但其实这类孩子的运动协调性可能不太好,运动协调性较弱的表象为:肢体动作较大、动作较粗鲁。[96]

参考文献[编辑]

参考数据[编辑]

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  169. ^ Parker J, Wales G, Chalhoub N, Harpin V. The long-term outcomes of interventions for the management of attention-deficit hyperactivity disorder in children and adolescents: a systematic review of randomized controlled trials. Psychology Research and Behavior Management. September 2013, 6: 87–99. PMC 3785407可免费查阅. PMID 24082796. doi:10.2147/PRBM.S49114. Results suggest there is moderate-to-high-level evidence that combined pharmacological and behavioral interventions, and pharmacological interventions alone can be effective in managing the core ADHD symptoms and academic performance at 14 months. However, the effect size may decrease beyond this period. ... There is high level evidence suggesting that pharmacological treatment can have a major beneficial effect on the core symptoms of ADHD (hyperactivity, inattention, and impulsivity) in approximately 80% of cases compared with placebo controls, in the short term.22 
  170. ^ Storebø OJ, Ramstad E, Krogh HB, Nilausen TD, Skoog M, Holmskov M, 等. Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). The Cochrane Database of Systematic Reviews. November 2015, 11 (11): CD009885. PMID 26599576. doi:10.1002/14651858.CD009885.pub2. 
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  176. ^ Hazell P. The challenges to demonstrating long-term effects of psychostimulant treatment for attention-deficit/hyperactivity disorder. Current Opinion in Psychiatry. July 2011, 24 (4): 286–90. PMID 21519262. doi:10.1097/YCO.0b013e32834742db. 
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  178. ^ Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J. Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies. The Journal of Clinical Psychiatry. September 2013, 74 (9): 902–17. PMC 3801446可免费查阅. PMID 24107764. doi:10.4088/JCP.12r08287. 
  179. ^ Frodl T, Skokauskas N. Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects. Acta Psychiatrica Scandinavica. February 2012, 125 (2): 114–26. PMID 22118249. doi:10.1111/j.1600-0447.2011.01786.x. Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure. 
  180. ^ Cortese, Samuele; Adamo, Nicoletta; Del Giovane, Cinzia; Mohr-Jensen, Christina; Hayes, Adrian J; Carucci, Sara; Atkinson, Lauren Z; Tessari, Luca; Banaschewski, Tobias; Coghill, David; Hollis, Chris; Simonoff, Emily; Zuddas, Alessandro; Barbui, Corrado; Purgato, Marianna; Steinhausen, Hans-Christoph; Shokraneh, Farhad; Xia, Jun; Cipriani, Andrea. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. The Lancet Psychiatry. September 2018, 5 (9): 727–738. doi:10.1016/S2215-0366(18)30269-4. 
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  182. ^ Stevens JR, Wilens TE, Stern TA. Using stimulants for attention-deficit/hyperactivity disorder: clinical approaches and challenges. The Primary Care Companion for CNS Disorders. 2013, 15 (2). PMC 3733520可免费查阅. PMID 23930227. doi:10.4088/PCC.12f01472. 
  183. ^ Young, Joel L. Individualizing Treatment for Adult ADHD: An Evidence-Based Guideline. Medscape. 2010 [2016-06-19]. (原始内容存档于2015-05-08). 
  184. ^ Biederman, Joseph. New-Generation Long-Acting Stimulants for the Treatment of Attention-Deficit/Hyperactivity Disorder. Medscape. 2003 [2016-06-19]. (原始内容存档于2003-12-07). As most treatment guidelines and prescribing information for stimulant medications relate to experience in school-aged children, prescribed doses for older patients are lacking. Emerging evidence for both methylphenidate and Adderall indicate that when weight-corrected daily doses, equipotent with those used in the treatment of younger patients, are used to treat adults with ADHD, these patients show a very robust clinical response consistent with that observed in pediatric studies. These data suggest that older patients may require a more aggressive approach in terms of dosing, based on the same target dosage ranges that have already been established – for methylphenidate, 1–1.5–2 mg/kg/day, and for D,L-amphetamine, 0.5–0.75–1 mg/kg/day....
    In particular, adolescents and adults are vulnerable to underdosing, and are thus at potential risk of failing to receive adequate dosage levels. As with all therapeutic agents, the efficacy and safety of stimulant medications should always guide prescribing behavior: careful dosage titration of the selected stimulant product should help to ensure that each patient with ADHD receives an adequate dose, so that the clinical benefits of therapy can be fully attained.
     
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    An estimated 40 to 60 percent of people with ASD have attention deficit hyperactivity disorder (ADHD), which encompasses such symptoms as difficulty paying attention, problems controlling behavior and hyperactivity. Co-investigators Geraldine Dawson, Ph.D., and Scott Kollins, Ph.D., aim to learn how ADHD may influence the diagnosis and treatment of autism and plan to observe children who have ASD alone, ASD and ADHD, and ADHD alone and compare them to typically developing children. They will also test whether the stimulant medication used to treat ADHD will help children with both conditions.
     
  254. ^ WHO. Pharmacological and nonpharmacological interventions for children with attention-deficit hyperactivity disorder (ADHD). 世界卫生组织 Wolrd Health Organization. [2017-02-22]. (原始内容存档于2017-01-08) (美国英语). 
  255. ^ 世界卫生组织. 注意缺陷多动障碍儿童的药物和非药物介入/干预. 世界卫生组织. [2017-02-22]. (原始内容存档于2016-11-29) (中文(简体)). 
  256. ^ 亞洲不應使用西方精神科對於注意力不足過動症(ADHD)的診斷,及興奮劑處方的治療. [2017-09-02]. (原始内容存档于2017-09-02). 
  257. ^ 郑毅; 刘靖. 《中国注意缺陷多动障碍防治指南》第二版解读. 中华精神科杂志. 2016, 0 (3): p.132–135 [2017-03-04]. (原始内容存档于2017-03-04). 
  258. ^ 【校園欺凌】產後抑鬱媽媽:過度活躍的七歲兒子,最怕他自殺. 明周文化. 2018-03-19 [2018-03-31]. (原始内容存档于2018-03-29) (中文). 

书目[编辑]

  • Edward M. Hallowell; John J. Ratey. 分心不是我的錯(增訂版):正確診療ADD,重建有計畫的生活方式 Driven to Distraction. 远流出版. 2015-09-01. ISBN 978-957-32-7700-2. 
  • Edward M. Hallowell, M.D.; John J. Ratey, M.D. 《分心也有好成績》. 丁凡译. 台北: 远流出版社. 2006. ISBN 9573259311. 
  • 高淑芬; 陈劭芊. 注意力不足過動症. 卫生福利部精神疾病卫教丛书. 中华民国卫生福利部. 2015-06 [2018-02-27]. ISBN 9789860454154. (原始内容存档 (PDF)于2017-02-19) (中文(繁体)). 

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