芬蘭的青少年研究認為需重新看待ADHD


  January 29, 2008 — 芬蘭針對青少年注意力不足過動障礙症(attention-deficit/hyperactivity disorder,ADHD)進行的族群基礎研究中,五篇文獻指出,ADHD盛行率為8.5%,無須辨識次類型,ADHD相關的執行功能缺損並不常見,過動症狀隨著年齡減弱,多巴胺相關基因可能有所影響。
  
  這些文獻登載在2007年12月的美國兒童和青少年精神病學協會期刊(Journal of the American Academy of Child & Adolescent Psychiatry)。
  
  參與這五篇文獻的加州大學洛杉磯分校(UCLA)的Susan L. Smalley博士在引言中表示,這些文獻讓我們對ADHD的思維有了新方向。
  
  她寫道,芬蘭的青少年都沒有接受刺激劑治療,芬蘭強調公共衛生可以早期偵測和予以生理社會協助。
  
  她在UCLA發表的新聞稿中表示,我們知道藥物在短期內非常有效,但是研究對於ADHD治療的長期效果提出了重要的疑問;對於治療,我們有兩種截然不同的文化和方法,然而,在青少年時期,ADHD相關的問題與表現少有不同。
  
  德州大學健康科學中心的Steven R. Pliszka醫師、「美國兒童與青少年精神ADHD學會實務參數」的主要作者,向Medscape精神病學表示,文獻中的主要訊息是,ADHD在不同的族群是廣泛且同樣盛行的,ADHD的小孩有多少發生為憂鬱或者傳導異常的臨床結果是相似的;不過,次類型並非如我們所假設般固定不變;我們仍需更多研究來了解潛在誘因;我們需檢視這些跨文化的差異,來了解有哪些不同的社會狀況影響了ADHD。
  
  【未使用刺激劑的族群】
  「Northern Finland Birth Cohort (NFBC)」這項ADHD研究始於2001年7月,希望在青少年基礎的樣本辨識ADHD的潛在風險基因,這些人從胎兒時期即被追蹤。
  
  對誕生的9,432名小孩在青少年時期(16到18歲)進行調查,有回覆的6,622人之中,藉由家長完成的篩選問卷,有457個ADHD案例。
  
  【常見的異常 頻繁的共病症】
  Smalley醫師和同事在第一篇檢視ADHD盛行率的文獻中報告指出,ADHD是芬蘭北部青少年常見的一種異常,盛行率估計為8.5%,與其他研究所指的ADHD盛行率一致;ADHD在男孩的比率是女孩的5.7倍。
  
  這些個案中有18.2% (男孩的比率是女孩的3.2 倍) 曾有ADHD診斷,相較於控制組者,有ADHD診斷的青少年發生破壞性行為異常的風險相當高(風險比 [OR], 17.3),心情異常(OR, 2.9)或者焦慮(OR, 2.4)的風險也升高。
  
  研究者寫道,有風險者出現各種的精神異常,大部分是破壞性的行為、心情異常、焦慮,與物質濫用/成癮 ,不過未達精神疾病診斷與統計手冊(Diagnostic and Statistical Manual of Mental Disorders, 4th ed (DSM-IV))第4版中的ADHD規範,對於早期偵測有重要的臨床意義。
  
  【統計模型爭論各種次類型】
  Notre Dame大學的Gitta H. Lubke博士等人在第二篇探討ADHD次類型的文獻中寫道,根據各種統計模型的結果,就這些青少年研究對象而言,看來並不需要對ADHD進行次類型分類。
  
  顯然有兩類:受到影響的和沒有受到影響的;有受到影響者也有各種的注意力不集中和過動-衝動性(hyperactive-impulsive)症狀,但是並不需要後續的次類型分類;如果研究發現被再度確認,支持這種觀念,那麼,至少在青少年族群,ADHD可以視為該族群的唯一類別。
  
  Pliszka醫師表示,此研究也指出,有關ADHD的注意力不足/過動類型仍有爭議,而合併ADHD的類型還需要基因與神經影像方面的研究。
  
  【影響工作記憶】
  根據UCLA的Sandra K. Loo博士等人研究認知功能的第三篇文獻,工作記憶的執行功能缺損、反應遲緩,或以上兩者,在青少年的ADHD並不普遍,但是在其他年紀的病患比較常見;約半數(52%)的ADHD個案 ,以及18% 的控制組、和29%的無ADHD但有行為異常者,有執行功能缺損,且合併不佳的認知表現。
  
  Pliszka醫師表示,這代表主要由前額皮質調節的執行功能問題只是ADHD的一部分,這和神經影像的研究結果一致;至於ADHD的小孩,影響執行功能的部位比較不固定,因此,若是檢查時小孩沒有發作,就會認為他看起來不錯,但是,如果檢查時剛好發作,那結果自然是恐怖的。
  
  【過動減少 注意力不集中持續】
  根據芬蘭Oulu大學Tuula Hurtig等人著眼於症狀和次類型的第四篇文獻,目前ADHD的青少年約有三分之二在孩童期有類似症狀;如果在孩童時期有注意力不集中的症狀、早發憂鬱、或者對立違抗障礙(oppositional defiance disorder),或對他們的父親有注意力的問題,比較可能在青少年時出現ADHD。
  
  Pliszka醫師表示,有過動/衝動的人,傾向隨著時間減少症狀,但事實上,孩童期或者青少年時期的ADHD特徵各有差異,這和第一篇報告的結果一致,或許過動/衝動、注意力不集中,以及合併次類型,並不像我們寫DSM-IV的時候所想的那麼獨立。
  
  【與多巴胺有關】
  第五篇文獻是ADHD候選基因的研究,由芬蘭國家公共健康研究中心的Emma S. Nyman所領銜,報告指出,多巴胺路徑與ADHD病理學有關,特別是多巴胺乙型羥化酶(dopamine beta hydroxylase,DBH)和多巴胺受體D2(dopamine receptor D2,DRD2),是未來的研究重點;這兩個比較少被研究的基因,對ADHD有輕微但是重要的影響。
  
  主要作者宣稱無相關資金上的往來,其他作者的資金往來列於報告中。

Need to Look at ADHD in a New<

By Marlene Busko
Medscape Medical News

January 29, 2008 — Five articles from a population-based study of attention-deficit/hyperactivity disorder (ADHD) in Finnish teens report an ADHD prevalence of 8.5%, no strong need to identify subtypes, no ubiquitous ADHD-related executive-function deficits, a weakening of hyperactive symptoms with age, and a possible role of dopamine-related genes.

The articles are published in the December 2007 issue of the Journal of the American Academy of Child & Adolescent Psychiatry.

"This set of articles thus brings to light the necessity of engaging in new ways of thinking about ADHD," Susan L. Smalley, PhD, from the University of California, Los Angeles (UCLA), and a contributor to the 5 articles, summarizes in her introduction.

None of the adolescents in the Finnish cohort had been or were being treated with stimulant medication, and Finland has comprehensive public healthcare that allows early detection and psychosocial intervention, she writes.

"We know medication is very effective in the short term," she said in a press release issued by UCLA. "But the study raises important questions concerning the long-term efficacy of ADHD treatment. Here we have 2 different cultures and 2 different approaches to treatment, yet at the time of adolescence, there are few differences in the presentation and problems associated with ADHD."

The main messages from the articles are that "ADHD is universal and has about the same prevalence in different populations," Steven R. Pliszka, MD, from the University of Texas Health Science Center, in San Antonio, and lead author of the American Academy of Child & Adolescent Psychiatry's ADHD practice parameter, told Medscape Psychiatry. "It appears to be clinically similar in terms of how often ADHD kids develop depression or conduct disorder," he continued. However, "the subtypes don’t appear to be as 'set in stone' as we perhaps assumed; we still need a lot more work to try to understand the underlying causes; and we need to look at some of these cross-cultural differences to see how some different societies handle ADHD behavior."

Stimulant-Naive Population

The Northern Finland Birth Cohort (NFBC) Study of ADHD was initiated in July 2001 to identify risk genes underlying ADHD in a population-based sample of adolescents who had been followed prospectively since the fetal period.

The birth cohort of 9432 children was surveyed at adolescence (ages 16 to 18 years). Among 6622 respondents, 457 cases of ADHD were identified by a screening questionnaire completed by the parents.

Common Disorder, Frequent Comorbidities

"ADHD is a common disorder among adolescents in northern Finland, with an estimated prevalence of 8.5%, consistent with rates of ADHD noted in other studies of adolescents," Dr. Smalley and colleagues report in the first article, which examined ADHD prevalence. ADHD was 5.7 times more likely to be present in boys than in girls.

A total of 18.2% of the subjects (3.2 times as many boys than girls) had a lifetime diagnosis of ADHD. Compared with individuals in the control group, the adolescents with a lifetime diagnosis of ADHD had a greatly increased risk of having a disruptive behavioral disorder (odds ratio [OR], 17.3) and an increased risk of having a mood disorder (OR, 2.9) or anxiety (OR, 2.4).

At-risk individuals may present with a variety of psychiatric disorders, most notably disruptive disorders, mood disorders, anxiety, and substance abuse/dependence, but fail to meet the full Diagnostic and Statistical Manual of Mental Disorders, 4th ed (DSM-IV) criteria for ADHD, which has important clinical implications for early detection, the group writes.

Statistical Models Dispute Distinct Subtypes

Based on results from statistical models, "there is no strong indication for the need to identify subgroups within ADHD in this particular sample" of adolescents, Gitta H. Lubke, PhD, from the University of Notre Dame, in Indiana, and colleagues write in the second article, which investigated ADHD subtypes.

There appear to be 2 classes of individuals: those who are affected or unaffected. Individuals who are affected have variations in inattentive and hyperactive-impulsive symptoms, but further subgroups are not necessary, they write. The findings, if replicated, "support the idea that at least in adolescence, ADHD may be seen as a single extreme along a continuum in the population," they note.

This study will add to the ongoing debate about whether the inattentive/hyperactive type of ADHD and the combined type of ADHD need to be separated in genetic and neuroimaging studies, said Dr. Pliszka.

Working Memory Affected

Executive-function deficits in working memory, response inhibition, or both were not ubiquitous in the adolescents with ADHD but were more frequent than in other groups, according to the third article, by Sandra K. Loo, PhD, from UCLA, and colleagues, which investigated cognitive functioning. About half (52%) of the subjects with ADHD, but also 18% of the controls and 29% of the subjects with no ADHD but with behavior disorders, had executive-function deficits, and these were associated with poorer cognitive performance.

This suggests that executive-function problems, which are thought to be modulated mostly in the prefrontal cortex, are only a part of ADHD, which is consistent with neuroimaging studies, said Dr. Pliszka. In children with ADHD, executive function might be turning on and off in an erratic manner, so that "if you test the child in the moment that the default mode is off, he looks great, but if you test him when it is intruding, he looks terrible."

Hyperactivity Declined, Inattentiveness Persisted

About two-thirds off the adolescentis with current ADHD had similar symptoms in early childhood, according to the fourth article, by Tuula Hurtig, from the University of Oulu, in Finland, and colleagues, which looked at symptoms and subtypes. Adolescents were more likely to still have ADHD if they had inattentive symptoms in childhood, early-onset depression, or oppositional defiance disorder or there were attention problems in their fathers.

"People who recalled being hyperactive/impulsive tended to lose that subtitle over time . . . but the fact that [individuals had different ADHD characteristics in childhood and adolescence] suggests that, consistent with the first paper, perhaps the hyperactive/impulsive, inattentive, and combined subtypes are not as separate as we thought when the DSM-IV was written," said Dr. Pliszka.

Dopamine Pathway Involved

The fifth article, an ADHD candidate gene study, "supports the involvement of the dopamine pathway in the etiology of ADHD, specifically that dopamine beta hydroxylase (DBH) and dopamine receptor D2 (DRD2) deserve more attention in further studies," the investigators, led by Emma S. Nyman, from the National Public Health Institute, in Helsinki, Finland, write. These 2 less-researched gene candidates were found to hold a modest but significant role in ADHD.

The lead authors have no financial relationships to disclose. The financial disclosures of the other authors are listed in the papers.

J Am Acad Child Adolesc Psychiatry. 2008;46:1573-1574, 1575-1583 Abstract, 1584-1593 Abstract, 1594-1604 Abstract, 1605-1613

    
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