AACAP: D-cycloserine Shows Promise in Treatment of Autistic Disorder
By Jerry Ingram
MIAMI BEACH, FL -- October 21, 2003 -- Symptoms of social withdrawal seen in autistic children might improve with D-cycloserine treatment, according to preliminary research presented here on October 18th at the 50th Anniversary Meeting of the American Academy of Child and Adolescent Psychiatry.
"There is a preliminary sense that D-cycloserine has some efficacy for social withdrawal in autism. We're following it up with a controlled study," stated David Posey, MD, lead researcher, assistant professor of psychiatry, Indiana University, Indianapolis, Indiana.
For this pilot study, investigators conducted a 2-week, single blind, placebo lead-in phase study of 10 drug-free patients with autistic disorder. Patients received three different doses of D-cycloserine during each of three 2-week periods. They were evaluated using Clinical Global Impressions (CGI) scale, Aberrant Behavior Checklist (ABC), the Social Responsiveness Scale, and the Children's Yale-Brown Obsessive Compulsive Scale.
Researchers found that 70% of 10 children had a CGI global improvement rating of "much improved" or "very much improved" while taking at least one dose level of D-cycloserine. The mean optimal dose for all subjects was 1.8 mg/kg/day (modal dose, 50 mg/day), they said.
Fifty percent of the patients were "classified as sustained," showing improvement in social withdrawal, amount and spontaneity of language, and repetitive behavior. The most noteworthy improvement was in the Lethargy subscales of the Aberrant Behavior Checklist, with a 57% decrease in symptom severity, Dr. Posey reported.
He also noted that D-cycloserine was well tolerated in all patients with the dose range used in this study. However, further controlled studies are necessary, he noted.
作者: 乌肖文 时间: 2004-6-25 06:43 标题: Re:D-cycloserine 治疗自闭症有前途? David Posey 博士回信,告知他的那篇文章大约在2个月后发表在American Journal of Psychiary. 这个结果是基于小样本得出的,他们目前正在进行大样本临床试验。由于从该药物的名字D-Cycloserine看,它的副作用几乎很少(当然我还将征求药物学家的意见)。因此我对此有教大的兴趣,让我们静候Posey 博士的佳音。
Glutamate and g-aminobutyric acid system in mood disorder
ZHOU Xuan1; WANG Xue-qi2
(1. Psychiatry and Health Subject 2000 Grade, 2.Dpartment of Neurobiology, Second Military Medical University, Shanghai 200433, China)
[Abstract] There is increasing evidence that glutamate and γ-aminobutyric acid (GABA) systems may contribute to mood disorder. For example, antidepressant drugs may reduce N-methyl-D-aspartate (NMDA)receptor function directly or indirectly; NMDA receptor antagonists may be antidepressant. Drugs that reduce glutamatergic activity or glutamate receptor-related signal transduction may also have antimanic effects. Recent studies employing magnetic resonance spectroscopy (MRS) also suggest that unipolar depression is associated with reduction in cortical GABA levels; Antidepressant and mood-stabilizing treatments also appear to raise cortical GABA levels and to ameliorate GABA deficits in patients with mood disorders. Future research will be needed to develop and evaluate new agents with specific glutamate and GABA receptor targets in the treatment of mood disorders.
NMDA受体拮抗剂对人的影响的最初证据主要来源于DCS(D-cycloserine)。治疗剂量(500 mg/d)的DCS可产生相当快速并与剂量相关的欣快感和记忆减退(euphoric and amnestic effects),这与非竞争性NMDA受体拮抗剂所产生的作用类似[7]。因此,DCS的抗抑郁效应可能与其降低NMDA受体功能相关。
2.3 情绪稳定剂对皮质GABA水平的影响 目前研究提示,对癫痫病人有效的治疗药物可提高皮质GABA的水平[18]。一些制剂可特异地提高GABA浓度,如氨烯乙酸(vigabatrin)可以阻断GABA转氨酶的作用,从而提高癫痫病人枕叶皮质的GABA浓度。苯二氮卓(benzodiazepines)对GABA的作用则比较复杂,它可升高癫痫患者皮质GABA浓度,却降低健康人群皮质GABA水平(Sanacora G et al,unpublished data),这可能是因为它在直接促进GABA受体作用的同时,抑制了谷氨酸脱羧酶的作用,从而降低了GABA水平。因此,情绪稳定类药物可对皮质GABA系统发挥多种多样的作用。