McDougle C J, Naylor S T, Cohen D J, Aghajanian G K, Heninger G R, Price L H
Clinical Neuroscience Research Unit, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, USA.
Arch Gen Psychiatry. 1996 Nov;53(11):993-1000. doi: 10.1001/archpsyc.1996.01830110029004.
The primary objective of this study was to investigate the behavioral and biochemical responses to acute tryptophan depletion in drug-free adult patients with autistic disorder.
Twenty drug-free adults with autistic disorder (16 men and 4 women) (mean [+/- SD] age, 30.5 +/- 8.5 years) underwent short-term tryptophan depletion in a double-blind, placebo-controlled, randomized crossover design. Patients received a 24-hour, low-tryptophan diet followed the next morning by an amino acid drink. Behavioral ratings were obtained on the morning of the amino acid drink (baseline) and 180, 300, and 420 minutes after the drink. Plasma free and total tryptophan levels were obtained at baseline and 5 hours after the drink. The active and sham testing sessions were separated by 7 days.
Eleven (65%) of the 17 patients who completed both test days showed a significant global worsening of behavioral symptoms with short-term tryptophan depletion, but none of the 17 patients showed any significant change in clinical status from baseline after sham depletion (P = .001). Tryptophan depletion led to a significant increase in behaviors such as whirling, flapping, pacing, banging and hitting self, rocking, and toe walking (P < .05). In addition, patients were significantly less calm and happy and more anxious. No significant change was observed in social relatedness or repetitive thoughts and behavior. Plasma total and free tryptophan levels were reduced 86% and 69%, respectively, 5 hours after the tryptophan-deficient amino acid drink. Patients who had a significant global exacerbation of symptoms had significantly higher baseline plasma total tryptophan levels (P < .001) and Autism Behavior Checklist scores (P = .005) than did patients who showed no significant change in symptoms after tryptophan depletion.
The results of this study are consistent with previous research that has implicated a dysregulation in serotonin function in some patients with autism. These data suggest that the short-term reduction of serotonin precursor availability may exacerbate some symptoms characteristic of autism in some patients. Continued investigation into the role of serotonin in the pathogenesis and treatment of autistic disorder is warranted.
本研究的主要目的是调查无药物治疗史的成年自闭症谱系障碍患者对急性色氨酸耗竭的行为和生化反应。
20名无药物治疗史的成年自闭症谱系障碍患者（16名男性和4名女性）（平均年龄[±标准差]为30.5±8.5岁）采用双盲、安慰剂对照、随机交叉设计进行短期色氨酸耗竭试验。患者先接受24小时低色氨酸饮食，次日早晨饮用氨基酸饮料。在饮用氨基酸饮料的当天早晨（基线）以及饮用后180、300和420分钟进行行为评分。在基线和饮用饮料5小时后检测血浆游离色氨酸和总色氨酸水平。活性测试和安慰剂测试之间间隔7天。
在完成两个测试日的17名患者中，11名（65%）在短期色氨酸耗竭后行为症状出现显著整体恶化，但在17名接受安慰剂耗竭的患者中，没有一人的临床状态与基线相比有任何显著变化（P = 0.001）。色氨酸耗竭导致旋转、拍打、踱步、撞头和自伤、摇晃以及踮脚行走等行为显著增加（P < 0.05）。此外，患者明显更不平静、不开心且更焦虑。社交相关性或重复思维及行为方面未观察到显著变化。在饮用缺乏色氨酸的氨基酸饮料5小时后，血浆总色氨酸和游离色氨酸水平分别降低了86%和69%。症状出现显著整体恶化的患者，其基线血浆总色氨酸水平（P < 0.001）和自闭症行为检查表评分（P = 0.005）显著高于色氨酸耗竭后症状无显著变化的患者。
本研究结果与先前研究一致，先前研究表明部分自闭症患者存在血清素功能失调。这些数据表明，短期内血清素前体可用性降低可能会加重部分自闭症患者的某些典型症状。有必要继续研究血清素在自闭症谱系障碍发病机制和治疗中的作用。
