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Effects of Tryptophan Depletion in Drug-Free Adults With Autistic Disorder

Christopher McDougle, MD; Susan T. Naylor, RN, MSN; Donald J. Cohen, MD; George K. Aghajanian, MD; George R. Heninger, MD; Lawrence H. Price, MD
Arch Gen Psychiatry. 1996;53(11):993-1000. doi:10.1001/archpsyc.1996.01830110029004.
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Background:  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.

Methods:  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 cross over design. Patients received a 24-hour, lowtryptophan 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.

Results:  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 showedno significant change in symptoms after tryptophan depletion.

Conclusions:  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.

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The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
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