Effects of tryptophan depletion in drug-free adults with autistic disorder
Abstract
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 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. 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 showed no 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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Data show decreased capacity for 5-HT synthesis in children with ASD and reports show worsening in repetitive behaviors after tryptophan depletion.
“This corresponds to data showing decreased capacity for 5′-HT synthesis in children with ASD as well as to reports showing a worsening in repetitive behaviors in individuals with ASD after tryptophan depletion [191,199].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [199]
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- Authors
- McDougle, C.
- Affiliations
- Connecticut Mental Health Center (US)
- Corresponding author
- McDougle, Christopher
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 1996-11-01
- Volume
- 53
- Issue
- 11
- Pages
- 993
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2149174165
- Cited by
- 301
- References
- 58
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 9 · 2023: 6 · 2022: 8 · 2021: 6 · 2020: 14 · 2019: 8 · 2018: 9 · 2017: 11 · 2016: 7 · 2015: 20 · 2014: 20 · 2013: 14 · 2012: 9
- FWCI
- 6.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50mh030929-14)
- National Institute of Mental Health (P50 MH30929-18)
- National Center for Research Resources (M01RR006022, M01 RR06022-33)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 03008-27, P01HD003008)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- tryptophan depletion, autism spectrum disorder, autistic disorder, serotonin, plasma tryptophan, behavioral symptoms, autistic adults, autism pathogenesis
- MeSH terms
- Adult, Amino Acids, Essential, Autistic Disorder, Child, Double-Blind Method, Female, Humans, Male, Placebos, Psychiatric Status Rating Scales, Serotonin, Severity of Illness Index, Tryptophan
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