Acute tryptophan depletion in autistic disorder: A controlled case study

McDougle, Christopher J.; Naylor, Susan T.; Goodman, Wayne K.; Volkmar, Fred R.; Cohen, Donald J.; Price, Lawrence H.

doi:10.1016/0006-3223(93)90011-2

Cited by 55 publications

(41 citation statements)

References 19 publications

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“…Consistent with this idea, short-term tryptophan depletion worsens ASD symptoms (McDougle et al, 1993). Three small, randomized, placebo-controlled trials have found beneficial effects of the SRIs clomipramine, fluvoxamine, and fluoxetine for OCD-like behavior in ASD (Gordon et al, 1993; …”

Section: Targeting Altered 5-ht Signaling In Asdmentioning

confidence: 61%

Networking in Autism: Leveraging Genetic, Biomarker and Model System Findings in the Search for New Treatments

Veenstra‐VanderWeele

Blakely

2011

Neuropsychopharmacol

110

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Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder affecting approximately 1% of children. ASD is defined by core symptoms in two domains: negative symptoms of impairment in social and communication function, and positive symptoms of restricted and repetitive behaviors. Available treatments are inadequate for treating both core symptoms and associated conditions. Twin studies indicate that ASD susceptibility has a large heritable component. Genetic studies have identified promising leads, with converging insights emerging from single-gene disorders that bear ASD features, with particular interest in mammalian target of rapamycin (mTOR)-linked synaptic plasticity mechanisms. Mouse models of these disorders are revealing not only opportunities to model behavioral perturbations across species, but also evidence of postnatal rescue of brain and behavioral phenotypes. An intense search for ASD biomarkers has consistently pointed to elevated platelet serotonin (5-HT) levels and a surge in brain growth in the first 2 years of life. Following a review of the diversity of ASD phenotypes and its genetic origins and biomarkers, we discuss opportunities for translation of these findings into novel ASD treatments, focusing on mTor-and 5-HT-signaling pathways, and their possible intersection. Paralleling the progress made in understanding the root causes of rare genetic syndromes that affect cognitive development, we anticipate progress in models systems using bona fide ASD-associated molecular changes that have the potential to accelerate the development of ASD diagnostics and therapeutics.

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Section: Targeting Altered 5-ht Signaling In Asdmentioning

confidence: 61%

Networking in Autism: Leveraging Genetic, Biomarker and Model System Findings in the Search for New Treatments

Veenstra‐VanderWeele

Blakely

2011

Neuropsychopharmacol

110

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“…For individuals with autism, tryptophan depletion can worsen repetitive behaviors 2 and PET neuroimaging reveals evidence of impaired serotonin synthesis. 3 Furthermore, selective serotonin transporter inhibitors often reduce rituals and routines common to individuals with autism.…”

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confidence: 99%

Autism and the serotonin transporter: the long and short of it

Devlin

Cook

Coon³

et al. 2005

Mol Psychiatry

170

143

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Autism is a neurodevelopmental disorder manifesting early in childhood. Some symptoms of autism are alleviated by treatment with selective serotonin reuptake inhibitors, which are known to interact with the serotonin transporter. Moreover, variation in the gene that encodes the transporter (SLC6A4), especially the HTTLPR locus, is known to modulate its expression. It is natural, therefore, to evaluate whether this variation plays a role in liability to autism. We investigated the impact of alleles at HTTLPR and three other loci in SLC6A4 by using a large, independent family-based sample (390 families, 1528 individuals) from the NIH Collaborative Programs of Excellence in Autism (CPEA) network. Allele transmissions to individuals diagnosed with autism were biased only for HTTLPR, both for the narrow diagnosis of autism (P ¼ 0.035) and for the broader diagnosis of autism spectrum (P ¼ 0.007). The short allele of HTTLPR was significantly overtransmitted. Investigation of haplotype transmissions suggested that, in our data, biased transmission was only due to HTTLPR. With respect to this locus, there are now seven of 12 studies reporting significant transmission bias of HTTLPR alleles, a noteworthy result in itself. However, the studies with significant findings are almost equally divided between overtransmission of short and overtransmission of long alleles. We place our results within this extremely heterogeneous field of studies. Determining the factors influencing the relationship between autism phenotypes and HTTLPR variation, as well as other loci in SLC6A4, could be an important advance in our understanding of this complex disorder.

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“…A mathematical sign correction to subtract normal behavior is necessary on subscales II, IV, and V; this results in some scores with a negative value. Different mood states were assessed on 10 clinician-rated visual analog scales, 37 scored on a 100-mm line where 0 indicates "not at all," and 100 indicates "most ever." The 10 items included "anxious or nervous," "calm," "depressed," "eye contact," "happy," "irritable," "restless," "social interaction," "talkative," and "tired."…”

Section: Rating Scalesmentioning

confidence: 99%