Cortical Serotonin Type-2 Receptor Density in Parents of Children with Autism Spectrum Disorders

Goldberg, Jeremy; Anderson, George M.; Zwaigenbaum, Lonnie; Hall, Geoffrey B.; Nahmias, Claude; Thompson, Ann; Szatmári, Péter

doi:10.1007/s10803-008-0604-4

Cited by 69 publications

(39 citation statements)

References 72 publications

(63 reference statements)

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“…Other studies have considered serotonin receptor or transporter binding. Paralleling platelet binding studies, two neuroimaging studies have found decreased 5-HT 2 receptor binding: a SPECT study in adults with Asperger’s syndrome (Murphy et al, 2006) and a PET study in parents of children with autism (Goldberg et al, 2009). A postmortem study found decreases in both 5-HT 2A and 5-HT 1A binding in ASD (Oblak et al, 2013).…”

Section: The Central Serotonin System In Autism Spectrum Disordermentioning

confidence: 98%

The serotonin system in autism spectrum disorder: From biomarker to animal models

2016

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Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophysiology remains incompletely understood. Studies of whole blood serotonin levels in ASD and in a large founder population indicate greater heritability than for the disorder itself and suggest an association with recurrence risk. Emerging data from both neuroimaging and postmortem samples also indicate changes in the brain serotonin system in ASD. Genetic linkage and association studies of both whole blood serotonin levels and of ASD risk point to the chromosomal region containing the serotonin transporter (SERT) gene in males but not in females. In ASD families with evidence of linkage to this region, multiple rare SERT amino acid variants lead to a convergent increase in serotonin uptake in cell models. A knock-in mouse model of one of these variants, SERT Gly56Ala, recapitulates the hyperserotonemia biomarker and shows increased brain serotonin clearance, increased serotonin receptor sensitivity, and altered social, communication, and repetitive behaviors. Data from other rodent models also suggest an important role for the serotonin system in social behavior, in cognitive flexibility, and in sensory development. Recent work indicates that reciprocal interactions between serotonin and other systems, such as oxytocin, may be particularly important for social behavior. Collectively, these data point to the serotonin system as a prime candidate for treatment development in a subgroup of children defined by a robust, heritable biomarker.

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Section: The Central Serotonin System In Autism Spectrum Disordermentioning

confidence: 98%

The serotonin system in autism spectrum disorder: From biomarker to animal models

2016

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“…Indeed, the SERT gene (SLC6A4) and the 5-HT receptor 5-HT 2A gene (HTR2A) encode the same protein in the platelets and brain (Cook et al, 1994;Lesch et al, 1993). Abnormalities in brain 5-HT systems have also been described in ASD, including an altered developmental trajectory of 5-HT turnover (Chugani et al, 1999) and decreased radioligand binding to both 5-HT 2A (Goldberg et al, 2009;Murphy et al, 2006) and SERT (Nakamura et al, 2010).…”

Section: Biomarkers In Asdmentioning

confidence: 99%

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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“…Recientemente, se observó una reducción en el potencial de unión de los receptores 5-HT2 en la corteza cerebral de padres de enfermos con autismo (63).…”

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Evidencia de asociación entre el gen SLC6A4 y efectos epistáticos con variantes en HTR2A en la etiología del autismo en población antioqueña

et al. 2012

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Cortical Serotonin Type-2 Receptor Density in Parents of Children with Autism Spectrum Disorders

Cited by 69 publications

References 72 publications

The serotonin system in autism spectrum disorder: From biomarker to animal models

The serotonin system in autism spectrum disorder: From biomarker to animal models

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

Evidencia de asociación entre el gen SLC6A4 y efectos epistáticos con variantes en HTR2A en la etiología del autismo en población antioqueña

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