Examination of association of genes in the serotonin system to autism

Anderson, Brent; Schnetz-Boutaud, Nathalie; Bartlett, Jacquelaine; Wotawa, A. M.; Wright, Harry H.; Abramson, Ruth K.; Cuccaro, M. L.; Gilbert, John R.; Pericak‐Vance, M. A.; Haines, Jonathan L.

doi:10.1007/s10048-009-0171-7

Cited by 67 publications

(55 citation statements)

References 64 publications

(58 reference statements)

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“…In addition to the described genetic variations in SLC6A4, there are other gene variants that may have an additional effect or modest influence on autism risk. These include de novo copy number variations [26], serotonergic receptor single nucleotide polymorphisms such as in the HTR3A gene [27], and also other genetic variants (for a recent overview see [28]). Since the impact of these genetic variations remains unclear or inconclusive, we did not collect these data.…”

Section: Discussionmentioning

confidence: 99%

Autism associated with low 5-hydroxyindolacetic acid in CSF and the heterozygous SLC6A4 gene Gly56Ala plus 5-HTTLPR L/L promoter variants

Adamsen

Meili

Blau

et al. 2011

Molecular Genetics and Metabolism

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The known Gly56Ala mutation in the serotonin transporter SERT (or 5-HTT), encoded by the SLC6A4 gene, causes increased serotonin reuptake and has been associated with autism and rigid-compulsive behavior. We report a patient with macrocephaly from birth, followed by hypotonia, developmental delay, ataxia and a diagnosis of atypical autism (PDD-NOS) in retrospect at the age of 4½ years. Low levels of the serotonin endmetabolite 5-hydroxyindolacetic acid (5HIAA) in CSF were detected, and SLC6A4 gene analysis revealed the heterozygous Gly56Ala alteration and the homozygous 5-HTTLPR L/L promoter variant. These changes are reported to be responsible for elevated SERT activity and expression, suggesting that these alterations were responsible in our patient for low serotonin turnover in the central nervous system (CNS). Daily treatment with 5-hydroxytryptophan (and carbidopa) led to clinical improvement and normalization of 5HIAA, implying that brain serotonin turnover normalized. We speculate that the mutated 56Ala SERT transporter with elevated expression and basal activity for serotonin re-uptake is accompanied with serotonin accumulation within pre-synaptic axons and their vesicles in the CNS, resulting in a steady-state of lowered serotonin turnover and degradation by monoamine-oxidase (MAO) enzymes in pre-synaptic or neighboring cells.

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Section: Discussionmentioning

confidence: 99%

Autism associated with low 5-hydroxyindolacetic acid in CSF and the heterozygous SLC6A4 gene Gly56Ala plus 5-HTTLPR L/L promoter variants

Adamsen

Meili

Blau

et al. 2011

Molecular Genetics and Metabolism

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“…Numerous observations have revealed that the pathophysiology of ASD involves hyperserotonemia in up to 50% of individuals with ASD (with a concomitantly lower brain serotonin levels), thereby indicating that ASD associates with a distorted serotonergic distribution [49,[53][54][55]. Likewise, a circumstantial evidence in support of 5-HT involvement in autism is that defective brain serotonin levels are known to associate with many repetitive and aggressive behaviors like spinning, stepping, and self-hitting, that are common in ASD patients [56].…”

Section: Neurotransmitter Signalling and Implications In Asdmentioning

confidence: 99%

Emerging Clues and Altered Metabolic Findings in Autism: Breakthroughs and Prospects from Omics Studies

Mowafy¹

2016

Autism Open Access

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Autism spectrum disorder (ASD) is a pervasive broad-spectrum disorder that involves multifaceted delays in the development of many basic, social, and communication skills. The etiology of ASD is multifactorial and involves interplay among genetic, neurologic, hormonal, metabolic, immune-inflammatory, and environmental factors; which further complicate both the diagnosis and management in affected individuals. This review delineates the underpinnings of clinical challenges posed by ASD, like clinical heterogeneity of patient presentation, unresolved ASD genomic map and deficient drug therapy. Besides, it addresses the emerging pathogenic, etiologic, and diagnostic clues of diverse origins, encompassing genetic-, neurotransmitter-, androgenic-and immunoinflammatory-anomalies in ASD patients, as availed by advances in Omics technologies (like genomics and proteomics). Moreover, as unravelled by metabolomics studies, metabolic flaws that pertain to amino acids, fatty acids, mitochondrial anomalies, and oxidative-stress are highlighted and further correlated with the extent of clinical picture and malbehaviors coherent with ASD patients. Lastly, future directions are underlined to promote and rationalize ASD research so as to help translate its findings into remedy.

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“…Several gene variants that may change the structure or function of the transporter protein are associated with autism. Variation within genes on the serotonin pathway, particularly HTR3A located on chromosome 11, were demonstrated modest effects on autism risk [58]. People with autism in France, Germany, Israel, Portugal, and the United States exhibited a preferential inheritance of SERT length polymorphism L variants [59].…”

Section: Neurotransmitter Systemmentioning

confidence: 99%

The Role of Thiamine in Autism

Lương¹

2013

AJPN

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Autism spectrum disorders are a group of neuro-developmental conditions characterized by varying degrees of language impairment, including verbal and non-verbal communication, impaired social skill, and repetitive behaviors. In this paper, we review the evidence for an association between autism and thiamine. A relationship between thiamine status and the development of autism has been established, with thiamine supplementation exhibiting a beneficial clinical effect on children with autism. Thiamine may involve in autism via apoptotic factors (transcription factor p53, Bcl-2, and caspase-3), neurotransmitter systems (serotonin, acetylcholine, and glutamate), and oxidative stress (prostaglandins, cyclooxygenase-2, reactive oxygen species, nitric oxide synthase, the reduced form of nicotinamide adenine dinucleotide phosphate, and mitochondrial dysfunction). In addition, thiamine has also been implicated in autism via its effects on basic myelin protein, glycogen synthetase kinase-3β, alpha-1 antitrypsin, and glyoxalase 1. Thiamine may play a role in children with autism. Additional investigation of thiamine in children with autism is needed.

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Examination of association of genes in the serotonin system to autism

Cited by 67 publications

References 64 publications

Autism associated with low 5-hydroxyindolacetic acid in CSF and the heterozygous SLC6A4 gene Gly56Ala plus 5-HTTLPR L/L promoter variants

Autism associated with low 5-hydroxyindolacetic acid in CSF and the heterozygous SLC6A4 gene Gly56Ala plus 5-HTTLPR L/L promoter variants

Emerging Clues and Altered Metabolic Findings in Autism: Breakthroughs and Prospects from Omics Studies

The Role of Thiamine in Autism

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