Modifier effects in autism at the MAO‐A and DBH loci

Jones, Marshall B.; Palmour, Roberta M.; Zwaigenbaum, Lonnie; Szatmári, Péter

doi:10.1002/ajmg.b.20172

Cited by 36 publications

(26 citation statements)

References 48 publications

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“…The power estimate for the prior study was 0.123 with 88 patients and 92 controls. Currently, there are more than 20 genes identified as being involved in serotonin level and serotonin effects, and polymorphism(s) in some of them have been associated with autism in some, but not other, reports [e.g., Veenstra-VanderWeele et al, 2002;Jones et al, 2004]. These genes should be investigated to explore the association of hyperserotonemia with autism and with the obsessive-compulsive behaviors and repetitive/stereotyped symptoms.…”

Section: Discussionmentioning

confidence: 96%

Family‐based association study of TPH1 and TPH2 polymorphisms in autism

Ramoz

Cai

Reichert

et al. 2006

American J of Med Genetics Pt B

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The TPH1 and TPH2 genes encode the rate-limiting enzymes that control serotonin biosynthesis, and serotonin is clearly altered in autism. In the current study, eight SNPs in the TPH1 gene region and eight SNPs within the TPH2 gene were examined by family-based association tests in a large cohort of 352 families with autism and in clinically defined subsets of these families with either severe obsessive-compulsive behaviors (sOCB) or self-stimulatory behaviors (SSB). We found no evidence for association between autism and single SNPs or haplotypes of the TPH1 and TPH2 genes in the cohort of all families or in the sOCB and SSB subsets. In particular, we failed to replicate the association between autism and variants of the TPH2 gene, rs4341581 (TRANSMIT P = 1; PDT P = 0.323; FBAT P = 0.446) and rs11179000 (TRANSMIT P = 0.174; PDT P = 0.293; FBAT P = 0.374). Furthermore, no evidence for linkage was observed between autism and SNPs in the TPH1 and TPH2 genes (although linkage at the TPH2 locus was observed in the SSB subset). Thus, it appears unlikely that the TPH1 and TPH2 genes play a significant role in the susceptibility to autism or to autism endophenotypes including sOCB and SSB.

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Section: Discussionmentioning

confidence: 96%

Family‐based association study of TPH1 and TPH2 polymorphisms in autism

Ramoz

Cai

Reichert

et al. 2006

American J of Med Genetics Pt B

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“…Furthermore, in their 1-year follow-up testing, those with the low-activity allele showed a worsening in IQ with no change in the severity of their autistic behavior. Jones et al 16 found that maternal genotypes at the MAOA locus may modify IQ in children with autism through the intrauterine environment.…”

Section: Autism Spectrum Disorders (Asd)mentioning

confidence: 99%

O papel do polimorfismo funcional VNTR da região promotora do gene MAOA nos transtornos psiquiátricos

Nishioka¹,

Perin²,

Sampaio³

et al. 2011

Rev. psiquiatr. clín.

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Introduction: A functional variable number of tandem repeats (VNTR) polymorphism of the promoter region of the monoamine oxidase A (MAOA) gene has been described and many studies have investigated the association of this polymorphism with human behaviors, as well as with several psychiatric disorders. Objective: This study aimed to review the literature on the role of the VNTR functional polymorphism of the promoter region of the MAOA gene on the modulation of human behavior for the development of psychiatric disorders. Method: Searches on the Medline, Embase, Web of Science and PsycInfo databases were performed including works from January 1998 to June 2009. The words used were: "MAOA and human behavior" and "MAOA and psychiatry". Results: Several studies were found (N = 3,873). After the selection process, 109 papers were included in the review. There was found an association of MAOA low activity alleles with antisocial personality disorder, conduct disorder, ADHD, pathological gambling, and substance abuse. High activity alleles were associated with neuroticism, anorexia nervosa and depression and anxiety disorders. There was no association between the MAOA polymorphisms and bipolar disorder and schizophrenia. Discussion: The main findings, summarized in this paper, support a role of MAOA VNTR polymorphism in some psychiatric disorders although some divergences were found due to methodological difficulties in genetic studies. In general, the studies associated the low activity alleles with impulsivity and aggressive behavior ("hyperactive behaviors"), and the high activity alleles of the gene with "hypoactive behaviors", such as depression and anxiety, which demonstrates a modulation of the MAOA enzyme in "hyperactive" and "hypoactive" disorders.

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“…Jones et al [2004] reported that maternal genotypes containing specific polymorphisms at the MAO-A locus showed significant negative correlations with the intelligence quotient (IQ) in children with autism. These results are consistent with those of Cohen et al [2003], who found that a low-activity MAO-A allele (due to an upstream variable-number tandem repeat region) is associated with both lower IQ and more severe autistic behavior in children, as compared to the high-activity allele.…”

Section: Altered Prenatal Serotonin-evidence For a Role In Autismmentioning

confidence: 99%

Serotonin in autism and pediatric epilepsies

Chugani

2004

Ment. Retard. Dev. Disabil. Res. Rev.

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Serotonergic abnormalities have been reported in both autism and epilepsy. This association may provide insights into underlying mechanisms of these disorders because serotonin plays an important neurotrophic role during brain development-and there is evidence for abnormal cortical development in both autism and some forms of epilepsy. This review explores the hypothesis that an early disturbance in the serotonin system affects cortical development and the development of thalamocortical innervation, and is a potential mechanism, common to autism and pediatric epilepsies associated with cortical dysplasia. An argument is made that cortical malformation leads to abnormalities of thalamocortical connectivity, and that serotonin plays a critical role in this process. Finally, a role for altered metabolism of the serotonin precursur, tryptophan, in both epilepsy and autism is discussed. Key Words: serotonin; autism; epilepsy; tryptophan; cortical development; kynurenine E pilepsy is more common among autistic children than in the general population; conversely, autism (or milder pervasive developmental disorders) is more common in epileptic children than in the general population. There is evidence for abnormalities of the neurotransmitter serotonin in both epilepsy and autism. The role of serotonin in brain development is briefly reviewed here and then the evidence considered for a role of an altered serotonin system in these developmental disorders. We hypothesize that serotonergic abnormalities during prenatal and early postnatal development may lead to changes in thalamocortical connectivity, which results in a predisposition for autism and epilepsy. In addition, we discuss the involvement of aberrant metabolism of tryptophan-the metabolic precursor of serotonin-as a potential mechanism for alterations in serotonin availability.

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Modifier effects in autism at the MAO‐A and DBH loci

Cited by 36 publications

References 48 publications

Family‐based association study of TPH1 and TPH2 polymorphisms in autism

Family‐based association study of TPH1 and TPH2 polymorphisms in autism

O papel do polimorfismo funcional VNTR da região promotora do gene MAOA nos transtornos psiquiátricos

Serotonin in autism and pediatric epilepsies

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