Serotonin Relationships of Autistic Probands and Their First-Degree Relatives

Kuperman, Samuel; Beeghly, James; Burns, Trudy L.; Tsai, Luke Y.

doi:10.1016/s0002-7138(09)60446-5

Cited by 55 publications

(22 citation statements)

References 14 publications

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“…It is difficult to reconcile this negative finding with studies that have found positive correlations in either platelet or whole blood 5-HT concentration between children with either autism or disruptive behavior disorders and their first-degree relatives (Abramson et al 1989;Cook et al 1990Cook et al , 1995Kuperman et al 1985). The present study may have failed to detect a correlation because 70% of the probands and 13% of the parents were taking antiobsessional/ antidepressant medication that resulted in their exclusion from the analysis.…”

Section: Discussioncontrasting

confidence: 59%

Serotonin Transporter and Seasonal Variation in Blood Serotonin in Families with Obsessive-Compulsive Disorder

Hanna

Himle

Curtis

et al. 1998

Neuropsychopharmacology

142

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The serotonin transporter (HTT) is a candidate gene for obsessive-compulsive disorder (OCD) that has been associated with anxiety-related traits. The long (1) and short (s) variants of theThe serotonin transporter (HTT = SLC6A4) is a plausible candidate gene for obsessive-compulsive disorder (OCD) and several other psychiatric disorders (Altemus et al. 1996;Lesch et al. 1995;Ogilvie et al. 1996). It has been associated with anxiety-related traits in two predominantly male samples (Gelernter et al. 1995;Ramamoorthy et al. 1993). A complementary deoxyribose nucleic acid (cDNA) encoding the 5-HTT in the human midbrain raphe complex has been isolated, and its identity with the human platelet serotonin (5-HT) transporter site has been demonstrated (Lesch et al. 1993a,b).HTT gene transcription is regulated by a deletion/ insertion polymorphism in the promoter (Heils et al. 1995). The long (I) and short (s) variants of this polymorphic region have different transcriptional efficiencies in transfection assays and lymphoblastoid cell lines Lesch et al. 1996). The short allele reduces the transcriptional efficiency of the HTT gene promoter, resulting in decreased 5-HTT binding and 5-HT uptake in lymphoblasts . Studies of HIT gene expression in lymphoblast cell lines from 10 subjects with different genotypes suggested that the polymorphism has more of a dominant-recessive than a codominant-additive effect, with the short variant ap-0893-133X/98/$19.00 PII S0893-133X(97)00097-3 NEUROPSYCHOPHARMACOLOGY 1998-VOL. 18, NO. 2 pearing dominant to the long variant. However, the dominant mode of action of the short allele has been questioned (Goldman 1996).Because of the small sample size in that study and the importance of the HTT, we examined the relationship between the HTT promoter variant and whole blood 5-HT concentration in 70 individuals from 20 families ascertained through children and adolescents between 10 and 17 years of age with a DSM-III-R diagnosis of OCD. Sampling through early-onset cases can be a useful strategy in identifying a more clearly genetic or homogeneous form of a disorder (Lander and Schork 1994). Family studies have demonstrated that OCD is often familial and that the morbid risk of the disorder is higher among the relatives of early-onset probands than among the relatives of late-onset probands (Bellodi et al. 1992;Pauls et al. 1995).The selective response of OCD to potent 5-HT transporter inhibitors (serotonin reuptake inhibitors, SRis) has suggested that a serotonergic abnormality may be involved in OCD (Goodman et al. 1990;Leonard et al. 1989). The 5-HTT is an initial site of action for those drugs and is crucial to the termination of serotonergic neurotransmission (Amara and Kuhar 1993). Two treatment studies of childhood OCD using clomipramine, a potent 5-HT transporter inhibitor, have demonstrated a significant correlation between clinical improvement and a marked reduction in either platelet 5-HT or whole blood 5-HT content, reflecting the effect of the drug on the platelet uptake site (F...

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Section: Discussioncontrasting

confidence: 59%

Serotonin Transporter and Seasonal Variation in Blood Serotonin in Families with Obsessive-Compulsive Disorder

Hanna

Himle

Curtis

et al. 1998

Neuropsychopharmacology

142

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“…One study has also found NE to be negatively associated with IQ [Cook, 1990]. Negative correlations have been reported between 5HT and NE levels and IQ in the first-degree relatives of children with autism [Cook, 1990;Kuperman et al, 1985]. There seems, in short, to be a tendency for both 5HT and NE levels to be negatively associated with IQ in autism and related conditions but this tendency is neither strong nor consistent.…”

Section: Discussionmentioning

confidence: 99%

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

Jones

Palmour

Zwaigenbaum

et al. 2004

American J of Med Genetics Pt B

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Autism is one of a group of pervasive developmental disorders (PDD) characterized by qualitative impairments in reciprocal social communication and by a preference for repetitive, stereotyped activities, interests, and behaviors. The disorder is caused in large part by genetic mechanisms, though no disease genes have yet been identified. The objective of this study was to investigate three markers, two in the DBH gene and one in the MAO-A gene, for maternal or fetal modifier effects on level of functioning (IQ). At the same time, the possibility of maternal or fetal susceptibility effects was also examined. We assembled 67 affected sibpairs and 45 singletons and determined allele frequencies at the three markers among the affected children and first degree relatives. Sizeable and significant modifier effects were found at the MAO locus and, to a lesser extent, at the DBH locus. Susceptibility effects were also found but not without qualification. We conclude that maternal genotypes at the MAO-A locus, and possibly at the DBH one, may modify IQ in children with autism through the intrauterine environment.

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“…Hyperserotonemia has been found to be familial -with a correlation between levels of parental and proband serotonin (Kuperman et al, 1985). It has also been noted that individuals with autism who had a sibling with autism showed higher platelet serotonin levels than other individuals with autism (Piven et al, 1991).…”

Section: Serotoninmentioning

confidence: 99%

Selective Attention and Perceptual Load in Autism Spectrum Disorder

et al. 2009

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This thesis examines selective attention in young adults with Autism Spectrum Disorder (ASD). Existing literature regarding this issue is mixed; some research suggesting an overly-focused attentional style (Rincover & Ducharme, 1987) while others highlight an abnormally broad attentional lens (Burack, 1994).The research presented here has, for the first time, examined selective attention in individuals with ASD using a theoretically-led approach based on Lavie's Load Theory of attention and cognitive control (Lavie et al., 2004). Load theory states that the perceptual load (amount of potentially task relevant information) of a task affects selective attention. This theory may explain the equivocal findings in the current data on selective attention and ASD.Using behavioural measures, the pattern of selective attention under various levels of load was explored in individuals with ASD and matched controls. The results provide evidence of increased perceptual capacity in ASD. This means that, at any one time, individuals with ASD may be able to process more information from the visual environment. This increase in capacity was evident on tasks of both unconscious and conscious perception.In light of the social deficits observed in the condition, the work in this thesis also explored selective attention in the presence of social distractor stimuli. Results indicated that faces are less salient for individuals with ASD and, unlike for typical adults, are not processed in an automatic and mandatory fashion. These results bring together findings on selective attention with work on social processing in an attempt to find basic abnormalities which might be fundamental in explaining the disorder. 4For Guy 5

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Serotonin Relationships of Autistic Probands and Their First-Degree Relatives

Cited by 55 publications

References 14 publications

Serotonin Transporter and Seasonal Variation in Blood Serotonin in Families with Obsessive-Compulsive Disorder

Serotonin Transporter and Seasonal Variation in Blood Serotonin in Families with Obsessive-Compulsive Disorder

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

Selective Attention and Perceptual Load in Autism Spectrum Disorder

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