Platelet serotonin studies in hyperserotonemic relatives of children with autistic disorder

Cook, Edwin H.; Arora, Ramesh; Anderson, George M.; Berry‐Kravis, Elizabeth; Yan, Suxia; Yeoh, H.C.; Sklena, Paul J.; Charak, David; Leventhal, Bennett L.

doi:10.1016/0024-3205(93)90685-v

Cited by 154 publications

(103 citation statements)

References 31 publications

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“…There are, however, discrepancies between the work of Cook et al (1997) and Klauck et al (1997) who found an association to the long rather than the short allele of the 5-HT transporter gene in autistic subjects. It has remained elusive, however, whether platelet paroxetine binding characteristics are altered in autism (Cook et al 1993).…”

Section: Serotonin (5-ht)mentioning

confidence: 99%

Peripheral Markers of Serotonergic and Noradrenergic Function in Post-Pubertal, Caucasian Males with Autistic Disorder

Croonenberghs

Delmeire²,

Verkerk³

et al. 2000

Neuropsychopharmacology

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Some studies have suggested that disorders in the peripheral and central metabolism of serotonin (5-HT) and noradrenaline may play a role in the pathophysiology of autistic disorder. This study examines serotonergic and noradrenergic markers in a study(5-15 per 10.000) and is four times more common in boys than in girls. Research on the biological pathophysiology of autism has found some evidence for a role of the turnover of serotonin (5-HT) and catecholamines.

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Section: Serotonin (5-ht)mentioning

confidence: 99%

Peripheral Markers of Serotonergic and Noradrenergic Function in Post-Pubertal, Caucasian Males with Autistic Disorder

Croonenberghs

Delmeire²,

Verkerk³

et al. 2000

Neuropsychopharmacology

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“…The abnormal patterns of cortical 5-HT synthesis capacity observed in children with autism are related to hemispheric language specialization since children with decreased 5-HT synthesis in the left cortex tended to have the most severe language impairment, while those children with right-sided or non-asymmetric patterns of cortical 5-HT synthesis had less severe language deficits [24]. Multiple studies have reported increased serum 5-HT levels, later identified at platelet-derived 5-HT, in patients with autism [2,32,35]. Pharmacotherapy with serotonergic agents that reduce CNS 5-HT generally worsen autistic symptoms [84] while those that increase available 5-HT via the high affinity 5-HT transporter (SERT) improve some autistic features [34].…”

Section: Introductionmentioning

confidence: 99%

Modeling early cortical serotonergic deficits in autism

Boylan

Blue

Höhmann

2007

Behavioural Brain Research

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Autism is a developmental brain disorder characterized by deficits in social interaction, language and behavior. Brain imaging studies demonstrate increased cerebral cortical volumes and micro-and macroscopic neuroanatomic changes in children with this disorder. Alterations in forebrain serotonergic function may underlie the neuroanatomic and behavioral features of autism. Serotonin is involved in neuronal growth and plasticity and these actions are likely mediated via serotonergic and glutamatergic receptors. Few animal models of autism have been described that replicate both etiology and pathophysiology. We report here on a selective serotonin (5-HT) depletion model of this disorder in neonatal mice that mimics neurochemical and structural changes in cortex and, in addition, displays a behavioral phenotype consistent with autism. Newborn male and female mice were depleted of forebrain 5-HT with injections of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), into the bilateral medial forebrain bundle (mfb). Behavioral testing of these animals as adults revealed alterations in social, sensory and stereotypic behaviors. Lesioned mice showed significantly increased cortical width. Serotonin immunocytochemistry showed a dramatic long-lasting depletion of 5-HT containing fibers in cerebral cortex until postnatal day (PND) 60. Autoradiographic binding to high affinity 5-HT transporters was significantly but transiently reduced in cerebral cortex of 5,7-DHT-depleted mice. AMPA glutamate receptor binding was decreased at PND 15. We hypothesize that increased cerebral cortical volume and sensorimotor, cognitive and social deficits observed in both 5-HT-depleted animals and in individuals with autism, may be the result of deficiencies in timely axonal pruning to key cerebral cortical areas.

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“…These two findings clustered in distinct subgroups. Of the eight hyperserotonemic subjects who had both 5-HT uptake and LSD binding studies performed, four subjects had 5-HT uptake that was at least 1 SD above the highest normoserotonemic subject and three different subjects had LSD binding that was at least 0.95 SDs below the lowest normoserotonemic subject (Cook et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…In our original study of first-degree relatives of patients with autism, hyperserotonemic subjects were found to have decreased 3 H-LSD-marked receptor density (Cook et al, 1993). LSD binds to 5-HT receptors including 5-HT 2A and 5-HT 7 , both of which are expressed in the platelet (Cook et al, 1994) (Cook EH, unpublished observation).…”

Section: Introductionmentioning

confidence: 99%

“…Finally, polymorphisms in ITGB3 and TPH1 were hypothesized to be associated with whole blood 5-HT levels. Our hypotheses were tested by genotyping the subjects previously studied for indices of the platelet serotonin system (Cook et al, 1993). Polymorphisms within each gene were selected based upon either reported association with autism or reported alteration in gene or protein function.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Genetics of the Platelet Serotonin System in First-Degree Relatives of Patients with Autism

Cross

Kim

Weiss

et al. 2007

Neuropsychopharmacol

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Elevated platelet serotonin (5-hydroxytryptamine, 5-HT) is found in a subset of children with autism and in some of their first-degree relatives. Indices of the platelet serotonin system, including whole blood 5-HT, 5-HT binding affinity for the serotonin transporter (K m ), 5-HT uptake (V max ), and lysergic acid diethylamide (LSD) receptor binding, were previously studied in 24 first-degree relatives of probands with autism, half of whom were selected for elevated whole blood 5-HT levels. All subjects were then genotyped for selected polymorphisms at the SLC6A4, HTR7, HTR2A, ITGB3, and TPH1 loci. Previous studies allowed an a priori prediction of SLC6A4 haplotypes that separated the subjects into three groups that showed significantly different 5-HT binding affinity (K m , p ¼ 0.005) and 5-HT uptake rate (V max , p ¼ 0.046). Genotypes at four individual polymorphisms in SLC6A4 were not associated with platelet 5-HT indices. Haplotypes at SLC6A4 and individual genotypes of polymorphisms at SLC6A4, HTR7, HTR2A, ITGB3, and TPH1 showed no significant association with whole blood 5-HT. Haplotype analysis of two polymorphisms in TPH1 revealed a nominally significant association with whole blood 5-HT (p ¼ 0.046). These initial studies of indices of the 5-HT system with several single-nucleotide polymorphisms at loci in this system generate hypotheses for testing in other samples.

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Platelet serotonin studies in hyperserotonemic relatives of children with autistic disorder

Cited by 154 publications

References 31 publications

Peripheral Markers of Serotonergic and Noradrenergic Function in Post-Pubertal, Caucasian Males with Autistic Disorder

Peripheral Markers of Serotonergic and Noradrenergic Function in Post-Pubertal, Caucasian Males with Autistic Disorder

Modeling early cortical serotonergic deficits in autism

Molecular Genetics of the Platelet Serotonin System in First-Degree Relatives of Patients with Autism

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