Platelet uptake of serotonin in psychotic children

Rotman, Avner; Caplan, Rochelle; Székely, George

doi:10.1007/bf00431264

Cited by 30 publications

(2 citation statements)

References 8 publications

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“…In addition, it is possible that enhanced 5-HT accumulation in platelets is responsible for the reduced PPP 5-HT level. This is supported by several studies [24][25][26], but not all [27], which have demonstrated increased 5-HT platelet uptake in autism. While speculative, this may be subsequently associated with increased platelet 5-HT levels and parallel diminished 'free' plasma 5-HT levels.…”

Section: Discussionsupporting

confidence: 67%

Low Platelet-Poor Plasma Levels of Serotonin in Adult Autistic Patients

Spivak

Golubchik²,

Mozes

et al. 2004

Neuropsychobiology

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Background: Hyperserotonemia has been reported in about a third of autistic patients. However, most studies have examined whole blood levels of serotonin (5-HT), the vast majority of which is found in platelets. The aim of this study was to determine 5-HT levels in platelet-poor plasma (PPP) in a group of adult patients with autism. Methods: Levels of PPP 5-HT were compared between 10 adult drug-free autistic patients and 12 healthy controls. The Ritvo-Freeman Real-Life Rating Scale and the Overt Aggression Scale (OAS) were administered to the autistic group as a measure of symptom severity. Results: Significantly lower PPP 5-HT levels were observed in the autistic group as compared to the controls (p = 0.03). In addition, PPP 5-HT levels were inversely correlated with OAS scores among subjects with autism (r = –0.64, p < 0.05). Conclusion: PPP 5-HT (‘free’) levels appear to be low in autistic patients and may play a role in the pathophysiology and symptomatology of the disorder.

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Section: Discussionsupporting

confidence: 67%

Low Platelet-Poor Plasma Levels of Serotonin in Adult Autistic Patients

Spivak

Golubchik²,

Mozes

et al. 2004

Neuropsychobiology

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“…Indeed, further studies provided evidence that blood 5-HT level is a highly heritable trait (Leventhal et al, 1990 ; Weiss et al, 2005 ; Muller et al, 2016 ), indicating that the changes found in hyperserotonemic ASD subjects may have identifiable genetic determinants. Because platelets do not synthesize 5-HT but acquire it from the bloodstream via SERT, and because a single gene expresses SERT found in both the brain and platelets (Lesch et al, 1993 ; Ramamoorthy et al, 1993 ) the transporter has been a major focus for models seeking to connect hyperserotonemia to ASD (Rotman et al, 1980 ; Piven et al, 1991 ; Cook and Leventhal, 1996 ).…”

Section: Introduction: Serotonergic Connections To Asdmentioning

confidence: 99%

Rare Opportunities for Insights Into Serotonergic Contributions to Brain and Bowel Disorders: Studies of the SERT Ala56 Mouse

Stilley

Blakely

2021

Front. Cell. Neurosci.

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Altered structure, expression, and regulation of the presynaptic serotonin (5-HT) transporter (SERT) have been associated with multiple neurobehavioral disorders, including mood disorders, obsessive-compulsive disorder (OCD), and autism spectrum disorder (ASD). Opportunities to investigate mechanistic links supporting these associations were spurred with the identification of multiple, rare human SERT coding variants in a study that established a male-specific linkage of ASD to a linkage marker on chromosome 17 which encompassed the location of the SERT gene (SLC6A4). We have explored the most common of these variants, SERT Ala56, in vitro and in vivo. Results support a tonic elevation of 5-HT transport activity in transfected cells and human lymphoblasts by the variant in vitro that leads to an increased 5-HT clearance rate in vivo when studied in the SERT Ala56 mouse model, along with altered sensitivity to SERT regulatory signaling pathways. Importantly, hyperserotonemia, or an elevated whole blood 5-HT, level, was found in SERT Ala56 mice, reproducing a well-replicated trait observed in a significant fraction of ASD subjects. Additionally, we found multiple biochemical, physiological, and behavioral alterations in the SERT Ala56 mice that can be analogized to those observed in ASD and its medical comorbidities. The similarity of the functional impact of the SERT Ala56 variant to the consequences of p38α MAPK activation, ascribed to the induction of a biased conformation of the transporter toward an outward-facing conformation, has resulted in successful efforts to restore normal behavioral and bowel function via pharmacological and genetic p38α MAPK targeting. Moreover, the ability of the inflammatory cytokine IL-1β to enhance SERT activity via a p38α MAPK-dependent pathway suggests that the SERT Ala56 conformation mimics that of a chronic inflammatory state, supporting findings in ASD of elevated inflammatory cytokine levels. In this report, we review studies of the SERT Ala56 variant, discussing opportunities for continued insight into how chronically altered synaptic 5-HT homeostasis can drive reversible, functional perturbations in 5-HT sensitive pathways in the brain and periphery, and how targeting the SERT regulome, particularly through activating pathways such as those involving IL-1β/p38α MAPK, may be of benefit for neurobehavioral disorders, including ASD.

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The Platelet as a Peripheral Model of Serotonergic Function in Child Psychiatry

Rehavi

Weizman

1990

Application of Basic Neuroscience to Child Psychiatry

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Platelet uptake of serotonin in psychotic children

Cited by 30 publications

References 8 publications

Low Platelet-Poor Plasma Levels of Serotonin in Adult Autistic Patients

Low Platelet-Poor Plasma Levels of Serotonin in Adult Autistic Patients

Rare Opportunities for Insights Into Serotonergic Contributions to Brain and Bowel Disorders: Studies of the SERT Ala56 Mouse

The Platelet as a Peripheral Model of Serotonergic Function in Child Psychiatry

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