Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis

Stefano Gabriele, Roberto Sacco, Antonio M. Persico

Research output: Contribution to journalArticle

Abstract

Elevated blood serotonin (5-HT) levels were the first biomarker identified in autism research. Many studies have contrasted blood 5-HT levels in autistic patients and controls, but different measurement protocols, technologies, and biomaterials have been used through the years. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and between-study heterogeneity, while verifying whether and to what extent different methodological approaches influence the strength of this association. Our literature search strategy identified 551 papers, from which 22 studies providing patient and control blood 5-HT values were selected for meta-analysis. Significantly higher 5-HT levels in autistic patients compared to controls were recorded both in whole blood (WB) [O.R.=4.6; (3.1-5.2); P=1.0×10-12], and in platelet-rich plasma (PRP) [O.R.=2.6 (1.8-3.9); P=2.7×10-7]. Predictably, studies measuring 5-HT levels in platelet-poor plasma (PPP) yielded no significant group difference [O.R.=0.54 (0.2-2-0); P=0.36]. Altogether, elevated 5-HT blood levels were recorded in 28.3% in WB and 22.5% in PRP samples of autistic individuals, as reported in 15 and 4 studies, respectively. Studies employing HPLC vs fluorometric assays yield similar cumulative effect sizes, but the former display much lower variability. In summary, despite some limitations mainly due to small study sample sizes, our results significantly reinforce the reliability of elevated 5-HT blood levels as a biomarker in ASD, providing practical indications potentially useful for its inclusion in multi-marker diagnostic panels for clinical use.

Original languageEnglish
Pages (from-to)919-929
Number of pages11
JournalEuropean Neuropsychopharmacology
Volume24
Issue number6
DOIs
Publication statusPublished - 2014

Fingerprint

Meta-Analysis
Serotonin
Platelet-Rich Plasma
Biomarkers
Autism Spectrum Disorder
Biocompatible Materials
Autistic Disorder
Sample Size
Blood Platelets
High Pressure Liquid Chromatography
Technology
Research

Keywords

  • 5-HT
  • Autism
  • Biomarker
  • Endophenotype
  • Meta-analysis

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Biological Psychiatry
  • Neurology
  • Pharmacology
  • Medicine(all)

Cite this

Blood serotonin levels in autism spectrum disorder : A systematic review and meta-analysis. / Gabriele, Stefano; Sacco, Roberto; Persico, Antonio M.

In: European Neuropsychopharmacology, Vol. 24, No. 6, 2014, p. 919-929.

Research output: Contribution to journalArticle

Gabriele, Stefano ; Sacco, Roberto ; Persico, Antonio M. / Blood serotonin levels in autism spectrum disorder : A systematic review and meta-analysis. In: European Neuropsychopharmacology. 2014 ; Vol. 24, No. 6. pp. 919-929.
@article{c28e6fe4141e487fb9c3ace58adff986,
title = "Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis",
abstract = "Elevated blood serotonin (5-HT) levels were the first biomarker identified in autism research. Many studies have contrasted blood 5-HT levels in autistic patients and controls, but different measurement protocols, technologies, and biomaterials have been used through the years. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and between-study heterogeneity, while verifying whether and to what extent different methodological approaches influence the strength of this association. Our literature search strategy identified 551 papers, from which 22 studies providing patient and control blood 5-HT values were selected for meta-analysis. Significantly higher 5-HT levels in autistic patients compared to controls were recorded both in whole blood (WB) [O.R.=4.6; (3.1-5.2); P=1.0×10-12], and in platelet-rich plasma (PRP) [O.R.=2.6 (1.8-3.9); P=2.7×10-7]. Predictably, studies measuring 5-HT levels in platelet-poor plasma (PPP) yielded no significant group difference [O.R.=0.54 (0.2-2-0); P=0.36]. Altogether, elevated 5-HT blood levels were recorded in 28.3{\%} in WB and 22.5{\%} in PRP samples of autistic individuals, as reported in 15 and 4 studies, respectively. Studies employing HPLC vs fluorometric assays yield similar cumulative effect sizes, but the former display much lower variability. In summary, despite some limitations mainly due to small study sample sizes, our results significantly reinforce the reliability of elevated 5-HT blood levels as a biomarker in ASD, providing practical indications potentially useful for its inclusion in multi-marker diagnostic panels for clinical use.",
keywords = "5-HT, Autism, Biomarker, Endophenotype, Meta-analysis",
author = "Stefano Gabriele and Roberto Sacco and Persico, {Antonio M.}",
year = "2014",
doi = "10.1016/j.euroneuro.2014.02.004",
language = "English",
volume = "24",
pages = "919--929",
journal = "European Neuropsychopharmacology",
issn = "0924-977X",
publisher = "Elsevier Science B.V.",
number = "6",

}

TY - JOUR

T1 - Blood serotonin levels in autism spectrum disorder

T2 - A systematic review and meta-analysis

AU - Gabriele, Stefano

AU - Sacco, Roberto

AU - Persico, Antonio M.

PY - 2014

Y1 - 2014

N2 - Elevated blood serotonin (5-HT) levels were the first biomarker identified in autism research. Many studies have contrasted blood 5-HT levels in autistic patients and controls, but different measurement protocols, technologies, and biomaterials have been used through the years. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and between-study heterogeneity, while verifying whether and to what extent different methodological approaches influence the strength of this association. Our literature search strategy identified 551 papers, from which 22 studies providing patient and control blood 5-HT values were selected for meta-analysis. Significantly higher 5-HT levels in autistic patients compared to controls were recorded both in whole blood (WB) [O.R.=4.6; (3.1-5.2); P=1.0×10-12], and in platelet-rich plasma (PRP) [O.R.=2.6 (1.8-3.9); P=2.7×10-7]. Predictably, studies measuring 5-HT levels in platelet-poor plasma (PPP) yielded no significant group difference [O.R.=0.54 (0.2-2-0); P=0.36]. Altogether, elevated 5-HT blood levels were recorded in 28.3% in WB and 22.5% in PRP samples of autistic individuals, as reported in 15 and 4 studies, respectively. Studies employing HPLC vs fluorometric assays yield similar cumulative effect sizes, but the former display much lower variability. In summary, despite some limitations mainly due to small study sample sizes, our results significantly reinforce the reliability of elevated 5-HT blood levels as a biomarker in ASD, providing practical indications potentially useful for its inclusion in multi-marker diagnostic panels for clinical use.

AB - Elevated blood serotonin (5-HT) levels were the first biomarker identified in autism research. Many studies have contrasted blood 5-HT levels in autistic patients and controls, but different measurement protocols, technologies, and biomaterials have been used through the years. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and between-study heterogeneity, while verifying whether and to what extent different methodological approaches influence the strength of this association. Our literature search strategy identified 551 papers, from which 22 studies providing patient and control blood 5-HT values were selected for meta-analysis. Significantly higher 5-HT levels in autistic patients compared to controls were recorded both in whole blood (WB) [O.R.=4.6; (3.1-5.2); P=1.0×10-12], and in platelet-rich plasma (PRP) [O.R.=2.6 (1.8-3.9); P=2.7×10-7]. Predictably, studies measuring 5-HT levels in platelet-poor plasma (PPP) yielded no significant group difference [O.R.=0.54 (0.2-2-0); P=0.36]. Altogether, elevated 5-HT blood levels were recorded in 28.3% in WB and 22.5% in PRP samples of autistic individuals, as reported in 15 and 4 studies, respectively. Studies employing HPLC vs fluorometric assays yield similar cumulative effect sizes, but the former display much lower variability. In summary, despite some limitations mainly due to small study sample sizes, our results significantly reinforce the reliability of elevated 5-HT blood levels as a biomarker in ASD, providing practical indications potentially useful for its inclusion in multi-marker diagnostic panels for clinical use.

KW - 5-HT

KW - Autism

KW - Biomarker

KW - Endophenotype

KW - Meta-analysis

UR - http://www.scopus.com/inward/record.url?scp=84899906322&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899906322&partnerID=8YFLogxK

U2 - 10.1016/j.euroneuro.2014.02.004

DO - 10.1016/j.euroneuro.2014.02.004

M3 - Article

C2 - 24613076

AN - SCOPUS:84899906322

VL - 24

SP - 919

EP - 929

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

IS - 6

ER -