Platelet serotonin levels in Pervasive Developmental Disorders and mental retardation: Diagnostic group differences, within-group distribution, and behavioral correlates
Abstract
Objective To investigate group differences, the within-group distributions, and the clinical correlates of platelet serotonin (5-HT) levels in pervasive developmental disorders (PDD).Method Platelet 5-HT levels were measured in Dutch children and young adults, recruited from 2001 through 2003, with PDD (autism, Asperger's, and PDD-not otherwise specified [PDD-NOS]; n = 81) or with mental retardation (MR; n = 54) but without PDD, and in normal controls (n = 60). The distribution of platelet 5-HT levels was assessed using mixture-modeling analyses. Relationships between platelet 5-HT levels and a full range of demographic, clinical, and behavioral variables were examined.Results Group mean (+/- SD) platelet 5-HT levels (nmol/10 platelets) were significantly higher in the autistic (4.51 +/- 1.61, n = 33) and PDD-NOS (4.90 +/- 1.54, n = 43) groups compared to the MR (3.48 +/- 1.33, n = 54) or the normal control (3.58 +/- 1.08, n = 60) groups (F4,190 = 9.35, p <.001). Platelet 5-HT values in the combined PDD group showed a bimodal distribution, and an empirical cutpoint for hyperserotonemia was determined. None of the behavioral variables examined was significantly associated with platelet 5-HT levels.Conclusions The platelet hyperserotonemia of autism was replicated in Dutch subjects. Platelet 5-HT levels were also increased in PDD-NOS, while no elevation was seen in MR. Platelet 5-HT levels appeared to be bimodally distributed in the PDD group, with an apparent hyperserotonemic subgroup.
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Abnormal serotonin concentrations in the brain and tissues outside the blood-brain barrier have been reported in populations with ASD.
“Lower levels of plasma oxytocin [185] and abnormal serotonin concentrations in the brain and tissues outside the blood-brain barrier have been reported in populations with ASD [186,187].”
From Vitamin D and Autism Spectrum Disorder: A Literature Review (2016) · cites this paper as [187]
Clinical correlates between hyperserotonemia and ASD-associated behaviors (e.g., stereotypy and self-injury) have been inconsistent.
“the clinical correlates between hyperserotonemia and ASD-associated behaviors (e.g., stereotypy and self-injury) have been inconsistent [36, 45–47].”
From Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders (2018) · cites this paper as [46]
Cites
Estimating the Dimension of a Model
Schwarz, G. (1978) · The Annals of Statistics · doi:10.1214/aos/1176344136 · Cited by 47,033 · see citing works
Lord, C., Rutter, M., & Le Couteur, A. (1994) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02172145 · Cited by 9,065 · see citing works
Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Leventhal, B. L., DiLavore, P. C., Pickles, A., & Rutter, M. (2000) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1005592401947 · Cited by 7,520 · see citing works
J Neuropsychiatry Clin Neurosci
Yudofsky, S. C., & Hales, R. E. (1992) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/jnp.4.4.359 · Cited by 3,818 · see citing works
Asymptotic Theory of Certain "Goodness of Fit" Criteria Based on Stochastic Processes
Anderson, T. W., & Darling, D. A. (1952) · The Annals of Mathematical Statistics · doi:10.1214/aoms/1177729437 · Cited by 3,542 · see citing works
How Many Clusters? Which Clustering Method? Answers Via Model-Based Cluster Analysis
Fraley, C. (1998) · The Computer Journal · doi:10.1093/comjnl/41.8.578 · Cited by 2,549 · see citing works
Children's Yale-Brown Obsessive Compulsive Scale: Reliability and Validity
SCAHILL, L., RIDDLE, M. A., McSWIGGIN-HARDIN, M., ORT, S. I., KING, R. A., GOODMAN, W. K., CICCHETTI, D., & LECKMAN, J. F. (1997) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199706000-00023 · Cited by 2,045 · see citing works
Krug, D. A., Arick, J. R., & Almond, P. (1980) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1980.tb01797.x · Cited by 903 · see citing works
Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children
Schain, R. J., & Freedman, D. X. (1961) · The Journal of Pediatrics · doi:10.1016/s0022-3476(61)80261-8 · Cited by 579 · see citing works
The serotonin system in autism
Cook, E. H., & LEVENTHAL, B. L. (1996) · Current Opinion in Pediatrics · doi:10.1097/00008480-199608000-00008 · Cited by 394 · see citing works
Whole blood serotonin in autistic and normal subjects
Anderson, G. M., Freedman, D. X., Cohen, D. J., Volkmar, F. R., Hoder, E. L., McPhedran, P., Minderaa, R. B., Hansen, C. R., & Young, J. G. (1987) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1987.tb00677.x · Cited by 313 · see citing works
Self-citationIncreased Blood Serotonin and Platelets in Early Infantile Autism
RITVO, E. R. (1970) · Archives of General Psychiatry · doi:10.1001/archpsyc.1970.01750060086009 · Cited by 249 · see citing works
Hyperserotonemia and amine metabolites in autistic and retarded children
Hanley, H. G. (1977) · Archives of General Psychiatry · doi:10.1001/archpsyc.1977.01770170031002 · Cited by 230 · see citing works
The Hyperserotonemia of Autisma
Anderson, G. M., Horne, W. C., Chatterjee, D., & Cohen, D. J. (1990) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1990.tb16893.x · Cited by 210 · see citing works
Self-citationLeboyer, M., Philippe, A., Bouvard, M., Guilloud-Bataille, M., Bondoux, D., Tabuteau, F., Feingold, J., Mouren-Simeoni, M.-C., & Launay, J.-M. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(97)00532-5 · Cited by 194 · see citing works
The Genetic Dissection of Complex Traits in a Founder Population
Ober, C., Abney, M., & McPeek, M. S. (2001) · The American Journal of Human Genetics · doi:10.1086/324025 · Cited by 189 · see citing works
Platelet serotonin studies in hyperserotonemic relatives of children with autistic disorder
Cook, E. H., Arora, R. C., Anderson, G. M., Berry‐Kravis, E., Yan, S., Yeoh, H. C., Sklena, P. J., Charak, D., & LEVENTHAL, B. L. (1993) · Life Sciences · doi:10.1016/0024-3205(93)90685-v · Cited by 166 · see citing works
Self-citationPlatelet serotonin, a possible marker for familial autism
Piven, J., Tsai, G. E., Nehme, E., COYLE, J. T., Chase, G. A., & Folstein, S. E. (1991) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02206997 · Cited by 147 · see citing works
MCBRIDE, P. A., ANDERSON, G. M., HERTZIG, M. E., SNOW, M. E., THOMPSON, S. M., KHAIT, V. D., SHAPIRO, T., & COHEN, D. J. (1998) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199807000-00017 · Cited by 141 · see citing works
Self-citationElevated blood serotonin in autistic probands and their first-degree relatives
Abramson, R. K., Wright, H. H., Carpenter, R., Brennan, W., Lumpuy, O., Cole, E., & Young, S. R. (1989) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02212938 · Cited by 123 · see citing works
Genetics of Childhood Disorders: XLV. Autism, Part 4: Serotonin in Autism
Anderson, G. M. (2002) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200212000-00025 · Cited by 116 · see citing works
Self-citationLuteijn, E., Luteijn, F., Jackson, S., Volkmar, F. R., & Minderaa, R. B. (2000) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1005527300247 · Cited by 111 · see citing works
Self-citationCook, E. H., LEVENTHAL, B. L., Heller, W., Metz, J. T., Wainwright, M. S., & Freedman, D. X. (1990) · Journal of Neuropsychiatry · doi:10.1176/jnp.2.3.268 · Cited by 104 · see citing works
Kema, I. P., Meijer, W. G., Meiborg, G., et al. (2001) · Clinical Chemistry · doi:10.1093/clinchem/47.10.1811 · Cited by 103 · see citing works
Self-citationRelationships of whole blood serotonin and plasma norepinephrine within families
Leventhal, B. L., Cook, E. H., Morford, M., Ravitz, A., & Freedman, D. X. (1990) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02216055 · Cited by 102 · see citing works
Distribution of the Anderson-Darling Statistic
Lewis, P. (1961) · The Annals of Mathematical Statistics · doi:10.1214/aoms/1177704850 · Cited by 88 · see citing works
Serotonin Relationships of Autistic Probands and Their First-Degree Relatives
Samuel Kuperman, C., Beeghly, J. H. L., Burns, T. L., & Tsai, L. Y. (1985) · Journal of the American Academy of Child Psychiatry · doi:10.1016/s0002-7138(09)60446-5 · Cited by 61 · see citing works
Maturational changes in blood serotonin levels and platelet counts
RITVO, E. R., Yuwiler, A., Geller, E., et al. (1971) · Biochemical Medicine · doi:10.1016/0006-2944(71)90077-9 · Cited by 60 · see citing works
Blood Serotonin Levels in Severe Mental Retardation
Partington, M. W., Tu, J., & Wong, C. Y. (1973) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.1973.tb05172.x · Cited by 59 · see citing works
Blood Serotonin in Schizophrenie Children
Campbell, M., Friedman, E., Green, W. H., Collins, P. J., Small, A. M., & Breuer, H. (2017) · International Pharmacopsychiatry · doi:10.1159/000468197 · Cited by 52 · see citing works
Association of serotonin concentration to behavior and IQ in autistic children
Kuperman, S., Beeghly, J. H. L., Burns, T. L., et al. (1987) · Journal of Autism and Developmental Disorders · doi:10.1007/bf01487265 · Cited by 43 · see citing works
Badcock, N. R., Spence, J. G., & Stern, L. M. (1987) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/000456328702400613 · Cited by 41 · see citing works
Cuccaro, M. L., Wright, H. H., Abramson, R. K., Marsteller, F., & Valentine, J. (1993) · Journal of Neuropsychiatry · doi:10.1176/jnp.5.1.94 · Cited by 38 · see citing works
Geller, E., Yuwiler, A., Freeman, B. J., & RITVO, E. R. (1988) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02211822 · Cited by 34 · see citing works
Whole blood serotonin and tryptophan in autism: Temporal stability and the effects of medication
Minderaa, R. B., Anderson, G. M., Volkmar, F. R., Harcherick, D., Akkerhuis, G. W., & Cohen, D. J. (1989) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02212724 · Cited by 28 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Lord, C., Brugha, T. S., Charman, T., Cusack, J., Dumas, G., Frazier, T., Jones, E. J. H., Jones, R. M., Pickles, A., State, M. W., et al. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0138-4 · Cited by 1,859 · see citing works
From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways
Rogers, G. B., Keating, D. J., Young, R. L., Wong, M.-L., Licinio, J., & Wesselingh, S. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.50 · Cited by 969 · see citing works
The serotonin system in autism spectrum disorder: From biomarker to animal models
Muller, C. L., Anacker, A. M. J., & Veenstra-VanderWeele, J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.11.010 · Cited by 531 · see citing works
Antidepressant Use During Pregnancy and Childhood Autism Spectrum Disorders
Croen, L. A. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.73 · Cited by 510 · see citing works
The Gut Microbiota and Autism Spectrum Disorders
Li, Q., Han, Y., Dy, A. B. C., & Hagerman, R. J. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00120 · Cited by 462 · see citing works
Vitamin D hormone regulates serotonin synthesis. Part 1: Relevance for autism
Patrick, R. P., & Ames, B. N. (2014) · The FASEB Journal · doi:10.1096/fj.13-246546 · Cited by 414 · see citing works
Blood serotonin levels in autism spectrum disorder: A systematic review and meta-analysis
Gabriele, S., Sacco, R., & Persico, A. M. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.02.004 · Cited by 346 · see citing works
Veenstra-VanderWeele, J., Muller, C. L., Iwamoto, H., Sauer, J. E., Owens, W. A., Shah, C. R., Cohen, J., Mannangatti, P., Jessen, T., Thompson, B. J., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1112345109 · Cited by 333 · see citing works
Social approach in genetically engineered mouse lines relevant to autism
Moy, S. S., Nadler, J. J., Young, N. B., Nonneman, R. J., Grossman, A. W., Murphy, D. L., D’Ercole, A. J., Crawley, J. N., Magnuson, T. R., & Lauder, J. M. (2009) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2008.00452.x · Cited by 246 · see citing works
Gastrointestinal issues in autism spectrum disorder
Hsiao, E. Y. (2014) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000029 · Cited by 209 · see citing works
Prenatal SSRI use and offspring with autism spectrum disorder or developmental delay
Harrington, R. A., Lee, L.-C., Crum, R. M., Zimmerman, A. W., & Hertz-Picciotto, I. (2014) · Pediatrics · doi:10.1542/peds.2013-3406 · Cited by 174 · see citing works
Autism Spectrum Disorder and low vitamin D at birth: A sibling control study
Fernell, E., Bejerot, S., Westerlund, J., Miniscalco, C., Simila, H., Eyles, D., Gillberg, C., & Humble, M. B. (2015) · Molecular Autism · doi:10.1186/2040-2392-6-3 · Cited by 160 · see citing works
Margolis, K. G., Li, Z., Stevanovic, K., Saurman, V., Israelyan, N., Anderson, G. M., Snyder, I., Veenstra-VanderWeele, J., Blakely, R. D., & Gershon, M. D. (2016) · Journal of Clinical Investigation · doi:10.1172/jci84877 · Cited by 139 · see citing works
Self-citationNaviaux, J. C., Schuchbauer, M. A., Li, K., Wang, L., Risbrough, V. B., Powell, S. B., & Naviaux, R. K. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.33 · Cited by 134 · see citing works
Veenstra-VanderWeele, J., & Blakely, R. D. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.185 · Cited by 128 · see citing works
Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders
Israelyan, N., & Margolis, K. G. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.03.020 · Cited by 122 · see citing works
Macrophage migration inhibitory factor and autism spectrum disorders
Grigorenko, E. L., Han, S. S., Yrigollen, C. M., Leng, L., Mizue, Y., Anderson, G. M., Mulder, E. J., de Bildt, A., Minderaa, R. B., Volkmar, F. R., et al. (2008) · PEDIATRICS · doi:10.1542/peds.2007-3604 · Cited by 118 · see citing works
Vitamin D and Autism Spectrum Disorder: A Literature Review
Mazahery, H., Camargo, C., Conlon, C., Beck, K., Kruger, M., & Von Hurst, P. (2016) · Nutrients · doi:10.3390/nu8040236 · Cited by 110 · see citing works
Factor structure of a sluggish cognitive tempo scale in clinically-referred children
Jacobson, L. A., Murphy-Bowman, S. C., Pritchard, A. E., Tart-Zelvin, A., Zabel, T. A., & Mahone, E. M. (2012) · Journal of Abnormal Child Psychology · doi:10.1007/s10802-012-9643-6 · Cited by 101 · see citing works
Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder
Marler, S., Ferguson, B. J., Lee, E. B., Peters, B., Williams, K. C., McDonnell, E., Macklin, E. A., Levitt, P., Gillespie, C. H., Anderson, G. M., et al. (2016) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-015-2646-8 · Cited by 95 · see citing works
Self-citationThe combined role of serotonin and interleukin-6 as biomarker for autism
Yang, C.-J., Liu, C.-L., Sang, B., Zhu, X.-M., & Du, Y.-J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.10.011 · Cited by 80 · see citing works
Altamura, C., Dell'Acqua, M., Moessner, R., Murphy, D., Lesch, K., & Persico, A. M. (2007) · Cerebral Cortex · doi:10.1093/cercor/bhl051 · Cited by 79 · see citing works
Approaches to Understanding Multisensory Dysfunction in Autism Spectrum Disorder
Siemann, J. K., Veenstra‐VanderWeele, J., & Wallace, M. T. (2020) · Autism Research · doi:10.1002/aur.2375 · Cited by 74 · see citing works
“The importance of these studies is reinforced by the fact that serotonin has been consistently implicated in ASD [Cook & Leventhal, 1996; Mulder et al., 2004; Muller et al., 2016], has been shown to be important for sensory cortical development [Cases et al.”
BackgroundRigid-compulsive behaviors are associated with mixed bowel symptoms in autism spectrum disorder
Peters, B., Williams, K. C., Gorrindo, P., Rosenberg, D., Lee, E. B., Levitt, P., & Veenstra-VanderWeele, J. (2014) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-013-2009-2 · Cited by 70 · see citing works
Chantiluke, K., Barrett, N., Giampietro, V., Santosh, P., Brammer, M., Simmons, A., Murphy, D. G., & Rubia, K. (2015) · Psychopharmacology · doi:10.1007/s00213-014-3837-2 · Cited by 63 · see citing works
Chantiluke, K., Barrett, N., Giampietro, V., Brammer, M., Simmons, A., Murphy, D. G., & Rubia, K. (2015) · Cerebral Cortex · doi:10.1093/cercor/bht365 · Cited by 59 · see citing works
Hagberg, K. W., Robijn, A. L., & Jick, S. S. (2018) · Clinical Epidemiology · doi:10.2147/clep.s180618 · Cited by 60 · see citing works
Walsh, J. J., Llorach, P., Cardozo Pinto, D. F., Wenderski, W., Christoffel, D. J., Salgado, J. S., Heifets, B. D., Crabtree, G. R., & Malenka, R. C. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01091-6 · Cited by 56 · see citing works
Nijmeijer, J. S., Hartman, C. A., Rommelse, N. N. J., Altink, M. E., Buschgens, C. J. M., Fliers, E. A., Franke, B., Minderaa, R. B., Ormel, J., Sergeant, J. A., et al. (2010) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2010.02277.x · Cited by 57 · see citing works
Self-citationThe meaning of significant mean group differences for biomarker discovery
Loth, E., Ahmad, J., Chatham, C., López, B., Carter, B., Crawley, D., Oakley, B., Hayward, H., Cooke, J., San José Cáceres, A., et al. (2021) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1009477 · Cited by 52 · see citing works
Serotonin neuron abnormalities in the BTBR mouse model of autism
Guo, Y., & Commons, K. G. (2017) · Autism Research · doi:10.1002/aur.1665 · Cited by 51 · see citing works
Relationship between whole blood serotonin and repetitive behaviors in autism
Kolevzon, A., Newcorn, J. H., Kryzak, L., Chaplin, W., Watner, D., Hollander, E., Smith, C. J., Cook, E. H., & Silverman, J. M. (2010) · Psychiatry Research · doi:10.1016/j.psychres.2009.02.008 · Cited by 50 · see citing works
The use of genetic epidemiology to guide classification in child and adult psychopathology
Szatmari, P., White, J., & Merikangas, K. R. (2007) · International Review of Psychiatry · doi:10.1080/09540260701563619 · Cited by 38 · see citing works
- Authors
- Mulder, E. J., Anderson, G. M., Kema, I. P., de Bildt, A., van Lang, N. D., den Boer, J. A., & Minderaa, R. B.
- Affiliations
- University of Groningen (NL)
- Corresponding author
- Mulder, Erik J.
- Venue
- Journal of the American Academy of Child & Adolescent Psychiatry
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 43
- Issue
- 4
- Pages
- 491-499
- ISSN
- 0890-8567 (ISSN-L)
- OpenAlex
- W2153657359
- Cited by
- 199
- References
- 35
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 10 · 2022: 5 · 2021: 8 · 2020: 11 · 2019: 5 · 2018: 5 · 2017: 15 · 2016: 14 · 2015: 10 · 2014: 21 · 2013: 15 · 2012: 10
- FWCI
- 4.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- platelet serotonin, pervasive developmental disorders, autism spectrum disorder, Asperger syndrome, pervasive developmental disorder not otherwise specified, intellectual disability, hyperserotonemia, bimodal distribution, mixture models, behavioral correlates, children and young adults
- MeSH terms
- Adolescent, Adult, Analysis of Variance, Behavior, Blood Platelets, Child, Child Development Disorders, Pervasive, Child, Preschool, Female, Humans, Language Development, Male, Intellectual Disability, Netherlands, Serotonin, Linear Models, Case-Control Studies, Statistics, Nonparametric
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