Altered Global mRNA Expressions of Pain and Aggression Related Genes in the Blood of Children with Autism Spectrum Disorders
Abstract
Autism spectrum disorder (ASD) is characterized by repetitive stereotypic behaviors, restricted interests, social withdrawal, and communication deficits. Aggression and insensitivity to pain are largely unexplained in these cases. We analyzed nine mRNA expressions of the candidate genes related to aggression and insensitivity to pain in the peripheral blood of patients with ASD. Whole blood samples were obtained from 40 autistic patients (33 boys, 7 girls) and 50 age- and sex-matched controls (37 boys and 13 girls) to isolate RNA. Gene expression was assessed by quantitative Real-Time PCR (qRT-PCR) in the Erciyes University Genome and Stem Cell Center (GENKOK). All of the gene expressions except CRHR1 and SLC6A4 were found to be statistically different between the ASD patients and controls. Gene expression also differed according to gender. Alterations in the mRNA expression patterns of the HTR1E, OPRL1, OPRM1, TACR1, PRKG1, SCN9A and DRD4 genes provide further evidence for a relevant effect of the respective candidate genes on the pathophysiology of ASD. Future studies may determine the sensitivity of these candidate markers in larger samples including further neuropsychiatric diagnosis.
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Other serotonin receptor encoding gene polymorphisms, including 5-hydroxytryptamine receptor 1B, 1E and 2C, demonstrated significant effects on childhood aggression.
“Other serotonin receptor encoding gene polymorphisms, including 5-hydroxytryptamine receptor 1B [93, 94], 1E [95] and 2 C [96] further demonstrated significant effects on childhood aggression”
From Genetics of child aggression, a systematic review (2024) · cites this paper as [95]
Cites
The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments
Bustin, S. A., Benes, V., Garson, J. A., Hellemans, J., Huggett, J., Kubista, M., Mueller, R., Nolan, T., Pfaffl, M. W., Shipley, G. L., et al. (2009) · Clinical Chemistry · doi:10.1373/clinchem.2008.112797 · Cited by 16,303 · see citing works
Straightforward Statistics for the Behavioral Sciences.
Wuensch, K. L., & Evans, J. D. (1996) · Journal of the American Statistical Association · doi:10.2307/2291607 · Cited by 2,417 · see citing works
Candidate gene studies of ADHD: a meta-analytic review
Gizer, I. R., Ficks, C., & Waldman, I. D. (2009) · Human Genetics · doi:10.1007/s00439-009-0694-x · Cited by 1,020 · see citing works
Steinhoff, M. S., von Mentzer, B., Geppetti, P., Pothoulakis, C., & Bunnett, N. W. (2014) · Physiological Reviews · doi:10.1152/physrev.00031.2013 · Cited by 628 · see citing works
Lecavalier, L. (2006) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-006-0147-5 · Cited by 569 · see citing works
Aggression in Children and Adolescents with ASD: Prevalence and Risk Factors
Kanne, S. M., & Mazurek, M. O. (2011) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-1118-4 · Cited by 533 · see citing works
Atypical behaviors in children with autism and children with a history of language impairment
Dominick, K. C., Davis, N. O., Lainhart, J. E., Tager-Flusberg, H. B., & Folstein, S. E. (2006) · Research in Developmental Disabilities · doi:10.1016/j.ridd.2006.02.003 · Cited by 496 · see citing works
Totsika, V., Hastings, R. P., Emerson, E., Lancaster, G., & Berridge, D. M. (2010) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2010.02295.x · Cited by 409 · see citing works
Holden, B., & Gitlesen, J. P. (2005) · Research in Developmental Disabilities · doi:10.1016/j.ridd.2005.06.001 · Cited by 367 · see citing works
Physical aggression in children and adolescents with autism spectrum disorders
Mazurek, M. O., Kanne, S. M., & Wodka, E. L. (2012) · Research in Autism · doi:10.1016/j.rasd.2012.11.004 · Cited by 292 · see citing works
Oades, R. D., Lasky-Su, J., Christiansen, H., Faraone, S. V., Sonuga-Barke, E. J. S., Banaschewski, T., Chen, W., Anney, R. J. L., Buitelaar, J. K., Ebstein, R. P., et al. (2008) · Behavioral and Brain Functions · doi:10.1186/1744-9081-4-48 · Cited by 200 · see citing works
Smith, K. R. M., & Matson, J. L. (2010) · Research in Developmental Disabilities · doi:10.1016/j.ridd.2010.04.003 · Cited by 181 · see citing works
Progress in the genetics of autism spectrum disorder
Woodbury‐Smith, M., & Scherer, S. W. (2018) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.13717 · Cited by 179 · see citing works
Coutinho, A. M., Sousa, I., Martins, M., Correia, C., Morgadinho, T., Bento, C., Marques, C., Ataíde, A., Miguel, T. S., Moore, J. H., et al. (2007) · Human Genetics · doi:10.1007/s00439-006-0301-3 · Cited by 153 · see citing works
Genetics and epigenetics of autism: A Review
Waye, M. M. Y., & Cheng, H. Y. (2017) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12606 · Cited by 153 · see citing works
Pain Reactivity and Plasma β-Endorphin in Children and Adolescents with Autistic Disorder
Tordjman, S., Anderson, G. M., Botbol, M., Brailly-Tabard, S., Pérez-Díaz, F., Graignic, R., Carlier, M., Schmit, G., Rolland, A.-C., Bonnot, O., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005289 · Cited by 152 · see citing works
Samaco, R. C., Mandel‐Brehm, C., McGraw, C. M., Shaw, C. A., McGill, B. E., & Zoghbi, H. Y. (2012) · Nature Genetics · doi:10.1038/ng.1066 · Cited by 146 · see citing works
Ressler, K. J., Bradley, B., Mercer, K. B., Deveau, T. C., Smith, A. K., Gillespie, C. F., Nemeroff, C. B., Cubells, J. F., & Binder, E. B. (2010) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31052 · Cited by 140 · see citing works
Pain Sensitivity and Observer Perception of Pain in Individuals with Autistic Spectrum Disorder
Allely, C. S. (2013) · The Scientific World Journal · doi:10.1155/2013/916178 · Cited by 135 · see citing works
Acute pain experience in individuals with autism spectrum disorders: A review
Moore, D. (2014) · Autism · doi:10.1177/1362361314527839 · Cited by 131 · see citing works
Autistic-Like Syndrome in Mu Opioid Receptor Null Mice is Relieved by Facilitated mGluR4 Activity
Becker, J. A. J., Clesse, D., Spiegelhalter, C., Schwab, Y., Merrer, J. L., & Kieffer, B. L. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.59 · Cited by 123 · see citing works
Geier, D. A., Kern, J. K., & Geier, M. R. (2013) · Journal of Mental Health Research in Intellectual Disabilities · doi:10.1080/19315864.2012.681340 · Cited by 121 · see citing works
Autism and serotonin transporter gene polymorphisms: A systematic review and meta‐analysis
Huang, C. H., & Santangelo, S. L. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30720 · Cited by 120 · see citing works
The neurodevelopmental effects of serotonin: A behavioural perspective
Kepser, L.-J., & Homberg, J. R. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.05.022 · Cited by 103 · see citing works
Zhao, Z., Webb, B. T., Jia, P., Bigdeli, T. B., Maher, B. S., van den Oord, E. J. C. G., Bergen, S. E., AMDUR, R. L., O’Neill, F. A., Walsh, D., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067776 · Cited by 103 · see citing works
Aggressive challenging behaviour and intellectual disability
Benson, B. A., & Brooks, W. T. (2008) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e328306a090 · Cited by 90 · see citing works
Autobiographical Accounts of Sensing in Asperger Syndrome and High-Functioning Autism
Elwin, M., Ek, L., Schröder, A., & Kjellin, L. (2012) · Archives of Psychiatric Nursing · doi:10.1016/j.apnu.2011.10.003 · Cited by 84 · see citing works
Furniss, F., & Biswas, A. B. (2012) · Journal of Intellectual Disability Research · doi:10.1111/j.1365-2788.2012.01534.x · Cited by 74 · see citing works
Suicide and serotonin: Study of variation at seven serotonin receptor genes in suicide completers
Turecki, G., Sequeira, A., Gingras, Y., Séguin, M., LESAGE, A. D., Tousignant, M., Chawky, N., Vanier, C., Lipp, O., Benkelfat, C., et al. (2002) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.10006 · Cited by 58 · see citing works
Gadow, K. D., DeVincent, C. J., Olvet, D. M., Pisarevskaya, V., & Hatchwell, E. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07382.x · Cited by 56 · see citing works
Farmer, C., & Aman, M. G. (2009) · Research in Developmental Disabilities · doi:10.1016/j.ridd.2009.09.014 · Cited by 51 · see citing works
Miceli, S., Negwer, M., van Eijs, F., Kalkhoven, C., van Lierop, I., Homberg, J., & Schubert, D. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00088 · Cited by 49 · see citing works
The involvement of substance P in the induction of aggressive behavior
Katsouni, E., Sakkas, P. N., Ζάρρος, Α., et al. (2009) · Peptides · doi:10.1016/j.peptides.2009.05.001 · Cited by 48 · see citing works
Rose, S., Wynne, R. A., Frye, R. E., Melnyk, S., & James, S. J. (2015) · Journal of Toxicology · doi:10.1155/2015/573701 · Cited by 46 · see citing works
MacLean, W. E., Tervo, R. C., Hoch, J. D., Tervo, M., & Symons, F. J. (2010) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2010.05.052 · Cited by 43 · see citing works
Serotonin transporter and integrin beta 3 genes interact to modulate serotonin uptake in mouse brain
Whyte, A. J., Jessen, T. N., Varney, S., & Carneiro, A. M. D. (2013) · Neurochemistry International · doi:10.1016/j.neuint.2013.09.014 · Cited by 40 · see citing works
Koishi, S., Yamamoto, K., Matsumoto, H., et al. (2006) · Brain and Development · doi:10.1016/j.braindev.2005.09.003 · Cited by 35 · see citing works
Longo, D., Schüler‐Faccini, L., Brandalize, A. P. C., Riesgo, R. D. S., & Bau, C. H. D. (2009) · Brain Research · doi:10.1016/j.brainres.2009.02.072 · Cited by 31 · see citing works
Taurines, R., Grünblatt, E., Schecklmann, M., Schwenck, C., Albantakis, L., Reefschläger, L., Walitza, S., Renner, T., Gerlach, M., Thome, J., et al. (2011) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2011.600297 · Cited by 31 · see citing works
Emanuele, E., Boso, M., Cassola, F., Broglia, D., Bonoldi, I., Mancini, L., Marini, M., & Politi, P. (2010) · PubMed · Cited by 30 · see citing works
An atypical case of SCN9A mutation presenting with global motor delay and a severe pain disorder
Meijer, I. A., Vanasse, M., Nizard, S., et al. (2013) · Muscle & Nerve · doi:10.1002/mus.23968 · Cited by 28 · see citing works
The roles of CC2D1A and HTR1A gene expressions in autism spectrum disorders
Şener, E. F., Uytun, M. Ç., Bayram, K. K., Zararsız, G., Öztop, D. B., Canatan, H., & Özkul, Y. (2016) · Metabolic Brain Disease · doi:10.1007/s11011-016-9795-0 · Cited by 28 · see citing works
Self-citationAutoextraction in a child with autistic spectrum disorder
Ross-Russell, M., & Sloan, P. (2005) · BDJ · doi:10.1038/sj.bdj.4812250 · Cited by 27 · see citing works
Reduction of Pain Sensitivity after Somatosensory Therapy in Children with Autism Spectrum Disorders
Riquelme, I., Hatem, S. M., & Montoya, P. (2018) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-017-0390-6 · Cited by 26 · see citing works
What can HPA axis-linked genes tell us about anxiety disorders in adolescents?
Bortoluzzi, A., Blaya, C., da Rosa, E. D., Paim, M. F., Rosa, V. D. O., Leistner‐Segal, S., & Manfro, G. G. (2015) · Trends in Psychiatry and Psychotherapy · doi:10.1590/2237-6089-2015-0035 · Cited by 19 · see citing works
Spratt, E. G., Granholm, A., Carpenter, L. A., Boger, H. A., Papa, C. E., Logan, S., Chaudhary, H., Boatwright, S.-W., & Brady, K. T. (2014) · International Neuropsychiatric Disease Journal · doi:10.9734/indj/2015/12118 · Cited by 18 · see citing works
Mieres, A. C., Smallwood, V., & Nicholson, S. K. (2011) · Pediatric Physical Therapy · doi:10.1097/pep.0b013e318218f35f · Cited by 16 · see citing works
Shoval, G., Bar-Shira, O., Zalsman, G., Mann, J. J., & Chechik, G. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.02.009 · Cited by 15 · see citing works
Association of the FGA and SLC6A4 Genes with Autistic Spectrum Disorder in a Korean Population
Ro, M., Won, S., Kang, H., Kim, S., Lee, S. K., Nam, M., Bang, H. J., Yang, J. W., Choi, K.-S., Kim, S. K., et al. (2013) · Neuropsychobiology · doi:10.1159/000355299 · Cited by 5 · see citing works
Valencia, A., Páez, A. L., Sampedro, M. E., Ávila, C., Cardona, J. C., Mesa, C., Galvis, L. M. R., Carrizosa, J., Camargo, M., Ruiz‐Linares, A., et al. (2012) · Biomédica · doi:10.7705/biomedica.v32i4.593 · Cited by 4 · see citing works
Computational Structural Biology of Opioid Receptors
Provasi, D. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1708-2_2 · Cited by 4 · see citing works
Şener, E. F., Şahin, M. Ç., Taheri, S., Bayram, K. K., Maraşlı, M. K., Zararsız, G., Canpolat, M., Şahın, N., & Öztop, D. B. (2017) · Psychiatry and Clinical Psychopharmacology · doi:10.1080/24750573.2017.1293248 · Cited by 4 · see citing works
Self-citationŞener, E. F., Sahin, M., Taheri, S., et al. (2016) · Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology · doi:10.5455/bcp.20161016114319 · Cited by 2 · see citing works
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Genetics of child aggression, a systematic review
Koyama, E., Kant, T., Takata, A., Kennedy, J. L., & Zai, C. C. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02870-7 · Cited by 33 · see citing works
- Authors
- Sener, E. F., Taheri, S., Sahin, M. C., Bayramov, K. K., Marasli, M. K., Zararsiz, G., Mehmetbeyoglu, E., Oztop, D. B., Canpolat, M., Canatan, H., & Ozkul, Y.
- Affiliations
- Erciyes University (TR)
- Venue
- Journal of Molecular Neuroscience
- Published
- 2018-12-05
- Volume
- 67
- Issue
- 1
- Pages
- 89-96
- ISSN
- 0895-8696 (ISSN-L)
- 1559-1166
- OpenAlex
- W2903124118
- Cited by
- 23
- References
- 53
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 2 · 2020: 6 · 2019: 3
- FWCI
- 1.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Molecular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- AYBU AVESIS (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- The Scientific & Technological Research Council (114S742)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- autism spectrum disorder, aggression, pain insensitivity, candidate genes, mRNA expression, peripheral blood, children, sex differences, OPRM1, neurokinin-1 receptor, PRKG1, SCN9A, DRD4, CRHR1, serotonin transporter
- MeSH terms
- Autism Spectrum Disorder, Aggression, Child, Preschool, Female, Humans, Male, Receptors, Opioid, RNA, Messenger, Biomarkers, Receptor, Serotonin, 5-HT1A, Receptors, Dopamine D4, Pain Perception, NAV1.7 Voltage-Gated Sodium Channel, Cyclic GMP-Dependent Protein Kinase Type I
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