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Increased serotonin axons (immunoreactive to 5-HT transporter) in postmortem brains from young autism donors
Abstract
Imaging studies of serotonin transporter binding or tryptophan retention in autistic patients suggest that the brain serotonin system is decreased. However, treatment with drugs which increase serotonin (5-HT) levels, specific serotonin reuptake inhibitors (SSRIs), commonly produce a worsening of the symptoms. In this study we examined 5-HT axons that were immunoreactive to a serotonin transporter (5-HTT) antibody in a number of postmortem brains from autistic patients and controls with no known diagnosis who ranged in age from 2 to 29 years. Fine, highly branched, and thick straight fibers were found in forebrain pathways (e.g. medial forebrain bundle, stria terminalis and ansa lenticularis). Many immunoreactive varicose fine fibers were seen in target areas (e.g. globus pallidus, amygdala and temporal cortex). Morphometric analysis of the stained axons at all ages studied indicated that the number of serotonin axons was increased in both pathways and terminal regions in cortex from autism donors. Our findings provide morphological evidence to warrant caution when using serotonin enhancing drugs (e.g. SSRIs and receptor agonist) to treat autistic children. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.
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“An increased number of 5-HT axons and terminals were reported in a variety of brain regions via immunocytochemical labeling of 5-HT transporter in post-mortem autism subjects aged 2–29 years old bringing into question the wide use of SSRIs as therapeutic agents [187].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [187]
Citations
Cites
Autism as a strongly genetic disorder: evidence from a British twin study
Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., & Rutter, M. (1995) · Psychological Medicine · doi:10.1017/s0033291700028099 · Cited by 2,461
Extensive Involvement of Autophagy in Alzheimer Disease: An Immuno-Electron Microscopy Study
Nixon, R. A., Wegiel, J., Kumar, A., Yu, W. H., Peterhoff, C., Cataldo, A., & Cuervo, A. M. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.2.113 · Cited by 1,588
Risperidone in Children with Autism and Serious Behavioral Problems
McCracken, J. T., McGough, J., Shah, B., Cronin, P., Hong, D., Aman, M. G., Arnold, L. E., Lindsay, R., Nash, P., Hollway, J., et al. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa013171 · Cited by 1,574
Aripiprazole, A Novel Atypical Antipsychotic Drug with a Unique and Robust Pharmacology
Shapiro, D. A., Renock, S. M., Arrington, E. G., Chiodo, L. A., Liu, L.-X., Sibley, D. R., Roth, B. L., & Mailman, R. B. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300203 · Cited by 982
Risk Factors for Autism: Perinatal Factors, Parental Psychiatric History, and Socioeconomic Status
Larsson, H. J., Eaton, W. W., Madsen, K. M., Vestergaard, M., Olesen, A. V., Agerbo, E., Schendel, D., Thorsen, P., & Mortensen, P. B. (2005) · American Journal of Epidemiology · doi:10.1093/aje/kwi123 · Cited by 727
Aripiprazole in the Treatment of Irritability in Children and Adolescents With Autistic Disorder
Owen, R., Sikich, L., Marcus, R. N., Corey-Lisle, P., Manos, G., McQuade, R. D., Carson, W. H., & Findling, R. L. (2009) · Pediatrics · doi:10.1542/peds.2008-3782 · Cited by 613
Binding of antipsychotic drugs to human brain receptors
Richelson, E., & Souder, T. (2000) · Life Sciences · doi:10.1016/s0024-3205(00)00911-5 · Cited by 608
Perinatal Factors and the Development of Autism
Glasson, E. J., Bower, C. I., Petterson, B., de Klerk, N. H., Chaney, G., & Hallmayer, J. F. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.6.618 · Cited by 542
King, B. H., Hollander, E., Sikich, L., McCracken, J. T., Scahill, L., Bregman, J. D., Donnelly, C. L., Anagnostou, E., Dukes, K., Sullivan, L., et al. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.30 · Cited by 482
Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD)
Williams, K., Brignell, A., Randall, M., Silove, N., & Hazell, P. (2013) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004677.pub3 · Cited by 415
Altered serotonin synthesis in the dentatothalamocortical pathway in autistic boys
Chugani, D. C., Muzik, O., Rothermel, R., Behen, M. E., Chakraborty, P. K., Mangner, T. J., Silva, E. A. D., & Chugani, H. T. (1997) · Annals of Neurology · doi:10.1002/ana.410420420 · Cited by 399
Timing of Prenatal Stressors and Autism
Beversdorf, D. Q., Manning, S. E., Hillier, A. J., Anderson, S. L., Nordgren, R. E., Walters, S., Nagaraja, H. N., Cooley, W. C., Gaelic, S. E., & Bauman, M. L. (2005) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-005-5037-8 · Cited by 371
Brain Serotonin and Dopamine Transporter Bindings in Adults With High-Functioning Autism
Nakamura, K., Sekine, Y., Ouchi, Y., Tsujii, M., Yoshikawa, E., Futatsubashi, M., Tsuchiya, K. J., Sugihara, G., Iwata, Y., Suzuki, K., et al. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.137 · Cited by 352
The HPA and immune axes in stress: the involvement of the serotonergic system
Leonard, B. E. (2005) · European Psychiatry · doi:10.1016/s0924-9338(05)80180-4 · Cited by 317
Autism Prevalence Following Prenatal Exposure to Hurricanes and Tropical Storms in Louisiana
Kinney, D. K., Miller, A. M., Crowley, D. J., Huang, E., & Gerber, E. (2008) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-007-0414-0 · Cited by 295
Azmitia, E. C., & Gannon, P. J. (1986) · PubMed · Cited by 290
Self-citationWhitaker‐Azmitia, P. M. (2004) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2004.07.022 · Cited by 277
Self-citationImaging the serotonin transporter during major depressive disorder and antidepressant treatment
Meyer, J. H. (2007) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0709 · Cited by 276
Veenema, A. H. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.03.003 · Cited by 275
Juul-Dam, N., Townsend, J., & Courchesne, E. (2001) · PEDIATRICS · doi:10.1542/peds.107.4.e63 · Cited by 232
Morrison, J. H., Foote, S. L., Molliver, M. E., Bloom, F. E., & Lidov, H. G. W. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.7.2401 · Cited by 211
Meijer, O. C., & de Kloet, E. R. (1998) · Critical Reviews in Neurobiology · doi:10.1615/critrevneurobiol.v12.i1-2.10 · Cited by 203
Prenatal and Perinatal Risk Factors for Autism in China
Zhang, X., Lv, C.-C., Tian, J., Miao, R.-J., Wei, X., Hertz‐Picciotto, I., & Qi, L. (2010) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-0992-0 · Cited by 191
Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system.
Azmitia, E. C., & Whitaker‐Azmitia, P. M. (1991) · PubMed · Cited by 184
Self-citationSelective Serotonin Reuptake Inhibitors in Autism
Kolevzon, A. L., Mathewson, K. A., & Hollander, E. (2006) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v67n0311 · Cited by 176
More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides
Boldrini, M., Underwood, M. D., Mann, J. J., & Arango, V. (2005) · Brain Research · doi:10.1016/j.brainres.2005.01.083 · Cited by 174
Serotonin and dopamine transporter binding in children with autism determined by SPECT
Makkonen, I., Riikonen, R., Kokki, H., Airaksinen, M. M., & Kuikka, J. T. (2008) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2008.03027.x · Cited by 169
Aripiprazole: A Novel Atypical Antipsychotic Drug With a Uniquely Robust Pharmacology
Davies, M. A., Sheffler, D. J., & Roth, B. L. (2004) · CNS Drug Reviews · doi:10.1111/j.1527-3458.2004.tb00030.x · Cited by 156
Variable cortisol circadian rhythms in children with autism and anticipatory stress
Corbett, B. A., Mendoza, S. P., Wegelin, J. A., Carmean, V., & Levine, S. D. (2008) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0823 · Cited by 149
Correia, C., Coutinho, A. M., Sequeira, A. F., Sousa, I., Venda, L. L., Almeida, J. P., Abreu, R., Lobo, C., Miguel, T. S., Conroy, J., et al. (2010) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2010.00627.x · Cited by 147
Whitaker‐Azmitia, P. M., Lauder, J. M., Shemer, A., & Azmitia, E. C. (1987) · Developmental Brain Research · doi:10.1016/0165-3806(87)90161-1 · Cited by 146
Self-citationCortisol: The Culprit Prenatal Stress Variable
Field, T. M., & Diego, M. (2008) · International Journal of Neuroscience · doi:10.1080/00207450701820944 · Cited by 145
Mitchell, J. B., Iny, L. J., & Meaney, M. J. (1990) · Developmental Brain Research · doi:10.1016/0165-3806(90)90204-c · Cited by 139
Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD)
Williams, K., Wheeler, D. M., Silove, N., & Hazell, P. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004677.pub2 · Cited by 131
Egliston, K.-A., McMahon, C. A., & Austin, M. (2006) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2006.10.003 · Cited by 130
BDNF‐Akt‐Bcl2 antiapoptotic signaling pathway is compromised in the brain of autistic subjects
Sheikh, A. M., Malik, M. N., Wen, G. Y., Chauhan, A., Chauhan, V. P. S., Gong, C., Liu, F., Brown, W. T., & Li, X. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22416 · Cited by 122
Fluoxetine in Treatment of Adolescent Patients with Autism: A Longitudinal Open Trial
Fatemi, S. H., Realmuto, G. M., Khan, L., & THURAS, P. D. (1998) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1026008602540 · Cited by 110
Brodkin, E. S., McDougle, C. J., NAYLOR, S. T., Cohen, D. J., & Price, L. H. (1997) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.1997.7.109 · Cited by 102
Austin, M. C., Whitehead, R. E., Edgar, C. L., Janosky, J. E., & Lewis, D. A. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00289-0 · Cited by 99
Lower Cortisol and Higher ACTH Levels in Individuals with Autism
Ćurin, J. M., Terzić, J., Petković, Z. B., Zekan, L., Marinovic‐Terzić, I., & Šušnjara, I. M. (2003) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1025019030121 · Cited by 92
In vivo Conversion of3H-L-Tryptophan into3H-Serotonin in Brain Areas of Adrenalectomized Rats
Azmitia, E. C., Algeri, S., & Costa, E. (1970) · Science · doi:10.1126/science.169.3941.201 · Cited by 89
Self-citationIncrease of tryptophan hydroxylase enzyme protein by dexamethasone in adrenalectomized rat midbrain
Azmitia, E. C., Liao, B., & Chen, Y. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-12-05041.1993 · Cited by 85
Self-citationThe Serotonergic System: Its Role in Pathogenesis and Early Developmental Treatment of Autism
Zafeiriou, D., Ververi, A., & Vargiami, E. (2009) · Current Neuropharmacology · doi:10.2174/157015909788848848 · Cited by 85
Prenatal and Birth Complications in Autism
Brimacombe, M. B., Ming, X., & Lamendola, M. (2006) · Maternal and Child Health Journal · doi:10.1007/s10995-006-0142-7 · Cited by 76
Dystrophic serotonergic axons in neurodegenerative diseases
Azmitia, E. C., & Nixon, R. A. (2008) · Brain Research · doi:10.1016/j.brainres.2008.03.060 · Cited by 63
Self-citationMehlinger, R., Scheftner, W. A., & Poznanski, E. O. (1990) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199011000-00032 · Cited by 50
Autism and mental retardation of young children in China.
Zhang, X., & Ji, C.-Y. (2005) · PubMed · Cited by 47
Hanania, T., Hillman, G. R., & Johnson, K. M. (1999) · Synapse · doi:10.1002/(sici)1098-2396(19990301)31:3 · Cited by 46
Self-citationGenes within the serotonergic system are differentially expressed in human brain
Sugden, K., Tichopád, A., Khan, N., Craig, I., & D’Souza, U. M. (2009) · BMC Neuroscience · doi:10.1186/1471-2202-10-50 · Cited by 45
Antagonist‐induced increase in 5‐HT1A‐receptor expression in adult rat hippocampus and cortex
Abbas, S. Y., Nogueira, M. I., & Azmitia, E. C. (2007) · Synapse · doi:10.1002/syn.20399 · Cited by 26
Self-citationL’autisme : surestimation des origines génétiques
Chamak, B. (2010) · médecine/sciences · doi:10.1051/medsci/2010266-7659 · Cited by 24
Falkenberg, V. R., & Rajeevan, M. S. (2010) · Journal of Molecular Neuroscience · doi:10.1007/s12031-009-9320-6 · Cited by 22
Price (1999) · doi:10.1002/1531-8249(199903)45:3
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Metadata
- Authors
- Azmitia, E. C., Singh, J. S., & Whitaker-Azmitia, P. M.
- Affiliations
- New York University (US)
- Corresponding author
- Azmitia, Efrain C.
- ORCID
- Azmitia, Efrain C.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 60
- Issue
- 7-8
- Pages
- 1347-1354
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W1999133104
- Cited by
- 107
- References
- 53
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 10 · 2019: 6 · 2018: 8 · 2017: 6 · 2016: 8 · 2015: 8 · 2014: 11 · 2013: 13 · 2012: 9
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- 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
- autism spectrum disorder, serotonin, serotonin transporter, serotonergic system, serotonin reuptake inhibitors, SSRI adverse effects, autism pharmacotherapy, postmortem brain, axon morphology, medial forebrain bundle, stria terminalis, ansa lenticularis, globus pallidus, amygdala, temporal cortex
- MeSH terms
- Adolescent, Adult, Autistic Disorder, Autopsy, Axons, Brain, Child, Child, Preschool, Female, Globus Pallidus, Humans, Male, Medial Forebrain Bundle, Nerve Fibers, Serotonin, Temporal Lobe, Prosencephalon, Subthalamus, Serotonin Plasma Membrane Transport Proteins, Young Adult
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