Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-15T09:21:41.476Z Has data issue: false hasContentIssue false
  • English
  • Français

Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in autism research: literature review

Published online by Cambridge University Press:  05 April 2021

B. Kowalewska ,
W. Drozdz  and
L. Kowalewski
B. Kowalewska*
Affiliation:
Department of Psychiatry, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Torun, Poland Department of Psychiatry, Beaumont Hospital, Royal College of Surgeons, Dublin, Ireland
W. Drozdz
Affiliation:
Department of Psychiatry, Collegium Medicum Bydgoszcz, Nicolaus Copernicus University, Torun, Poland
L. Kowalewski
Affiliation:
Department of Psychiatry, Cavan-Monaghan Community Mental Health Services, Cavan, Ireland
*
*Address for correspondence: Dr B. Kowalewska, Royal College of Surgeons, Smurfit Building, Beaumont Hospital, Hospital Road, Beaumont, Dublin, Ireland. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

Autism spectrum disorder (ASD) remains a behaviourally defined condition. Its molecular basis is unknown; however, its prevalence has been increasing significantly. There have been several abnormalities in neurotransmitter systems reported in ASD. In our review, we described studies involving positron emission tomography (PET) and single-photon emission computed tomography (SPECT) that can provide useful and corroborative data.

Method:

We conducted a literature review by comprehensive database searching on EMBASE, Scopus, PubMed, and PsychINFO looking for articles published since January 2009. Thirty-one studies were carefully selected – 22 PET studies and 9 SPECT studies – and reviewed by 2 independent researchers. References of the articles were also cross-checked.

Results:

Results of the studies, which mainly involve small groups of participants, are frequently inconclusive and often controversial due to the nature of ASD and its wide spectrum. Studies are conducted under different conditions and with poor control for confounding factors which creates difficulties in comparing the data.

Conclusions:

There is ongoing need to improve methodology of the studies involving molecular imaging in ASD. Lack of consistent findings causes difficulties in evaluation, diagnosis, and treatment of the condition.

Keywords

Autism spectrum disordermolecular imagingpositron emission tomographysingle-photon emission computed tomography
Type
Review Article
Information
Irish Journal of Psychological Medicine , Volume 39 , Issue 3: Themed Issue: Autism Spectrum Disorders , September 2022 , pp. 272 - 286
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The College of Psychiatrists of Ireland

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ameis, SH, Catani, M (2015). Altered white matter connectivity as a neural substrate for social impairment in autism spectrum disorder. Cortex 62, 158–181.CrossRefGoogle ScholarPubMed
American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (DSM-5®), 5th edn., Arlington, VA.Google Scholar
Asperger, H (1938). Das psychisch abnorme kind. Winer Klinische Wochenschrift 49, 1–12.Google Scholar
Baio, J, Wiggins, L, Christensen, DL, Maenner, MJ, Daniels, J, Warren, Z, et al. (2018). Prevalence of autism spectrum disorder among children aged 8 years — autism and developmental disabilities monitoring network, 11 sites, United States, 2014. MMWR Surveillance Summaries 67, 1–23.CrossRefGoogle ScholarPubMed
Bernier, R, Mao, A, Yen, J (2010). Psychopathology, families, and culture: autism. Child and Adolescent Psychiatric Clinics of North America 19, 855–867.CrossRefGoogle ScholarPubMed
Beversdorf, DQ, Nordgren, RE, Bonab, AA, Fischman, AJ, Weise, ST, Dougherty, DD, Felopulos, GJ, Zhou, FC, Bauman, ML (2012). 5-HT2 receptor distribution shown by (18F) setoperone PET in high-functioning autistic adults. Journal of Neuropsychiatry and Clinical Neurosciences 24, 191–197.CrossRefGoogle ScholarPubMed
Brieber, S, Neufang, S, Bruning, N, Kamp-Becker, I, Remschmidt, H, Herpertz-Dahlmann, B, Fink, GR, Konrad, K (2007). Structural brain abnormalities in adolescents with autism spectrum disorder and patients with attention deficit/hyperactivity disorder. Journal of Child Psychology and Psychiatry 48, 1251–1258.CrossRefGoogle ScholarPubMed
Burroni, L, Orsi, A, Monti, L, Hayek, Y, Rocchi, R, Vattimo, AG (2008). Regional cerebral blood flow in childhood autism: a SPET study with SPM evaluation. Nuclear Medicine Communications 29, 150–156.CrossRefGoogle ScholarPubMed
Chandana, SR, Behen, ME, Juhász, C, Muzik, O, Rothermel, RD, Mangner, TJ, Chakraborty, PK, Chugani, HT, Chugani, DC (2005). Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism. International Journal of Developmental Neuroscience 23, 171–182.CrossRefGoogle ScholarPubMed
Chivate, R, Thakrar, P, Narang, J, Kumar, S, Verma, M, Patkar, D, Chivate, S (2016). PET/CT in autism, A diagnostic tool?. International Journal of Health Sciences and Research 6, 99–106.Google Scholar
Cohen, J (1960). A coefficient of agreement for nominal scales. Educational and Psychological Measurement 20, 37.CrossRefGoogle Scholar
Degirmenci, B, Miral, S, Capa Kaya, G, İyilikçi, L, Arslan, G, Baykara, A, Evren, I, Durak, H (2008). Technetium-99m HMPAO brain SPECT in autistic children and their families. Psychiatry Research 162, 236–243.CrossRefGoogle ScholarPubMed
Dilber, C, Çalışkan, M, Sönmezoğlu, K, Nişli, S, Motavalli Mukaddes, N, Tatli, B, Aydinli, N, Ekici, B, Özmen, M (2013). Positron emission tomography findings in children with infantile spasms and autism. Journal of Clinical Neuroscience 20, 373–376.CrossRefGoogle ScholarPubMed
Duchesnay, E, Cachia, A, Boddaert, N, Chabane, N, Mangin, J-F, Martinot, J-L, Brunelle, F, Zilbovicius, M (2011). Feature selection and classification of imbalanced datasets. Application to PET images of children with autistic spectrum disorders. NeuroImage 57, 1003–1014.CrossRefGoogle ScholarPubMed
Emond, A, Emmett, P, Steer, C, Golding, J (2010). Feeding symptoms, dietary patterns, and growth in young children with autism spectrum disorders. Pediatrics 126, e337–e342.CrossRefGoogle ScholarPubMed
EU-AIMS (2020). European Autism Interventions - A Multicentre Study for Developing New Medications (https://www.eu-aims.eu). June, 2020.Google Scholar
Fatemi, SH, Wong, DF, Brašić, JR, Kuwabara, H, Mathur, A, Folsom, TD, Jacob, S, Realmuto, GM, Pardo, JV, Lee, S (2018). Metabotropic glutamate receptor 5 tracer (18F)-FPEB displays increased binding potential in postcentral gyrus and cerebellum of male individuals with autism: a pilot PET study. Cerebellum and Ataxias 5, 3.CrossRefGoogle ScholarPubMed
Fernell, E, Watanabe, Y, Adolfsson, I, Tani, Y, Bergstrom, M, Hartvig, P, Lilja, A, von Knooring, AL, Gillberg, C, Långström, B (1997). Possible effects of tetrahydrobiopterin treatment in six children with autism - clinical and positron emission tomography data: a pilot study. Developmental Medicine and Child Neurology 39, 313–318.CrossRefGoogle ScholarPubMed
Girgis, RR, Slifstein, M, Xu, X, Frankle, WG, Anagnostou, E, Wasserman, S, Pepa, L, Kolevzon, A, Abi-Dargham, A, Laruelle, M, Hollander, E (2011). The 5-HT 2A receptor and serotonin transporter in Asperger’s disorder: a PET study with (11C)MDL 100907 and (11C)DASB. Psychiatry Research - Neuroimaging 194, 230–234.CrossRefGoogle Scholar
Goldberg, J, Anderson, GM, Zwaigenbaum, L, Hall, GBC, Nahmias, C, Thompson, A, Szatmari, P (2009). Cortical serotonin type-2 receptor density in parents of children with autism spectrum disorders. Journal of Autism and Developmental Disorders 39, 97–104.CrossRefGoogle ScholarPubMed
Grinker, R (2007). Unstrange minds. Basic Books, New York.Google Scholar
Grossman, AW, Aldridge, GM, Weiler, IJ, Greenough, WT (2006). Local protein synthesis and spine morphogenesis: fragile X syndrome and beyond. The Journal of neuroscience: the official journal of the Society for Neuroscience 26, 7151–7155.CrossRefGoogle ScholarPubMed
Gupta, SK, Ratnam, BV (2008). Cerebral perfusion abnormalities in children with autism and mental retardation: a segmental quantitative SPECT study. Indian Pediatrics 46, 161–164.Google Scholar
Hamilton, PJ, Campbell, NG, Sharma, S, Erreger, K, Herbor, Hansen F, Saunders, C, Belovich, AN, NIH ARRA Autism Sequencing Consortium, Sahai, MA, Cook, EH, Gether, U, McHaourab, HS, Matthies, HJ, Sutcliffe, JS, Galli, A (2013). De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder. Molecular Psychiatry 18, 1315–1323.CrossRefGoogle Scholar
Haznedar, M, Buchsbaum, MS, Hazlett, EA, LiCalzi, EM, Cartwright, C, Hollander, E (2006). Volumetric analysis and three-dimensional glucose metabolic mapping of the striatum and thalamus in patients with autism spectrum disorders. American Journal of Psychiatry 163, 1252–1263.CrossRefGoogle ScholarPubMed
Hirosawa, T, Kikuchi, M, Ouchi, Y, Takahashi, T, Yoshimura, Y, Kosaka, H, Furutani, N, Hiraishi, H, Fukai, M, Yokokura, M, Yoshikawa, E, Bunai, T, Minabe, Y (2017). A pilot study of serotonergic modulation after long-term administration of oxytocin in autism spectrum disorder. Autism Research 10, 821–828.CrossRefGoogle ScholarPubMed
, E, Soorya, L, Chaplin, W, Anagnostou, E, Taylor BP, Ferretti CJ, Wasserman S, Swanson E,Je, BO (2012). A double-blind placebo-controlled trail of fluoxetine for repetitive behaviors and global severity in adult autism spectrum disorders. American Journal of Psychiatry 169, 292–299.CrossRefGoogle Scholar
Hong, SJ, de Wael, RV, Bethlehem, RAI, Lariviere, S, Paquola, C, Valk, SL, Milham, MP, Di, Martino A, Margulies, DS, Smallwood, J, Bernhardt, BC (2019). Atypical functional connectome hierarchy in autism. Nature Communications 10, 1022.CrossRefGoogle ScholarPubMed
Horder, J, Andersson, M, Mendez, MA, Singh, N, … Borg, J (2018). GABA receptor availability is not altered in adults with autism spectrum disorder or in mouse models. Science Translational Medicine 10, eaam8434.CrossRefGoogle Scholar
Kadwa, RA, Sahu, JK, Singhi, P, Malhi, P, Mittal, BR (2019). Prevalence and characteristics of sensory processing abnormalities and its correlation with FDG-PET Findings in children with autism. The Indian Journal of Pediatrics 86, 1036–1042.CrossRefGoogle ScholarPubMed
Kanner, L (1943). Autistic disturbances of affective contact. Nervous Child 2, 217–250.Google Scholar
Koyama, M, Kawashima, R, Ito, H, Ono, S, Sato, K, Goto, R, Kinomura, S, Yoshioka, S, Sato, T, Fukuda, H (1997). SPECT imaging of normal subjects with technetium-99m-HMPAO and technetium-99m-ECD. Journal of Nuclear Medicine 38, 587–592.Google ScholarPubMed
Kumar, BN, Malhotra, S, Bhattacharya, A, Grover, S, Batra, YK (2017). Regional Cerebral Glucose Metabolism and its Association with Phenotype and Cognitive Functioning in Patients with Autism. Indian Journal of Psychological Medicine 39, 262–270.CrossRefGoogle Scholar
Lammertsma, AA (2001). PET/SPECT: functional imaging beyond flow. Vision Research 41, 1277–1281.CrossRefGoogle ScholarPubMed
Lavelle, TA, Weinstein, MC, Newhouse, JP, Munir, K, Kuhlthau, KA, Prosser, LA (2014). Economic burden of childhood autism spectrum disorders. Pediatrics 133, e520–e529.CrossRefGoogle ScholarPubMed
Lefevre, A, Mottolese, R, Redouté, J, Costes, N, Le Bars, D, Geoffray, MM, Leboyer, M, Sirigu, A (2018). Oxytocin fails to recruit serotonergic neurotransmission in the autistic brain. Cerebral Cortex 28, 4169–4178.CrossRefGoogle ScholarPubMed
Lefevre, A, Sirigu, A (2016). The two fold role of oxytocin in social developmental disorders: a cause and a remedy?. Neuroscience and Biobehavioral Reviews 63, 168–176.CrossRefGoogle ScholarPubMed
Loomes, R, Hull, L, Mandy, WPL (2017). What is the male-to-female ratio in autism spectrum disorder? a systematic review and meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry 56, 466–474.CrossRefGoogle ScholarPubMed
Lucchina, L, Depino, AM (2014). Altered peripheral and central inflammatory responses in a mouse model of autism. Autism Research 7, 273–289.CrossRefGoogle Scholar
Maenner, MJ, Shaw, KA, Baio, J, Washington, A, Patrick, M, DiRienzo, M et al. (2020). Prevalence of autism spectrum disorder among children aged 8 years — autism and developmental disabilities monitoring network, 11 sites, United States, 2016. MMWR Surveillance Summaries 69, 1–12.CrossRefGoogle ScholarPubMed
Makkonen, I, Riikonen, R, Kokki, H, Airaksinen, MM, Kuikka, JT (2008). Serotonin and dopamine transporter binding in children with autism determined by SPECT. Developmental Medicine and Child Neurology 50, 593–597.CrossRefGoogle ScholarPubMed
Mannion, A, Leader, G (2013). Comorbidity in autism spectrum disorder: a literature review. Research in Autism Spectrum Disorders 7, 1595–1616.CrossRefGoogle Scholar
Masi, A, Demayo, MM, Glozier, N, Guastella, AJ (2017). An overview of autism spectrum disorder, heterogeneity and treatment options. Neuroscience Bulletin 33, 183–193.CrossRefGoogle ScholarPubMed
Matson, JL, Sipes, M, Fodstad, JC, Fitzgerald, ME (2011). Issues in the management of challenging behaviours of adults with autism spectrum disorder. CNS Drugs 25, 597–606.CrossRefGoogle ScholarPubMed
Mendez, MA, Horder, J, Myers, J, Coghlan, S, Stokes, P, Erritzoe, D, Howes, O, Lingford-Hughes, A, Murphy, D, Nutt, D (2013). ‘The brain GABA-benzodiazepine receptor alpha-5 subtype in autism spectrum disorder: A pilot [11C]Ro15–4513 positron emission tomography study. Neuropharmacology 68, 195–201.CrossRefGoogle ScholarPubMed
Mitelman, SA, Bralet, MC, Mehmet Haznedar, M, Hollander, E, Shihabuddin, L, Hazlett, EA, Buchsbaum, MS (2018). ‘Positron emission tomography assessment of cerebral glucose metabolic rates in autism spectrum disorder and schizophrenia. Brain Imaging and Behavior 12, 532–546.CrossRefGoogle ScholarPubMed
Mori, T, Mori, K, Fujii, E, Toda, Y, Miyazaki, M, Harada, M, Hashimoto, T, Kagami, S (2012). ‘Evaluation of the GABAergic nervous system in autistic brain: 123I-iomazenil SPECT study. Brain and Development 34, 648–654.CrossRefGoogle ScholarPubMed
Murphy, DG, Daly, E, Schmitz, N, Toal, F, Murphy, K, Curran, S, Erlandsson, K, Eersels, J, Kerwin, R, Ell, P, Travis, M (2006). Cortical serotonin 5-HT 2A receptor binding and social communication in adults with Asperger’s syndrome: an in vivo SPECT study. American Journal of Psychiatry 163, 934–936.CrossRefGoogle Scholar
Nakamura, K, Sekine, Y, Ouchi, Y, Tsujii, M, Yoshikawa, E, Futatsubashi, M, Tsuchija, KJ, Sugihara, G, Iwata, Y, Suzuki, K, Matsuzaki, H, Sugiyama, T, Takei, N, Mori, N (2010). Brain serotonin and dopamine transporter bindings in adults with high-functioning autism. Archives of General Psychiatry 67, 59–68.CrossRefGoogle ScholarPubMed
Nicolson, R, Craven-Thuss, B, Smith, J (2006). A prospective, open-label trial of galantamine in autistic disorder. Journal of Child and Adolescent Psychopharmacology 16, 621–629.CrossRefGoogle ScholarPubMed
Nieminen-Von Wendt, TS, Metsìhonkala, L, Kulomìki, TA, Aalto, S, Autti, TH, Vanhala, R, Eskola, O, Bergman, J, Hietala, JA, Von Wendt, LO (2004). Increased presynaptic dopamine function in Asperger syndrome. Neuroreport 15, 757–760.CrossRefGoogle ScholarPubMed
Pinto, D, Pagnamenta, AT, Klei, L, Anney, R, Merico, D, Regan, R et al. (2010). Functional impact of global rare copy number variation in autism spectrum disorders. Nature 466, 368–372.CrossRefGoogle ScholarPubMed
Reddihough, DS, Marraffa, C, Mouti, A, O’Sullivan, M, Lee, KJ, Orsini, F, Hazell, P, Granich, J, Whitehouse, AJO, Wray, J, Dossetor, D, Santosh, P, Silove, N, Kohn, M (2019). Effect of fluoxetine on obsessive-compulsive behaviors in children and adolescents with autism spectrum disorders: a randomized clinical trial. JAMA - Journal of the American Medical Association 322, 1561–1569.CrossRefGoogle ScholarPubMed
Richardson, D (2016). Toilet training for children with autism. Nursing Children and Young People 28, 16–22.CrossRefGoogle ScholarPubMed
Roddy, A, O’Neill, C (2019). The economic costs and its predictors for childhood autism spectrum disorders in Ireland: how is the burden distributed?. Autism 23, 1106–1118.CrossRefGoogle Scholar
Rubenstein, JLR, Merzenich, MM (2003). Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes Brain Behaviour 2003, 255–267.CrossRefGoogle Scholar
Sasaki, M, Nakagawa, E, Sugai, K, Shimizu, Y, Hattori, A, Nonoda, Y, Sato, N (2010). Brain perfusion SPECT and EEG findings in children with autism spectrum disorders and medically intractable epilepsy. Brain and Development 32, 776–782.CrossRefGoogle ScholarPubMed
Shandal, V, Sundaram, SK, Chugani, DC, Kumar, A, Behen, ME, Chugani, HT (2011). Abnormal brain protein synthesis in language areas of children with pervasive developmental disorder: a L-[1-11C]-leucine PET study. Journal of Child Neurology 26, 1347–1354.CrossRefGoogle Scholar
Smith, CJ, Bhanot, A, Norman, E, Mullett, JE, Bilbo, SD, McDougle, CJ, Zurcher, NR, Hooker, JM (2019). A protocol for sedation free MRI and pet imaging in adults with autism spectrum disorder. Journal of Autism and Developmental Disorders 49, 3036–3044.CrossRefGoogle ScholarPubMed
Stigler, KA, Sweeten, TL, Posey, DJ, McDougle, CJ (2009). Autism and immune factors: a comprehensive review. Research in Autism Spectrum Disorders 3, 840–860.CrossRefGoogle Scholar
Suzuki, K, Sugihara, G, Ouchi, Y, Nakamura, K, Futasubashi, M, Takebayashi, K, Toshihara, Y, Omata, K, Matsumoto, K, Tsuchiya, KJ, Iwata, Y, Tsujii, M, Sugiyama, M, Mori, N (2013). Microglial activation in young adults with autism spectrum disorder. Archives of General Psychiatry 70, 49–58.Google ScholarPubMed
Suzuki, K, Sugihara, G, Ouchi, Y, Nakamura, K, Tsujii, M, Futatsubashi, M, Iwata, Y, Tsuchiya, KJ, Matsumoto, K, Takebayashi, K, Wakuda, T, Yoshihara, Y, Suda, S, Kikuchi, M, Takei, N, Sugiyama, T, Irie, T, Mori, N (2011). Reduced Acetylcholinesterase Activity in the Fusiform Gyrus in Adults With Autism Spectrum Disorders. Archives of General Psychiatry 68, 306–313.CrossRefGoogle ScholarPubMed
Watanabe, T, Abe, O, Kuwabara, H, Yahata, N, Takano, Y, Iwashiro, N, Natsubori, T, Aoki, Y, Kawakubo, Y, Kamio, Y, Kato, N, Miyashita, Y, Kasai, K, Yamasue, H (2014). Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity a randomized trial. JAMA Psychiatry 71, 166–175.CrossRefGoogle ScholarPubMed
Williams, K, Brignell, A, Randall, M, Silove, N, Hazell, P (2013). Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database of Systematic Reviews, Issue 8, CD004677.CrossRefGoogle Scholar
Yang, CJ, Tan, HP, Du, YJ (2014). The developmental disruptions of serotonin signaling may involved in autism during early brain development. Neuroscience 267, 1–10.CrossRefGoogle ScholarPubMed
Yang, W, Jing, J, Xiu, L, Cheng, MH, Wang, X, Bao, P, Wang, QX (2011). Regional cerebral blood flow in children with autism spectrum disorders: a quantitative 99mTc-ECD brain SPECT study with statistical parametric mapping evaluation. Chinese Medical Journal 124, 1362–1366.Google ScholarPubMed
Żarnowska, I, Chrapko, B, Gwizda, G, Nocuń, A, Mitosek-Szewczyk, K, Gasior, M (2018). Therapeutic use of carbohydrate-restricted diets in an autistic child; a case report of clinical and 18FDG PET findings. Metabolic Brain Disease 33, 1187–1192.CrossRefGoogle Scholar
Zhao, ZQ, Jia, SW, Hu, S, Sun, W (2014). Evaluating the effectiveness of electro-acupuncture as a treatment for childhood autism using single photon emission computed tomography. Chinese Journal of Integrative Medicine 20, 19–23.CrossRefGoogle ScholarPubMed
Zilbovicius, M, Boddaert, N, Belin, P, Poline, J-B, Remy, P, Mangin, JF, Thivard, L, Barthelemy, C, Samson, Y (2000). Temporal lobe dysfunction in childhood autism: a PET study. American Journal of Psychiatry 157, 1988–1993.CrossRefGoogle ScholarPubMed
Zürcher, NR, Bhanot, A, McDougle, CJ, Hooker, JM (2015). A systematic review of molecular imaging (PET and SPECT) in autism spectrum disorder: current state and future research opportunities. Neuroscience and Biobehavioral Reviews 52, 56–73. CrossRefGoogle ScholarPubMed