Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-26T05:14:56.690Z Has data issue: false hasContentIssue false

Molecular biomarkers to track clinical improvement following an integrative treatment model in autistic toddlers

Published online by Cambridge University Press:  30 April 2021

Ignazio S. Piras
Affiliation:
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ85004, USA
Filippo Manti
Affiliation:
Department of Human, Neuroscience Sapienza University, Rome, Italy
Anna Costa
Affiliation:
Service for Neurodevelopmental Disorders, University Campus Bio-Medico, Rome, Italy
Valentina Carone
Affiliation:
CRC Balbuzie, Rome, Italy
Bruna Scalese
Affiliation:
CRC Balbuzie, Rome, Italy
Joshua S. Talboom
Affiliation:
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ85004, USA
Christian Veronesi
Affiliation:
CRC Balbuzie, Rome, Italy
Claudio Tabolacci
Affiliation:
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy
Antonio M. Persico
Affiliation:
Interdepartmental Program “Autism 0-90”, “Gaetano Martino” University Hospital, University of Messina, Messina, Italy
Matthew J. Huentelman
Affiliation:
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ85004, USA
Roberto Sacco
Affiliation:
Service for Neurodevelopmental Disorders, University Campus Bio-Medico, Rome, Italy
Carla Lintas*
Affiliation:
Service for Neurodevelopmental Disorders, University Campus Bio-Medico, Rome, Italy
*
Author for correspondence: Carla Lintas, Email: C.lintas@unicampus.it

Abstract

Objectives:

Identifying an objective, laboratory-based diagnostic tool (e.g. changes in gene expression), when used in conjunction with disease-specific clinical assessment, could increase the accuracy of the effectiveness of a therapeutic intervention.

Methods:

We assessed the association between treatment outcome and blood RNA expression before the therapeutic intervention to post-treatment (after 1 year) of five autism spectrum disorder (ASD) toddlers who underwent an intensive cognitive-behavioural intervention integrated with psychomotor and speech therapy.

Results:

We found 113 significant differentially expressed genes enriched for the nervous system, immune system, and transcription and translation-related pathways. Some of these genes, as MALAT-1, TSPO, and CFL1, appear to be promising candidates.

Conclusions:

Our findings show that changes in peripheral gene expression could be used in conjunction with clinical scales to monitor a rehabilitation intervention’s effectiveness in toddlers affected by ASD. These results need to be validated in a larger cohort.

Type
Short Communication
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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

Afridi, R, Seol, S, Kang, HJ, Suk, K (2021) Brain-immune interactions in neuropsychiatric disorders: Lessons from transcriptome studies for molecular targeting. England Biochemical Pharmacology 188, 114532.CrossRefGoogle ScholarPubMed
American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders : DSM-5. American Psychiatric Association. Washington DC: DSM.CrossRefGoogle Scholar
Barichello, T, Simões, LR, Collodel, A, Giridharan, VV, Dal-Pizzol, F, Macedo, D, Quevedo, J (2017) The translocator protein (18 kDa) and its role in neuropsychiatric disorders. Neuroscience and Biobehavioral Reviews 83, 183  –199.CrossRefGoogle Scholar
Bernard, D, Prasanth, KV, Tripathi, V, Colasse, S, Nakamura, T, Xuan, Z, Zhang, MQ, Sedel, F, Jourdren, L, Coulpier, F, Triller, A, Spector, DL, Bessis, A (2010) A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression. EMBO Journal 29, 30823093.CrossRefGoogle ScholarPubMed
Chen, ZL, Liu, JY, Wang, F, Jing, X (2019) Suppression of MALAT1 ameliorates chronic constriction injury-induced neuropathic pain in rats via modulating miR-206 and ZEB2. Journal of Cellular Physiology. 234, 1564715653 CrossRefGoogle Scholar
Cheng, Y, Imanirad, P, Jutooru, I, Hedrick, E, Jin, U-H, Rodrigues Hoffman, A, Leal de Araujo, J, Morpurgo, B, Golovko, A, Safe, S (2018) Role of metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) in pancreatic cancer. United States PloS One 13, e0192264.CrossRefGoogle Scholar
Coleman, JR, Lester, KJ, Roberts, S, Keers, R, Lee, SH, De Jong, S, Gaspar, H, Teismann, T, Wannemüller, A, Schneider, S, Jöhren, P, Margraf, J, Breen, G, Eley, TC. Separate and combined effects of genetic variants and pre-treatment whole blood gene expression on response to exposure-based cognitive behavioural therapy for anxiety disorders. World J Biol Psychiatry. 2017 Apr;18(3):215226 CrossRefGoogle ScholarPubMed
Gandal, MJ, Zhang, P, Hadjimichael, E, Walker, RL, Chen, C, Liu, S, Won, H, Van Bakel, H, Varghese, M, Wang, Y, Shieh, AW, Haney, J, Parhami, S, Belmont, J, Kim, M, Losada, PM, Khan, Z, Mleczko, J, Xia, Y, Dai, R, Wang, D, Yang, YT, Xu, M, Fish, K, Hof, PR, Warrell, J, Fitzgerald, D, White, K, Jaffe, AE, Peters, MA, Gerstein, M, Liu, C, Iakoucheva, LM, Pinto, D, Geschwind, DH (2018) Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder. Science 362, eaat8127.CrossRefGoogle ScholarPubMed
Garbett, K, Ebert, PJ, Mitchell, A, Lintas, C, Manzi, B, Mirnics, K, Persico, AM (2008) Immune transcriptome alterations in the temporal cortex of subjects with autism. Neurobiology of Disease 30, 303311.CrossRefGoogle ScholarPubMed
Gibney, SM, Drexhage, HA (2013) Evidence for a dysregulated immune system in the etiology of psychiatric disorders. Journal of Neuroimmune Pharmacology. 8, 900920. CrossRefGoogle ScholarPubMed
Han, K, Chapman, SB, Krawczyk, DC (2018) Neuroplasticity of cognitive control networks following cognitive training for chronic traumatic brain injury. NeuroImage: Clinical 18, 262278.CrossRefGoogle ScholarPubMed
Hirvonen, J, Hietala, J, Kajander, J, Markkula, J, Rasi-Hakala, H, Salminen, JK, Någren, K, Aalto, S, Karlsson, H (2011) Effects of antidepressant drug treatment and psychotherapy on striatal and thalamic dopamine D2/3 receptors in major depressive disorder studied with [11C]raclopride PET. Journal of Psychopharmacology 25, 13291336.CrossRefGoogle ScholarPubMed
Ishii, A, Furusho, M, Dupree, JL, Bansal, R (2014) Role of ERK1/2 MAPK signaling in the maintenance of myelin and axonal integrity in the adult CNS. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 34, 1603116045.CrossRefGoogle ScholarPubMed
Kandel, ER (1998) A new intellectual framework for psychiatry. United States The American Journal of Psychiatry 155, 457469.CrossRefGoogle ScholarPubMed
Kéri, S, Szabó, C, Kelemen, O (2014) Expression of Toll-Like Receptors in peripheral blood mononuclear cells and response to cognitive-behavioral therapy in major depressive disorder. Brain, Behavior, and Immunity 164, 118122.Google Scholar
Kilinc, D (2018) The emerging role of mechanics in synapse formation and plasticity. Frontiers in Cellular Neuroscience. 12, 483 CrossRefGoogle ScholarPubMed
Kryger, R, Fan, L, Wilce, PA, Jaquet, V (2012) MALAT-1, a non protein-coding RNA is upregulated in the cerebellum, hippocampus and brain stem of human alcoholics. Alcohol 46, 629634.CrossRefGoogle ScholarPubMed
Lehto, SM, Tolmunen, T, Kuikka, J, Valkonen-Korhonen, M, Joensuu, M, Saarinen, PI, Vanninen, R, Ahola, P, Tiihonen, J, Lehtonen, J (2008) Midbrain serotonin and striatum dopamine transporter binding in double depression: a one-year follow-up study. Neuroscience Letters 441, 291295.CrossRefGoogle ScholarPubMed
Levy-Gigi, E, Szabó, C, Kelemen, O, Kéri, S (2013) Association among clinical response, hippocampal volume, and FKBP5 gene expression in individuals with posttraumatic stress disorder receiving cognitive behavioral therapy. Biological Psychiatry 74, 793800.CrossRefGoogle ScholarPubMed
Pontrello, CG, Sun, M-Y, Lin, A, Fiacco, TA, DeFea, KA, Ethell, IM (2012) Cofilin under control of -arrestin-2 in NMDA-dependent dendritic spine plasticity, long-term depression (LTD), and learning. Proceedings of the National Academy of Sciences 109, E442E451.CrossRefGoogle Scholar
Quan, Z, Zheng, D, Qing, H (2017) Regulatory roles of long non-coding RNAs in the central nervous system and associated neurodegenerative diseases. Frontiers in Cellular Neuroscience 30, 175.CrossRefGoogle Scholar
Reichow, B, Barton, EE, Boyd, BA, Hume, K (2012) Early intensive behavioral intervention (EIBI) for young children with autism spectrum disorders (ASD). Cochrane Database of Systematic Reviews 5, CD009260.Google Scholar
Rusconi, F, Battaglioli, E, Venturin, M (2020) Psychiatric disorders and lncRNAs: a synaptic match. International Journal of Molecular Sciences 21, 3030.CrossRefGoogle ScholarPubMed
Rust, MB, Gurniak, CB, Renner, M, Vara, H, Morando, L, Görlich, A, Sassoè-Pognetto, M, Al, Banchaabouchi M, Giustetto, M, Triller, A, Choquet, D, Witke, W (2010) Learning, AMPA receptor mobility and synaptic plasticity depend on n-cofilin-mediated actin dynamics. EMBO Journal 29, 18891902.CrossRefGoogle ScholarPubMed
Sehovic, E, Spahic, L, Smajlovic-Skenderagic, L, Pistoljevic, N, Dzanko, E, Hajdarpasic, A (2020) Identification of developmental disorders including autism spectrum disorder using salivary miRNAs in children from Bosnia and Herzegovina. PloS One 15, e0232351.CrossRefGoogle ScholarPubMed
Tylee, DS, Hess, JL, Quinn, TP, Barve, R, Huang, H, Zhang-James, Y, Chang, J, Stamova, BS, Sharp, FR, Hertz-Picciotto, I, Faraone, S V., Kong, SW, Glatt, SJ (2017) Blood transcriptomic comparison of individuals with and without autism spectrum disorder: a combined-samples mega-analysis. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics 174, 181201.CrossRefGoogle ScholarPubMed
Wright, C, Shin, JH, Rajpurohit, A, Deep-Soboslay, A, Collado-Torres, L, Brandon, NJ, Hyde, TM, Kleinman, JE, Jaffe, AE, Cross, AJ, Weinberger, DR (2017) Altered expression of histamine signaling genes in autism spectrum disorder. Translational Psychiatry 7, e1126..CrossRefGoogle ScholarPubMed
Supplementary material: PDF

Piras et al. supplementary material

Piras et al. supplementary material 1

Download Piras et al. supplementary material(PDF)
PDF 1.5 MB
Supplementary material: File

Piras et al. supplementary material

Piras et al. supplementary material 2

Download Piras et al. supplementary material(File)
File 94.5 KB