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Neurotrophin blood-based gene expression and social cognition analysis in patients with autism spectrum disorder

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Abstract

Autism spectrum disorders (ASD) comprise neurodevelopmental disorders with clinical onset during the first years of life. The identification of peripheral biomarkers could significantly impact diagnosis and an individualized, early treatment. Although the aetiology of ASD remains poorly understood, there is increasing evidence that neurotrophins and their receptors represent a group of candidate genes for ASD pathophysiology and biomarker research. Total messenger RNA (mRNA) from whole blood was obtained from adolescents and adults diagnosed as ASD (n = 21) according to DSM-IV criteria and confirmed by the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R) algorithms, as well as healthy controls (n = 10). The mRNA expression of neurotrophins (BDNF, NT3 and NT4) and their receptors (TrkA, TrkB and p75 NTR) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, social cognition abilities of ASD patients and controls were determined according to three Theory of Mind (ToM) tests (Reading the Mind in the Eyes, Faux pas, and Happé stories). The NT3 and NT4 mRNA expression in the whole blood was significantly lower in ASD compared to healthy controls, while p75NTR was higher (P < 0.005). In addition, lower scores in three of the ToM tests were observed in ASD subjects compared to controls. A significant (P < 0.005) ToM impairment in Happé stories test was demonstrated in ASD. Nevertheless, no correlations were observed between neurotrophins and their receptors expressions and measures of ToM. Given their potential as peripheral blood-based biomarkers, NT3, NT4 and p75 NTR mRNA expression patterns may be useful tools for a more personalized diagnostics and therapy in ASD. Further investigations with larger numbers of samples are needed to verify these results.

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Acknowledgments

This research was supported by an unrestricted research grant from María Francisca de Roviralta Fundation (Madrid, Spain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work has been also funded by the FI-DRG2010 grant and the BE-DRG2010 grant sponsored by the Departament d’Educació i Universitats de la Generalitat de Catalunya and European Social Fund. We are grateful to all patients and controls for their participation in our study, to clinical collaborators for patient’s assessment and to Irene Bolea for critical comments.

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Authors and Affiliations

  1. Department of Basic Sciences, Facultat de Medicina, Universitat Internacional de Catalunya, C/ Josep Trueta s/n, 08195, Sant Cugat del Vallès, Spain

    Mònica Segura & Alejandro Gella

  2. Department of Clinical and Health Psychology, Psychopathology and Neuropsychology Research Unit, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    Carla Pedreño & Jordi Obiols

  3. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Fuechsleinstraße 15, 97080, Würzburg, Germany

    Regina Taurines

  4. Department of Mental Health, Corporació Sanitària Parc Taulí de Sabadell, Campus d’Excellència Internacional, 08193, Bellaterra, Spain

    Montserrat Pàmias

  5. Department of Psychiatry, Psychosomatic and Psychotherapy, University Hospital of Würzburg, Fuechsleinstraße 15, 97080, Würzburg, Germany

    Edna Grünblatt

  6. Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland

    Edna Grünblatt

  7. University Clinics of Child and Adolescent Psychiatry, University of Zurich, Neumünsterallee 9, 8032, Zurich, Switzerland

    Edna Grünblatt

  8. Brain and Mind Research Institute, Weill Medical College of Cornell University, New York, NY, 10065, USA

    Alejandro Gella

  9. Neurochemistry Working Group of the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC), 08025, Barcelona, Spain

    Alejandro Gella

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  1. Mònica Segura
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Correspondence to Alejandro Gella.

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Mònica Segura and Carla Pedreño contributed equally to this work.

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Segura, M., Pedreño, C., Obiols, J. et al. Neurotrophin blood-based gene expression and social cognition analysis in patients with autism spectrum disorder. Neurogenetics 16, 123–131 (2015). https://doi.org/10.1007/s10048-014-0434-9

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