Autoren |
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Natalie Walter
Department of Child and Adolescent Psychiatry and Psychotherapy
Vortragender
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Cristine Marie Yde Ohki
Psychiatric University Hospital Zurich
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Jose Salazar
Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry, Zurich
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Sina Ruhstaller
Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland
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Darya Dzmitranitsa
Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry, Zurich
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Orysia Vityk
Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry, Zurich
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Christian Döring
Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry, Zurich
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Anna Werling
Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry, Zurich
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Susanne Walitza
Psychiatrische Universitätsklinik Zürich
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Edna Grünblatt
University of Zurich
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Abstract
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Attention-deficit hyperactivity disorder (ADHD) is the most frequently reported neurodevelopmental disorder, with a worldwide prevalence of ca. 5%, affecting children and adolescents. Moreover, 60% of childhood ADHD cases persist into adulthood, leaving treatment approaches more difficult and thus, reducing estimated life expectancies. To increase treatment success in ADHD, alternative or combined treatment, alongside with the first line treatment Methylphenidate (MPH), may be favourable. The non-pharmacological treatment of omega-3 (ω-3) polyunsaturated fatty acid (PUFAS) components, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), display potential candidates, as they take part in several biological processes, including the attenuation of inflammation and oxidative stress, and improving cellular signalling processes, such as Wnt-signalling, which are recognized to be pivotal during neurodevelopment. However, the underlying molecular mechanisms of ω-3 PUFAs involved in ADHD remains unknown. Thus, investigations with a focused on Wnt-signalling, neuroinflammatory responses and oxidative stress is being approached by using human induced pluripotent stem cell (iPSC)-derived neural precursor cells (NPC) and forebrain cortical neurons (FCNs) from ADHD patients and healthy individuals as control. NPCs and FCNs are treated with ω-3 PUFA components DHA and EPA (0-50uM) with and without MPH to elucidate the evoked mechanism on a proteomic and transcriptomic level. More specifically, proteins involved in Wnt signalling are determined via western blot and Wnt-signalling activity via luminescence reporter assay. Furthermore, considering oxidative stress, mitochondria demonstrate the main source of reactive oxygen species production. Therefore, further analysis of detecting mitochondrial DNA (mtDNA) copy number variation (CNV) will be observed by performing qPCR on saliva, iPSC and FCN DNA samples, to identify the presence of mitochondrial disturbances in ADHD. These findings will contribute to alternative treatment approaches in ADHD in a patient specific manner.
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