Improving treatment of neurodevelopmental disorders: recommendations based on preclinical studies

Judith Homberg, Evan Kyzar, Adam Stewart, Michael Nguyen, Manoj Poudel, David Echevarria, Adam Collier, Siddharth Gaikwad, Viktor Klimenko, William Norton, Julian Pittman, Shun Nakamura, Mamiko Koshiba, Hideo Yamanouchi, Sergey Apryatin, Maria Luisa Scattoni, David Diamond, Jeremy FP Ullmann, Matthew Parker, Richard BrownCai Song, Allan V Kalueff

Research output: Contribution to journalArticlepeer-review

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Abstract

Introduction: Neurodevelopmental disorders (NDDs) are common and severely debilitating. Their chronic nature and reliance on both genetic and environmental factors makes studying NDDs and their treatment a challenging task. Here, we discuss neurobiological mechanisms of NDDs, and present recommendations on their translational research and therapy, outlined by the International Stress and Behavior Society.

Areas covered: Common NDDs are a heterogeneous group which includes autism spectrum disorder, intellectual disability, communication/speech disorders, motor/tic disorders and attention deficit hyperactivity disorder. Various drugs currently prescribed to treat NDDs also represent a highly diverse group. Acting on various neurotransmitter and physiological systems, these drugs often lack specificity of action, and are commonly used to treat multiple other psychiatric conditions. There has also been relatively little progress in the development of novel medications to treat NDDs. Based on clinical, preclinical and translational models of NDDs, our recommendations cover a wide range of methodological approaches and conceptual strategies.

Expert opinion: To improve pharmacotherapy and drug discovery for NDDs, we need a stronger emphasis on targeting multiple endophenotypes, a better dissection of genetic/epigenetic factors or ‘hidden heritability’, and a careful consideration of potential developmental/trophic roles of brain neurotransmitters. The validity of animal NDD models can be improved through discovery of novel (behavioral, physiological and neuroimaging) biomarkers, applying proper environmental enrichment, widening the spectrum of model organisms, targeting developmental trajectories of NDD-related behaviors and comorbid conditions beyond traditional NDDs. While these recommendations cannot be addressed all in once, our increased understanding of NDD pathobiology may trigger innovative cross-disciplinary research expanding beyond traditional methods and concepts.
Original languageEnglish
Pages (from-to)11-25
Number of pages15
JournalExpert Opinion on Drug Discovery
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016

Keywords

  • animal models
  • autism
  • ADHD
  • translational research
  • neurodevelopmental disorders

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