title: Improving treatment of neurodevelopmental disorders: recommendations based on preclinical studies.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Herein, the authors discuss the neurobiological mechanisms of NDDs, and present recommendations on their translational research and therapy, outlined by the International Stress and Behavior Society. 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition, and Behaviour , Radboud University Medical Centre , Nijmegen , The Netherlands.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
authors.affiliation: b Department of Psychiatry, College of Medicine , University of Illinois at Chicago , Chicago , IL , USA.|c The International Stress and Behavior Society (ISBS) , Kiev , Ukraine.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Kyzar
authors.affiliation: d ZENEREI Research Center , Slidell , LA , USA.
authors.forename: Adam Michael
authors.initials: AM
authors.lastname: Stewart
authors.affiliation: d ZENEREI Research Center , Slidell , LA , USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Nguyen
authors.affiliation: d ZENEREI Research Center , Slidell , LA , USA.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Poudel
authors.affiliation: c The International Stress and Behavior Society (ISBS) , Kiev , Ukraine.|e Department of Psychology , University of Southern Mississippi , Hattiesburg , MS , USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Echevarria
authors.affiliation: e Department of Psychology , University of Southern Mississippi , Hattiesburg , MS , USA.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Collier
authors.affiliation: c The International Stress and Behavior Society (ISBS) , Kiev , Ukraine.|f Research Institute of Marine Drugs and Nutrition , College of Food Science and Technology, Guangdong Ocean University , Zhanjiang , Guangdong , China.|g Neuroscience Graduate Hospital , China Medical University Hospital , Taichung , Taiwan.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Gaikwad
authors.affiliation: c The International Stress and Behavior Society (ISBS) , Kiev , Ukraine.|h Pavlov Physiology Department , Institute of Experimental Medicine , St. Petersburg , Russia.
authors.forename: Viktor M
authors.initials: VM
authors.lastname: Klimenko
authors.affiliation: i Department of Neuroscience, Psychology and Behaviour , University of Leicester , Leicester , UK.
authors.forename: William
authors.initials: W
authors.lastname: Norton
authors.affiliation: j Department of Biological and Environmental Sciences , Troy University , Troy , AL , USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Pittman
authors.affiliation: c The International Stress and Behavior Society (ISBS) , Kiev , Ukraine.|k Tokyo University of Agriculture and Technology , Tokyo , Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: c The International Stress and Behavior Society (ISBS) , Kiev , Ukraine.|l Departments of Pediatrics and Biochemistry , Saitama University Medical School , Saitama , Japan.
authors.forename: Mamiko
authors.initials: M
authors.lastname: Koshiba
authors.affiliation: l Departments of Pediatrics and Biochemistry , Saitama University Medical School , Saitama , Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yamanouchi
authors.affiliation: m Institute of Nutrition RAS , Moscow , Russia.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Apryatin
authors.affiliation: n Department of Cell Biology and Neurosciences , Istituto Superiore di Sanita , Rome , Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Scattoni
authors.affiliation: o Department of Psychology , University of South Florida , Tampa , FL , USA.|p Research and Development Service , J.A. Haley Veterans Hospital , Tampa , FL , USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Diamond
authors.affiliation: q Centre for Advanced Imaging , University of Queensland , Brisbane , Queensland , Australia.
authors.forename: Jeremy F P
authors.initials: JF
authors.lastname: Ullmann
authors.affiliation: r School of Health Sciences and Social Work , University of Portsmouth , Portsmouth , UK.
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Parker
authors.affiliation: s Department of Psychology and Neuroscience , Dalhousie University , Halifax , Nova Scotia , Canada.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Brown
authors.affiliation: f Research Institute of Marine Drugs and Nutrition , College of Food Science and Technology, Guangdong Ocean University , Zhanjiang , Guangdong , China.|g Neuroscience Graduate Hospital , China Medical University Hospital , Taichung , Taiwan.|s Department of Psychology and Neuroscience , Dalhousie University , Halifax , Nova Scotia , Canada.
authors.forename: Cai
authors.initials: C
authors.lastname: Song
authors.affiliation: f Research Institute of Marine Drugs and Nutrition , College of Food Science and Technology, Guangdong Ocean University , Zhanjiang , Guangdong , China.|t Institute for Translational Biomedicine, St. Petersburg State University , St. Petersburg , Russia.|u Institute of Chemical Technology and Institute of Natural Sciences , Ural Federal University , Ekaterinburg , Russia.
authors.forename: Allan V
authors.initials: AV
authors.lastname: Kalueff
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D058068:Endophenotypes / Q000378:metabolism; D006801:Humans; D065886:Neurodevelopmental Disorders / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D018377:Neurotransmitter Agents / Q000378:metabolism; D057170:Translational Research, Biomedical / Q000379:methods
chemical_list: D015415:Biomarkers; D018377:Neurotransmitter Agents
keywords: ADHD; animal models; autism; neurodevelopmental disorders; translational research