Editorial Perspective: Bridging the translational neuroscience gap in autism – development of the ‘shiftability’ paradigm

Tobias P. Whelan; Eileen Daly; Nicolaas A. Puts; Ekaterina Malievskaia; Declan G.M. Murphy; Grainne M. McAlonan

doi:10.1111/jcpp.13940

Editorial Perspective: Bridging the translational neuroscience gap in autism – development of the ‘shiftability’ paradigm

Tobias P. Whelan, Eileen Daly, Nicolaas A. Puts, Ekaterina Malievskaia, Declan G.M. Murphy, Grainne M. McAlonan^*

^*Corresponding author for this work

Research output: Contribution to journal › Editorial › peer-review

1 Citation (Scopus)

Abstract

Clinical trials of pharmacological candidates targeting the core features of autism have largely failed. This is despite evidence linking differences in multiple neurochemical systems to brain function in autism. While this has in part been explained by the heterogeneity of the autistic population, the field has largely relied upon association studies to link brain chemistry to function. The only way to directly establish that a neurotransmitter or neuromodulator is involved in a candidate brain function is to change it and observe a shift in that function. This experimental approach dominates preclinical neuroscience, but not human studies. There is little direct experimental evidence describing how neurochemical systems modulate information processing in the living human brain. Thus, our understanding of how neurochemical differences contribute to neurodiversity is limited, impeding our ability to translate findings from animal studies into humans. Here, we introduce our ‘shiftability’ paradigm, an approach to bridge the translational gap in autism research. We provide an overview of the guiding principles and methodologies we use to directly test the hypothesis that neurochemical systems function differently in autistic and non-autistic individuals.

Original language	English
Journal	Journal of Child Psychology and Psychiatry and Allied Disciplines
DOIs	https://doi.org/10.1111/jcpp.13940
Publication status	Accepted/In press - 2023

Keywords

Autism spectrum disorders
biomarkers
neurodevelopmental disorders
neuroimaging
pharmacology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1111/jcpp.13940

Cite this

@article{e578829c98854419bcc8b66a4ac917d7,

title = "Editorial Perspective: Bridging the translational neuroscience gap in autism – development of the {\textquoteleft}shiftability{\textquoteright} paradigm",

abstract = "Clinical trials of pharmacological candidates targeting the core features of autism have largely failed. This is despite evidence linking differences in multiple neurochemical systems to brain function in autism. While this has in part been explained by the heterogeneity of the autistic population, the field has largely relied upon association studies to link brain chemistry to function. The only way to directly establish that a neurotransmitter or neuromodulator is involved in a candidate brain function is to change it and observe a shift in that function. This experimental approach dominates preclinical neuroscience, but not human studies. There is little direct experimental evidence describing how neurochemical systems modulate information processing in the living human brain. Thus, our understanding of how neurochemical differences contribute to neurodiversity is limited, impeding our ability to translate findings from animal studies into humans. Here, we introduce our {\textquoteleft}shiftability{\textquoteright} paradigm, an approach to bridge the translational gap in autism research. We provide an overview of the guiding principles and methodologies we use to directly test the hypothesis that neurochemical systems function differently in autistic and non-autistic individuals.",

keywords = "Autism spectrum disorders, biomarkers, neurodevelopmental disorders, neuroimaging, pharmacology",

author = "Whelan, {Tobias P.} and Eileen Daly and Puts, {Nicolaas A.} and Ekaterina Malievskaia and Murphy, {Declan G.M.} and McAlonan, {Grainne M.}",

note = "Funding Information: The authors also receive support from EU‐AIMS (European Autism Interventions)/EU AIMS‐2‐TRIALS, an Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 777394. In addition, this paper represents independent research part funded by the infrastructure of the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. T.P.W. and E.M. are employees of COMPASS Pathfinder Ltd. and hold shares in the company. N.A.P. has consulted for Deerfield Discovery and Research. D.G.M.M. has consulted for Jaguar Gene Therapy LLC. G.M.M. has received funding for investigator‐initiated studies from GW Pharmaceuticals and COMPASS Pathfinder Ltd. G.M.M. has consulted for Greenwich Biosciences, Inc. Publisher Copyright: {\textcopyright} 2023 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.",

year = "2023",

doi = "10.1111/jcpp.13940",

language = "English",

journal = "Journal of Child Psychology and Psychiatry and Allied Disciplines",

issn = "0021-9630",

}

TY - JOUR

T1 - Editorial Perspective

T2 - Bridging the translational neuroscience gap in autism – development of the ‘shiftability’ paradigm

AU - Whelan, Tobias P.

AU - Daly, Eileen

AU - Puts, Nicolaas A.

AU - Malievskaia, Ekaterina

AU - Murphy, Declan G.M.

AU - McAlonan, Grainne M.

N1 - Funding Information: The authors also receive support from EU‐AIMS (European Autism Interventions)/EU AIMS‐2‐TRIALS, an Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 777394. In addition, this paper represents independent research part funded by the infrastructure of the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. T.P.W. and E.M. are employees of COMPASS Pathfinder Ltd. and hold shares in the company. N.A.P. has consulted for Deerfield Discovery and Research. D.G.M.M. has consulted for Jaguar Gene Therapy LLC. G.M.M. has received funding for investigator‐initiated studies from GW Pharmaceuticals and COMPASS Pathfinder Ltd. G.M.M. has consulted for Greenwich Biosciences, Inc. Publisher Copyright: © 2023 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.

PY - 2023

Y1 - 2023

N2 - Clinical trials of pharmacological candidates targeting the core features of autism have largely failed. This is despite evidence linking differences in multiple neurochemical systems to brain function in autism. While this has in part been explained by the heterogeneity of the autistic population, the field has largely relied upon association studies to link brain chemistry to function. The only way to directly establish that a neurotransmitter or neuromodulator is involved in a candidate brain function is to change it and observe a shift in that function. This experimental approach dominates preclinical neuroscience, but not human studies. There is little direct experimental evidence describing how neurochemical systems modulate information processing in the living human brain. Thus, our understanding of how neurochemical differences contribute to neurodiversity is limited, impeding our ability to translate findings from animal studies into humans. Here, we introduce our ‘shiftability’ paradigm, an approach to bridge the translational gap in autism research. We provide an overview of the guiding principles and methodologies we use to directly test the hypothesis that neurochemical systems function differently in autistic and non-autistic individuals.

AB - Clinical trials of pharmacological candidates targeting the core features of autism have largely failed. This is despite evidence linking differences in multiple neurochemical systems to brain function in autism. While this has in part been explained by the heterogeneity of the autistic population, the field has largely relied upon association studies to link brain chemistry to function. The only way to directly establish that a neurotransmitter or neuromodulator is involved in a candidate brain function is to change it and observe a shift in that function. This experimental approach dominates preclinical neuroscience, but not human studies. There is little direct experimental evidence describing how neurochemical systems modulate information processing in the living human brain. Thus, our understanding of how neurochemical differences contribute to neurodiversity is limited, impeding our ability to translate findings from animal studies into humans. Here, we introduce our ‘shiftability’ paradigm, an approach to bridge the translational gap in autism research. We provide an overview of the guiding principles and methodologies we use to directly test the hypothesis that neurochemical systems function differently in autistic and non-autistic individuals.

KW - Autism spectrum disorders

KW - biomarkers

KW - neurodevelopmental disorders

KW - neuroimaging

KW - pharmacology

UR - http://www.scopus.com/inward/record.url?scp=85180165493&partnerID=8YFLogxK

U2 - 10.1111/jcpp.13940

DO - 10.1111/jcpp.13940

M3 - Editorial

AN - SCOPUS:85180165493

SN - 0021-9630

JO - Journal of Child Psychology and Psychiatry and Allied Disciplines

JF - Journal of Child Psychology and Psychiatry and Allied Disciplines

ER -

Editorial Perspective: Bridging the translational neuroscience gap in autism – development of the ‘shiftability’ paradigm

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this