Skip to content
DraconiticResearch
Search Sources API
194,220 studies31 sourcesUpdated 36 min ago
Peer-reviewedCC BY-NC-NDTranslational Psychiatry

Autistic neural ‘shiftability’: the distinct pharmacological landscape of the autistic brain

  • Tobias P. Whelan1,2
  • Lucas G. S. França3,1,4,5
  • Mihail Dimitrov1,2
  • Charlotte M. Pretzsch1,2
  • Hester Velthuis1,2
  • Andreia Carvalho Pereira6,1,7
  • Claire L. Ellis1,2
  • Glynis Ivin8,9
  • James L. Findon10,2
  • Robert Wichers11,2
  • Francesca M. Ponteduro1,2
  • Johanna Kangas1,2
7 more authors
  • Naoise Mulcrone1,2
  • Nichol M. L. Wong12,13,14
  • Dafnis Batallé3,1,2
  • Nicolaas A.J. Puts1,15,16,2
  • Eileen Daly1,2
  • Declan Murphy1,15,16,2
  • Grainne Mary McAlonan1,15,16,2
16 affiliations
  1. 1Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
  2. 2King's College London
  3. 3Department of Early Life Imaging, School of Biomedical Engineering & Imaging Sciences, King’s College London, London, UK
  4. 4School of Computer Science, Faculty of Science and Environment, Northumbria University, Newcastle upon Tyne, UK
  5. 5Northumbria University
  6. 6Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal
  7. 7University of Coimbra
  8. 8South London and Maudsley NHS Foundation Trust Pharmacy, London, UK
  9. 9South London and Maudsley NHS Foundation Trust Pharmacy
  10. 10Department of Psychology, School of Mental Health and Psychological Sciences, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
  11. 11N=You Neurodevelopmental Precision Center, Department of Child and Adolescent Psychiatry & Psychosocial Care, Division of Woman-Child, Amsterdam UMC, Amsterdam, The Netherlands
  12. 12Centre for Psychosocial Health, The Education University of Hong Kong, Ting Kok, Hong Kong
  13. 13Department of Psychology, The Education University of Hong Kong, Ting Kok, Hong Kong
  14. 14The Education University of Hong Kong
  15. 15MRC Centre for Neurodevelopmental Disorders, King’s College London, London, UK
  16. 16NIHR Biomedical Research Centre: Maudsley, South London and Maudsley NHS Foundation Trust and King’s College London, London, UK
Open at sourcePDFDOICite

Abstract

Functionally inter-connected large-scale brain networks regulated by multiple neurotransmitter systems underpin complex human behaviour. A wide range of alterations in this neurofunctional landscape have been associated with autism. However, this evidence is mostly derived from cross-sectional analyses and thus assumes that any differences are ‘static’. Indeed, large sample sizes are required to identify reproducible baseline differences in functional connectivity between autistic and non-autistic individuals. Instead, we propose that what is different in autism is not necessarily the baseline functional connectivity of resting-state networks, but rather their responsivity or regulation by neurotransmitter systems. We tested this hypothesis using a uniform analytical framework to capture the modulation of functional connectivity by single doses of pharmacological probes targeting three major neurotransmitter systems implicated in autism, namely gamma-aminobutyric-acid (GABA), serotonin (5HT) and μ-opioid systems. Every drug challenge altered resting-state network connectivity differentially in the autistic compared to the non-autistic group. However, regardless of the neurotransmitter system probed, drug challenge elicited increases in between-network connectivity in autistic participants but minimal or decreased between-network connectivity in their non-autistic peers. There was no group difference in the responsivity of within-network connectivity. Thus, there is altered responsivity of neurotransmitter systems in the autistic brain. This has important implications for pharmacotherapy in autism because these neurotransmitter systems are the targets of several medications commonly prescribed to manage mental health conditions that frequently co-occur in autism. Investigating if these drug-induced ‘shifts’ in functional connectivity can help provide better targeted clinical interventions will be an important next translational step.

Related

  1. Dynamic excitatory-inhibitory differences in autistic and non-autistic adults: Evidence from a pharmacological challenge with arbaclofen
    Claire L. Ellis, Jumana Ahmad, Alexia Zoumpoulaki +12
    Journal of PsychopharmacologyPeer-reviewedCC BY8 citedNeuroscienceOpenAlex
  2. Unfulfilled promises: educational and policy barriers for autistic children in Uruguay
    María Montenegro, Gabriela Garrido, Ney Alliey +3
    International Journal of Developmental DisabilitiesPeer-reviewedLicence not statedFull text1 citedNeurosciencePMC
  3. Sex-dependent effects of imperatorin on autistic-like behaviors and BDNF signaling in rats prenatally exposed to valproic acid
    Marjan Mohamadian, Fatemeh Barzi, Marzieh Jalalian-Javadpour +4
    IBRO neuroscience reportsPeer-reviewedCC BY-NC-NDFull textNeuroscienceEurope PMC
  4. Development of a Communication Characteristics Module for Autistic Adults and the Creation of a Communication Profile Variable
    R. Kripke-Ludwig, J. W. Vera, I. Moura +7
    medRxivPreprintAll rights reservedFull textNeurosciencemedRxiv
  5. Towards Neurodiversity-Affirming, Co-Produced Competence Frameworks in Psychotherapy: An Autistic-Led Call to Action
    Laurence Cobbaert, Marie Camin, K. W. Schweizer +10
    AutismPeer-reviewedLicence not statedFull text6 citedNeuroscienceOpenAlex

Cite

BibTeXRIS
BibTeX
@article{whelan2026autistic,
  title = {{Autistic neural ‘shiftability’: the distinct pharmacological landscape of the autistic brain}},
  author = {Tobias P. Whelan and Lucas G. S. França and Mihail Dimitrov and Charlotte M. Pretzsch and Hester Velthuis and Andreia Carvalho Pereira and Claire L. Ellis and Glynis Ivin and James L. Findon and Robert Wichers and Francesca M. Ponteduro and Johanna Kangas and Naoise Mulcrone and Nichol M. L. Wong and Dafnis Batallé and Nicolaas A.J. Puts and Eileen Daly and Declan Murphy and Grainne Mary McAlonan},
  journal = {Translational Psychiatry},
  year = {2026},
  month = aug,
  doi = {10.1038/s41398-026-04371-1},
  url = {https://doi.org/10.1038/s41398-026-04371-1},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Autistic neural ‘shiftability’: the distinct pharmacological landscape of the autistic brain
AU  - Tobias P. Whelan
AU  - Lucas G. S. França
AU  - Mihail Dimitrov
AU  - Charlotte M. Pretzsch
AU  - Hester Velthuis
AU  - Andreia Carvalho Pereira
AU  - Claire L. Ellis
AU  - Glynis Ivin
AU  - James L. Findon
AU  - Robert Wichers
AU  - Francesca M. Ponteduro
AU  - Johanna Kangas
AU  - Naoise Mulcrone
AU  - Nichol M. L. Wong
AU  - Dafnis Batallé
AU  - Nicolaas A.J. Puts
AU  - Eileen Daly
AU  - Declan Murphy
AU  - Grainne Mary McAlonan
PY  - 2026
DA  - 2026/08/31
JO  - Translational Psychiatry
DO  - 10.1038/s41398-026-04371-1
UR  - https://doi.org/10.1038/s41398-026-04371-1
AB  - Functionally inter-connected large-scale brain networks regulated by multiple neurotransmitter systems underpin complex human behaviour. A wide range of alterations in this neurofunctional landscape have been associated with autism. However, this evidence is mostly derived from cross-sectional analyses and thus assumes that any differences are ‘static’. Indeed, large sample sizes are required to identify reproducible baseline differences in functional connectivity between autistic and non-autistic individuals. Instead, we propose that what is different in autism is not necessarily the baseline functional connectivity of resting-state networks, but rather their responsivity or regulation by neurotransmitter systems. We tested this hypothesis using a uniform analytical framework to capture the modulation of functional connectivity by single doses of pharmacological probes targeting three major neurotransmitter systems implicated in autism, namely gamma-aminobutyric-acid (GABA), serotonin (5HT) and μ-opioid systems. Every drug challenge altered resting-state network connectivity differentially in the autistic compared to the non-autistic group. However, regardless of the neurotransmitter system probed, drug challenge elicited increases in between-network connectivity in autistic participants but minimal or decreased between-network connectivity in their non-autistic peers. There was no group difference in the responsivity of within-network connectivity. Thus, there is altered responsivity of neurotransmitter systems in the autistic brain. This has important implications for pharmacotherapy in autism because these neurotransmitter systems are the targets of several medications commonly prescribed to manage mental health conditions that frequently co-occur in autism. Investigating if these drug-induced ‘shifts’ in functional connectivity can help provide better targeted clinical interventions will be an important next translational step.
SN  - 2158-3188
ER  -