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Peer-reviewedCC BYJournal of Psychopharmacology

Dynamic excitatory-inhibitory differences in autistic and non-autistic adults: Evidence from a pharmacological challenge with arbaclofen

  • Claire L. Ellis1,2
  • Jumana Ahmad1,3
  • Alexia Zoumpoulaki4
  • Mihail Dimitrov1,2
  • Hester Velthuis1,2
  • Andreia Carvalho Pereira1,5,2
  • Nichol M. L. Wong1,6,2
  • Francesca M. Ponteduro1,2
  • Łukasz Kowalewski1,7,2,8
  • Alison Leonard1,2
  • Pilar Garces9
  • Qiyun Huang1,2
3 more authors
  • Eileen Daly1,2
  • Declan G. Murphy1,2,10
  • Grainne Mary McAlonan1,2,10
10 affiliations
  1. 1Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
  2. 2Sackler Institute for Translational Neurodevelopment, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
  3. 3School of Human Sciences, University of Greenwich, London, UK
  4. 4School of Computer Science and Informatics, Cardiff University, Cardiff, UK
  5. 5Institute for Nuclear Sciences Applied to Health (ICNAS), Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Portugal
  6. 6Department of Psychology, The University of Hong Kong, Hong Kong
  7. 7Mental Health and Intellectual Disability, Stewarts Care, Dublin, Ireland
  8. 8Saint John of God Community Services, Liffey Services, Intellectual Disability Psychiatry, Celbridge, Ireland
  9. 9Roche Pharma Research and Early Development, Neuroscience and Rare Diseases, Roche Innovation Center Basel, Basel, Switzerland
  10. 10South London and Maudsley, NHS Foundation Trust
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Abstract

BACKGROUND: Brain function is the dynamic output of coordinated excitatory and inhibitory (E-I) activity. E-I alterations, arising from differences in excitatory glutamate and inhibitory GABA pathways, are implicated in the development and heterogeneity of autism, and are consequently targets for pharmacological support options. Existing tools, such as Magnetic Resonance Spectroscopy, are limited in capturing the dynamic nature of E-I regulation. The aperiodic 1/f exponent of the EEG power spectrum has shown sensitivity to E-I perturbations in animals and neurotypical humans, but its applicability to neurodiverse populations remains underexplored. METHODS: Therefore, as proof-of-concept, this study tested the hypotheses that (i) the aperiodic 1/f exponent of resting-state EEG changes following a pharmacological E-I challenge with arbaclofen (STX209), a GABAB receptor agonist; and (ii) dynamic responsivity to GABAergic challenge is different in autism. Participants were 40 adults, 15 autistic. EEG was recorded at rest after randomised, double-blind administration of a placebo, 15 mg of arbaclofen, and 30 mg of arbaclofen. Aperiodic 1/f exponents were extracted. RESULTS: As predicted, in both groups the aperiodic 1/f exponent significantly increased following a high (30 mg) dose of arbaclofen, replicating the effect observed in animals. Furthermore, a lower (15 mg) dose showed a different response pattern across groups, with aperiodic exponents tending to increase in autistic individuals but decrease in non-autistic individuals, suggesting differences in GABAergic responsivity. CONCLUSIONS: These findings support the aperiodic 1/f exponent as a metric for dynamic E-I regulation and provide preliminary evidence of distinct homeostatic E-I dynamics in autism.

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Cite

BibTeXRIS
BibTeX
@article{ellis2026dynamic,
  title = {{Dynamic excitatory-inhibitory differences in autistic and non-autistic adults: Evidence from a pharmacological challenge with arbaclofen}},
  author = {Claire L. Ellis and Jumana Ahmad and Alexia Zoumpoulaki and Mihail Dimitrov and Hester Velthuis and Andreia Carvalho Pereira and Nichol M. L. Wong and Francesca M. Ponteduro and Łukasz Kowalewski and Alison Leonard and Pilar Garces and Qiyun Huang and Eileen Daly and Declan G. Murphy and Grainne Mary McAlonan},
  journal = {Journal of Psychopharmacology},
  year = {2026},
  month = may,
  doi = {10.1177/02698811261449378},
  url = {https://doi.org/10.1177/02698811261449378},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Dynamic excitatory-inhibitory differences in autistic and non-autistic adults: Evidence from a pharmacological challenge with arbaclofen
AU  - Claire L. Ellis
AU  - Jumana Ahmad
AU  - Alexia Zoumpoulaki
AU  - Mihail Dimitrov
AU  - Hester Velthuis
AU  - Andreia Carvalho Pereira
AU  - Nichol M. L. Wong
AU  - Francesca M. Ponteduro
AU  - Łukasz Kowalewski
AU  - Alison Leonard
AU  - Pilar Garces
AU  - Qiyun Huang
AU  - Eileen Daly
AU  - Declan G. Murphy
AU  - Grainne Mary McAlonan
PY  - 2026
DA  - 2026/05/15
JO  - Journal of Psychopharmacology
DO  - 10.1177/02698811261449378
UR  - https://doi.org/10.1177/02698811261449378
AB  - BACKGROUND: Brain function is the dynamic output of coordinated excitatory and inhibitory (E-I) activity. E-I alterations, arising from differences in excitatory glutamate and inhibitory GABA pathways, are implicated in the development and heterogeneity of autism, and are consequently targets for pharmacological support options. Existing tools, such as Magnetic Resonance Spectroscopy, are limited in capturing the dynamic nature of E-I regulation. The aperiodic 1/f exponent of the EEG power spectrum has shown sensitivity to E-I perturbations in animals and neurotypical humans, but its applicability to neurodiverse populations remains underexplored. METHODS: Therefore, as proof-of-concept, this study tested the hypotheses that (i) the aperiodic 1/f exponent of resting-state EEG changes following a pharmacological E-I challenge with arbaclofen (STX209), a GABAB receptor agonist; and (ii) dynamic responsivity to GABAergic challenge is different in autism. Participants were 40 adults, 15 autistic. EEG was recorded at rest after randomised, double-blind administration of a placebo, 15 mg of arbaclofen, and 30 mg of arbaclofen. Aperiodic 1/f exponents were extracted. RESULTS: As predicted, in both groups the aperiodic 1/f exponent significantly increased following a high (30 mg) dose of arbaclofen, replicating the effect observed in animals. Furthermore, a lower (15 mg) dose showed a different response pattern across groups, with aperiodic exponents tending to increase in autistic individuals but decrease in non-autistic individuals, suggesting differences in GABAergic responsivity. CONCLUSIONS: These findings support the aperiodic 1/f exponent as a metric for dynamic E-I regulation and provide preliminary evidence of distinct homeostatic E-I dynamics in autism.
SN  - 0269-8811
SN  - 1461-7285
ER  -