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2. Frontal and occipital brain glutathione levels are unchanged in autistic adults.

Author

Pereira, Andreia C., Leonard, Alison, Velthuis, Hester, Wong, Nichol M. L., Ponteduro, Francesca M., Dimitrov, Mihail, Ellis, Claire L., Kowalewski, Lukasz, Lythgoe, David J., Rotaru, Diana-Georgina, Edden, Richard A. E., Ivin, Glynis, Pretzsch, Charlotte M., Daly, Eileen, Murphy, Declan G. M., and McAlonan, Gráinne M.

Subjects
AUTISM spectrum disorders, PREFRONTAL cortex, OXIDATIVE stress, GLUTATHIONE, ADULTS
Abstract

Background: The neurobiological underpinnings of Autism Spectrum Disorder (ASD) are diverse and likely multifactorial. One possible mechanism is increased oxidative stress leading to altered neurodevelopment and brain function. However, this hypothesis has mostly been tested in post-mortem studies. So far, available in vivo studies in autistic individuals have reported no differences in glutathione (GSH) levels in frontal, occipital, and subcortical regions. However, these studies were limited by the technically challenging quantification of GSH, the main brain antioxidant molecule. This study aimed to overcome previous studies' limitations by using a GSH-tailored spectroscopy sequence and optimised quantification methodology to provide clarity on GSH levels in autistic adults. Methods: We used spectral editing proton-magnetic resonance spectroscopy (1H-MRS) combined with linear combination model fitting to quantify GSH in the dorsomedial prefrontal cortex (DMPFC) and medial occipital cortex (mOCC) of autistic and non-autistic adults (male and female). We compared GSH levels between groups. We also examined correlations between GSH and current autism symptoms, measured using the Autism Quotient (AQ). Results: Data were available from 31 adult autistic participants (24 males, 7 females) and 40 non-autistic participants (21 males, 16 females); the largest sample to date. The GSH levels did not differ between groups in either region. No correlations with AQ were observed. Conclusion: GSH levels as measured using 1H-MRS are unaltered in the DMPFC and mOCC regions of autistic adults, suggesting that oxidative stress in these cortical regions is not a marked neurobiological signature of ASD. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without Autism Spectrum Disorder (ASD): a single dose trial during magnetic resonance spectroscopy

Author

Pretzsch, Charlotte M, Voinescu, Bogdan, Lythgoe, David, Horder, Jamie, Mendez, Maria Andreina, Wichers, Robert, Ajram, Laura, Ivin, Glynis, Heasman, Martin, Edden, Richard A. E., Williams, Steven, Murphy, Declan G. M., Daly, Eileen, and McAlonan, Gráinne M.

Published
2019
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4. GABAergic regulation of auditory repetition suppression in adults with and without Autism Spectrum Disorder

Author

Huang, Qiyun, primary, Velthuis, Hester, additional, Pereira, Andreia C., additional, Ahmad, Jumana, additional, Cooke, Samuel F., additional, Ellis, Claire L., additional, Ponteduro, Francesca M., additional, Puts, Nicolaas A. J., additional, Dimitrov, Mihail, additional, Batalle, Dafnis, additional, Wong, Nichol M. L., additional, Kowalewski, Lukasz, additional, Ivin, Glynis, additional, Daly, Eileen, additional, Murphy, Declan G. M., additional, and McAlonan, Gráinne M., additional

Published
2023
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5. GABABreceptor modulation of visual sensory processing in adults with and without autism spectrum disorder

Author

Huang, Qiyun, primary, Pereira, Andreia C., additional, Velthuis, Hester, additional, Wong, Nichol M. L., additional, Ellis, Claire L., additional, Ponteduro, Francesca M., additional, Dimitrov, Mihail, additional, Kowalewski, Lukasz, additional, Lythgoe, David J., additional, Rotaru, Diana, additional, Edden, Richard A. E., additional, Leonard, Alison, additional, Ivin, Glynis, additional, Ahmad, Jumana, additional, Pretzsch, Charlotte M., additional, Daly, Eileen, additional, Murphy, Declan G. M., additional, and McAlonan, Gráinne M., additional

Published
2022
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6. Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin

Author

Pretzsch, Charlotte M., primary, Floris, Dorothea L., additional, Voinescu, Bogdan, additional, Elsahib, Malka, additional, Mendez, Maria A., additional, Wichers, Robert, additional, Ajram, Laura, additional, Ivin, Glynis, additional, Heasman, Martin, additional, Pretzsch, Elise, additional, Williams, Steven, additional, Murphy, Declan G. M., additional, Daly, Eileen, additional, and McAlonan, Gráinne M., additional

Published
2021
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7. Additional file 1 of Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin

Author

Pretzsch, Charlotte M., Floris, Dorothea L., Voinescu, Bogdan, Elsahib, Malka, Mendez, Maria A., Wichers, Robert, Ajram, Laura, Ivin, Glynis, Heasman, Martin, Pretzsch, Elise, Williams, Steven, Murphy, Declan G. M., Daly, Eileen, and McAlonan, Gráinne M.

Abstract

Additional file 1. Figure S1. Placement of striatal seeds. Numbers above slices indicate Montreal Neurological Institute (MNI) z-coordinates. Abbreviations: A, anterior; DC, dorsal caudate; dcP, dorsal-caudal putamen; drP, dorsal-rostral putamen; I, inferior; L, left; P, posterior; R, right; ROI, region of interest; S, superior; vrP, ventral-rostral putamen; VSi, inferior ventral striatum; VSs, superior ventral striatum. Table S1. Between-group (ASD>neurotypicals) differences in striatal functional connectivity at baseline. Table displays statistics for targets (regions containing the cluster peak), including cluster size (in voxels), test statistics, and peak coordinates in Montreal Neurological Institute (MNI) space (x,y,z). Abbreviations: d, Cohen’s d; L, left; R, right; ROI, region of interest; vrP, ventral-rostral putamen; VSi, inferior ventral striatum. Table S2. Interaction effect (ASD>neurotypicals, CBDV>PLC) on atypical baseline striatal functional connectivity. Abbreviations: d, Cohen’s d; L, left; R, right; vrP, ventral-rostral putamen; VSi, inferior ventral striatum.

Published
2021
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8. GABAB receptor modulation of visual sensory processing in adults with and without autism spectrum disorder.

Author

Huang, Qiyun, Pereira, Andreia C., Velthuis, Hester, Wong, Nichol M. L., Ellis, Claire L., Ponteduro, Francesca M., Dimitrov, Mihail, Kowalewski, Lukasz, Lythgoe, David J., Rotaru, Diana, Edden, Richard A. E., Leonard, Alison, Ivin, Glynis, Ahmad, Jumana, Pretzsch, Charlotte M., Daly, Eileen, Murphy, Declan G. M., and McAlonan, Gráinne M.

Published
2022
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9. The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD)

Author

Pretzsch, Charlotte M, primary, Voinescu, Bogdan, additional, Mendez, Maria A, additional, Wichers, Robert, additional, Ajram, Laura, additional, Ivin, Glynis, additional, Heasman, Martin, additional, Williams, Steven, additional, Murphy, Declan GM, additional, Daly, Eileen, additional, and McAlonan, Gráinne M, additional

Published
2019
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10. Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder

Author

Pretzsch, Charlotte Marie, primary, Freyberg, Jan, additional, Voinescu, Bogdan, additional, Lythgoe, David, additional, Horder, Jamie, additional, Mendez, Maria Andreina, additional, Wichers, Robert, additional, Ajram, Laura, additional, Ivin, Glynis, additional, Heasman, Martin, additional, Edden, Richard A. E., additional, Williams, Steven, additional, Murphy, Declan G. M., additional, Daly, Eileen, additional, and McAlonan, Gráinne M., additional

Published
2019
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12. Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without Autism Spectrum Disorder (ASD): a single dose trial during magnetic resonance spectroscopy

Author

Pretzsch, Charlotte M., Voinescu, Bogdan, Lythgoe, David, Horder, Jamie, Mendez, Maria Andreina, Wichers, Robert, Ajram, Laura, Ivin, Glynis, Heasman, Martin, Edden, Richard A.E., Williams, Steven, Murphy, Declan G.M., Daly, Eileen, and McAlonan, Grainne M.

Subjects
3. Good health
Abstract

The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders.

13. CONSORT_2010_Checklist__cmpretzsch_falff – Supplemental material for The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD)

Author

Pretzsch, Charlotte M, Voinescu, Bogdan, Mendez, Maria A, Wichers, Robert, Ajram, Laura, Ivin, Glynis, Heasman, Martin, Williams, Steven, Murphy, Declan GM, Daly, Eileen, and McAlonan, Gráinne M

Subjects
FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 3. Good health, 110904 Neurology and Neuromuscular Diseases
Abstract

Supplemental material, CONSORT_2010_Checklist__cmpretzsch_falff for The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD) by Charlotte M Pretzsch, Bogdan Voinescu, Maria A Mendez, Robert Wichers, Laura Ajram, Glynis Ivin, Martin Heasman, Steven Williams, Declan GM Murphy, Eileen Daly and Gráinne M McAlonan in Journal of Psychopharmacology

14. CONSORT_2010_Flow_Diagram_cmpretzsch – Supplemental material for The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD)

Author

Pretzsch, Charlotte M, Voinescu, Bogdan, Mendez, Maria A, Wichers, Robert, Ajram, Laura, Ivin, Glynis, Heasman, Martin, Williams, Steven, Murphy, Declan GM, Daly, Eileen, and McAlonan, Gráinne M

Subjects
FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 3. Good health, 110904 Neurology and Neuromuscular Diseases
Abstract

Supplemental material, CONSORT_2010_Flow_Diagram_cmpretzsch for The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD) by Charlotte M Pretzsch, Bogdan Voinescu, Maria A Mendez, Robert Wichers, Laura Ajram, Glynis Ivin, Martin Heasman, Steven Williams, Declan GM Murphy, Eileen Daly and Gráinne M McAlonan in Journal of Psychopharmacology

15. Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder

Author

Pretzsch, Charlotte Marie, Freyberg, Jan, Voinescu, Bogdan, Lythgoe, David, Horder, Jamie, Mendez, Maria Andreina, Wichers, Robert, Ajram, Laura, Ivin, Glynis, Heasman, Martin, Edden, Richard A.E., Williams, Steven, Murphy, Declan G.M., Daly, Eileen, and McAlonan, Gráinne M.

Subjects
3. Good health
Abstract

The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders.

16. CONSORT_2010_Flow_Diagram_cmpretzsch – Supplemental material for The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD)

Author

Pretzsch, Charlotte M, Voinescu, Bogdan, Mendez, Maria A, Wichers, Robert, Ajram, Laura, Ivin, Glynis, Heasman, Martin, Williams, Steven, Murphy, Declan GM, Daly, Eileen, and McAlonan, Gráinne M

Subjects
FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 3. Good health, 110904 Neurology and Neuromuscular Diseases
Abstract

Supplemental material, CONSORT_2010_Flow_Diagram_cmpretzsch for The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD) by Charlotte M Pretzsch, Bogdan Voinescu, Maria A Mendez, Robert Wichers, Laura Ajram, Glynis Ivin, Martin Heasman, Steven Williams, Declan GM Murphy, Eileen Daly and Gráinne M McAlonan in Journal of Psychopharmacology

17. CONSORT_2010_Checklist__cmpretzsch_falff – Supplemental material for The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD)

Author

Pretzsch, Charlotte M, Voinescu, Bogdan, Mendez, Maria A, Wichers, Robert, Ajram, Laura, Ivin, Glynis, Heasman, Martin, Williams, Steven, Murphy, Declan GM, Daly, Eileen, and McAlonan, Gráinne M

Subjects
FOS: Psychology, FOS: Clinical medicine, 170199 Psychology not elsewhere classified, 110319 Psychiatry (incl. Psychotherapy), 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified, 3. Good health, 110904 Neurology and Neuromuscular Diseases
Abstract

Supplemental material, CONSORT_2010_Checklist__cmpretzsch_falff for The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD) by Charlotte M Pretzsch, Bogdan Voinescu, Maria A Mendez, Robert Wichers, Laura Ajram, Glynis Ivin, Martin Heasman, Steven Williams, Declan GM Murphy, Eileen Daly and Gráinne M McAlonan in Journal of Psychopharmacology

18. Effects of cannabidivarin (CBDV) on brain excitation and inhibition systems in adults with and without Autism Spectrum Disorder (ASD): a single dose trial during magnetic resonance spectroscopy

Author

Pretzsch, Charlotte M., Voinescu, Bogdan, Lythgoe, David, Horder, Jamie, Mendez, Maria Andreina, Wichers, Robert, Ajram, Laura, Ivin, Glynis, Heasman, Martin, Edden, Richard A.E., Williams, Steven, Murphy, Declan G.M., Daly, Eileen, and McAlonan, Grainne M.

Subjects
3. Good health
Abstract

The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders.

19. GABA B receptor modulation of visual sensory processing in adults with and without autism spectrum disorder.

Author

Huang Q, Pereira AC, Velthuis H, Wong NML, Ellis CL, Ponteduro FM, Dimitrov M, Kowalewski L, Lythgoe DJ, Rotaru D, Edden RAE, Leonard A, Ivin G, Ahmad J, Pretzsch CM, Daly E, Murphy DGM, and McAlonan GM

Subjects
Adult, Evoked Potentials, Visual, Humans, Magnetic Resonance Spectroscopy methods, Receptors, GABA, Visual Perception, gamma-Aminobutyric Acid, Autism Spectrum Disorder
Abstract

Sensory atypicalities in autism spectrum disorder (ASD) are thought to arise at least partly from differences in γ-aminobutyric acid (GABA) receptor function. However, the evidence to date has been indirect, arising from correlational studies in patients and preclinical models. Here, we evaluated the role of GABA receptor directly, in 44 adults ( n = 19 ASD). Baseline concentration of occipital lobe GABA+ (GABA plus coedited macromolecules) was measured using proton magnetic resonance spectroscopy ( 1 H-MRS). Steady-state visual evoked potential (SSVEP) elicited by a passive visual surround suppression paradigm was compared after double-blind randomized oral administration of placebo or 15 to 30 mg of arbaclofen (STX209), a GABA type B (GABA B ) receptor agonist. In the placebo condition, the neurotypical SSVEP response was affected by both the foreground stimuli contrast and background interference (suppression). In ASD, however, all stimuli conditions had equal salience and background suppression of the foreground response was weaker. In the placebo condition, although there was no difference in GABA+ between groups, GABA+ concentration positively correlated with response to maximum foreground contrast during maximum background interference in neurotypicals, but not ASD. In neurotypicals, sensitivity to visual stimuli was disrupted by 30 mg of arbaclofen, whereas in ASD, it was made more “typical” and visual processing differences were abolished. Hence, differences in GABAergic function are fundamental to autistic (visual) sensory neurobiology and are modulated by GABA B activity.

Published
2022
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