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Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin
- Source :
- Pretzsch, C M, Floris, D L, Voinescu, B, Elsahib, M, Mendez, M A, Wichers, R, Ajram, L, Ivin, G, Heasman, M, Pretzsch, E, Williams, S, Murphy, D G M, Daly, E & McAlonan, G M 2021, ' Modulation of striatal functional connectivity differences in adults with and without autism spectrum disorder in a single-dose randomized trial of cannabidivarin ', Molecular Autism, vol. 12, no. 1, 49 . https://doi.org/10.1186/s13229-021-00454-6, Molecular Autism, Molecular Autism, 12, Molecular Autism, Vol 12, Iss 1, Pp 1-14 (2021), Molecular Autism, 12, 1
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Background Autism spectrum disorder (ASD) has a high cost to affected individuals and society, but treatments for core symptoms are lacking. To expand intervention options, it is crucial to gain a better understanding of potential treatment targets, and their engagement, in the brain. For instance, the striatum (caudate, putamen, and nucleus accumbens) plays a central role during development and its (atypical) functional connectivity (FC) may contribute to multiple ASD symptoms. We have previously shown, in the adult autistic and neurotypical brain, the non-intoxicating cannabinoid cannabidivarin (CBDV) alters the balance of striatal ‘excitatory–inhibitory’ metabolites, which help regulate FC, but the effects of CBDV on (atypical) striatal FC are unknown. Methods To examine this in a small pilot study, we acquired resting state functional magnetic resonance imaging data from 28 men (15 neurotypicals, 13 ASD) on two occasions in a repeated-measures, double-blind, placebo-controlled study. We then used a seed-based approach to (1) compare striatal FC between groups and (2) examine the effect of pharmacological probing (600 mg CBDV/matched placebo) on atypical striatal FC in ASD. Visits were separated by at least 13 days to allow for drug washout. Results Compared to the neurotypicals, ASD individuals had lower FC between the ventral striatum and frontal and pericentral regions (which have been associated with emotion, motor, and vision processing). Further, they had higher intra-striatal FC and higher putamenal FC with temporal regions involved in speech and language. In ASD, CBDV reduced hyperconnectivity to the neurotypical level. Limitations Our findings should be considered in light of several methodological aspects, in particular our participant group (restricted to male adults), which limits the generalizability of our findings to the wider and heterogeneous ASD population. Conclusion In conclusion, here we show atypical striatal FC with regions commonly associated with ASD symptoms. We further provide preliminary proof of concept that, in the adult autistic brain, acute CBDV administration can modulate atypical striatal circuitry towards neurotypical function. Future studies are required to determine whether modulation of striatal FC is associated with a change in ASD symptoms. Trial registration clinicaltrials.gov, Identifier: NCT03537950. Registered May 25th, 2018—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03537950?term=NCT03537950&draw=2&rank=1.
- Subjects :
- Adult
Male
Cannabidivarin
Autism Spectrum Disorder
Population
Pilot Projects
Striatum
CBDV
Magnetic Resonance Imaging/methods
Functional connectivity
03 medical and health sciences
0302 clinical medicine
Developmental Neuroscience
Brain Mapping/methods
Humans
Medicine
RC346-429
education
Molecular Biology
030304 developmental biology
Brain Mapping
0303 health sciences
education.field_of_study
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
Autism Spectrum Disorder/diagnostic imaging
Cannabinoids
business.industry
Research
Putamen
Ventral striatum
Neuropsychology
220 Statistical Imaging Neuroscience
Brain
Brain/diagnostic imaging
medicine.disease
Magnetic Resonance Imaging
Psychiatry and Mental health
medicine.anatomical_structure
Autism spectrum disorder
Neurology. Diseases of the nervous system
Autism spectrum condition
business
Neuroscience
030217 neurology & neurosurgery
Neurotypical
Developmental Biology
medicine.drug
Subjects
Details
- ISSN :
- 20402392
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Molecular Autism
- Accession number :
- edsair.doi.dedup.....aab6ea3363f7abae7e70e2c9ce46a7ef
- Full Text :
- https://doi.org/10.1186/s13229-021-00454-6