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Bruno JL, Hosseini SH, Lightbody AA, et al. Brain circuitry, behavior, and cognition: A randomized placebo-controlled trial of donepezil in fragile X syndrome. J Psychopharmacol. 2019;33(8):975-985doi: 10.1177/0269881119858304.
Bruno, J. L., Hosseini, S. H., Lightbody, A. A., Manchanda, M. K., & Reiss, A. L. (2019). Brain circuitry, behavior, and cognition: A randomized placebo-controlled trial of donepezil in fragile X syndrome. Journal of psychopharmacology (Oxford, England), 33(8), 975-985. https://doi.org/10.1177/0269881119858304
Bruno, Jennifer L, et al. "Brain circuitry, behavior, and cognition: A randomized placebo-controlled trial of donepezil in fragile X syndrome." Journal of psychopharmacology (Oxford, England) vol. 33,8 (2019): 975-985. doi: https://doi.org/10.1177/0269881119858304
Bruno JL, Hosseini SH, Lightbody AA, Manchanda MK, Reiss AL. Brain circuitry, behavior, and cognition: A randomized placebo-controlled trial of donepezil in fragile X syndrome. J Psychopharmacol. 2019 Aug;33(8):975-985. doi: 10.1177/0269881119858304. Epub 2019 Jul 02. PMID: 31264943; PMCID: PMC6894490.
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J Psychopharmacol. 2019 Aug;33(8):975-985. doi: 10.1177/0269881119858304. Epub 2019 Jul 02.

Brain circuitry, behavior, and cognition: A randomized placebo-controlled trial of donepezil in fragile X syndrome.

Journal of psychopharmacology (Oxford, England)

Jennifer L Bruno, Sm Hadi Hosseini, Amy A Lightbody, Mai K Manchanda, Allan L Reiss

Affiliations

  1. 1 Division of Interdisciplinary Brain Sciences, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
  2. 3 Department of Pediatrics, Stanford University, Stanford, CA, USA.

PMID: 31264943 PMCID: PMC6894490 DOI: 10.1177/0269881119858304

Abstract

BACKGROUND: Fragile X syndrome, the most common inherited cause for intellectual disability, is associated with alterations in cholinergic among other neurotransmitter systems. This study investigated the effects of donepezil hydrochloride, a cholinesterase inhibitor that has potential to correct aberrant cholinergic signaling.

METHOD: Forty-two individuals with fragile X syndrome (mean age=19.61 years) were randomized to receive 2.5-10.0 mg of donepezil (

RESULTS: There were no significant differences between active and placebo groups on cognitive (contingency naming task) or behavioral (total score or subscales of the aberrant behavior checklist) outcomes. At baseline, the active and placebo groups did not differ in functional magnetic resonance imaging activation patterns during the gaze task. After 12 weeks of treatment the active group displayed reduced activation in response to the averted vs direct gaze contrast, relative to the placebo group, in the left superior frontal gyrus.

CONCLUSIONS: Reduced functional brain activation for the active group may represent less arousal in response to direct eye gaze, relative to the placebo group. Change in functional magnetic resonance imaging activation patterns may serve as a more sensitive metric and predictor of response to treatment when compared to cognitive and behavioral assessments. Our results suggest that donepezil may have an impact on brain functioning, but longer term follow-up and concomitant behavioral intervention may be required to demonstrate improvement in cognition and behavior.

Keywords: Clinical trial; autism spectrum disorder; fragile X syndrome; functional magnetic resonance imaging; neuroimaging

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