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Electrocortical changes associated with minocycline treatment in fragile X syndrome
Open accessAbstract
Minocycline normalizes synaptic connections and behavior in the knockout mouse model of fragile X syndrome (FXS). Human-targeted treatment trials with minocycline have shown benefits in behavioral measures and parent reports. Event-related potentials (ERPs) may provide a sensitive method of monitoring treatment response and changes in coordinated brain activity. Measurement of electrocortical changes due to minocycline was done in a double-blind, placebo-controlled crossover treatment trial in children with FXS. Children with FXS (Mean age 10.5 years) were randomized to minocycline or placebo treatment for 3 months then changed to the other treatment for 3 months. The minocycline dosage ranged from 25–100 mg daily, based on weight. Twelve individuals with FXS (eight male, four female) completed ERP studies using a passive auditory oddball paradigm. Current source density (CSD) and ERP analysis at baseline showed high-amplitude, long-latency components over temporal regions. After 3 months of treatment with minocycline, the temporal N1 and P2 amplitudes were significantly reduced compared with placebo. There was a significant amplitude increase of the central P2 component on minocycline. Electrocortical habituation to auditory stimuli improved with minocycline treatment. Our study demonstrated improvements of the ERP in children with FXS treated with minocycline, and the potential feasibility and sensitivity of ERPs as a cognitive biomarker in FXS treatment trials.
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“The ERP habituation deficits in humans with FXS are reversed by minocycline treatment but the underlying mechanisms are not known (Schneider et al. 2013).”
From Matrix metalloproteinase-9 deletion rescues auditory evoked potential habituation deficit in a mouse model of Fragile X Syndrome (2016) · cites this paper as Schneider et al. 2013
In the citing paper
“The reduced habituation of N1 amplitude in Fmr1 KO mice is similar to observations in humans with FXS providing, for the first time, an analogous functional sensory outcome measure in mice and humans (Castren et al., 2003; Van der Molen et al., 2012; Schneider et al., 2013).”
From Matrix metalloproteinase-9 deletion rescues auditory evoked potential habituation deficit in a mouse model of Fragile X Syndrome (2016) · cites this paper as Schneider et al., 2013
In the citing paper
“Treatment with minocycline, which reduces MMP-9 activity and levels, reduces ERP habituation deficits humans with FXS (Schneider et al., 2013).”
From Matrix metalloproteinase-9 deletion rescues auditory evoked potential habituation deficit in a mouse model of Fragile X Syndrome (2016) · cites this paper as Schneider et al., 2013
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“Treatment with candidate pharmacotherapy minocycline can decrease N1 and P2 amplitudes in individuals with FXS (Schneider et al., 2013), suggesting that auditory ERP abnormalities can be used as outcome measures in drug treatment in human studies.”
Metadata
- Authors
- Schneider, A., Leigh, M. J., Adams, P., Nanakul, R., Chechi, T., Olichney, J., Hagerman, R., & Hessl, D.
- Affiliations
- University of California Davis Medical Center (US)
- University of Washington (US)
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2013-08-27
- Volume
- 27
- Issue
- 10
- Pages
- 956-963
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- PMC
- PMC4962861
- OpenAlex
- W2006050076
- Cited by
- 108
- References
- 29
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4 · 2023: 2 · 2022: 15 · 2021: 12 · 2020: 10 · 2019: 11 · 2018: 10 · 2017: 13 · 2016: 7 · 2015: 6 · 2014: 8
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Fragile X Foundation
- Centers for Disease Control and Prevention (U50DD000596)
- National Institute on Aging (NIARL1AG032115, RL1AG032115)
- National Center for Research Resources (UL1RR024141, UL1RR024146, KL2RR024141)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- fragile X syndrome, minocycline, event-related potentials, auditory oddball paradigm, current source density, N1 and P2 components, cognitive biomarkers, treatment response monitoring, children
- MeSH terms
- Anti-Bacterial Agents, Child, Double-Blind Method, Evoked Potentials, Auditory, Female, Fragile X Syndrome, Habituation, Psychophysiologic, Humans, Male, Minocycline, Cross-Over Studies, Biomarkers, Pharmacological
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