title: Electrocortical changes associated with minocycline treatment in fragile X syndrome.
abstract: 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 (Meanage 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.
authors: 1MIND Institute, University of California at Davis Medical Center, Sacramento, California, USA.
authors: Andrea
authors: A
authors: Schneider
authors: Mary Jacena
authors: MJ
authors: Leigh
authors: Patrick
authors: P
authors: Adams
authors: Rawi
authors: R
authors: Nanakul
authors: Tasleem
authors: T
authors: Chechi
authors: John
authors: J
authors: Olichney
authors: Randi
authors: R
authors: Hagerman
authors: David
authors: D
authors: Hessl
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005072:Evoked Potentials, Auditory / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005600:Fragile X Syndrome / Q000188:drug therapy* / Q000503:physiopathology*; D006185:Habituation, Psychophysiologic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D054316:Biomarkers, Pharmacological; D008911:Minocycline
keywords: EEG; ERP; Fragile X syndrome; cortical parameters; minocycline
references: Epilepsia. 2000 Jan;41(1):19-23
references: 10643918
references: Brain Topogr. 2003 Spring;15(3):165-71
references: 12705812
references: Psychophysiology. 2000 Mar;37(2):127-52
references: 10731765
references: Brain Cogn. 2012 Apr;78(3):206-17
references: 22261226
references: J Neurosci. 2005 Aug 31;25(35):8048-55
references: 16135762
references: Clin Neurophysiol. 2012 Dec;123(12):2328-45
references: 22796039
references: Sci Transl Med. 2011 Jan 5;3(64):64ra1
references: 21209411
references: Clin Neurophysiol. 2012 Apr;123(4):720-9
references: 21958658
references: Am J Med Genet B Neuropsychiatr Genet. 2009 Jun 5;150B(4):545-53
references: 18785205
references: BMC Neurol. 2010 Oct 11;10:91
references: 20937127
references: Ital J Neurol Sci. 1994 Oct;15(7):365-8
references: 7698895
references: Clin Neurophysiol. 2012 Mar;123(3):424-58
references: 22169062
references: Clin Neurophysiol. 2012 Jul;123(7):1309-18
references: 22192499
references: Neurophysiol Clin. 1995;25(1):28-30
references: 7746224
references: J Med Genet. 2009 Feb;46(2):94-102
references: 18835858
references: Clin Neurophysiol. 2009 Nov;120(11):1883-1908
references: 19796989
references: Electroencephalogr Clin Neurophysiol. 1989 Feb;72(2):184-7
references: 2464490
references: Hum Mol Genet. 1992 Sep;1(6):397-400
references: 1301913
references: Trends Neurosci. 2004 Jul;27(7):370-7
references: 15219735
references: Am J Med Genet. 2001 Jan 15;98(2):161-7
references: 11223852
references: Am J Intellect Dev Disabil. 2010 Sep;115(5):433-43
references: 20687826
references: Trends Neurosci. 2007 Aug;30(8):425-31
references: 17590448
references: Neuroreport. 2001 Aug 8;12(11):2573-6
references: 11496151
references: Dev Med Child Neurol. 2002 Nov;44(11):724-8
references: 12418611
references: Epilepsia. 1999 Aug;40(8):1092-9
references: 10448821
references: J Neurosci. 2009 Aug 12;29(32):9977-86
references: 19675232
references: Dev Disabil Res Rev. 2009;15(4):333-42
references: 20014363