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Randomized Controlled Trial
. 2013 Oct;27(10):956-63.
doi: 10.1177/0269881113494105. Epub 2013 Aug 27.

Electrocortical changes associated with minocycline treatment in fragile X syndrome

Andrea Schneider  1 , Mary Jacena Leigh, Patrick Adams, Rawi Nanakul, Tasleem Chechi, John Olichney, Randi Hagerman, David Hessl
Affiliations
Randomized Controlled Trial

Electrocortical changes associated with minocycline treatment in fragile X syndrome

Andrea Schneider et al. J Psychopharmacol. 2013 Oct.

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.

Keywords: EEG; ERP; Fragile X syndrome; cortical parameters; minocycline.

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Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(a) Grand averaged waveforms to standard tone at electrode positions T7 (left), Cz (center), and T8 (right) at baseline, placebo and minocycline conditions. Negative is plotted upwards. (b) Amplitudes for N1, P2, and N2 components; patients demonstrated a significant reduction of N1 amplitudes at T7 and T8 on minocycline compared with baseline, increased P2 amplitude at Cz and T8, and an increased N2 amplitude at Cz. (c) Grand averaged waveforms to standard tone at electrode positions T7 (left), Cz (center), and T8 (right), comparison of the minocycline group with a control sample. (d) Amplitudes for N1, P2, and N2 components; individuals with FXS on minocycline compared with controls show similar N1 amplitudes at T7 and T8, a significant higher N1 component at Cz, and a larger P2 amplitude at T7 and Cz.
Figure 2
Figure 2
Current Source Density group grand average maps for 200 ms after stimulus presentation, top view from scalp, nose on top. Arrows indicate differences in activation patterns for the different conditions. (1) reduced early left-temporal component (N1 equivalent) from baseline to minocycline condition, similar to controls (2) reduced temporal negative components in both hemispheres, a finding that is absent in controls (3) increased central positive component (P2 equivalent at Cz), which is absent in controls.
Figure 3
Figure 3
(a) Grand average waveforms at Cz, highlighted in yellow the N1 component, the P2 component in blue. Black line signifies first 45 stimuli, the red line last 45 stimuli potentials. Negative plotted upwards. (b) Significantly improved attenuation of N1 and P2 in minocycline condition, not significant for baseline and placebo.
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