Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome
| Autor: | Crystal Hervey, Stephen W. Porges, Elizabeth Berry-Kravis, Ning Weng, Allison Sumis, William T. Greenough, Michael N. Nelson, Ivan Jeanne Weiler |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Adult
medicine.medical_specialty Lithium (medication) Adolescent Visual analogue scale medicine.drug_class Administration Oral Thyrotropin Pilot Projects Irritability Receptors Metabotropic Glutamate Cognition Lithium Carbonate Internal medicine Developmental and Educational Psychology medicine Humans Learning Child Extracellular Signal-Regulated MAP Kinases Psychiatric Status Rating Scales Psychological Tests Mood stabilizer medicine.disease FMR1 Vineland Adaptive Behavior Scale Antidepressive Agents Blood Cell Count Fragile X syndrome Psychiatry and Mental health Endocrinology Treatment Outcome Fragile X Syndrome Pediatrics Perinatology and Child Health medicine.symptom Psychology Polydipsia medicine.drug |
| Zdroj: | Journal of developmental and behavioral pediatrics : JDBP. 29(4) |
| ISSN: | 1536-7312 |
| Popis: | Objective: In fragile X syndrome (FXS), it is hypothesized that absence of the fragile X mental retardation protein (FMRP) disrupts regulation of group 1 metabotropic glutamate receptor (mGluR and mGluR5)-dependent translation in dendrites. Lithium reduces mGluR-activated translation and reverses phe- notypes in the dfxr mutant fly and fmr1 knockout mouse. This pilot add-on trial was conducted to evaluate safety and efficacy of lithium in humans with FXS. Methods: Fifteen individuals with FXS, ages 6-23, received lithium titrated to levels of 0.8-1.2 mEq/L. The primary outcome measure, the Aberrant Behavior Checklist - Community Edition (ABC-C) Irritability Subscale, secondary outcome measures (other ABC-C subscales, clinical global improvement scale (CGI), visual analog scale for behavior (VAS), Vineland Adaptive Behavior Scale (VABS)), exploratory cognitive and psychophysiological measures and an extracellular signal-regulated kinase (ERK) activation assay were administered at baseline and 2 months of treatment. Side effects were quantified with a standardized checklist and lithium level, complete blood count (CBC), thyroid stimulating hormone (TSH), and chemistry screen were done at baseline, 2 weeks, 4 weeks and 2 months. Results: The only significant treatment-related side effects were polyuria/polydipsia (n 7) and elevated TSH (n 4). Although the ABC-C Irritability Subscale showed only a trend toward improvement, there was significant improvement in the Total ABC-C score (p 0.005), VAS (p 0.003), CGI (p 0.002), VABS Maladaptive Behavior Subscale (p 0.007), and RBANS List Learning (p 0.03) and an enhanced ERK activation rate (p 0.007). Several exploratory tasks proved too difficult for lower-functioning FXS subjects. Conclusions: Results from this study are consistent with results in mouse and fly models of FXS, and suggest that lithium is well-tolerated and provides functional benefits in FXS, possibly by modifying the underlying neural defect. A placebo-controlled trial of lithium in FXS is warranted. (J Dev Behav Pediatr 29:293-302, 2008) Index terms: fragile X syndrome, lithium, FMR1, dendritic translation. |
| Databáze: | OpenAIRE |
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