Psychological symptoms correlate with reduced hippocampal volume in fragile X premutation carriers
Year: 2009
Type: article
Study design: Observational Study
Abstract: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder occurring in male and occasional female carriers of a premutation expansion (55-200 CGG repeats) of the fragile X mental retardation 1 gene (FMR1). This study assessed the relationship between hippocampal volume and psychological symptoms in carriers, both with and without FXTAS, and controls. Volumetric MRI measures, clinical staging, cognitive testing, molecular analysis, and measures of psychological symptoms were performed for female premutation carriers both with FXTAS (n = 16, age: 57.50 + or - 12.46) and without FXTAS (n = 17, age: 44.94 + or - 11.23), in genetically normal female controls (n = 8, age: 50.63 + or - 11.43), male carriers with FXTAS (n = 34, age: 66.44 + or - 6.77) and without FXTAS (n = 21, age: 52.38 + or - 12.11), and genetically normal male controls (n = 30, age: 57.20 + or - 14.12). We examined the relationship between psychological symptom severity and hippocampal volume, as well as correlations with molecular data. We found a significant negative correlation between total hippocampal volume and anxiety in female carriers, with and without FXTAS. This finding was mainly driven by the significant negative correlation between right hippocampal volume and anxiety. Other anxiety-related subscales also correlated with the right hippocampus in females. In male carriers with and without FXTAS, only paranoid ideation negatively correlated with hippocampal volume. Female premutation carriers demonstrated a negative association between hippocampal volume and the severity of anxiety-related psychological symptoms. Though the presentation of FXTAS symptoms is less common in females, anxiety-related problems are common both prior to and after the onset of FXTAS, and may be related to hippocampal changes.
DOI: 10.1002/ajmg.b.31046
Authors: P.E. Adams, J.S. Adams, D.V. Nguyen, D. Hessl, J.A. Brunberg, F. Tassone, W. Zhang, K. Koldewyn, S.M. Rivera, J. Grigsby, L. Zhang, C. DeCarli, P.J. Hagerman, R.J. Hagerman
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: National Institute on Aging, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Dental and Craniofacial Research, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1264619266, UC Davis Alzheimer's Disease Core Center, G1500619533, G1855666826, G2163302634, Development of targeted therapeutic agents for the treatment of FXTAS (2 of 6), G2853460972, Fragile X Spectrum as Model for Neurogenetic Mechanisms of Cognitive Dysfunction, G2973466140, G3306906556, Characterization and Treatment of CNS Abnormalities in Premutation Carriers (4 of, Action tremor & dementia in male carriers of fragile X, G3982541408, G4657237763, Research in Intellectual and Developmental Disabilities, G5914551266, G6010579943, G6061585444, G6231962548, G6814286829, G802620026
OpenAlex ID: W2167311801