Psychological symptoms correlate with reduced hippocampal volume in fragile X premutation carriers
- PMID:19908235
- PMCID: PMC2868927
- DOI: 10.1002/ajmg.b.31046
Psychological symptoms correlate with reduced hippocampal volume in fragile X premutation carriers
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.
Figures


Similar articles
- Volumetric brain changes in females with fragile X-associated tremor/ataxia syndrome (FXTAS).Adams JS, Adams PE, Nguyen D, Brunberg JA, Tassone F, Zhang W, Koldewyn K, Rivera SM, Grigsby J, Zhang L, DeCarli C, Hagerman PJ, Hagerman RJ.Adams JS, et al.Neurology. 2007 Aug 28;69(9):851-9. doi: 10.1212/01.wnl.0000269781.10417.7b.Neurology. 2007.PMID:17724287
- Static and dynamic postural control deficits in aging fragile X mental retardation 1 (FMR1) gene premutation carriers.Wang Z, Khemani P, Schmitt LM, Lui S, Mosconi MW.Wang Z, et al.J Neurodev Disord. 2019 Jan 21;11(1):2. doi: 10.1186/s11689-018-9261-x.J Neurodev Disord. 2019.PMID:30665341Free PMC article.
- Characterization and Early Detection of Balance Deficits in Fragile X Premutation Carriers With and Without Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS).O'Keefe JA, Robertson-Dick E, Dunn EJ, Li Y, Deng Y, Fiutko AN, Berry-Kravis E, Hall DA.O'Keefe JA, et al.Cerebellum. 2015 Dec;14(6):650-62. doi: 10.1007/s12311-015-0659-7.Cerebellum. 2015.PMID:25763861
- The spectrum of tremor among carriers of the FMR1 premutation with or without the fragile X-associated tremor/ataxia syndrome (FXTAS).Fay-Karmon T, Hassin-Baer S.Fay-Karmon T, et al.Parkinsonism Relat Disord. 2019 Aug;65:32-38. doi: 10.1016/j.parkreldis.2019.05.010. Epub 2019 May 7.Parkinsonism Relat Disord. 2019.PMID:31126791Review.
- Neuropsychiatry of fragile X-premutation carriers with and without fragile X-associated tremor-ataxia syndrome: implications for neuropsychology.Bourgeois JA.Bourgeois JA.Clin Neuropsychol. 2016 Aug;30(6):913-28. doi: 10.1080/13854046.2016.1192134. Epub 2016 Jun 29.Clin Neuropsychol. 2016.PMID:27355575Review.
Cited by
- Fragile X-associated disorders: a clinical overview.Gallagher A, Hallahan B.Gallagher A, et al.J Neurol. 2012 Mar;259(3):401-13. doi: 10.1007/s00415-011-6161-3. Epub 2011 Jul 12.J Neurol. 2012.PMID:21748281Review.
- Reduced vagal tone in women with theFMR1 premutation is associated withFMR1 mRNA but not depression or anxiety.Klusek J, LaFauci G, Adayev T, Brown WT, Tassone F, Roberts JE.Klusek J, et al.J Neurodev Disord. 2017 May 2;9:16. doi: 10.1186/s11689-017-9197-6. eCollection 2017.J Neurodev Disord. 2017.PMID:28469730Free PMC article.
- Fragile X syndrome: a pilot proton magnetic resonance spectroscopy study in premutation carriers.Hallahan BP, Daly EM, Simmons A, Moore CJ, Murphy KC, Murphy DD.Hallahan BP, et al.J Neurodev Disord. 2012 Aug 30;4(1):23. doi: 10.1186/1866-1955-4-23.J Neurodev Disord. 2012.PMID:22958351Free PMC article.
- Widespread non-central nervous system organ pathology in fragile X premutation carriers with fragile X-associated tremor/ataxia syndrome and CGG knock-in mice.Hunsaker MR, Greco CM, Spath MA, Smits AP, Navarro CS, Tassone F, Kros JM, Severijnen LA, Berry-Kravis EM, Berman RF, Hagerman PJ, Willemsen R, Hagerman RJ, Hukema RK.Hunsaker MR, et al.Acta Neuropathol. 2011 Oct;122(4):467-79. doi: 10.1007/s00401-011-0860-9. Epub 2011 Jul 23.Acta Neuropathol. 2011.PMID:21785977Free PMC article.
- Genetic counseling and testing for FMR1 gene mutations: practice guidelines of the national society of genetic counselors.Finucane B, Abrams L, Cronister A, Archibald AD, Bennett RL, McConkie-Rosell A.Finucane B, et al.J Genet Couns. 2012 Dec;21(6):752-60. doi: 10.1007/s10897-012-9524-8. Epub 2012 Jul 14.J Genet Couns. 2012.PMID:22797890
References
- Adams JS, Adams PE, Nguyen D, Brunberg JA, Tassone F, Zhang W, Koldewyn K, Rivera SM, Grigsby J, Zhang L, et al. Volumetric brain changes in females with fragile X-associated tremor/ataxia syndrome (FXTAS) Neurology. 2007;69(9):851–859. - PubMed
- Allingham-Hawkins DJ, Babul-Hirji R, Chitayat D, Holden JJA, Yang KT, Lee C, Hudson R, Gorwill RH, Nolin SL, Glicksman A, et al. Fragile X premutation is a significant risk factor for premature ovarian failure: The international collaborative POF in fragile X study— Preliminary data. Am J Med Genet. 1999;83:322–325. - PMC - PubMed
- Arocena DG, Iwahashi CK, Won N, Beilina A, Ludwig AL, Tassone F, Schwartz PH, Hagerman PJ. Induction of inclusion formation and disruption of lamin A/C structure by premutation CGG-repeat RNA in human cultured neural cells. Hum Mol Genet. 2005;14(23):3661–3671. - PubMed
- Bacalman S, Farzin F, Bourgeois JA, Cogswell J, Goodlin-Jones BL, Gane LW, Grigsby J, Leehey MA, Tassone F, Hagerman RJ. Psychiatric phenotype of the fragile X-associated tremor/ataxia syndrome (FXTAS) in males: Newly described fronto-subcortical dementia. J Clin Psychiatry. 2006;67(1):87–94. - PubMed
- Bannerman DM, Grubb M, Deacon RM, Yee BK, Feldon J, Rawlins JN. Ventral hippocampal lesions affect anxiety but not spatial learning. Behav Brain Res. 2003;139(1–2):197–213. - PubMed
Publication types
MeSH terms
Substances
Related information
Grants and funding
- HD36071/HD/NICHD NIH HHS/United States
- K23 MH077554/MH/NIMH NIH HHS/United States
- RR024922/RR/NCRR NIH HHS/United States
- R01 NS044299/NS/NINDS NIH HHS/United States
- P30 AG1029/AG/NIA NIH HHS/United States
- RL1AG032115/AG/NIA NIH HHS/United States
- R01 HD036071/HD/NICHD NIH HHS/United States
- R01 HD036071-11/HD/NICHD NIH HHS/United States
- P30 AG10129/AG/NIA NIH HHS/United States
- P30 HD002274/HD/NICHD NIH HHS/United States
- AG032115/AG/NIA NIH HHS/United States
- RL1 AG032115-01/AG/NIA NIH HHS/United States
- R01 MH078041/MH/NIMH NIH HHS/United States
- MH078041/MH/NIMH NIH HHS/United States
- UL1 DE019583/DE/NIDCR NIH HHS/United States
- RL1 NS062412/NS/NINDS NIH HHS/United States
- MH77554/MH/NIMH NIH HHS/United States
- HD02274/HD/NICHD NIH HHS/United States
- UL1 RR024922/RR/NCRR NIH HHS/United States
- RL1AG032119/AG/NIA NIH HHS/United States
- P30 AG010129-18/AG/NIA NIH HHS/United States
- P30 AG010129-19S1/AG/NIA NIH HHS/United States
- RL1 AG032119/AG/NIA NIH HHS/United States
- NS044299/NS/NINDS NIH HHS/United States
- UL1DE019583/DE/NIDCR NIH HHS/United States
- P30 AG010129/AG/NIA NIH HHS/United States
- RL1 AG032115/AG/NIA NIH HHS/United States
- NS062412/NS/NINDS NIH HHS/United States
LinkOut - more resources
Full Text Sources
Medical