title: Ages of Onset of Mood and Anxiety Disorders in Fragile X Premutation Carriers.
abstract: OBJECTIVE
  FMR1premutation carriers of both genders have a high lifetime prevalence of anxiety and depressive disorders, however little is known regarding the onset ages of these conditions. This study compared onset ages of mood and anxiety disorders in premutation carriers with typical onset ages of the same disorders in the general population.
  
  
  METHODS
  Eighty-one premutation carriers (42% men; average age 62, SD 10) with and without FXTAS completed the Structured Clinical Interview for DSM-IV-TR. Onset ages of mood and anxiety disorders were compared to the corresponding typical population onset ages using the signed rank test.
  
  
  RESULTS
  Overall median onset ages of MDD (46 years old, p < 0.0001), panic disorder (40 years old, p = 0.0067), and specific phobia (11.5 years old, p = 0.0003) were significantly higher in premutation carriers compared to the general population. Median MDD onset ages in male carriers (52 years old) and those with FXTAS (49.5 years old) were significantly higher relative to the general population (median 32, both p < 0.0001). Tremor and ataxia emerged significantly later than MDD and the anxiety disorders studied.
  
  
  CONCLUSIONS
  Depressive and anxiety disorders in premutation carriers have a later onset compared to the general population, but precede the onset of motor symptoms. This may be due to progressive mRNA toxicity in the limbic system, white matter changes leading to neuronal dysconnectivity, and interaction with environmental factors. Psychosocial factors may be protective. Further research is needed to understand the full spectrum of psychiatric phenotypes inFMR1premutation carriers.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of California Davis Medical Center, Sacramento, California ; Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California Davis Medical Center, Sacramento, California.
authors.forename: Andreea L
authors.initials: AL
authors.lastname: Seritan
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: James A
authors.initials: JA
authors.lastname: Bourgeois
authors.affiliation: Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California Davis Medical Center, Sacramento, California ; Department of Pediatrics, University of California Davis Medical Center, Sacramento, California.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schneider
authors.affiliation: Department of Public Health Sciences, University of California Davis, Davis, California.
authors.forename: Yi
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute, University of California Davis Medical Center, Sacramento, California ; Department of Pediatrics, University of California Davis Medical Center, Sacramento, California.
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
authors.affiliation: Department of Public Health Sciences, University of California Davis, Davis, California.
authors.forename: Danh V
authors.initials: DV
authors.lastname: Nguyen
keywords: FMR1 premutation; MDD; anxiety; depression; fragile X tremor/ataxia syndrome (FXTAS); onset age
references.citation: Neurology. 2010 Oct 12;75(15):1370-6
references.pmid: 20938029
references.citation: Am J Med Genet A. 2008 Mar 15;146A(6):720-9
references.pmid: 18266246
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2009 Jan 5;150B(1):130-9
references.pmid: 18553360
references.citation: Psychol Med. 2007 Jul;37(7):1047-59
references.pmid: 17335637
references.citation: J Neurol Neurosurg Psychiatry. 2008 Jun;79(6):738-9
references.pmid: 18487560
references.citation: Ther Adv Neurol Disord. 2009 Jan;2(1):13-29
references.pmid: 21180640
references.citation: Aging Ment Health. 2010 Nov;14(8):1000-7
references.pmid: 21069606
references.citation: J Clin Exp Neuropsychol. 2008 Nov;30(8):853-69
references.pmid: 18608667
references.citation: J Neurol Neurosurg Psychiatry. 2009 Jul;80(7):812-4
references.pmid: 19531693
references.citation: Mult Scler. 2010 Jun;16(6):742-8
references.pmid: 20350959
references.citation: JAMA. 2003 Jun 18;289(23):3095-105
references.pmid: 12813115
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: J Clin Psychiatry. 2008 Oct;69(10):1606-16
references.pmid: 19192444
references.citation: J Psychiatr Res. 2011 Jan;45(1):111-20
references.pmid: 20684833
references.citation: Am J Hum Genet. 2000 Jan;66(1):6-15
references.pmid: 10631132
references.citation: J Mol Diagn. 2008 Jan;10(1):43-9
references.pmid: 18165273
references.citation: Psychol Med. 1999 May;29(3):539-53
references.pmid: 10405076
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2005 Nov 5;139B(1):115-21
references.pmid: 16184602
references.citation: J Med Genet. 2008 Aug;45(8):498-9
references.pmid: 18413371
references.citation: Acta Neuropathol. 2011 Oct;122(4):467-79
references.pmid: 21785977
references.citation: Mov Disord. 2011 Jun;26(7):1329-36
references.pmid: 21484870
references.citation: Am J Hum Genet. 2004 May;74(5):1051-6
references.pmid: 15065016
references.citation: Eur J Hum Genet. 2009 Oct;17(10):1359-62
references.pmid: 19367323
references.citation: Soc Psychiatry Psychiatr Epidemiol. 2010 Dec;45(12):1161-6
references.pmid: 19888542
references.citation: J Wound Ostomy Continence Nurs. 2006 Jan-Feb;33(1):26-9
references.pmid: 16444100
references.citation: J Urol. 2007 Apr;177(4):1434-7
references.pmid: 17382748
references.citation: JAMA. 2004 Jan 28;291(4):460-9
references.pmid: 14747503
references.citation: Neurology. 2001 Jul 10;57(1):127-30
references.pmid: 11445641
references.citation: Am J Med Genet A. 2008 Apr 15;146A(8):1009-16
references.pmid: 18348275
references.citation: J Clin Psychiatry. 2006 Jan;67(1):87-94
references.pmid: 16426093
references.citation: Arch Gen Psychiatry. 2008 May;65(5):513-20
references.pmid: 18458203
references.citation: Alzheimer Dis Assoc Disord. 2007 Jul-Sep;21(3):262-4
references.pmid: 17804960
references.citation: Lancet Neurol. 2011 Jan;10(1):83-98
references.pmid: 21163446
references.citation: Int Clin Psychopharmacol. 2010 May;25(3):172-9
references.pmid: 20305566
references.citation: Psychol Med. 2007 Jun;37(6):883-91
references.pmid: 17306047
references.citation: J Neuropsychiatry Clin Neurosci. 2006 Spring;18(2):171-7
references.pmid: 16720793
references.citation: Arch Gen Psychiatry. 2005 Jun;62(6):593-602
references.pmid: 15939837
references.citation: Gen Hosp Psychiatry. 2007 Jul-Aug;29(4):349-56
references.pmid: 17591512
references.citation: J Neurol Sci. 2006 Oct 25;248(1-2):227-33
references.pmid: 16780889
references.citation: Addiction. 2004 Jul;99(7):885-96
references.pmid: 15200584
references.citation: PLoS Curr. 2010 Sep 28;2:
references.pmid: 20890398
references.citation: Ment Retard Dev Disabil Res Rev. 2004;10(1):25-30
references.pmid: 14994285
references.citation: Cogn Behav Neurol. 2010 Mar;23(1):39-43
references.pmid: 20299862
references.citation: Brain. 2006 Jan;129(Pt 1):243-55
references.pmid: 16332642
references.citation: Mov Disord. 2007 Apr 15;22(5):645-50
references.pmid: 17266074
references.citation: Rheumatology (Oxford). 2011 Dec;50(12):2233-6
references.pmid: 21926154
references.citation: Clin Genet. 2010 Jul;78(1):38-46
references.pmid: 20497189
references.citation: J Clin Psychiatry. 2011 Feb;72(2):175-82
references.pmid: 20816038
references.citation: Arch Gen Psychiatry. 2006 Apr;63(4):415-24
references.pmid: 16585471
references.citation: Am J Hum Genet. 2003 Apr;72(4):869-78
references.pmid: 12638084
references.citation: Am J Med Genet A. 2009 Nov;149A(11):2501-6
references.pmid: 19842197
references.citation: Mov Disord. 2007 Jan 15;22(2):203-6
references.pmid: 17133502
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2008 Oct 5;147B(7):1138-44
references.pmid: 18384046
references.citation: Psychiatr Genet. 2008 Aug;18(4):153-5
references.pmid: 18628675