title: White-matter microstructure and gray-matter volumes in adolescents with subthreshold bipolar symptoms.
abstract: Abnormalities in white-matter (WM) microstructure, as lower fractional anisotropy (FA), have been reported in adolescent-onset bipolar disorder and in youth at familial risk for bipolarity. We sought to determine whether healthy adolescents with subthreshold bipolar symptoms (SBP) would have early WM microstructural alterations and whether those alterations would be associated with differences in gray-matter (GM) volumes. Forty-two adolescents with three core manic symptoms and no psychiatric diagnosis, and 126 adolescents matched by age and sex, with no psychiatric diagnosis or symptoms, were identified after screening the IMAGEN database of 2223 young adolescents recruited from the general population. After image quality control, voxel-wise statistics were performed on the diffusion parameters using tract-based spatial statistics in 25 SBP adolescents and 77 controls, and on GM and WM images using voxel-based morphometry in 30 SBP adolescents and 106 controls. As compared with healthy controls, adolescents with SBP displayed lower FA values in a number of WM tracts, particularly in the corpus callosum, cingulum, bilateral superior and inferior longitudinal fasciculi, uncinate fasciculi and corticospinal tracts. Radial diffusivity was mainly higher in posterior parts of bilateral superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculi and right cingulum. As compared with controls, SBP adolescents had lower GM volume in the left anterior cingulate region. This is the first study to investigate WM microstructure and GM morphometric variations in adolescents with SBP. The widespread FA alterations in association and projection tracts, associated with GM changes in regions involved in mood disorders, suggest altered structural connectivity in those adolescents.
authors: 1] AP-HP, Department of Adolescent Psychopathology and Medicine, Maison de Solenn, Cochin Hospital, Paris, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France [3] INSERM, UMR 1000, Research unit Imaging and Psychiatry, IFR49, CEA, DSV, IBM-Service Hospitalier Frédéric Joliot, Orsay, France [4] Université Paris-Sud 11, Orsay, France.
authors: M-L
authors: ML
authors: Paillère Martinot
authors: 1] Université Paris Descartes, Sorbonne Paris Cité, Paris, France [2] INSERM, UMR 1000, Research unit Imaging and Psychiatry, IFR49, CEA, DSV, IBM-Service Hospitalier Frédéric Joliot, Orsay, France [3] Université Paris-Sud 11, Orsay, France.
authors: H
authors: H
authors: Lemaitre
authors: 1] Université Paris Descartes, Sorbonne Paris Cité, Paris, France [2] INSERM, UMR 1000, Research unit Imaging and Psychiatry, IFR49, CEA, DSV, IBM-Service Hospitalier Frédéric Joliot, Orsay, France [3] Université Paris-Sud 11, Orsay, France [4] Psychiatry Department 91G16, Orsay Hospital, Orsay, France.
authors: E
authors: E
authors: Artiges
authors: 1] Université Paris Descartes, Sorbonne Paris Cité, Paris, France [2] INSERM, UMR 1000, Research unit Imaging and Psychiatry, IFR49, CEA, DSV, IBM-Service Hospitalier Frédéric Joliot, Orsay, France [3] Université Paris-Sud 11, Orsay, France.
authors: R
authors: R
authors: Miranda
authors: Institute of Psychiatry, King's College London, London, UK.
authors: R
authors: R
authors: Goodman
authors: University of Tampere, School of Medicine, Tampere, Finland.
authors: J
authors: J
authors: Penttilä
authors: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors: M
authors: M
authors: Struve
authors: Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany.
authors: T
authors: T
authors: Fadai
authors: Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Charité-Universitätsmedizin, Berlin, Germany.
authors: V
authors: V
authors: Kappel
authors: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors: L
authors: L
authors: Poustka
authors: 1] Institute of Psychiatry, King's College London, London, UK [2] Department of Psychiatry, Université de Montréal, CHU Ste Justine Hospital, Montréal, QC, Canada.
authors: P
authors: P
authors: Conrod
authors: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors: T
authors: T
authors: Banaschewski
authors: Neurospin, Commissariat à l'Energie Atomique et aux Energies Alternatives, Paris, France.
authors: A
authors: A
authors: Barbot
authors: Institute of Psychiatry, King's College London, London, UK.
authors: G J
authors: GJ
authors: Barker
authors: Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany.
authors: C
authors: C
authors: Büchel
authors: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors: H
authors: H
authors: Flor
authors: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin, Berlin, Germany.
authors: J
authors: J
authors: Gallinat
authors: 1] Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland [2] Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
authors: H
authors: H
authors: Garavan
authors: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin, Berlin, Germany.
authors: A
authors: A
authors: Heinz
authors: Physikalisch-Technische Bundesanstalt (PTB), Braunschweig und Berlin, Germany.
authors: B
authors: B
authors: Ittermann
authors: School of Psychology, University of Nottingham, Nottingham, UK.
authors: C
authors: C
authors: Lawrence
authors: 1] Institute of Psychiatry, King's College London, London, UK [2] MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, UK.
authors: E
authors: E
authors: Loth
authors: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors: K
authors: K
authors: Mann
authors: 1] School of Psychology, University of Nottingham, Nottingham, UK [2] Rotman Research Institute, University of Toronto, Toronto, ON, Canada [3] Montreal Neurological Institute, McGill University, Toronto, QC, Canada.
authors: T
authors: T
authors: Paus
authors: Department of Physiology and Nutritional Sciences, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors: Z
authors: Z
authors: Pausova
authors: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
authors: M
authors: M
authors: Rietschel
authors: Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.
authors: T W
authors: TW
authors: Robbins
authors: 1] Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany [2] Neuroimaging Center, Department of Psychology, Technische Universität Dresden, Dresden, Germany.
authors: M N
authors: MN
authors: Smolka
authors: 1] Institute of Psychiatry, King's College London, London, UK [2] MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, UK.
authors: G
authors: G
authors: Schumann
authors: 1] Université Paris Descartes, Sorbonne Paris Cité, Paris, France [2] INSERM, UMR 1000, Research unit Imaging and Psychiatry, IFR49, CEA, DSV, IBM-Service Hospitalier Frédéric Joliot, Orsay, France [3] Université Paris-Sud 11, Orsay, France.
authors: J-L
authors: JL
authors: Martinot
mesh_terms: D000293:Adolescent; D016880:Anisotropy; D001714:Bipolar Disorder / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D016009:Chi-Square Distribution; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D011569:Psychiatric Status Rating Scales; D057566:Self Report
references: Biol Psychiatry. 2009 Aug 1;66(3):238-44
references: 19389661
references: Neuroimage. 2010 Jan 1;49(1):94-103
references: 19679191
references: Arch Gen Psychiatry. 2010 Mar;67(3):270-6
references: 20194827
references: Dev Psychobiol. 2010 Apr;52(3):225-35
references: 20222060
references: Bipolar Disord. 2000 Sep;2(3 Pt 2):281-93
references: 11249806
references: Neuroimage. 2011 Jul 1;57(1):214-224
references: 21511039
references: Am J Psychiatry. 2005 Jul;162(7):1256-65
references: 15994707
references: Neuroimage. 2008 Apr 1;40(2):570-582
references: 18255316
references: J Nerv Ment Dis. 1983 Nov;171(11):676-82
references: 6631433
references: Addiction. 1993 Jun;88(6):791-804
references: 8329970
references: Neuropsychopharmacology. 2011 Feb;36(3):684-91
references: 21085111
references: Arch Gen Psychiatry. 2006 Oct;63(10):1139-48
references: 17015816
references: J Child Psychol Psychiatry. 2000 Jul;41(5):645-55
references: 10946756
references: J Am Acad Child Adolesc Psychiatry. 1995 Apr;34(4):454-63
references: 7751259
references: J Clin Psychiatry. 2005;66 Suppl 7:21-8
references: 16124838
references: Brain Imaging Behav. 2010 Dec;4(3-4):220-31
references: 20686873
references: J Neurosci. 2008 Sep 17;28(38):9519-24
references: 18799683
references: Proc Natl Acad Sci U S A. 2010 May 25;107(21):9885-90
references: 20457896
references: Neuroimage. 2008 Apr 15;40(3):1044-55
references: 18295509
references: J Am Acad Child Adolesc Psychiatry. 2008 May;47(5):532-539
references: 18356765
references: J Child Psychol Psychiatry. 2009 Dec;50(12):1485-94
references: 19573034
references: Arch Gen Psychiatry. 2005 Jul;62(7):734-41
references: 15997014
references: Neuroimage. 2011 Jan 1;54(1):25-31
references: 20708693
references: IEEE Trans Med Imaging. 1999 Aug;18(8):712-21
references: 10534053
references: Bipolar Disord. 2012 Jun;14(4):313-25
references: 22631617
references: Proc Natl Acad Sci U S A. 2004 May 25;101(21):8174-9
references: 15148381
references: Am J Psychiatry. 2009 Jul;166(7):795-804
references: 19448190
references: Neurosci Biobehav Rev. 2010 Mar;34(4):533-54
references: 19896972
references: J Am Acad Child Adolesc Psychiatry. 2010 Feb;49(2):173-83.e1
references: 20215939
references: Brain Struct Funct. 2008 Sep;213(1-2):93-118
references: 18704495
references: Cereb Cortex. 2010 Sep;20(9):2122-31
references: 20051363
references: Bipolar Disord. 2012 Sep;14(6):585-96
references: 22938166
references: Hum Brain Mapp. 2002 Nov;17(3):143-55
references: 12391568
references: Neuroimage. 2003 Jul;19(3):1233-9
references: 12880848
references: Neuroimage. 2010 Aug 15;52(2):415-28
references: 20420929
references: Neuroimage. 2006 Jul 15;31(4):1487-505
references: 16624579
references: Am J Psychiatry. 2005 Sep;162(9):1637-43
references: 16135622
references: NMR Biomed. 2012 Jul;25(7):900-8
references: 22246940
references: Nat Rev Neurosci. 2008 Dec;9(12):947-57
references: 19002191
references: Psychiatry Res. 2004 May 30;131(1):57-69
references: 15246455
references: J Abnorm Child Psychol. 2011 Oct;39(7):925-37
references: 21625986
references: Psychol Med. 2010 Feb;40(2):289-99
references: 19515266
references: Compr Psychiatry. 1965 Oct;6(5):313-22
references: 5825998
references: Am J Psychiatry. 2006 Feb;163(2):322-4
references: 16449490
references: Psychol Med. 1998 Jan;28(1):51-61
references: 9483683
references: Biol Psychiatry. 2006 Apr 1;59(7):611-8
references: 16414030
references: Bipolar Disord. 2007 Dec;9(8):799-809
references: 18076529
references: Neuroimage. 2006 Apr 1;30(2):485-97
references: 16256376
references: Trends Cogn Sci. 2000 Jun;4(6):215-222
references: 10827444
references: J Child Psychol Psychiatry. 1997 Jul;38(5):581-6
references: 9255702
references: Neurosci Lett. 2004 Jun 3;363(1):65-8
references: 15157998
references: Br J Psychiatry. 2010 Feb;196(2):102-8
references: 20118453
references: J Am Acad Child Adolesc Psychiatry. 2010 Dec;49(12):1249-59, 1259.e1
references: 21093774
references: Bipolar Disord. 2011 Nov-Dec;13(7-8):587-603
references: 22085472
references: Bipolar Disord. 2004 Feb;6(1):43-52
references: 14996140
references: Psychiatry Res. 2011 Dec 30;194(3):319-325
references: 22041532
references: Mol Psychiatry. 2010 Dec;15(12):1128-39
references: 21102431
references: J Youth Adolesc. 1988 Apr;17(2):117-33
references: 24277579
references: J Am Acad Child Adolesc Psychiatry. 2011 Oct;50(10):1017-26
references: 21961776
references: Neuroimage. 2007 Jul 1;36(3):630-44
references: 17481925
references: Neuroimage. 2005 Jul 1;26(3):839-51
references: 15955494
references: J Child Psychol Psychiatry. 2007 Sep;48(9):852-62
references: 17714370
references: Science. 1999 Mar 19;283(5409):1908-11
references: 10082463
references: BMC Med. 2004 Jan 29;2:2
references: 14969587
references: Neuroimage. 2002 Nov;17(3):1429-36
references: 12414282
references: J Am Acad Child Adolesc Psychiatry. 2011 Oct;50(10):1001-16.e3
references: 21961775