title: Subcortical volumetric abnormalities in bipolar disorder.
abstract: Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10-7) and thalamus (d=-0.148; P=4.27 × 10-3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10-5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.
authors: Imaging Genetics Center, University of Southern California, Los Angeles, CA, USA.
authors: D P
authors: DP
authors: Hibar
authors: Division of Mental Health and Addiction, Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.|Department of Psychology, University of Oslo, Oslo, Norway.
authors: L T
authors: LT
authors: Westlye
authors: Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
authors: T G M
authors: TG
authors: van Erp
authors: Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA.
authors: J
authors: J
authors: Rasmussen
authors: Imaging Genetics Center, University of Southern California, Los Angeles, CA, USA.
authors: C D
authors: CD
authors: Leonardo
authors: Imaging Genetics Center, University of Southern California, Los Angeles, CA, USA.
authors: J
authors: J
authors: Faskowitz
authors: Division of Mental Health and Addiction, Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.|Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
authors: U K
authors: UK
authors: Haukvik
authors: Division of Mental Health and Addiction, Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.
authors: C B
authors: CB
authors: Hartberg
authors: Division of Mental Health and Addiction, Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.
authors: N T
authors: NT
authors: Doan
authors: Division of Mental Health and Addiction, Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.|Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
authors: I
authors: I
authors: Agartz
authors: MMIL, Department of Radiology, University of California, San Diego, CA, USA.|Department of Cognitive Science, Neurosciences and Psychiatry, University of California, San Diego, CA, USA.
authors: A M
authors: AM
authors: Dale
authors: Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, Georg August University Goettingen, Goettingen, Germany.|Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
authors: O
authors: O
authors: Gruber
authors: Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, Georg August University Goettingen, Goettingen, Germany.
authors: B
authors: B
authors: Krämer
authors: Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, Georg August University Goettingen, Goettingen, Germany.
authors: S
authors: S
authors: Trost
authors: Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
authors: B
authors: B
authors: Liberg
authors: Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: C
authors: C
authors: Abé
authors: Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
authors: C J
authors: CJ
authors: Ekman
authors: Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden.|Karolinska MR Research Center, Karolinska Institutet, Stockholm, Sweden.|Department of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden.
authors: M
authors: M
authors: Ingvar
authors: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: M
authors: M
authors: Landén
authors: Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA.|Center for Neurobehavioral Genetics, University of California, Los Angeles, CA, USA.
authors: S C
authors: SC
authors: Fears
authors: Center for Neurobehavioral Genetics, University of California, Los Angeles, CA, USA.
authors: N B
authors: NB
authors: Freimer
authors: Center for Neurobehavioral Genetics, University of California, Los Angeles, CA, USA.|Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.|Department of Psychology, University of California, Los Angeles, CA, USA.
authors: C E
authors: CE
authors: Bearden
authors: Department of Psychiatry, Yale University, New Haven, CT, USA.|Olin Neuropsychiatric Research Center, Institute of Living, Hartford, CT, USA.
authors: E
authors: E
authors: Sprooten
authors: Department of Psychiatry, Yale University, New Haven, CT, USA.|Olin Neuropsychiatric Research Center, Institute of Living, Hartford, CT, USA.
authors: D C
authors: DC
authors: Glahn
authors: Department of Psychiatry, Yale University, New Haven, CT, USA.|Olin Neuropsychiatric Research Center, Institute of Living, Hartford, CT, USA.|Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA.
authors: G D
authors: GD
authors: Pearlson
authors: Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors: L
authors: L
authors: Emsell
authors: Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors: J
authors: J
authors: Kenney
authors: Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors: C
authors: C
authors: Scanlon
authors: Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors: C
authors: C
authors: McDonald
authors: Clinical Neuroimaging Laboratory, College of Medicine, Nursing and Health Sciences, National University of Ireland Galway, Galway, Ireland.
authors: D M
authors: DM
authors: Cannon
authors: Department of Psychiatry, Brown University, Providence, RI, USA.
authors: J
authors: J
authors: Almeida
authors: Department of Psychiatry, University of Pittsburgh, Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA.
authors: A
authors: A
authors: Versace
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors: X
authors: X
authors: Caseras
authors: School of Psychology, University of Exeter, Exeter, UK.
authors: N S
authors: NS
authors: Lawrence
authors: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors: M L
authors: ML
authors: Phillips
authors: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.|Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: D
authors: D
authors: Dima
authors: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
authors: G
authors: G
authors: Delvecchio
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: S
authors: S
authors: Frangou
authors: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors: T D
authors: TD
authors: Satterthwaite
authors: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors: D
authors: D
authors: Wolf
authors: Neurospin, Uniact, I2BM, CEA Saclay, Saclay, France.|Inserm, U955, Equipe 15 Psychiatrie génétique, Créteil, France.
authors: J
authors: J
authors: Houenou
authors: Inserm, U955, Equipe 15 Psychiatrie génétique, Créteil, France.|Université Paris-Est, UMR-S955, UPEC, Créteil, France.
authors: C
authors: C
authors: Henry
authors: Department of Psychosomatic Medicine, Oslo University Hospital-Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Research and Education, Oslo University Hospital, Oslo, Norway.
authors: U F
authors: UF
authors: Malt
authors: Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.|Department of Psychosomatic Medicine, Oslo University Hospital-Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Norwegian Research Network On Mood Disorders, Oslo, Norway.
authors: E
authors: E
authors: Bøen
authors: Division of Mental Health and Addiction, Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.|Department of Psychosomatic Medicine, Oslo University Hospital-Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors: T
authors: T
authors: Elvsåshagen
authors: Centre for Affective Disorders, King's College London, London, UK.
authors: A H
authors: AH
authors: Young
authors: Academic Psychiatry and Regional Affective Disorders Service, Newcastle University, Newcastle, UK.
authors: A J
authors: AJ
authors: Lloyd
authors: Department of Psychiatry, University of Oxford, Oxford, UK.
authors: G M
authors: GM
authors: Goodwin
authors: Department of Psychiatry, University of Oxford, Oxford, UK.
authors: C E
authors: CE
authors: Mackay
authors: Department of Psychiatry, University of Oxford, Oxford, UK.|Department of Psychology and Counselling, Newman University, Birmingham, UK.
authors: C
authors: C
authors: Bourne
authors: Department of Psychiatry, University of Oxford, Oxford, UK.|University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford, UK.
authors: A
authors: A
authors: Bilderbeck
authors: Department of Psychiatry, University Medical Centre Utrecht - Brain Centre Rudolf Magnus, Utrecht, The Netherlands.
authors: L
authors: L
authors: Abramovic
authors: Department of Psychiatry, University Medical Centre Utrecht - Brain Centre Rudolf Magnus, Utrecht, The Netherlands.
authors: M P
authors: MP
authors: Boks
authors: Department of Psychiatry, University Medical Centre Utrecht - Brain Centre Rudolf Magnus, Utrecht, The Netherlands.
authors: N E M
authors: NE
authors: van Haren
authors: Center for Neurobehavioral Genetics, University of California, Los Angeles, CA, USA.|Department of Psychiatry, University Medical Centre Utrecht - Brain Centre Rudolf Magnus, Utrecht, The Netherlands.
authors: R A
authors: RA
authors: Ophoff
authors: Department of Psychiatry, University Medical Centre Utrecht - Brain Centre Rudolf Magnus, Utrecht, The Netherlands.
authors: R S
authors: RS
authors: Kahn
authors: Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Medizinische Fakultät, Technische Universität Dresden, Dresden, Germany.
authors: M
authors: M
authors: Bauer
authors: Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Medizinische Fakultät, Technische Universität Dresden, Dresden, Germany.
authors: A
authors: A
authors: Pfennig
authors: Department of Psychiatry, Dalhousie University, Halifax, Canada.
authors: M
authors: M
authors: Alda
authors: Department of Psychiatry, Dalhousie University, Halifax, Canada.|National Institute of Mental Health, Klecany, Czech Republic.
authors: T
authors: T
authors: Hajek
authors: UT Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, UT Houston Medical School, Houston, TX, USA.
authors: B
authors: B
authors: Mwangi
authors: UT Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, UT Houston Medical School, Houston, TX, USA.
authors: J C
authors: JC
authors: Soares
authors: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors: T
authors: T
authors: Nickson
authors: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors: R
authors: R
authors: Dimitrova
authors: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors: J E
authors: JE
authors: Sussmann
authors: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors: S
authors: 0000-0001-9697-8596
authors: S
authors: Hagenaars
authors: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors: H C
authors: HC
authors: Whalley
authors: Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
authors: A M
authors: AM
authors: McIntosh
authors: Imaging Genetics Center, University of Southern California, Los Angeles, CA, USA.|Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
authors: P M
authors: PM
authors: Thompson
authors: Division of Mental Health and Addiction, Norwegian Centre for Mental Disorders Research, KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway.
authors: O A
authors: OA
authors: Andreassen
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000503:physiopathology*; D001921:Brain / Q000033:anatomy & histology / Q000503:physiopathology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000502:physiology; D012189:Retrospective Studies