title: A study of genetic and environmental contributions to structural brain changes over time in twins concordant and discordant for bipolar disorder.
abstract: This is the first longitudinal twin study examining genetic and environmental contributions to the association between liability to bipolar disorder (BD) and changes over time in global brain volumes, and global and regional measures of cortical surface area, cortical thickness and cortical volume. A total of 50 twins from pairs discordant or concordant for BD (monozygotic: 8 discordant and 3 concordant pairs, and 1 patient and 3 co-twins from incomplete pairs; dizygotic: 6 discordant and 2 concordant pairs, and 1 patient and 7 co-twins from incomplete pairs) underwent magnetic resonance imaging twice. In addition, 57 twins from healthy twin pairs (15 monozygotic and 10 dizygotic pairs, and 4 monozygotic and 3 dizygotic subjects from incomplete pairs) were also scanned twice. Mean follow-up duration for all twins was 7.5 years (standard deviation: 1.5 years). Data were analyzed using structural equation modeling software OpenMx. The liability to BD was not associated with global or regional structural brain changes over time. Although we observed a subtle increase in cerebral white matter in BD patients, this effect disappeared after correction for multiple comparisons. Heritability of brain changes over time was generally low to moderate. Structural brain changes appear to follow similar trajectories in BD patients and healthy controls. Existing brain abnormalities in BD do not appear to progressively change over time, but this requires additional confirmation. Further study with large cohorts is recommended to assess genetic and environmental influences on structural brain abnormalities in BD, while taking into account the influence of lithium on the brain.
authors.affiliation: University Medical Center Utrecht Brain Center Rudolf Magnus, Utrecht, The Netherlands. Electronic address: f.bootsman@umcutrecht.nl.
authors.forename: F
authors.initials: F
authors.lastname: Bootsman
authors.affiliation: University Medical Center Utrecht Brain Center Rudolf Magnus, Utrecht, The Netherlands.
authors.forename: R M
authors.initials: RM
authors.lastname: Brouwer
authors.affiliation: University Medical Center Utrecht Brain Center Rudolf Magnus, Utrecht, The Netherlands.
authors.forename: H G
authors.initials: HG
authors.lastname: Schnack
authors.affiliation: University Medical Center Utrecht Brain Center Rudolf Magnus, Utrecht, The Netherlands.
authors.forename: S M
authors.initials: SM
authors.lastname: Kemner
authors.affiliation: University Medical Center Utrecht Brain Center Rudolf Magnus, Utrecht, The Netherlands.
authors.forename: M H J
authors.initials: MHJ
authors.lastname: Hillegers
authors.affiliation: University Medical Center Utrecht Brain Center Rudolf Magnus, Utrecht, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Sarkisyan
authors.affiliation: Alzheimer Nederland, Amersfoort, The Netherlands.
authors.forename: A C
authors.initials: AC
authors.lastname: van der Schot
authors.affiliation: Reinier van Arkel, 's-Hertogenbosch, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Vonk
authors.affiliation: University Medical Center Utrecht Brain Center Rudolf Magnus, Utrecht, The Netherlands.
authors.forename: H E
authors.initials: HE
authors.lastname: Hulshoff Pol
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Psychiatry, Groningen, The Netherlands.
authors.forename: W A
authors.initials: WA
authors.lastname: Nolen
authors.affiliation: University Medical Center Utrecht Brain Center Rudolf Magnus, Utrecht, The Netherlands.
authors.forename: R S
authors.initials: RS
authors.lastname: Kahn
authors.affiliation: University Medical Center Utrecht Brain Center Rudolf Magnus, Utrecht, The Netherlands.
authors.forename: N E M
authors.initials: NEM
authors.lastname: van Haren
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects; D004200:Diseases in Twins; D005260:Female; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D006801:Humans; D018020:Lithium Compounds / Q000627:therapeutic use; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009929:Organ Size; D012959:Socioeconomic Factors; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds
keywords: Bipolar disorder; Brain volume; Cortex; Heritability; Longitudinal twin study; Magnetic resonance imaging