A study of genetic and environmental contributions to structural brain changes over time in twins concordant and discordant for bipolar disorder

F. Bootsman*, R. M. Brouwer, H. G. Schnack, S. M. Kemner, M. H.J. Hillegers, G. Sarkisyan, A. C. van der Schot, R. Vonk, H. E. Hulshoff Pol, W. A. Nolen, R. S. Kahn, N. E.M. van Haren

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)116-124
Number of pages9
JournalJournal of Psychiatric Research
Publication statusPublished - 1 Aug 2016
Externally publishedYes

Bibliographical note

Funding Information:
Funding for this study was provided by the Netherlands Organization for Scientific Research (NWO), grant 9120818. The NWO had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Publisher Copyright:
© 2016 Elsevier Ltd.


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