Subcortical volumetric abnormalities in bipolar disorder.
van Erp, TG
Costa Rica/Colombia Consortium for Genetic Investigation of Bipolar Endophenotypes
van Haren, NE
Nature Publishing Group
This is the final version of the article. Available from Nature via the DOI in this record.
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.Molecular Psychiatry advance online publication, 9 February 2016; doi:10.1038/mp.2015.227.
We acknowledge members of the International Group for the Study of Lithium Treated Patients (IGSLi) and Costa Rica/Colombia Consortium for Genetic Investigation of Bipolar Endophenotypes. The Halifax studies have been supported by grants from Canadian Institutes of Health Research (103703, 106469 and 64410), the Nova Scotia Health Research Foundation, Dalhousie Clinical Research Scholarship to T Hajek. We also acknowledge research funding sources: TOP is supported by the Research Council of Norway, the South East Norway Health Authority, the Kristian Gerhard Jebsen Foundation and the European Community's Seventh Framework Programme (FP7/2007–2013), grant agreement no. 602450. Cardiff is supported by the National Centre for Mental Health (NCMH) and Bipolar Disorder Research Network (BDRN). The Paris sample is supported by the French National Agency for Research (MNP 2008) and the Fondamental Foundation. The St Göran bipolar project (SBP) is supported by grants from the Swedish Medical Research Council, the Swedish foundation for Strategic Research, the Swedish Brain foundation and the Swedish Federal Government under the LUA/ALF agreement. The Malt-Oslo sample is supported by the South East Norway Health Authority and by generous unrestricted grants from Mrs Throne-Holst. The UT Houston sample is supported by NIH grant, MH085667. TDS was supported by R01MH107703 and K23MH098130. The UCLA-BP study is supported by NIH grants R01MH075007, R01MH095454, P30NS062691 (NBF), K23MH074644-01 and the Joanne and George Miller Family Endowed Term Chair (CEB) and K08MH086786 (SF). Data collection for the UMCU sample is funded by the NIMH R01 MH090553 (PI Ophoff). The Oxford/Newcastle sample was funded by the Brain Behavior Research Foundation. ENIGMA was supported in part by a Consortium grant (U54 EB020403 to PMT) from the NIH Institutes contributing to the Big Data to Knowledge (BD2K) Initiative, including the NIBIB and NCI.