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. 2016 Dec;21(12):1710-1716.
doi: 10.1038/mp.2015.227. Epub 2016 Feb 9.

Subcortical Volumetric Abnormalities in Bipolar Disorder

D P Hibar  1 L T Westlye  2   3 T G M van Erp  4 J Rasmussen  4 C D Leonardo  1 J Faskowitz  1 U K Haukvik  2   5 C B Hartberg  2 N T Doan  2 I Agartz  2   5 A M Dale  6   7 O Gruber  8   9 B Krämer  8 S Trost  8 B Liberg  10 C Abé  11 C J Ekman  10 M Ingvar  11   12   13 M Landén  14   15 S C Fears  16   17 N B Freimer  17 C E Bearden  17   18   19 Costa Rica/Colombia Consortium for Genetic Investigation of Bipolar EndophenotypesE Sprooten  20   21 D C Glahn  20   21 G D Pearlson  20   21   22 L Emsell  23 J Kenney  23 C Scanlon  23 C McDonald  23 D M Cannon  23 J Almeida  24 A Versace  25 X Caseras  26 N S Lawrence  27 M L Phillips  26 D Dima  28   29 G Delvecchio  28 S Frangou  29 T D Satterthwaite  30 D Wolf  30 J Houenou  31   32 C Henry  32   33 U F Malt  34   35   36 E Bøen  5   34   35   37 T Elvsåshagen  2   34   35   38 A H Young  39 A J Lloyd  40 G M Goodwin  41 C E Mackay  41 C Bourne  41   42 A Bilderbeck  41   43 L Abramovic  44 M P Boks  44 N E M van Haren  44 R A Ophoff  17   44 R S Kahn  44 M Bauer  45 A Pfennig  45 M Alda  46 T Hajek  46   47 B Mwangi  48 J C Soares  48 T Nickson  49 R Dimitrova  49 J E Sussmann  49 S Hagenaars  49 H C Whalley  49 A M McIntosh  49 P M Thompson  1   18 O A Andreassen  2
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Free PMC article

Subcortical Volumetric Abnormalities in Bipolar Disorder

D P Hibar et al. Mol Psychiatry. .
Free PMC article

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.

Figures

Figure 1
Figure 1
Adjusted Cohen's d estimates for all BD patients versus controls. Effect sizes for the volumetric differences between bipolar disorder (BD) cases and controls (CTL), after accounting for age, sex and intracranial volume over all brain regions of interest. Error bars show mean effect size ± s.e.m. Effect sizes were considered significant (marked with *) if they exceeded the study-wide significance threshold (P<4.91 × 10−3).
Figure 2
Figure 2
Adjusted Cohen's d estimates for BD patients split by diagnosis subtype (type I or type II) versus controls. Effect sizes for the volumetric differences between bipolar disorder (BD) type I and controls (CTL) are shown in red and BD II and controls are shown in green. All effect sizes are reported after accounting for age, sex and intracranial volume. Error bars show mean effect size ± s.e.m. Effect sizes were considered significant (marked with *) if they exceeded the study-wide significance threshold (P<4.91 × 10−3).

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