Subcortical volumetric abnormalities in bipolar disorder

D. P. Hibar, L. T. Westlye, T. G M Van Erp, J. Rasmussen, C. D. Leonardo, J. Faskowitz, U. K. Haukvik, C. B. Hartberg, N. T. Doan, I. Agartz, A. M. Dale, O. Gruber, B. Krämer, S. Trost, B. Liberg, C. Abé, C. J. Ekman, M. Ingvar, M. Landén, S. C. FearsN. B. Freimer, C. E. Bearden, E. Sprooten, D. C. Glahn, G. D. Pearlson, L. Emsell, J. Kenney, C. Scanlon, C. McDonald, D. M. Cannon, J. Almeida, A. Versace, X. Caseras, N. S. Lawrence, M. L. Phillips, D. Dima, G. Delvecchio, S. Frangou, T. D. Satterthwaite, D. Wolf, J. Houenou, C. Henry, U. F. Malt, E. BØen, T. Elvs'shagen, A. H. Young, A. J. Lloyd, G. M. Goodwin, C. E. Mackay, C. Bourne, A. Bilderbeck, L. Abramovic, M. P. Boks, N. E M Van Haren, R. A. Ophoff, R. S. Kahn, M. Bauer, A. Pfennig, M. Alda, T. Hajek, B. Mwangi, J. C. Soares, T. Nickson, R. Dimitrova, J. E. Sussmann, S. Hagenaars, H. C. Whalley, A. M. McIntosh, P. M. Thompson, O. A. Andreassen

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1710-1716
Number of pages7
JournalMolecular Psychiatry
Volume21
Issue number12
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

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Bipolar Disorder
Lateral Ventricles
Hippocampus
Amygdala
Thalamus
Lithium
Uncertainty
Brain
Globus Pallidus
Putamen
Nucleus Accumbens
Age of Onset
Neuroimaging
Disease Progression
Biomarkers

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

Hibar, D. P., Westlye, L. T., Van Erp, T. G. M., Rasmussen, J., Leonardo, C. D., Faskowitz, J., ... Andreassen, O. A. (2016). Subcortical volumetric abnormalities in bipolar disorder. Molecular Psychiatry, 21(12), 1710-1716. https://doi.org/10.1038/mp.2015.227

Subcortical volumetric abnormalities in bipolar disorder. / Hibar, D. P.; Westlye, L. T.; Van Erp, T. G M; Rasmussen, J.; Leonardo, C. D.; Faskowitz, J.; Haukvik, U. K.; Hartberg, C. B.; Doan, N. T.; Agartz, I.; Dale, A. M.; Gruber, O.; Krämer, B.; Trost, S.; Liberg, B.; Abé, C.; Ekman, C. J.; Ingvar, M.; Landén, M.; Fears, S. C.; Freimer, N. B.; Bearden, C. E.; Sprooten, E.; Glahn, D. C.; Pearlson, G. D.; Emsell, L.; Kenney, J.; Scanlon, C.; McDonald, C.; Cannon, D. M.; Almeida, J.; Versace, A.; Caseras, X.; Lawrence, N. S.; Phillips, M. L.; Dima, D.; Delvecchio, G.; Frangou, S.; Satterthwaite, T. D.; Wolf, D.; Houenou, J.; Henry, C.; Malt, U. F.; BØen, E.; Elvs'shagen, T.; Young, A. H.; Lloyd, A. J.; Goodwin, G. M.; Mackay, C. E.; Bourne, C.; Bilderbeck, A.; Abramovic, L.; Boks, M. P.; Van Haren, N. E M; Ophoff, R. A.; Kahn, R. S.; Bauer, M.; Pfennig, A.; Alda, M.; Hajek, T.; Mwangi, B.; Soares, J. C.; Nickson, T.; Dimitrova, R.; Sussmann, J. E.; Hagenaars, S.; Whalley, H. C.; McIntosh, A. M.; Thompson, P. M.; Andreassen, O. A.

In: Molecular Psychiatry, Vol. 21, No. 12, 01.12.2016, p. 1710-1716.

Research output: Contribution to journalArticle

Hibar, DP, Westlye, LT, Van Erp, TGM, Rasmussen, J, Leonardo, CD, Faskowitz, J, Haukvik, UK, Hartberg, CB, Doan, NT, Agartz, I, Dale, AM, Gruber, O, Krämer, B, Trost, S, Liberg, B, Abé, C, Ekman, CJ, Ingvar, M, Landén, M, Fears, SC, Freimer, NB, Bearden, CE, Sprooten, E, Glahn, DC, Pearlson, GD, Emsell, L, Kenney, J, Scanlon, C, McDonald, C, Cannon, DM, Almeida, J, Versace, A, Caseras, X, Lawrence, NS, Phillips, ML, Dima, D, Delvecchio, G, Frangou, S, Satterthwaite, TD, Wolf, D, Houenou, J, Henry, C, Malt, UF, BØen, E, Elvs'shagen, T, Young, AH, Lloyd, AJ, Goodwin, GM, Mackay, CE, Bourne, C, Bilderbeck, A, Abramovic, L, Boks, MP, Van Haren, NEM, Ophoff, RA, Kahn, RS, Bauer, M, Pfennig, A, Alda, M, Hajek, T, Mwangi, B, Soares, JC, Nickson, T, Dimitrova, R, Sussmann, JE, Hagenaars, S, Whalley, HC, McIntosh, AM, Thompson, PM & Andreassen, OA 2016, 'Subcortical volumetric abnormalities in bipolar disorder', Molecular Psychiatry, vol. 21, no. 12, pp. 1710-1716. https://doi.org/10.1038/mp.2015.227
Hibar DP, Westlye LT, Van Erp TGM, Rasmussen J, Leonardo CD, Faskowitz J et al. Subcortical volumetric abnormalities in bipolar disorder. Molecular Psychiatry. 2016 Dec 1;21(12):1710-1716. https://doi.org/10.1038/mp.2015.227
Hibar, D. P. ; Westlye, L. T. ; Van Erp, T. G M ; Rasmussen, J. ; Leonardo, C. D. ; Faskowitz, J. ; Haukvik, U. K. ; Hartberg, C. B. ; Doan, N. T. ; Agartz, I. ; Dale, A. M. ; Gruber, O. ; Krämer, B. ; Trost, S. ; Liberg, B. ; Abé, C. ; Ekman, C. J. ; Ingvar, M. ; Landén, M. ; Fears, S. C. ; Freimer, N. B. ; Bearden, C. E. ; Sprooten, E. ; Glahn, D. C. ; Pearlson, G. D. ; Emsell, L. ; Kenney, J. ; Scanlon, C. ; McDonald, C. ; Cannon, D. M. ; Almeida, J. ; Versace, A. ; Caseras, X. ; Lawrence, N. S. ; Phillips, M. L. ; Dima, D. ; Delvecchio, G. ; Frangou, S. ; Satterthwaite, T. D. ; Wolf, D. ; Houenou, J. ; Henry, C. ; Malt, U. F. ; BØen, E. ; Elvs'shagen, T. ; Young, A. H. ; Lloyd, A. J. ; Goodwin, G. M. ; Mackay, C. E. ; Bourne, C. ; Bilderbeck, A. ; Abramovic, L. ; Boks, M. P. ; Van Haren, N. E M ; Ophoff, R. A. ; Kahn, R. S. ; Bauer, M. ; Pfennig, A. ; Alda, M. ; Hajek, T. ; Mwangi, B. ; Soares, J. C. ; Nickson, T. ; Dimitrova, R. ; Sussmann, J. E. ; Hagenaars, S. ; Whalley, H. C. ; McIntosh, A. M. ; Thompson, P. M. ; Andreassen, O. A. / Subcortical volumetric abnormalities in bipolar disorder. In: Molecular Psychiatry. 2016 ; Vol. 21, No. 12. pp. 1710-1716.
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AU - Hibar, D. P.

AU - Westlye, L. T.

AU - Van Erp, T. G M

AU - Rasmussen, J.

AU - Leonardo, C. D.

AU - Faskowitz, J.

AU - Haukvik, U. K.

AU - Hartberg, C. B.

AU - Doan, N. T.

AU - Agartz, I.

AU - Dale, A. M.

AU - Gruber, O.

AU - Krämer, B.

AU - Trost, S.

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AU - Abé, C.

AU - Ekman, C. J.

AU - Ingvar, M.

AU - Landén, M.

AU - Fears, S. C.

AU - Freimer, N. B.

AU - Bearden, C. E.

AU - Sprooten, E.

AU - Glahn, D. C.

AU - Pearlson, G. D.

AU - Emsell, L.

AU - Kenney, J.

AU - Scanlon, C.

AU - McDonald, C.

AU - Cannon, D. M.

AU - Almeida, J.

AU - Versace, A.

AU - Caseras, X.

AU - Lawrence, N. S.

AU - Phillips, M. L.

AU - Dima, D.

AU - Delvecchio, G.

AU - Frangou, S.

AU - Satterthwaite, T. D.

AU - Wolf, D.

AU - Houenou, J.

AU - Henry, C.

AU - Malt, U. F.

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AU - Young, A. H.

AU - Lloyd, A. J.

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AU - Bilderbeck, A.

AU - Abramovic, L.

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AU - Bauer, M.

AU - Pfennig, A.

AU - Alda, M.

AU - Hajek, T.

AU - Mwangi, B.

AU - Soares, J. C.

AU - Nickson, T.

AU - Dimitrova, R.

AU - Sussmann, J. E.

AU - Hagenaars, S.

AU - Whalley, H. C.

AU - McIntosh, A. M.

AU - Thompson, P. M.

AU - Andreassen, O. A.

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N2 - 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.

AB - 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.

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