Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis

T Wise¹, J Radua^{2

3

4}, E Via^{5

6}, N Cardoner⁵, O Abe⁷, T M Adams¹, F Amico⁸, Y Cheng⁹, J H Cole¹⁰, C de Azevedo Marques Périco^{11

12}, D P Dickstein¹³, T F D Farrow¹⁴, T Frodl^{15

16}, G Wagner¹⁷, I H Gotlib¹⁸, O Gruber¹⁹, B J Ham²⁰, D E Job^{21

22

23}, M J Kempton^{2

24}, M J Kim²⁵, P C M P Koolschijn²⁶, G S Malhi²⁷, D Mataix-Cols^{2

4}, A M McIntosh²⁸, A C Nugent²⁹, J T O'Brien^{30

31}, S Pezzoli^{2

32}, M L Phillips³³, P S Sachdev^{34

35}, G Salvadore³⁶, S Selvaraj³⁷, A C Stanfield³⁸, A J Thomas³⁰, M J van Tol³⁹, N J A van der Wee^{40

41}, D J Veltman⁴², A H Young¹, C H Fu^{1

43}, A J Cleare¹, D Arnone¹

Affiliations

¹ Department of Psychological Medicine, Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
² Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
³ Research Unit, FIDMAG Germanes Hospitalàries - CIBERSAM, Sant Boi de Llobregat, Barcelona, Spain.
⁴ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁵ Mental Health, Parc Taulí Sabadell-CIBERSAM, University Hospital, Sabadell, Barcelona, Spain.
⁶ Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain.
⁷ Department of Radiology, Nihon University School of Medicine, Tokyo, Japan.
⁸ Department of Psychiatry, Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland.
⁹ Department of Psychiatry, The 1st Affiliated Hospital of Kunming Medical University, Kunming, PR China.
¹⁰ Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, London, UK.
¹¹ Department of Neuroscience, Medical School, Fundação do ABC, Santo André, SP, Brazil.
¹² ABC Center of Studies on Mental Health, Santo André, SP, Brazil.
¹³ PediMIND Program, Bradley Hospital, Department of Psychiatry, Brown University, East Providence, RI, USA.
¹⁴ Academic Clinical Neurology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
¹⁵ Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany.
¹⁶ Department of Psychiatry, University of Dublin, Trinity College, Dublin, Ireland.
¹⁷ Psychiatric Brain and Body Research Group Jena, Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
¹⁸ Department of Psychology, Stanford University, Stanford, CA, USA.
¹⁹ Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
²⁰ Department of Psychiatry, Korea University College of Medicine, Seoul, South Korea.
²¹ Neuroimaging Sciences, University of Edinburgh, Edinburgh, UK.
²² Scottish Imaging Network-A Platform for Scientific Excellence (SINAPSE), Giffnock, UK.
²³ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
²⁴ Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁵ Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA.
²⁶ Department of Psychology, Dutch Autism and ADHD Research Center, Brain and Cognition, University of Amsterdam, Amsterdam, The Netherlands.
²⁷ CADE Clinic, Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
²⁸ Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
²⁹ Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
³⁰ Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK.
³¹ Department of Psychiatry, University of Cambridge, Cambridge, UK.
³² Department of Neuroscience, Medical School, University of Sheffield, Sheffield, UK.
³³ Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, PA.
³⁴ Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Randwick, NSW, Australia.
³⁵ Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Australia.
³⁶ Janssen Research and Development, Titusville, NJ, USA.
³⁷ Department of Psychiatry and Behavioral Sciences, Center of Excellence on Mood Disorders, Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
³⁸ The Patrick Wild Centre, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK.
³⁹ NeuroImaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁴⁰ Department of Psychiatry, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.
⁴¹ Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
⁴² Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
⁴³ School of Psychology, University of East London, London, UK.

PMID: 27217146
PMCID: PMC5622121
DOI: 10.1038/mp.2016.72

Meta-Analysis

Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis

T Wise et al. Mol Psychiatry. 2017 Oct.

. 2017 Oct;22(10):1455-1463.

doi: 10.1038/mp.2016.72. Epub 2016 May 24.

Authors

Affiliations

¹ Department of Psychological Medicine, Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
² Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
³ Research Unit, FIDMAG Germanes Hospitalàries - CIBERSAM, Sant Boi de Llobregat, Barcelona, Spain.
⁴ Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁵ Mental Health, Parc Taulí Sabadell-CIBERSAM, University Hospital, Sabadell, Barcelona, Spain.
⁶ Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain.
⁷ Department of Radiology, Nihon University School of Medicine, Tokyo, Japan.
⁸ Department of Psychiatry, Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland.
⁹ Department of Psychiatry, The 1st Affiliated Hospital of Kunming Medical University, Kunming, PR China.
¹⁰ Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of Medicine, Imperial College London, London, UK.
¹¹ Department of Neuroscience, Medical School, Fundação do ABC, Santo André, SP, Brazil.
¹² ABC Center of Studies on Mental Health, Santo André, SP, Brazil.
¹³ PediMIND Program, Bradley Hospital, Department of Psychiatry, Brown University, East Providence, RI, USA.
¹⁴ Academic Clinical Neurology, Department of Neuroscience, University of Sheffield, Sheffield, UK.
¹⁵ Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany.
¹⁶ Department of Psychiatry, University of Dublin, Trinity College, Dublin, Ireland.
¹⁷ Psychiatric Brain and Body Research Group Jena, Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
¹⁸ Department of Psychology, Stanford University, Stanford, CA, USA.
¹⁹ Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University Hospital, Heidelberg, Germany.
²⁰ Department of Psychiatry, Korea University College of Medicine, Seoul, South Korea.
²¹ Neuroimaging Sciences, University of Edinburgh, Edinburgh, UK.
²² Scottish Imaging Network-A Platform for Scientific Excellence (SINAPSE), Giffnock, UK.
²³ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
²⁴ Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁵ Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, USA.
²⁶ Department of Psychology, Dutch Autism and ADHD Research Center, Brain and Cognition, University of Amsterdam, Amsterdam, The Netherlands.
²⁷ CADE Clinic, Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, NSW, Australia.
²⁸ Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
²⁹ Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
³⁰ Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK.
³¹ Department of Psychiatry, University of Cambridge, Cambridge, UK.
³² Department of Neuroscience, Medical School, University of Sheffield, Sheffield, UK.
³³ Department of Psychiatry, University of Pittsburgh, School of Medicine, Pittsburgh, PA.
³⁴ Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Randwick, NSW, Australia.
³⁵ Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Australia.
³⁶ Janssen Research and Development, Titusville, NJ, USA.
³⁷ Department of Psychiatry and Behavioral Sciences, Center of Excellence on Mood Disorders, Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
³⁸ The Patrick Wild Centre, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, UK.
³⁹ NeuroImaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁴⁰ Department of Psychiatry, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.
⁴¹ Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
⁴² Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
⁴³ School of Psychology, University of East London, London, UK.

PMID: 27217146
PMCID: PMC5622121
DOI: 10.1038/mp.2016.72

Abstract

Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

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Conflict of interest statement

AJC has within the last 3 years received honoraria for speaking from Astra Zeneca and Pfizer; and received research grant support from Lundbeck. MLP is a consultant for Roche Pharmaceuticals. GS is employed by Janssen Pharmaceuticals. DA has received travel grants from Janssen-Cilag and Servier. The remaining authors declare no conflicts of interest.

Figures

**Figure 1**
(a) Results of major depressive disorder (MDD) meta-analysis. (b) Results of meta-regression with depression severity in MDD. (c) Results of meta-regression with sex in MDD. (d) Results of meta-regression with patient age in MDD. (e) Results of bipolar disorder (BD) meta-analysis. (**f, g**) Results of meta-regressions with age in BD. Orange represents lower volume in patients relative to controls or positive relationships with regressors in meta-regressions, blue represents greater volume relative to controls or negative relationships with regressors. In meta-regression plots, point size represents study weights. All images are shown in neurological convention; left on the image corresponds to left in the brain. Effect sizes represent effect sizes at the peak of the cluster.

**Figure 2**
(a) Regions showing differences between major depression disorder (MDD) and bipolar disorder (BD). Orange clusters represent smaller grey-matter volume than controls, which is more substantial in MDD. (b) Results of the conjunction analysis showing regions with similar volumetric alterations in both conditions. Here, orange represents regions showing significantly lower volume in both conditions relative to controls. IPL, inferior parietal lobule; ITG, inferior temporal gyrus; L, left; MFG, middle frontal gyrus; R, right. Effect sizes represent effect sizes at the peak of the cluster.

See this image and copyright information in PMC

References

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Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis

Affiliations

Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical