Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-26T08:04:57.794Z Has data issue: false hasContentIssue false
  • English
  • Français

White matter microstructural abnormalities in families multiply affected with bipolar I disorder: a diffusion tensor tractography study

Published online by Cambridge University Press:  26 November 2013

L. Emsell ,
C. Chaddock ,
N. Forde ,
W. Van Hecke ,
G. J. Barker ,
A. Leemans ,
S. Sunaert ,
M. Walshe ,
E. Bramon  and
D. Cannon
...Show all authors
L. Emsell*
Affiliation:
Translational MRI, Department of Imaging and Pathology, KU Leuven and Radiology, University Hospitals Leuven, Belgium Clinical Science Institute, National University of Ireland, Galway, Ireland
C. Chaddock
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, UK
N. Forde
Affiliation:
Clinical Science Institute, National University of Ireland, Galway, Ireland
W. Van Hecke
Affiliation:
icoMetrix NV, Leuven, Belgium
G. J. Barker
Affiliation:
Department of Neuroimaging, Institute of Psychiatry, King's College London, UK
A. Leemans
Affiliation:
Image Sciences Institute, University Medical Centre Utrecht, The Netherlands
S. Sunaert
Affiliation:
Translational MRI, Department of Imaging and Pathology, KU Leuven and Radiology, University Hospitals Leuven, Belgium
M. Walshe
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, UK
E. Bramon
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, UK
D. Cannon
Affiliation:
Clinical Science Institute, National University of Ireland, Galway, Ireland
R. Murray
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, UK
C. McDonald
Affiliation:
Clinical Science Institute, National University of Ireland, Galway, Ireland
*
*Address for correspondence: Dr L. Emsell, Ph.D., Medical Imaging Research Centre, Department of Radiology, University Hospital Leuven, Herestraat 49 bus 7003, 3000 Leuven, Belgium. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

White matter (WM) abnormalities are proposed as potential endophenotypic markers of bipolar disorder (BD). In a diffusion tensor imaging (DTI) voxel-based analysis (VBA) study of families multiply affected with BD, we previously reported that widespread abnormalities of fractional anisotropy (FA) are associated with both BD and genetic liability for illness. In the present study, we further investigated the endophenotypic potential of WM abnormalities by applying DTI tractography to specifically investigate tracts implicated in the pathophysiology of BD.

Method

Diffusion magnetic resonance imaging (MRI) data were acquired from 19 patients with BD type I from multiply affected families, 21 of their unaffected first-degree relatives and 18 healthy volunteers. DTI tractography was used to identify the cingulum, uncinate fasciculus (UF), arcuate portion of the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), corpus callosum, and the anterior limb of the internal capsule (ALIC). Regression analyses were conducted to investigate the effect of participant group and genetic liability on FA and radial diffusivity (RD) in each tract.

Results

We detected a significant effect of group on both FA and RD in the cingulum, SLF, callosal splenium and ILF driven by reduced FA and increased RD in patients compared to controls and relatives. Increasing genetic liability was associated with decreased FA and increased RD in the UF, and decreased FA in the SLF, among patients.

Conclusions

WM microstructural abnormalities in limbic, temporal and callosal pathways represent microstructural abnormalities associated with BD whereas alterations in the SLF and UF may represent potential markers of endophenotypic risk.

Keywords

Bipolar disorderdiffusion tensor imagingendophenotypesgenetic riskwhite matter
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 10 , July 2014 , pp. 2139 - 2150
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Altman, EG, Hedeker, D, Peterson, JL, Davis, JM (1997). The Altman Self-Rating Mania Scale. Biological Psychiatry 42, 948–955.CrossRefGoogle ScholarPubMed
Ambrosi, E, Rossi-Espagnet, MC, Kotzalidis, GD, Comparelli, A, Del Casale, A, Carducci, F, Romano, A, Manfredi, G, Tatarelli, R, Bozzao, A, Girardi, P (2013). Structural brain alterations in bipolar disorder II: a combined voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) study. Journal of Affective Disorders 150, 610–615.CrossRefGoogle ScholarPubMed
Basser, PJ, Pajevic, S, Pierpaoli, C, Duda, J, Aldroubi, A (2000). In vivo fiber tractography using DT-MRI data. Magnetic Resonance in Medicine 44, 625–632.Google Scholar
Beaulieu, C (2002). The basis of anisotropic water diffusion in the nervous system – a technical review. NMR in Biomedicine 15, 435–455.Google Scholar
Benedetti, F, Absinta, M, Rocca, MA, Radaelli, D, Poletti, S, Bernasconi, A, Dallaspezia, S, Pagani, E, Falini, A, Copetti, M, Colombo, C, Comi, G, Smeraldi, E, Filippi, M (2011 a). Tract-specific white matter structural disruption in patients with bipolar disorder. Bipolar Disorders 13, 414–424.CrossRefGoogle ScholarPubMed
Benedetti, F, Yeh, PH, Bellani, M, Radaelli, D, Nicoletti, MA, Poletti, S, Falini, A, Dallaspezia, S, Colombo, C, Scotti, G, Smeraldi, E, Soares, JC, Brambilla, P (2011 b). Disruption of white matter integrity in bipolar depression as a possible structural marker of illness. Biological Psychiatry 69, 309–317.CrossRefGoogle ScholarPubMed
Blokland, GA, de Zubicaray, GI, McMahon, KL, Wright, MJ (2012). Genetic and environmental influences on neuroimaging phenotypes: a meta-analytical perspective on twin imaging studies. Twin Research and Human Genetics 15, 351–371.Google Scholar
Borgwardt, S, Fusar-Poli, P (2012). White matter pathology – an endophenotype for bipolar disorder? BMC Psychiatry 12, 138.CrossRefGoogle ScholarPubMed
Cannon, DM, Walshe, M, Dempster, E, Collier, DA, Marshall, N, Bramon, E, Murray, RM, McDonald, C (2012). The association of white matter volume in psychotic disorders with genotypic variation in NRG1, MOG and CNP: a voxel-based analysis in affected individuals and their unaffected relatives. Translational Psychiatry 2, e167.Google Scholar
Catani, M, Thiebaut de Schotten, M (2008). A diffusion tensor imaging tractography atlas for virtual in vivo dissections. Cortex 44, 1105–1132.CrossRefGoogle ScholarPubMed
Chaddock, CA, Barker, GJ, Marshall, N, Schulze, K, Hall, MH, Fern, A, Walshe, M, Bramon, E, Chitnis, XA, Murray, R, McDonald, C (2009). White matter microstructural impairments and genetic liability to familial bipolar I disorder. British Journal of Psychiatry 194, 527–534.Google Scholar
Chiang, MC, Barysheva, M, McMahon, KL, de Zubicaray, GI, Johnson, K, Montgomery, GW, Martin, NG, Toga, AW, Wright, MJ, Shapshak, P, Thompson, PM (2012). Gene network effects on brain microstructure and intellectual performance identified in 472 twins. Journal of Neuroscience 32, 8732–8745.CrossRefGoogle ScholarPubMed
Craven, JL, Rodin, GM, Littlefield, C (1988). The Beck Depression Inventory as a screening device for major depression in renal dialysis patients. International Journal of Psychiatry in Medicine 18, 365–374.Google Scholar
Emsell, L, Langan, C, Van Hecke, W, Barker, GJ, Leemans, A, Sunaert, S, McCarthy, P, Nolan, R, Cannon, DM, McDonald, C (2013 a). White matter differences in euthymic bipolar I disorder: a combined magnetic resonance imaging and diffusion tensor imaging voxel-based study. Bipolar Disorders 15, 365–376.CrossRefGoogle ScholarPubMed
Emsell, L, Leemans, A, Langan, C, Van Hecke, W, Barker, GJ, McCarthy, P, Jeurissen, B, Sijbers, J, Sunaert, S, Cannon, DM, McDonald, C (2013 b). Limbic and callosal white matter changes in euthymic bipolar I disorder: an advanced diffusion magnetic resonance imaging tractography study. Biological Psychiatry 73, 194–201.Google Scholar
Emsell, L, McDonald, C (2009). The structural neuroimaging of bipolar disorder. International Review of Psychiatry 21, 297–313.Google Scholar
Endicott, J, Spitzer, RL (1978). A diagnostic interview: the Schedule for Affective Disorders and Schizophrenia. Archives of General Psychiatry 35, 837–844.Google Scholar
Hafeman, DM, Chang, KD, Garrett, AS, Sanders, EM, Phillips, ML (2012). Effects of medication on neuroimaging findings in bipolar disorder: an updated review. Bipolar Disorders 14, 375–410.Google Scholar
Hulshoff Pol, HE, Schnack, HG, Posthuma, D, Mandl, RCW, Baare, WF, van Oel, C, van Haren, NE, Collins, DL, Evans, AC, Amunts, K, Buergel, U, Zilles, K, de Geus, E, Boomsma, DI, Kahn, RS (2006). Genetic contributions to human brain morphology and intelligence. Journal of Neuroscience 26, 10235–10242.Google Scholar
Hulshoff Pol, HE, van Baal, GC, Schnack, HG, Brans, RG, van der Schot, AC, Brouwer, RM, van Haren, NE, Lepage, C, Collins, DL, Evans, AC, Boomsma, DI, Nolen, W, Kahn, RS (2012). Overlapping and segregating structural brain abnormalities in twins with schizophrenia or bipolar disorder. Archives of General Psychiatry 69, 349–359.Google Scholar
Jahanshad, N, Kochunov, P, Sprooten, E, Mandl, RC, Nichols, TE, Almassy, L, Blangero, J, Brouwer, RM, Curran, JE, de Zubicaray, GI, Duggirala, R, Fox, PT, Hong, LE, Landman, BA, Martin, NG, McMahon, KL, Medland, SE, Mitchell, BD, Olvera, RL, Peterson, CP, Starr, JM, Sussmann, JE, Toga, AW, Wardlaw, JM, Wright, MJ, Hulshoff Pol, HE, Bastin, ME, McIntosh, AM, Deary, IJ, Thompson, PM, Glahn, DC (2013). Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA-DTI working group. NeuroImage 81, 455–469.Google Scholar
Jeurissen, B, Leemans, A, Tournier, JD, Jones, DK, Sijbers, J (2012). Investigating the prevalence of complex fiber configurations in white matter tissue with diffusion magnetic resonance imaging. Human Brain Mapping 34, 2747–2766.Google Scholar
Jones, DK (2010). The signal intensity must be modulated by the determinant of the Jacobian when correcting for eddy currents in diffusion MRI. In Proceedings of the International Society for Magnetic Resonance in Medicine. 18th Scientific Meeting, Stockholm, Sweden (http://cds.ismrm.org/protected/10MProceedings/files/1644_129.pdf).Google Scholar
Jones, DK, Williams, SC, Gasston, D, Horsfield, MA, Simmons, A, Howard, R (2002). Isotropic resolution diffusion tensor imaging with whole brain acquisition in a clinically acceptable time. Human Brain Mapping 15, 216–230.Google Scholar
Kempton, MJ, Geddes, JR, Ettinger, U, Williams, SC, Grasby, PM (2008). Meta-analysis, database, and meta-regression of 98 structural imaging studies in bipolar disorder. Archives of General Psychiatry 65, 1017–1032.Google Scholar
Kieseppa, T, van Erp, TG, Haukka, J, Partonen, T, Cannon, TD, Poutanen, VP, Kaprio, J, Lonnqvist, J (2003). Reduced left hemispheric white matter volume in twins with bipolar I disorder. Biological Psychiatry 54, 896–905.Google Scholar
Kim, S, Webster, MJ (2010). Correlation analysis between genome-wide expression profiles and cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders. Molecular Psychiatry 15, 326–336.CrossRefGoogle ScholarPubMed
Kochunov, P, Glahn, DC, Nichols, TE, Winkler, AM, Hong, EL, Holcomb, HH, Stein, JL, Thompson, PM, Curran, JE, Carless, MA, Olvera, RL, Johnson, MP, Cole, SA, Kochunov, V, Kent, J, Blangero, J (2011). Genetic analysis of cortical thickness and fractional anisotropy of water diffusion in the brain. Frontiers in Neuroscience 5, 120.CrossRefGoogle ScholarPubMed
Lagopoulos, J, Hermens, DF, Hatton, SN, Tobias-Webb, J, Griffiths, K, Naismith, SL, Scott, EM, Hickie, IB (2013). Microstructural white matter changes in the corpus callosum of young people with bipolar disorder: a diffusion tensor imaging study. PloS One 8, e59108.CrossRefGoogle ScholarPubMed
Leemans, A, Jeurissen, B, Sijbers, J, Jones, D (2009). ExploreDTI: a graphical toolbox for processing, analyzing, and visualizing diffusion MR data. In Proceedings of the International Society for Magnetic Resonance in Medicine. 18th Scientific Meeting, Hawaii, USA, p. 3537.Google Scholar
Leemans, A, Jones, DK (2009). The B-matrix must be rotated when correcting for subject motion in DTI data. Magnetic Resonance Imaging in Medicine 61, 1336–1349.Google Scholar
Macritchie, KA, Lloyd, AJ, Bastin, ME, Vasudev, K, Gallagher, P, Eyre, R, Marshall, I, Wardlaw, JM, Ferrier, IN, Moore, PB, Young, AH (2010). White matter microstructural abnormalities in euthymic bipolar disorder. British Journal of Psychiatry 196, 52–58.Google Scholar
Mahon, K, Burdick, KE, Ikuta, T, Braga, RJ, Gruner, P, Malhotra, AK, Szeszko, PR (2013). Abnormal temporal lobe white matter as a biomarker for genetic risk of bipolar disorder. Biological Psychiatry 73, 177–182.Google Scholar
Mahon, K, Burdick, KE, Szeszko, PR (2010). A role for white matter abnormalities in the pathophysiology of bipolar disorder. Neuroscience and Biobehavioral Reviews 34, 533–554.Google Scholar
Maxwell, ME (1992). Family Interview for Genetic Studies. Clinical Neurogenetics Branch, National Institute for Mental Health, Bethesda, MD.Google Scholar
McDonald, C, Bullmore, E, Sham, P, Chitnis, X, Suckling, J, MacCabe, J, Walshe, M, Murray, RM (2005). Regional volume deviations of brain structure in schizophrenia and psychotic bipolar disorder: computational morphometry study. British Journal of Psychiatry 186, 369–377.CrossRefGoogle ScholarPubMed
McDonald, C, Bullmore, ET, Sham, PC, Chitnis, X, Wickham, H, Bramon, E, Murray, RM (2004). Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes. Archives of General Psychiatry 61, 974–984.Google Scholar
Paillere Martinot, ML, Lemaitre, H, Artiges, E, Miranda, R, Goodman, R, Penttila, J, Struve, M, Fadai, T, Kappel, V, Poustka, L, Conrod, P, Banaschewski, T, Barbot, A, Barker, GJ, Buchel, C, Flor, H, Gallinat, J, Garavan, H, Heinz, A, Ittermann, B, Lawrence, C, Loth, E, Mann, K, Paus, T, Pausova, Z, Rietschel, M, Robbins, TW, Smolka, MN, Schumann, G, Martinot, JL; IMAGEN Consortium (2013). White-matter microstructure and gray-matter volumes in adolescents with subthreshold bipolar symptoms. Molecular Psychiatry. Published online: 30 April 2013 . doi:10.1038/mp.2013.44.Google Scholar
Schmahmann, J, Pandya, D (eds) (2006). Fiber Pathways of the Brain. Oxford University Press: New York.Google Scholar
Skudlarski, P, Schretlen, DJ, Thaker, GK, Stevens, MC, Keshavan, MS, Sweeney, JA, Tamminga, CA, Clementz, BA, O'Neil, K, Pearlson, GD (2013). Diffusion tensor imaging white matter endophenotypes in patients with schizophrenia or psychotic bipolar disorder and their relatives. American Journal of Psychiatry 170, 886–898.Google Scholar
Smoller, JW, Craddock, N, Kendler, K, Lee, PH, Neale, BM, Nurnberger, JI, Ripke, S, Santangelo, S, Sullivan, PF (2013). Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381, 1371–1379.Google Scholar
Sprooten, E, Fleming, KM, Thomson, PA, Bastin, ME, Whalley, HC, Hall, J, Sussmann, JE, McKirdy, J, Blackwood, D, Lawrie, SM, McIntosh, AM (2013). White matter integrity as an intermediate phenotype: exploratory genome-wide association analysis in individuals at high risk of bipolar disorder. Psychiatry Research 206, 223–231.Google Scholar
Sprooten, E, Sussmann, JE, Clugston, A, Peel, A, McKirdy, J, Moorhead, TW, Anderson, S, Shand, AJ, Giles, S, Bastin, ME, Hall, J, Johnstone, EC, Lawrie, SM, McIntosh, AM (2011). White matter integrity in individuals at high genetic risk of bipolar disorder. Biological Psychiatry 70, 350–356.CrossRefGoogle ScholarPubMed
Thompson, PM, Cannon, TD, Narr, KL, van Erp, T, Poutanen, VP, Huttunen, M, Lonnqvist, J, Standertskjold-Nordenstam, CG, Kaprio, J, Khaledy, M, Dail, R, Zoumalan, CI, Toga, AW (2001). Genetic influences on brain structure. Nature Neuroscience 4, 1253–1258.Google Scholar
Tighe, SK, Reading, SA, Rivkin, P, Caffo, B, Schweizer, B, Pearlson, G, Potash, JB, Depaulo, JR, Bassett, SS (2012). Total white matter hyperintensity volume in bipolar disorder patients and their healthy relatives. Bipolar Disorders 14, 888–893.Google Scholar
Uranova, NA, Vostrikov, VM, Orlovskaya, DD, Rachmanova, VI (2004). Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophrenia Research 67, 269–275.Google Scholar
van der Schot, AC, Vonk, R, Brans, RG, van Haren, NE, Koolschijn, PC, Nuboer, V, Schnack, HG, van Baal, GC, Boomsma, DI, Nolen, WA, Hulshoff Pol, HE, Kahn, RS (2009). Influence of genes and environment on brain volumes in twin pairs concordant and discordant for bipolar disorder. Archives of General Psychiatry 66, 142–151.Google Scholar
Van Hecke, W, Leemans, A, D'Agostino, E, De Backer, S, Vandervliet, E, Parizel, PM, Sijbers, J (2007). Nonrigid coregistration of diffusion tensor images using a viscous fluid model and mutual information. IEEE Transactions on Medical Imaging 26, 1598–1612.CrossRefGoogle ScholarPubMed
Van Hecke, W, Leemans, A, Sage, CA, Emsell, L, Veraart, J, Sijbers, J, Sunaert, S, Parizel, PM (2011). The effect of template selection on diffusion tensor voxel-based analysis results. NeuroImage 55, 566–573.Google Scholar
Van Hecke, W, Sijbers, J, D'Agostino, E, Maes, F, De Backer, S, Vandervliet, E, Parizel, PM, Leemans, A (2008). On the construction of an inter-subject diffusion tensor magnetic resonance atlas of the healthy human brain. NeuroImage 43, 69–80.Google Scholar
Vederine, FE, Wessa, M, Leboyer, M, Houenou, J (2011). A meta-analysis of whole-brain diffusion tensor imaging studies in bipolar disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry 35, 1820–1826.CrossRefGoogle ScholarPubMed
Versace, A, Andreazza, AC, Young, LT, Fournier, JC, Almeida, JR, Stiffler, RS, Lockovich, JC, Aslam, HA, Pollock, MH, Park, H, Nimgaonkar, VL, Kupfer, DJ, Phillips, ML (2013). Elevated serum measures of lipid peroxidation and abnormal prefrontal white matter in euthymic bipolar adults: toward peripheral biomarkers of bipolar disorder. Molecular Psychiatry. Published online: 29 January 2013 . doi:10.1038/mp.2012.188.Google Scholar
Vos, SB, Jones, DK, Viergever, MA, Leemans, A (2011). Partial volume effect as a hidden covariate in DTI analyses. NeuroImage 55, 1566–1576.Google Scholar
Whalley, HC, Sprooten, E, Hackett, S, Hall, L, Blackwood, DH, Glahn, DC, Bastin, M, Hall, J, Lawrie, SM, Sussmann, JE, McIntosh, AM (2013). Polygenic risk and white matter integrity in individuals at high risk of mood disorder. Biological Psychiatry 74, 280–286.CrossRefGoogle ScholarPubMed
Williams, HJ, Craddock, N, Russo, G, Hamshere, ML, Moskvina, V, Dwyer, S, Smith, RL, Green, E, Grozeva, D, Holmans, P, Owen, MJ, O'Donovan, MC (2011). Most genome-wide significant susceptibility loci for schizophrenia and bipolar disorder reported to date cross-traditional diagnostic boundaries. Human Molecular Genetics 20, 387–391.Google Scholar
Supplementary material: File

Emsell et al. Supplementary Material

Table

Download Emsell et al. Supplementary Material(File)
File 146.4 KB