Hostname: page-component-78c5997874-m6dg7 Total loading time: 0 Render date: 2024-11-14T10:08:42.423Z Has data issue: false hasContentIssue false
  • English
  • Français

The neuroanatomy of subthreshold depressive symptoms in Huntington's disease: a combined diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) study

Published online by Cambridge University Press:  07 October 2013

R. Sprengelmeyer ,
M. Orth ,
H.-P. Müller ,
R. C. Wolf ,
G. Grön ,
M. S. Depping ,
J. Kassubek ,
D. Justo ,
E. M. Rees  and
S. Haider
...Show all authors
R. Sprengelmeyer*
Affiliation:
Department of Neurology, University of Ulm, Ulm, Germany School of Psychology and Neuroscience, University of St Andrews, St Andrews, UK
M. Orth
Affiliation:
Department of Neurology, University of Ulm, Ulm, Germany
H.-P. Müller
Affiliation:
Department of Neurology, University of Ulm, Ulm, Germany
R. C. Wolf
Affiliation:
Centre for Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany
G. Grön
Affiliation:
Department of Psychiatry, University of Ulm, Ulm, Germany
M. S. Depping
Affiliation:
Centre for Psychosocial Medicine, Department of General Psychiatry, University of Heidelberg, Heidelberg, Germany
J. Kassubek
Affiliation:
Department of Neurology, University of Ulm, Ulm, Germany
D. Justo
Affiliation:
Institut du Cerveau et de la Moelle épinière, Pitié-Salpêtrière Hospital, Pierre and Marie Curie University (UPMC), Paris, France Unité Mixte de Recherche S975, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Pitie-Salpêtrière Hospital, Pierre and Marie Curie University (UPMC), Paris, France Unité 975, Institut National de la Santé et de la Recherche Médicale, Paris, France Unité Mixte de Recherche 7225, Centre National de la Recherche Scientifique, Paris, France
E. M. Rees
Affiliation:
Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK
S. Haider
Affiliation:
Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK
J. H. Cole
Affiliation:
Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK
N. Z. Hobbs
Affiliation:
Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK
R. A. C. Roos
Affiliation:
Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
A. Dürr
Affiliation:
Institut du Cerveau et de la Moelle épinière, Pitié-Salpêtrière Hospital, Pierre and Marie Curie University (UPMC), Paris, France Unité Mixte de Recherche S975, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Pitie-Salpêtrière Hospital, Pierre and Marie Curie University (UPMC), Paris, France Unité 975, Institut National de la Santé et de la Recherche Médicale, Paris, France Unité Mixte de Recherche 7225, Centre National de la Recherche Scientifique, Paris, France Genetic Department, Pitié-Salpêtrière Hospital, Pierre and Marie Curie University (UPMC), Paris, France
S. J. Tabrizi
Affiliation:
Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK
S. D. Süssmuth
Affiliation:
Department of Neurology, University of Ulm, Ulm, Germany
G. B. Landwehrmeyer
Affiliation:
Department of Neurology, University of Ulm, Ulm, Germany
*
*Address for correspondence: Dr R. Sprengelmeyer, School of Psychology and Neuroscience, University of St Andrews, St Andrews, UK. (Email: rhs3@st-and.ac.uk)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Depressive symptoms are prominent psychopathological features of Huntington's disease (HD), making a negative impact on social functioning and well-being.

Method

We compared the frequencies of a history of depression, previous suicide attempts and current subthreshold depression between 61 early-stage HD participants and 40 matched controls. The HD group was then split based on the overall HD group's median Hospital Anxiety and Depression Scale-depression score into a group of 30 non-depressed participants (mean 0.8, s.d. = 0.7) and a group of 31 participants with subthreshold depressive symptoms (mean 7.3, s.d. = 3.5) to explore the neuroanatomy underlying subthreshold depressive symptoms in HD using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).

Results

Frequencies of history of depression, previous suicide attempts or current subthreshold depressive symptoms were higher in HD than in controls. The severity of current depressive symptoms was also higher in HD, but not associated with the severity of HD motor signs or disease burden. Compared with the non-depressed HD group DTI revealed lower fractional anisotropy (FA) values in the frontal cortex, anterior cingulate cortex, insula and cerebellum of the HD group with subthreshold depressive symptoms. In contrast, VBM measures were similar in both HD groups. A history of depression, the severity of HD motor signs or disease burden did not correlate with FA values of these regions.

Conclusions

Current subthreshold depressive symptoms in early HD are associated with microstructural changes – without concomitant brain volume loss – in brain regions known to be involved in major depressive disorder, but not those typically associated with HD pathology.

Keywords

DTIHuntington's diseasesubthreshold depressionVBM
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 9 , July 2014 , pp. 1867 - 1878
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

Ashburner, J (2007). A fast diffeomorphic image registration algorithm. Neuroimage 38, 95–113.CrossRefGoogle ScholarPubMed
Basser, PJ, Jones, DK (2002). Diffusion-tensor MRI: theory, experimental design and data analysis – a technical review. NMR in Biomedicine 15, 456–467.CrossRefGoogle ScholarPubMed
Bjelland, I, Dahl, AA, Haug, TT, Neckelmann, D (2002). The validity of the Hospital Anxiety and Depression Scale. An updated literature review. Journal of Psychosomatic Research 52, 69–77.Google Scholar
Brett, M, Johnsrude, IS, Owen, AM (2002). The problem of functional localization in the human brain. Nature Reviews. Neuroscience 3, 243–249.Google Scholar
Bush, G, Luu, P, Posner, MI (2000). Cognitive and emotional influences in anterior cingulate cortex. Trends in Cognitive Science 4, 215–222.CrossRefGoogle ScholarPubMed
Cole, J, Chaddock, CA, Farmer, AE, Aitchison, KJ, Simmons, A, McGuffin, P, Fu, CH (2012). White matter abnormalities and illness severity in major depressive disorder. British Journal of Psychiatry 201, 33–39.Google Scholar
Cuijpers, P, Smit, F (2004). Subthreshold depression as a risk indicator for major depressive disorder: a systematic review of prospective studies. Acta Psychiatrica Scandinavica 109, 325–331.CrossRefGoogle ScholarPubMed
Damasio, AR, Grabowski, TJ, Bechara, A, Damasio, H, Ponto, LL, Parvizi, J, Hichwa, RD (2000). Subcortical and cortical brain activity during the feeling of self-generated emotions. Nature Neuroscience 3, 1049–1056.Google Scholar
Drevets, WC, Price, JL, Furey, ML (2008). Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Structure and Function 213, 93–118.Google Scholar
Epping, EA, Mills, JA, Beglinger, LJ, Fiedorowicz, JG, Craufurd, D, Smith, MM, Groves, M, Bijanki, KR, Downing, N, Williams, JK, Long, JD, Paulsen, JS (2013). Characterization of depression in prodromal Huntington disease in the neurobiological predictors of HD (PREDICT-HD) study. Journal of Psychiatric Research 47, 1423–1431.Google Scholar
Epping, EA, Paulsen, JS (2011). Depression in the early stages of Huntington disease. Neurodegenerative Disease Management 1, 407–414.Google Scholar
Fitzgerald, PB, Laird, AR, Maller, J, Daskalakis, ZJ (2008). A meta-analytic study of changes in brain activation in depression. Human Brain Mapping 29, 683–695.Google Scholar
Folstein, S, Abbott, MH, Chase, GA, Jensen, BA, Folstein, MF (1983). The association of affective disorder with Huntington's disease in a case series and in families. Psychological Medicine 13, 537–542.CrossRefGoogle Scholar
Folstein, SE, Folstein, MF (1983). Psychiatric features of Huntington's disease: recent approaches and findings. Psychiatric Developments 1, 193–205.Google Scholar
Genovese, CR, Lazar, NA, Nichols, T (2002). Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage 15, 870–878.CrossRefGoogle ScholarPubMed
Grasby, PM, Frith, CD, Friston, KJ, Bench, C, Frackowiak, RS, Dolan, RJ (1993). Functional mapping of brain areas implicated in auditory–verbal memory function. Brain 116, 1–20.CrossRefGoogle ScholarPubMed
Ho, AK, Gilbert, AS, Mason, SL, Goodman, AO, Barker, RA (2009). Health-related quality of life in Huntington's disease: which factors matter most? Movement Disorders 24, 574–578.Google Scholar
Hobbs, NZ, Pedrick, AV, Say, MJ, Frost, C, Dar Santos, R, Coleman, A, Sturrock, A, Craufurd, D, Stout, JC, Leavitt, BR, Barnes, J, Tabrizi, SJ, Scahill, RI (2011). The structural involvement of the cingulate cortex in premanifest and early Huntington's disease. Movement Disorders 26, 1684–1690.Google Scholar
Huntington Study Group (1996). Unified Huntington's Disease Rating Scale: reliability and consistency. Movement Disorders 11, 136–142.Google Scholar
Iacoviello, BM, Alloy, LB, Abramson, LY, Choi, JY (2010). The early course of depression: a longitudinal investigation of prodromal symptoms and their relation to the symptomatic course of depressive episodes. Journal of Abnormal Psychology 119, 459–467.CrossRefGoogle Scholar
Julien, CL, Thompson, JC, Wild, S, Yardumian, P, Snowden, JS, Turner, G, Craufurd, D (2007). Psychiatric disorders in preclinical Huntington's disease. Journal of Neurology, Neurosurgery and Psychiatry 78, 939–943.Google Scholar
Jurgens, CK, van de Wiel, L, van Es, AC, Grimbergen, YM, Witjes-Ane, MN, van der Grond, J, Middelkoop, HA, Roos, RA (2008). Basal ganglia volume and clinical correlates in ‘preclinical’ Huntington's disease. Journal of Neurology 255, 1785–1791.Google Scholar
Kunimatsu, A, Aoki, S, Masutani, Y, Abe, O, Hayashi, N, Mori, H, Masumoto, T, Ohtomo, K (2004). The optimal trackability threshold of fractional anisotropy for diffusion tensor tractography of the corticospinal tract. Magnetic Resonance in Medical Sciences 3, 11–17.CrossRefGoogle ScholarPubMed
Liao, Y, Huang, X, Wu, Q, Yang, C, Kuang, W, Du, M, Lui, S, Yue, Q, Chan, RC, Kemp, GJ, Gong, Q (2013). Is depression a disconnection syndrome? Meta-analysis of diffusion tensor imaging studies in patients with MDD. Journal of Psychiatry and Neuroscience 38, 49–56.CrossRefGoogle ScholarPubMed
Liu, Z, Xu, C, Xu, Y, Wang, Y, Zhao, B, Lv, Y, Cao, X, Zhang, K, Du, C (2010). Decreased regional homogeneity in insula and cerebellum: a resting-state fMRI study in patients with major depression and subjects at high risk for major depression. Psychiatry Research 182, 211–215.Google Scholar
Manes, F, Springer, J, Jorge, R, Robinson, RG (1999). Verbal memory impairment after left insular cortex infarction. Journal of Neurology, Neurosurgery and Psychiatry 67, 532–534.CrossRefGoogle ScholarPubMed
Manjon, JV, Coupe, P, Marti-Bonmati, L, Collins, DL, Robles, M (2010). Adaptive non-local means denoising of MR images with spatially varying noise levels. Journal of Magnetic Resonance Imaging 31, 192–203.CrossRefGoogle ScholarPubMed
Mayberg, HS (2009). Targeted electrode-based modulation of neural circuits for depression. Journal of Clinical Investigation 119, 717–725.Google Scholar
Mayberg, HS, Liotti, M, Brannan, SK, McGinnis, S, Mahurin, RK, Jerabek, PA, Silva, JA, Tekell, JL, Martin, CC, Lancaster, JL, Fox, PT (1999). Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. American Journal of Psychiatry 156, 675–682.Google Scholar
Mayberg, HS, Starkstein, SE, Peyser, CE, Brandt, J, Dannals, RF, Folstein, SE (1992). Paralimbic frontal lobe hypometabolism in depression associated with Huntington's disease. Neurology 42, 1791–1797.Google Scholar
Mueller, HP, Groen, G, Sprengelmeyer, R, Kassubek, J, Ludolph, AC, Hobbs, NZ, Cole, J, Roos, RAC, Duerr, A, Tabrizi, SJ, Landwehrmeyer, BG, Suessmuth, SD (2013). Evaluating multicenter DTI data in Huntington's disease on site specific effects: an ex post facto approach. Neuroimage Clinical 2, 161–167.Google Scholar
Mueller, HP, Suessmuth, SD, Landwehrmeyer, GB, Ludolph, AC, Tabrizi, SJ, Kloppel, S, Kassubek, J (2011). Stability effects on results of diffusion tensor imaging analysis by reduction of the number of gradient directions due to motion artifacts: an application to presymptomatic Huntington's disease. PLoS Currents: Huntington Disease 3, RRN1292.Google Scholar
Mueller, HP, Unrath, A, Sperfeld, AD, Ludolph, AC, Riecker, A, Kassubek, J (2007). Diffusion tensor imaging and tractwise fractional anisotropy statistics: quantitative analysis in white matter pathology. Biomedical Engineering Online 6, 42.Google Scholar
Nehl, C, Ready, RE, Hamilton, J, Paulsen, JS (2001). Effects of depression on working memory in presymptomatic Huntington's disease. Journal of Neuropsychiatry and Clinical Neurosciences 13, 342–346.Google Scholar
Paulsen, JS, Nehl, C, Hoth, KF, Kanz, JE, Benjamin, M, Conybeare, R, McDowell, B, Turner, B (2005). Depression and stages of Huntington's disease. Journal of Neuropsychiatry and Clinical Neurosciences 17, 496–502.Google Scholar
Peng, J, Liu, J, Nie, B, Li, Y, Shan, B, Wang, G, Li, K (2011). Cerebral and cerebellar gray matter reduction in first-episode patients with major depressive disorder: a voxel-based morphometry study. European Journal of Radiology 80, 395–399.CrossRefGoogle ScholarPubMed
Penney, JB Jr, Vonsattel, JP, MacDonald, ME, Gusella, JF, Myers, RH (1997). CAG repeat number governs the development rate of pathology in Huntington's disease. Annals of Neurology 41, 689–692.Google Scholar
Rajapakse, JC, Giedd, JN, Rapoport, JL (1997). Statistical approach to segmentation of single-channel cerebral MR images. IEEE Transactions on Medical Imaging 16, 176–186.CrossRefGoogle ScholarPubMed
Sexton, CE, Mackay, CE, Ebmeier, KP (2009). A systematic review of diffusion tensor imaging studies in affective disorders. Biological Psychiatry 66, 814–823.Google Scholar
Smith, MM, Mills, JA, Epping, EA, Westervelt, HJ, Paulsen, JS (2012). Depressive symptom severity is related to poorer cognitive performance in prodromal Huntington disease. Neuropsychology 26, 664–669.Google Scholar
Snaith, RP, Constantopoulos, AA, Jardine, MY, McGuffin, P (1978). A clinical scale for the self-assessment of irritability. British Journal of Psychiatry 132, 164–171.Google Scholar
Soriano-Mas, C, Hernandez-Ribas, R, Pujol, J, Urretavizcaya, M, Deus, J, Harrison, BJ, Ortiz, H, Lopez-Sola, M, Menchon, JM, Cardoner, N (2011). Cross-sectional and longitudinal assessment of structural brain alterations in melancholic depression. Biological Psychiatry 69, 318–325.Google Scholar
Sprengelmeyer, R, Steele, JD, Mwangi, B, Kumar, P, Christmas, D, Milders, M, Matthews, K (2011). The insular cortex and the neuroanatomy of major depression. Journal of Affective Disorders 133, 120–127.Google Scholar
Tabrizi, SJ, Langbehn, DR, Leavitt, BR, Roos, RA, Durr, A, Craufurd, D, Kennard, C, Hicks, SL, Fox, NC, Scahill, RI, Borowsky, B, Tobin, AJ, Rosas, HD, Johnson, H, Reilmann, R, Landwehrmeyer, B, Stout, JC (2009). Biological and clinical manifestations of Huntington's disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data. Lancet Neurology 8, 791–801.Google Scholar
Tabrizi, SJ, Scahill, RI, Durr, A, Roos, RA, Leavitt, BR, Jones, R, Landwehrmeyer, GB, Fox, NC, Johnson, H, Hicks, SL, Kennard, C, Craufurd, D, Frost, C, Langbehn, DR, Reilmann, R, Stout, JC (2011). Biological and clinical changes in premanifest and early stage Huntington's disease in the TRACK-HD study: the 12-month longitudinal analysis. Lancet Neurology 10, 31–42.CrossRefGoogle Scholar
Takahashi, T, Yücel, M, Lorenzetti, V, Tanino, R, Whittle, S, Suzuki, M, Walterfang, M, Pantelis, C, Allen, NB (2010). Volumetric MRI study of the insular cortex in individuals with current and past major depression. Journal of Affective Disorders 121, 231–238.Google Scholar
Tohka, J, Zijdenbos, A, Evans, A (2004). Fast and robust parameter estimation for statistical partial volume models in brain MRI. Neuroimage 23, 84–97.Google Scholar
Unrath, A, Müller, HP, Riecker, A, Ludolph, AC, Sperfeld, AD, Kassubek, J (2010). Whole brain-based analysis of regional white matter tract alterations in rare motor neuron diseases by diffusion tensor imaging. Human Brain Mapping 31, 1727–1740.Google Scholar
van Duijn, E, Kingma, EM, Timman, R, Zitman, FG, Tibben, A, Roos, RA, van der Mast, RC (2008). Cross-sectional study on prevalences of psychiatric disorders in mutation carriers of Huntington's disease compared with mutation-negative first-degree relatives. Journal of Clinical Psychiatry 69, 1804–1810.Google Scholar
van Duijn, E, Reedeker, N, Giltay, E, Roos, R, van der Mast, R (2012). Course of irritability, depression, and apathy in Huntington's disease during a 2-year follow-up period. Journal of Neurology, Neurosurgery and Psychiatry 83, A42.Google Scholar
Vodermaier, A, Millman, RD (2011). Accuracy of the Hospital Anxiety and Depression Scale as a screening tool in cancer patients: a systematic review and meta-analysis. Supportive Care in Cancer 19, 1899–1908.Google Scholar
Zappacosta, B, Monza, D, Meoni, C, Austoni, L, Soliveri, P, Gellera, C, Alberti, R, Mantero, M, Penati, G, Caraceni, T, Girotti, F (1996). Psychiatric symptoms do not correlate with cognitive decline, motor symptoms, or CAG repeat length in Huntington's disease. Archives of Neurology 53, 493–497.Google Scholar
Zeng, LL, Shen, H, Liu, L, Wang, L, Li, B, Fang, P, Zhou, Z, Li, Y, Hu, D (2012). Identifying major depression using whole-brain functional connectivity: a multivariate pattern analysis. Brain 135, 1498–1507.Google Scholar
Zigmond, AS, Snaith, RP (1983). The Hospital Anxiety and Depression Scale. Acta Psychiatrica Scandinavica 67, 361–370.Google Scholar
Supplementary material: File

Sprengelmeyer Supplementary Material

Table S1

Download Sprengelmeyer Supplementary Material(File)
File 21.5 KB