Abstract
Identifying data-driven biotypes of major depressive disorder (MDD) has promise for the clarification of diagnostic heterogeneity. However, few studies have focused on white-matter abnormalities for MDD subtyping. This study included 116 patients with MDD and 118 demographically-matched healthy controls assessed by diffusion tensor imaging and neurocognitive evaluation. Hierarchical clustering was applied to the major fiber tracts, in conjunction with tract-based spatial statistics, to reveal white-matter alterations associated with MDD. Clinical and neurocognitive differences were compared between identified subgroups and healthy controls. With fractional anisotropy extracted from 20 fiber tracts, cluster analysis revealed 3 subgroups based on the patterns of abnormalities. Patients in each subgroup versus healthy controls showed a stepwise pattern of white-matter alterations as follows: subgroup 1 (25.9% of patient sample), widespread white-matter disruption; subgroup 2 (43.1% of patient sample), intermediate and more localized abnormalities in aspects of the corpus callosum and left cingulate; and subgroup 3 (31.0% of patient sample), possible mild alterations, but no statistically significant tract disruption after controlling for family-wise error. The neurocognitive impairment in each subgroup accompanied the white-matter alterations: subgroup 1, deficits in sustained attention and delayed memory; subgroup 2, dysfunction in delayed memory; and subgroup 3, no significant deficits. Three subtypes of white-matter abnormality exist in individuals with major depression, those having widespread abnormalities suffering more neurocognitive impairments, which may provide evidence for parsing the heterogeneity of the disorder and help optimize type-specific treatment approaches.
Similar content being viewed by others
References
Organization WH. International statistical classification of diseases and related health problems. World Health Organization, 2004.
Association AP. Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Pub, 2013.
Paykel ES. Basic concepts of depression. Dialogues Clin Neurosci 2008, 10: 279–289.
van Loo HM, de Jonge P, Romeijn JW, Kessler RC, Schoevers RA. Data-driven subtypes of major depressive disorder: a systematic review. BMC Med 2012, 10: 156.
Drysdale AT, Grosenick L, Downar J, Dunlop K, Mansouri F, Meng Y, et al. Erratum: Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nat Med 2017, 23: 264.
Price RB, Gates K, Kraynak TE, Thase ME, Siegle GJ. Data-driven subgroups in depression derived from directed functional connectivity paths at rest. Neuropsychopharmacology 2017, 42: 2623–2632.
Wager TD, Woo CW. Imaging biomarkers and biotypes for depression. Nat Med 2017, 23: 16–17.
Song M, Yang Z, Sui J, Jiang T. Biological subtypes bridge diagnoses and biomarkers: a novel research track for mental disorders. Neurosci Bull 2017, 33: 351–353.
Williams LM. Precision psychiatry: a neural circuit taxonomy for depression and anxiety. Lancet Psychiatry 2016, 3: 472–480.
Yu C, Arcos-Burgos M, Licinio J, Wong ML. A latent genetic subtype of major depression identified by whole-exome genotyping data in a Mexican-American cohort. Transl Psychiatry 2017, 7: e1134.
Price RB, Lane S, Gates K, Kraynak TE, Horner MS, Thase ME, et al. Parsing heterogeneity in the brain connectivity of depressed and healthy adults during positive mood. Biol Psychiatry 2017, 81: 347–357.
Feder S, Sundermann B, Wersching H, Teuber A, Kugel H, Teismann H, et al. Sample heterogeneity in unipolar depression as assessed by functional connectivity analyses is dominated by general disease effects. J Affect Disord 2017, 222: 79–87.
Le Bihan D, Mangin JF, Poupon C, Clark CA, Pappata S, Molko N, et al. Diffusion tensor imaging: concepts and applications. J Magn Reson Imaging 2001, 13: 534–546.
Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, et al. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 2006, 31: 1487–1505.
Winston GP. The physical and biological basis of quantitative parameters derived from diffusion MRI. Quant Imaging Med Surg 2012, 2: 254–265.
Kieseppa T, Eerola M, Mantyla R, Neuvonen T, Poutanen VP, Luoma K, et al. Major depressive disorder and white matter abnormalities: a diffusion tensor imaging study with tract-based spatial statistics. J Affect Disord 2010, 120: 240–244.
Cole J, Chaddock CA, Farmer AE, Aitchison KJ, Simmons A, McGuffin P, et al. White matter abnormalities and illness severity in major depressive disorder. Br J Psychiatry 2012, 201: 33–39.
Vilgis V, Vance A, Cunnington R, Silk TJ. White matter microstructure in boys with persistent depressive disorder. J Affect Disord 2017, 221: 11–16.
Jiang J, Zhao YJ, Hu XY, Du MY, Chen ZQ, Wu M, et al. Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging. J Psychiatry Neurosci 2017, 42: 150–163.
Gong Y. Wechsler adult intelligence scale-revised in China Version. Hunan Medical College, Changsha, Hunan/China 1992.
Sahakian B, Owen A. Computerized assessment in neuropsychiatry using CANTAB: discussion paper. J R Soc Med 1992, 85: 399–402.
Maric NP, Stojanovic Z, Andric S, Soldatovic I, Dolic M, Spiric Z. The acute and medium-term effects of treatment with electroconvulsive therapy on memory in patients with major depressive disorder. Psychol Med 2016, 46: 797–806.
Oguz I, Farzinfar M, Matsui J, Budin F, Liu Z, Gerig G, et al. DTIPrep: quality control of diffusion-weighted images. Front Neuroinform 2014, 8: 4.
Jenkinson M, Beckmann CF, Behrens TE, Woolrich MW, Smith SM. FSL. Neuroimage 2012, 62: 782–790.
Mori S, Oishi K, Faria AV. White matter atlases based on diffusion tensor imaging. Curr Opin Neurol 2009, 22: 362–369.
Wakana S, Caprihan A, Panzenboeck MM, Fallon JH, Perry M, Gollub RL, et al. Reproducibility of quantitative tractography methods applied to cerebral white matter. Neuroimage 2007, 36: 630–644.
Sidak Z. Rectangular confidence regions for the means of multivariate normal distributions. JAm Stat Assoc 1967, 62: 626–633.
Winkler AM, Ridgway GR, Webster MA, Smith SM, Nichols TE. Permutation inference for the general linear model. Neuroimage 2014, 92: 381–397.
Kemp A, MacMaster FP, Jaworska N, Yang XR, Pradhan S, Mahnke D, et al. Age of onset and corpus callosal morphology in major depression. J Affect Disord 2013, 150: 703–706.
Ma N, Li L, Shu N, Liu J, Gong G, He Z, et al. White matter abnormalities in first-episode, treatment-naive young adults with major depressive disorder. Am J Psychiatry 2007, 164: 823–826.
Snyder HR. Major depressive disorder is associated with broad impairments on neuropsychological measures of executive function: a meta-analysis and review. Psychol Bull 2013, 139: 81–132.
Hammar A, Ardal G. Cognitive functioning in major depression–a summary. Front Hum Neurosci 2009, 3: 26.
Liang S, Vega R, Kong X, Deng W, Wang Q, Ma X, et al. Neurocognitive graphs of first-episode schizophrenia and major depression based on cognitive features. Neurosci Bull 2018, 34: 312–320.
Yamada S, Takahashi S, Ukai S, Tsuji T, Iwatani J, Tsuda K, et al. Microstructural abnormalities in anterior callosal fibers and their relationship with cognitive function in major depressive disorder and bipolar disorder: a tract-specific analysis study. J Affect Disord 2015, 174: 542-548.
Schermuly I, Fellgiebel A, Wagner S, Yakushev I, Stoeter P, Schmitt R, et al. Association between cingulum bundle structure and cognitive performance: an observational study in major depression. Eur Psychiatry 2010, 25: 355–360.
Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008, 9: 46–56.
Petschner P, Gonda X, Baksa D, Eszlari N, Trivaks M, Juhasz G, et al. Genes linking mitochondrial function, cognitive impairment and depression are associated with endophenotypes serving precision medicine. Neuroscience 2018, 370: 207–217.
Won E, Choi S, Kang J, Kim A, Han KM, Chang HS, et al. Association between reduced white matter integrity in the corpus callosum and serotonin transporter gene DNA methylation in medication-naive patients with major depressive disorder. Transl Psychiatry 2016, 6: e866.
Choi S, Han KM, Won E, Yoon BJ, Lee MS, Ham BJ. Association of brain-derived neurotrophic factor DNA methylation and reduced white matter integrity in the anterior corona radiata in major depression. J Affect Disord 2015, 172: 74–80.
Nagy C, Suderman M, Yang J, Szyf M, Mechawar N, Ernst C, et al. Astrocytic abnormalities and global DNA methylation patterns in depression and suicide. Mol Psychiatry 2015, 20: 320–328.
Booij L, Wang D, Levesque ML, Tremblay RE, Szyf M. Looking beyond the DNA sequence: the relevance of DNA methylation processes for the stress-diathesis model of depression. Philos Trans R Soc Lond B Biol Sci 2013, 368: 20120251.
Aston C, Jiang L, Sokolov BP. Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder. Mol Psychiatry 2005, 10: 309–322.
Acknowledgements
All participants in the study are most warmly thanked. This work was supported by the National Natural Science Foundation of China (81630030, 81130024, 81801326, and 81571320), the National Natural Science Foundation of China/Research Grants Council of Hong Kong Joint Research Scheme (81461168029), the National Basic Research Development Program of China (2016YFC0904300), the 1.3.5 Project for Disciplines of Excellence, West China Hospital of Sichuan University, the National High-Technology Research and Development Project (863 Project) of China (2015AA020513), and a Scientific Project of Sichuan Science and Technology Department, China (2015JY0173).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Liang, S., Wang, Q., Kong, X. et al. White Matter Abnormalities in Major Depression Biotypes Identified by Diffusion Tensor Imaging. Neurosci. Bull. 35, 867–876 (2019). https://doi.org/10.1007/s12264-019-00381-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12264-019-00381-w