Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Psychiatry
Published in: BMC Psychiatry 1/2013

Open Access 01-12-2013 | Research article

Abnormalities of cortical-limbic-cerebellar white matter networks may contribute to treatment-resistant depression: a diffusion tensor imaging study

Authors: Hong-jun Peng, Hui-rong Zheng, Yu-ping Ning, Yan Zhang, Bao-ci Shan, Li Zhang, Hai-chen Yang, Jun Liu, Ze-xuan Li, Jian-song Zhou, Zhi-jun Zhang, Ling-jiang Li

Published in: BMC Psychiatry | Issue 1/2013

Login to get access

Abstract

Background

White matter abnormalities can cause network dysfunction that underlies major depressive disorder (MDD). Diffusion tensor imaging (DTI) is used to examine the neural connectivity and integrity of the white matter. Previous studies have implicated frontolimbic neural networks in the pathophysiology of MDD. Approximately 30% of MDD patients demonstrate treatment-resistant depression (TRD). However, the neurobiology of TRD remains unclear.

Methods

We used a voxel-based analysis method to analyze DTI data in young patients with TRD (n = 30; 19 males, 11 females) compared with right-handed, age- and sex-matched healthy volunteers (n = 25; 14 males, 11 females).

Results

We found a significant decrease in fractional anisotropy (FA) (corrected, cluster size >50) in the left middle frontal gyrus (peak coordinates [−18 46–14]), left limbic lobe uncus (peak coordinates [−18 2–22]), and right cerebellum posterior lobe (peak coordinates [26–34 -40]). There was no increase in FA in any brain region in patients. We also found a significant negative correlation between mean regional FA values in the three areas and Beck Depression Inventory symptom scores.

Conclusions

We found significant differences in white matter FA in the frontal lobe, limbic lobe and cerebellum between TRD patients and controls. These data suggest that abnormalities of cortical-limbic-cerebellar white matter networks may contribute to TRD in young patients.
Appendix
Available only for authorised users
Literature
1.
Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B: Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet. 2007, 370 (9590): 851-858. 10.1016/S0140-6736(07)61415-9.CrossRefPubMed
2.
Amital D, Fostick L, Silberman A, Beckman M, Spivak B: Serious life events among resistant and non-resistant MDD patients. J Affect Disord. 2008, 110 (3): 260-264. 10.1016/j.jad.2008.01.006.CrossRefPubMed
3.
Ananth J: Treatment-resistant depression. Psychother Psychosom. 1998, 67 (2): 61-70. 10.1159/000012261.CrossRefPubMed
4.
Fava M, Davidson KG: Definition and epidemiology of treatment-resistant depression. Psychiatr Clin N Am. 1996, 19 (2): 179-200. 10.1016/S0193-953X(05)70283-5.CrossRef
5.
Keller MB: Issues in treatment-resistant depression. Journal of Clinical Psychiatry. 2005, 66: 5-12. 10.4088/JCP.v66n0101.CrossRefPubMed
6.
Rush AJ, Thase ME, Dube S: Research issues in the study of difficult-to-treat depression. Biol Psychiatry. 2003, 53 (8): 743-753. 10.1016/S0006-3223(03)00088-X.CrossRefPubMed
7.
Zhang TJ, Wu QZ, Huang XQ, Sun XL, Zou K, Lui S, Liu F, Hu JM, Kuang WH, Li DM: Magnetization transfer imaging reveals the brain deficit in patients with treatment-refractory depression. J Affect Disord. 2009, 117 (3): 157-161. 10.1016/j.jad.2009.01.003.CrossRefPubMed
8.
Drevets WC, Price JL, Furey ML: Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Structure & Function. 2008, 213 (1–2): 93-118.CrossRef
9.
Lim KO, Helpen JA: Neuropsychiatric applications of DTI - a review. NMR Biomed. 2002, 15 (7–8): 587-593.CrossRefPubMed
10.
Taylor WD, Hsu E, Krishnan KRR, MacFall JR: Diffusion tensor imaging: Background, potential, and utility in psychiatric research. Biol Psychiatry. 2004, 55 (3): 201-207. 10.1016/j.biopsych.2003.07.001.CrossRefPubMed
11.
12.
Sexton CE, Mackay CE, Ebmeier KP: A Systematic Review of Diffusion Tensor Imaging Studies in Affective Disorders. Biol Psychiatry. 2009, 66 (9): 814-823. 10.1016/j.biopsych.2009.05.024.CrossRefPubMed
13.
Beyer JL, Taylor WD, MacFall JR, Kuchibhatla M, Payne ME, Provenzale JM, Cassidy F, Krishnan KRR: Cortical white matter microstructural abnormalities in bipolar disorder. Neuropsychopharmacology. 2005, 30 (12): 2225-2229. 10.1038/sj.npp.1300802.CrossRefPubMed
14.
Cullen KR, Klimes-Dougan B, Muetzel R, Mueller BA, Camchong J, Houri A, Kurma S, Lim KO: Altered White Matter Microstructure in Adolescents With Major Depression: A Preliminary Study. J Am Acad Child Adolesc Psychiatry. 2009, 49 (2): 173-183.
15.
Li LJ, Ma N, Li ZX, Tan LW, Liu J, Gong GL, Shu N, He Z, Jiang TZ, Xu L: Prefrontal white matter abnormalities in young adult with major depressive disorder: A diffusion tensor imaging study. Brain Research. 2007, 1168: 124-128.CrossRefPubMed
16.
Yang Q, Huang XB, Hong N, Yu X: White matter microstructural abnormalities in late-life depression. Int Psychogeriatr. 2007, 19 (4): 757-766. 10.1017/S1041610207004875.CrossRefPubMed
17.
Xl L, Wang YZ, Liu HH, Liu ZN, Zhou WB: Diffusion tensor imaging and resting state functional magnetic resonance imaging on young patients with major depressive disorder. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010, 35 (1): 25-31.
18.
Fagiolini A, Kupfer DJ: Is treatment-resistant depression a unique subtype of depression?. Biol Psychiatry. 2003, 53 (8): 640-648. 10.1016/S0006-3223(02)01670-0.CrossRefPubMed
19.
Phillips ML, Drevets WC, Rauch SL, Lane R: Neurobiology of emotion perception II: Implications for major psychiatric disorders. Biol Psychiatry. 2003, 54 (5): 515-528. 10.1016/S0006-3223(03)00171-9.CrossRefPubMed
20.
Nauta WJH, Domesick VB: Afferent and efferent relationships of the basal ganglia. Ciba Foundation Symposia. 1984, 107: 3-29.PubMed
21.
Ongur D, Ferry AT, Price JL: Architectonic subdivision of the human orbital and medial prefrontal cortex. J Comp Neurol. 2003, 460 (3): 425-449. 10.1002/cne.10609.CrossRefPubMed
22.
Li CX, Sun XL, Zou K, Yang H, Huang XQ, Wang YQ, Liu S, Li DM, Zhou L, Chen HF: Voxel based Analysis of DTI in Depression Patients. Inter J Magn Reson Imaging. 2007, 01: 043-048.
23.
Zheng HR, Zhang L, Li LJ, Liu P, Gao JL, Liu XY, Zou JA, Zhang Y, Liu J, Zhang ZJ: High-frequency rTMS treatment increases left prefrontal myo-inositol in young patients with treatment-resistant depression. Prog Neuropsychopharmacol Biol Psychiatry. 2010, 34 (7): 1189-1195. 10.1016/j.pnpbp.2010.06.009.CrossRefPubMed
24.
Beck AT, Beamesderfer A: Assessment of depression: the depression inventory. Mod Probl Pharmacopsychiatry. 1974, 7: 151-169.CrossRefPubMed
25.
Liao Y, Tang J, Ma M, Wu Z, Yang M, Wang X, Liu T, Chen X, Fletcher PC, Hao W: Frontal white matter abnormalities following chronic ketamine use: a diffusion tensor imaging study. Brain. 2010, 133: 2115-2122. 10.1093/brain/awq131.CrossRefPubMed
26.
Peng H, Zheng H, Li L, Liu J, Zhang Y, Shan B, Zhang L, Yin Y, Li W: High-frequency rTMS treatment increases white matter FA in the left middle frontal gyrus in young patients with treatment-resistant depression. J Affect Disord. 2012, 136: 249-257. 10.1016/j.jad.2011.12.006.CrossRefPubMed
27.
Tang J, Liao Y, Zhou B, Tan C, Liu T, Hao W, Hu D, Chen X: Abnormal anterior cingulum integrity in first episode, early-onset schizophrenia: a diffusion tensor imaging study. Brain research. 2010, 1343: 199-205.CrossRefPubMed
28.
Genovese CR, Lazar NA, Nichols T: Thresholding of statistical maps in functional neuroimaging using the false discovery rate. NeuroImage. 2002, 15 (4): 870-878. 10.1006/nimg.2001.1037.CrossRefPubMed
29.
Hao Y, Yan Q, Liu H, Xu L, Xue Z, Song X, Kaneko Y, Jiang T, Liu Z, Shan B: Schizophrenia patients and their healthy siblings share disruption of white matter integrity in the left prefrontal cortex and the hippocampus but not the anterior cingulate cortex. Schizophr Res. 2009, 114 (1–3): 128-135.CrossRefPubMed
30.
Abe O, Yamasue H, Kasai K, Yamada H, Aoki S, Inoue H, Takei K, Suga M, Matsuo K, Kato T: Voxel-based analyses of gray/white matter volume and diffusion tensor data in major depression. Psychiatry Research-Neuroimaging. 2009, 181 (1): 64-70.CrossRef
31.
Kempton MJ, Salvador Z, Munafo MR, Geddes JR, Simmons A, Frangou S, Williams SCR: Structural neuroimaging studies in major depressive disorder: meta-analysis and comparison with bipolar disorder. Arch Gen Psychiatry. 2011, 68: 675-10.1001/archgenpsychiatry.2011.60.CrossRefPubMed
32.
Kieseppa T, Eerola M, Mantyla R, Neuvonen T, Poutanen VP, Luoma K, Tuulio-Henriksson A, Jylha P, Mantere O, Melartin T: Major depressive disorder and white matter abnormalities: A diffusion tensor imaging study with tract-based spatial statistics. J Affect Disord. 2009, 120 (1–3): 240-244.
33.
Konarski JZ, McIntyre RS, Kennedy SH, Soczynska JK, Ketter TA: Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder. Bipolar disorders. 2008, 10: 1-37.CrossRefPubMed
34.
Versace A, Almeida JRC, Quevedo K, Thompson WK, Terwilliger RA, Hassel S, Kupfer DJ, Phillips ML: Right Orbitofrontal Corticolimbic and Left Corticocortical White Matter Connectivity Differentiate Bipolar and Unipolar Depression. Biol Psychiatry. 2010, 68 (6): 560-567. 10.1016/j.biopsych.2010.04.036.CrossRefPubMedPubMedCentral
35.
Zhu XL, Wang XA, Xiao J, Zhong MT, Liao JA, Yao SQ: Altered white matter integrity in first-episode, treatment-naive young adults with major depressive disorder: A tract-based spatial statistics study. Brain Research. 2011, 1369: 223-229.CrossRefPubMed
36.
Mayberg HS: Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. Br Med Bull. 2003, 65: 193-195. 10.1093/bmb/65.1.193.CrossRefPubMed
37.
Mayberg HS: Limbic-cortical dysregulation: A proposed model of depression. J Neuropsychiatry Clin Neurosci. 1997, 9 (3): 471-481.CrossRefPubMed
38.
Mayberg HS: Modulating limbic-cortical circuits in depression: targets of antidepressant treatments. Semin Clin Neuropsychiatry. 2002, 7 (4): 255-256. 10.1053/scnp.2002.35223.CrossRefPubMed
39.
Tekin S, Cummings JL: Frontal-subcortical neuronal circuits and clinical neuropsychiatry - An update. J Psychosom Res. 2002, 53: 647-654. 10.1016/S0022-3999(02)00428-2.CrossRefPubMed
40.
Dietrich DE, Bonnemann C, Emrich HM: Cortico-limbic mechanisms of affect regulation in the therapy of depression. Psychiatr Prax. 2007, 34: S287-S291. 10.1055/s-2007-971019.CrossRefPubMed
41.
Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S, Mayberg H: Modulation of cortical-limbic pathways in major depression - Treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry. 2004, 61 (1): 34-41. 10.1001/archpsyc.61.1.34.CrossRefPubMed
42.
Grace AA: Disruption of cortical-limbic interaction as a substrate for comorbidity. Neurotox Res. 2006, 10 (2): 93-101. 10.1007/BF03033238.CrossRefPubMed
43.
Wager TD, Davidson ML, Hughes BL, Lindquist MA, Ochsner KN: Prefrontal-subcortical pathways mediating successful emotion regulation. Neuron. 2008, 59 (6): 1037-1050. 10.1016/j.neuron.2008.09.006.CrossRefPubMedPubMedCentral
44.
Seminowicz D, Mayberg H, McIntosh A, Goldapple K, Kennedy S, Segal Z, Rafi-Tari S: Limbic–frontal circuitry in major depression: a path modeling metanalysis. NeuroImage. 2004, 22: 409-418. 10.1016/j.neuroimage.2004.01.015.CrossRefPubMed
45.
Mervaala E, Fohr J, Kononen M, Valkonen-Korhonen M, Vainio P, Partanen K, Partanen J, Tiihonen J, Viinamaki H, Karjalainen AK: Quantitative MRI of the hippocampus and amygdala in severe depression. Psychol Med. 2000, 30 (1): 117-125. 10.1017/S0033291799001567.CrossRefPubMed
46.
Glickstein M, Doron K: Cerebellum: Connections and Functions. Cerebellum. 2008, 7 (4): 589-594. 10.1007/s12311-008-0074-4.CrossRefPubMed
47.
Schmahmann JD: The Role of the Cerebellum in Cognition and Emotion: Personal Reflections Since 1982 on the Dysmetria of Thought Hypothesis, and Its Historical Evolution from Theory to Therapy. Neuropsychol Rev. 2010, 20 (3): 236-260. 10.1007/s11065-010-9142-x.CrossRefPubMed
48.
Lee GP, Meador KJ, Loring DW, Allison JD, Brown WS, Paul LK, Pillai JJ, Lavin TB: Neural substrates of emotion as revealed by functional magnetic resonance imaging. Cogn Behav Neurol. 2004, 17 (1): 9-17. 10.1097/00146965-200403000-00002.CrossRefPubMed
49.
Doron KW, Funk CM, Glickstein M: Fronto-cerebellar circuits and eye movement control: A diffusion imaging tractography study of human cortico-pontine projections. Brain Research. 2009, 1307: 63-71.CrossRefPubMed
50.
Baillieux H, De Smet HJ, Dobbeleir A, Paquier PF, De Deyn PP, Marien P: Cognitive and affective disturbances following focal cerebellar damage in adults: A neuropsychological and SPECT study. Cortex. 2009, 46 (7): 869-879.CrossRefPubMed
51.
Katharine A, Smith AP, Cowen PJ, Mccleery JM, Goodwin GM, Smith S, Tracey I, Matthews PM: Cerebellar responses during anticipation of noxious stimuli in subjects recovered from depression: functional magnetic resonance imaging study. Br J Psychiatry. 2002, 181: 411-415. 10.1192/bjp.181.5.411.CrossRef
52.
Stoodley CJ, Schmahmann JD: Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex. 2009, 46 (7): 831-844.CrossRef
53.
Belger A, Puce A, Krystal JH, Gore JC, Goldman-Rakic P, McCarthy G: Dissociation of mnemonic and perceptual processes during spatial and nonspatial working memory using fMRI. Human Brain Mapping. 1998, 6 (1): 14-32. 10.1002/(SICI)1097-0193(1998)6:1<14::AID-HBM2>3.0.CO;2-O.CrossRefPubMed
54.
Liu CL, Hue CW, Chen CC, Chuang KH, Liang KC, Wang YH, Wu CW, Chen JH: Dissociated roles of the middle frontal gyri in the processing of Chinese characters. Neuroreport. 2006, 17 (13): 1397-1401. 10.1097/01.wnr.0000233090.00463.35.CrossRefPubMed
55.
Miller EK, Cohen JD: An integrative theory of prefrontal cortex function. Annu Rev Neurosci. 2001, 24: 167-202. 10.1146/annurev.neuro.24.1.167.CrossRefPubMed
56.
Yao ZJ, Liu HY, Teng GJ, Lu Q, Wang L, Cao YX: The preliminary study of gender difference in brain white matter in major depression. Chin J Nerv Ment Dis. 2008, 34: 161-164.
Metadata
Title
Abnormalities of cortical-limbic-cerebellar white matter networks may contribute to treatment-resistant depression: a diffusion tensor imaging study
Authors
Hong-jun Peng
Hui-rong Zheng
Yu-ping Ning
Yan Zhang
Bao-ci Shan
Li Zhang
Hai-chen Yang
Jun Liu
Ze-xuan Li
Jian-song Zhou
Zhi-jun Zhang
Ling-jiang Li
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2013
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/1471-244X-13-72

Other articles of this Issue 1/2013

BMC Psychiatry 1/2013 Go to the issue

Research article

Reduced duration mismatch negativity in adolescents with psychotic symptoms: further evidence for mismatch negativity as a possible biomarker for vulnerability to psychosis

Research article

Assessing the prevalence of non-medical prescription opioid use in the Canadian general adult population: evidence of large variation depending on survey questions used

Study protocol

Expectations, experiences and attitudes of patients and primary care health professionals regarding online psychotherapeutic interventions for depression: protocol for a qualitative study

Study protocol

A randomised controlled trial of time limited CBT informed psychological therapy for anxiety in bipolar disorder

Study protocol

Don’t turn your back on the symptoms of psychosis: a proof-of-principle, quasi-experimental public health trial to reduce the duration of untreated psychosis in Birmingham, UK

Research article

Rumination, anxiety, depressive symptoms and subsequent depression in adolescents at risk for psychopathology: a longitudinal cohort study