Neuroimaging findings in depression

Author/s
Thomas Frodl, Leonardo Tozzi
Citation
Issue 5 Winter 2018
CEPiP.2018.1.37-41
Abstract

Neuroimaging techniques are important clinically, to exclude organic disorders as origins of depression. For research, they provide insight into brain structure, function and network organization, indicating the relevance of different brain circuits for certain brain functions and how these are altered in major depressive disorder (MDD). Here, the findings from cross-sectional and longitudinal neuroimaging studies on major depression will be reviewed, focusing on structural, functional and diffusion imaging, as well as MR spectroscopy. Overall, structural, functional and diffusion imaging studies show alterations in networks consisting of the cingulate cortices, prefrontal cortices, amygdala and subcortical regions like the hippocampus and basal ganglia which may play key roles in MDD. Excitatory and inhibitory neurotransmitters as well as glutathione measured using MR spectroscopy were found to be decreased in MDD compared to controls, while membrane turnover is thought to be increased in some regions. Assessing distinct functional deficits associated with different underlying pathophysiological mechanisms, which in turn might inform about different promising therapies, is currently a research direction.

Cite as: Cutting Edge Psychiatry in Practice 2018, 5(1):37-41; https://doi.org/10.65031/mcig8139

References

  1. McKinnon MC, Yucel K, Nazarov A, MacQueen GM. A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. Journal of Psychiatry & Neuroscience: JPN. 2009 Jan;34(1):41. https://doi.org/10.1139/jpn.0905
  2. Campbell S, Marriott M, Nahmias C, MacQueen GM. Lower hippocampal volume in patients suffering from depression: a meta-analysis. American Journal of Psychiatry. 2004 Apr 1;161(4):598-607. https://doi.org/10.1176/appi.ajp.161.4.598
  3. Videbech P, Ravnkilde B. Hippocampal volume and depression: a meta-analysis of MRI studies. American Journal of Psychiatry. 2004 Nov 1;161(11):1957-66. https://doi.org/10.1176/appi.ajp.161.11.1957
  4. Kempton MJ, Salvador Z, Munafò MR, Geddes JR, Simmons A, Frangou S, Williams SC. Structural neuroimaging studies in major depressive disorder: meta-analysis and comparison with bipolar disorder. Archives of General Psychiatry. 2011 Jul 4;68(7):675-90. https://doi.org/10.1001/archgenpsychiatry.2011.60
  5. Frodl TS, Koutsouleris N, Bottlender R, Born C, Jäger M, Scupin I, Reiser M, Möller HJ, Meisenzahl EM. Depression-related variation in brain morphology over 3 years: effects of stress? Archives of General Psychiatry. 2008 Oct 6;65(10):1156-65. https://doi.org/10.1001/archpsyc.65.10.1156
  6. Fu CH, Williams SC, Cleare AJ, Brammer MJ, Walsh ND, Kim J, Andrew CM, Pich EM, Williams PM, Reed LJ, Mitterschiffthaler MT. Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. Archives of General Psychiatry. 2004 Sep 1;61(9):877-89. https://doi.org/10.1001/archpsyc.61.9.877
  7. Surguladze S, Brammer MJ, Keedwell P, Giampietro V, Young AW, Travis MJ, Williams SC, Phillips ML. A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biological Psychiatry. 2005 Feb 1;57(3):201-9. https://doi.org/10.1016/j.biopsych.2004.10.028
  8. Frodl T, Scheuerecker J, Albrecht J, Kleemann AM, Müller-Schunk S, Koutsouleris N, Möller HJ, Brückmann H, Wiesmann M, Meisenzahl E. Neuronal correlates of emotional processing in patients with major depression. The World Journal of Biological Psychiatry. 2009 Jan 1;10(3):202-8. https://doi.org/10.1080/15622970701624603
  9. Hamilton JP, Gotlib IH. Neural substrates of increased memory sensitivity for negative stimuli in major depression. Biological Psychiatry. 2008 Jun 15;63(12):1155-62. https://doi.org/10.1016/j.biopsych.2007.12.015
  10. Dannlowski U, Ohrmann P, Konrad C, Domschke K, Bauer J, Kugel H, Hohoff C, Schöning S, Kersting A, Baune BT, Mortensen LS. Reduced amygdala–prefrontal coupling in major depression: association with MAOA genotype and illness severity. International Journal of Neuropsychopharmacology. 2009 Feb 1;12(1):11-22. https://doi.org/10.1017/s1461145708008973
  11. Castellanos FX, Proal E. Large-scale brain systems in ADHD: beyond the prefrontal–striatal model. Trends in Cognitive Sciences. 2012 Jan 1;16(1):17-26. https://doi.org/10.1016/j.tics.2011.11.007
  12. Zhou Y, Yu C, Zheng H, Liu Y, Song M, Qin W, Li K, Jiang T. Increased neural resources recruitment in the intrinsic organization in major depression. Journal of Affective Disorders. 2010 Mar 1;121(3):220-30. https://doi.org/10.1016/j.jad.2009.05.029
  13. Sheline YI, Barch DM, Price JL, Rundle MM, Vaishnavi SN, Snyder AZ, Mintun MA, Wang S, Coalson RS, Raichle ME. The default mode network and self-referential processes in depression. Proceedings of the National Academy of Sciences. 2009 Feb 10;106(6):1942-7. https://doi.org/10.1073/pnas.0812686106
  14. Sheline YI, Price JL, Yan Z, Mintun MA. Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proceedings of the National Academy of Sciences. 2010 Jun 15;107(24):11020-5. https://doi.org/10.1073/pnas.1000446107
  15. Grimm S, Boesiger P, Beck J, Schuepbach D, Bermpohl F, Walter M, Ernst J, Hell D, Boeker H, Northoff G. Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychopharmacology. 2009 Mar;34(4):932. https://doi.org/10.1038/npp.2008.81
  16. Sexton CE, Mackay CE, Ebmeier KP. A systematic review of diffusion tensor imaging studies in affective disorders. Biological Psychiatry. 2009 Nov 1;66(9):814-23. https://doi.org/10.1016/j.biopsych.2009.05.024
  17. Frodl T, Ferguson Y, Fagan A, Lisiecka D, Carballedo A, Daly I, Meaney J, Kelleher D. Microstructural correlates of resilience against major depressive disorder: epigenetic mechanisms. Journal of Psychiatry & Neuroscience. 2010 Aug 20. https://doi.org/10.1038/npre.2010.4793.2
  18. Liao Y, Huang X, Wu Q, Yang C, Kuang W, Du M, Lui S, Yue Q, Chan RC, Kemp GJ, Gong Q. Is depression a disconnection syndrome? Meta-analysis of diffusion tensor imaging studies in patients with MDD. Journal of Psychiatry & Neuroscience: JPN. 2013 Jan;38(1):49. https://doi.org/10.1503/jpn.110180
  19. Murphy ML, Frodl T. Meta-analysis of diffusion tensor imaging studies shows altered fractional anisotropy occurring in distinct brain areas in association with depression. Biology of Mood & Anxiety Disorders. 2011 Dec;1(1):3. https://doi.org/10.1186/2045-5380-1-3
  20. Crow TJ, Cross AJ, Cooper SJ, Deakin JF, Ferrier IN, Johnson JA, Joseph MH, Owen F, Poulter M, Lofthouse R, Corsellis JA. Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression, and suicides. Neuropharmacology. 1984 Dec 1;23(12):1561-9. https://doi.org/10.1016/0028-3908(84)90100-x
  21. Jansen JF, Backes WH, Nicolay K, Kooi ME. 1H MR spectroscopy of the brain: absolute quantification of metabolites. Radiology. 2006 Aug;240(2):318-32. https://doi.org/10.1148/radiol.2402050314
  22. Bustillo JR. Use of proton magnetic resonance spectroscopy in the treatment of psychiatric disorders: a critical update. Dialogues in Clinical Neuroscience. 2013 Sep;15(3):329. https://doi.org/10.31887/dcns.2013.15.3/jbustillo
  23. Rae CD. A guide to the metabolic pathways and function of metabolites observed in human brain 1 H magnetic resonance spectra. Neurochemical Research. 2014 Jan 1;39(1):1-36. https://doi.org/10.1007/s11064-013-1199-5
  24. Terpstra M, Henry PG, Gruetter R. Measurement of reduced glutathione (GSH) in human brain using LCModel analysis of difference‐edited spectra. Magnetic Resonance in Medicine: An Official Journal of the International Society for Magnetic Resonance in Medicine. 2003 Jul;50(1):19-23. https://doi.org/10.1002/mrm.10499
  25. Miladinovic T, Nashed M, Singh G. Overview of glutamatergic dysregulation in central pathologies. Biomolecules. 2015 Dec;5(4):3112-41. https://doi.org/10.3390/biom5043112
  26. Luykx JJ, Laban KG, Van Den Heuvel MP, Boks MP, Mandl RC, Kahn RS, Bakker SC. Region and state specific glutamate downregulation in major depressive disorder: a meta-analysis of 1H-MRS findings. Neuroscience & Biobehavioral Reviews. 2012 Jan 1;36(1):198-205. https://doi.org/10.1016/j.neubiorev.2011.05.014
  27. Martinez-Hernandez A, Bell KP, Norenberg MD. Glutamine synthetase: glial localization in brain. Science. 1977 Mar 25;195(4284):1356-8. https://doi.org/10.1126/science.14400
  28. Walter M, Henning A, Grimm S, Schulte RF, Beck J, Dydak U, Schnepf B, Boeker H, Boesiger P, Northoff G. The relationship between aberrant neuronal activation in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in major depression. Archives of General Psychiatry. 2009 May 1;66(5):478-86. https://doi.org/10.1001/archgenpsychiatry.2009.39
  29. Pehrson AL, Sanchez C. Altered γ-aminobutyric acid neurotransmission in major depressive disorder: a critical review of the supporting evidence and the influence of serotonergic antidepressants. Drug Design, Development and Therapy. 2015;9:603. https://doi.org/10.2147/dddt.s62912
  30. Godlewska BR, Near J, Cowen PJ. Neurochemistry of major depression: a study using magnetic resonance spectroscopy. Psychopharmacology. 2015 Feb 1;232(3):501-7. https://doi.org/10.1007/s00213-014-3687-y
  31. Jung RE, Yeo RA, Love TM, Petropoulos H, Sibbitt Jr WL, Brooks WM. Biochemical markers of mood: a proton magnetic resonance spectroscopy study of normal human brain. Biological Psychiatry. 2002 Feb 1;51(3):224-9. https://doi.org/10.1016/s0006-3223(01)01224-0
  32. Yildiz-Yesiloglu A, Ankerst DP. Review of 1H magnetic resonance spectroscopy findings in major depressive disorder: a meta-analysis. Psychiatry Research: Neuroimaging. 2006 Jun 30;147(1):1-25. https://doi.org/10.1016/j.pscychresns.2005.12.004
  33. Venkatraman TN, Krishnan RR, Steffens DC, Song AW, Taylor WD. Biochemical abnormalities of the medial temporal lobe and medial prefrontal cortex in late-life depression. Psychiatry Research: Neuroimaging. 2009 Apr 30;172(1):49-54. https://doi.org/10.1016/j.pscychresns.2008.07.001
  34. Frodl T, Scheuerecker J, Schoepf V, Linn J, Koutsouleris N, Bokde AL, Hampel H, Möller HJ, Brückmann H, Wiesmann M, Meisenzahl E. Different effects of mirtazapine and venlafaxine on brain activation: an open randomized controlled fMRI study. Journal of Clinical Psychiatry. 2011 Apr 4;72(4):448. https://doi.org/10.4088/jcp.09m05393blu
  35. Delaveau P, Jabourian M, Lemogne C, Guionnet S, Bergouignan L, Fossati P. Brain effects of antidepressants in major depression: a meta-analysis of emotional processing studies. Journal of Affective Disorders. 2011 Apr 1;130(1-2):66-74. https://doi.org/10.1016/j.jad.2010.09.032