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Chapter 2 - Neuroanatomical Findings in Unipolar Depression and the Role of the Hippocampus

from Section 2 - Anatomical Studies

Published online by Cambridge University Press:  12 January 2021

By
Danilo Arnone
Edited by
Sudhakar Selvaraj ,
Paolo Brambilla  and
Jair C. Soares
Sudhakar Selvaraj
Affiliation:
UTHealth School of Medicine, USA
Paolo Brambilla
Affiliation:
Università degli Studi di Milano
Jair C. Soares
Affiliation:
UT Harris County Psychiatric Center, USA
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Summary

Depressive disorders are common conditions with a life prevalence of 15% in high-income countries (1) and significant economic implications for individuals and society. Major depressive disorders have negative repercussions on the overall quality of life of the people affected with an excess number of years lived with a disability (2). Although effective treatment is available, up to 65% of individuals do not fully respond or continue to experience residual symptoms, which contribute to significant disease burden (3). It is essential to improve our understanding of the neuroanatomy of depressive disorders and the functional implications to develop new targets for more efficacious treatments.

Type
Chapter
Information
Mood Disorders
Brain Imaging and Therapeutic Implications
 , pp. 7 - 15
Publisher: Cambridge University Press
Print publication year: 2021

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References

Bromet, E, Andrade, LH, Hwang, I, et al. Cross-national epidemiology of DSM-IV major depressive episode. BMC Med. 2011 July; 26(9): 90.CrossRefGoogle Scholar
WHO. World Health: Reducing Risks, Promoting Health Life. WHO, Geneva, Switzerland; 2002.Google Scholar
Cleare, A, Pariante, CM, Young, AH, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol Oxf Engl. 2015 May; 29(5): 459–525.CrossRefGoogle ScholarPubMed
Lee, AL, Ogle, WO, Sapolsky, RM. Stress and depression: possible links to neuron death in the hippocampus. Bipolar Disord. 2002 April; 4(2): 117–128.CrossRefGoogle ScholarPubMed
Arnone, D, McIntosh, AM, Ebmeier, KP, Munafò, MR, Anderson, IM. Magnetic resonance imaging studies in unipolar depression: systematic review and meta-regression analyses. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol. 2012 January; 22(1): 1–16.CrossRefGoogle ScholarPubMed
Koolschijn, PCMP, van Haren, NEM, Lensvelt-Mulders, GJLM, Hulshoff Pol, HE, Kahn, RS. Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Hum Brain Mapp. 2009 November; 30(11): 3719–3735.Google Scholar
Arnone, D, Cavanagh, J, Gerber, D, et al. Magnetic resonance imaging studies in bipolar disorder and schizophrenia: meta-analysis. Br J Psychiatry J Ment Sci. 2009 September; 195(3): 194–201.CrossRefGoogle ScholarPubMed
Bora, E, Fornito, A, Pantelis, C, Yücel, M. Gray matter abnormalities in major depressive disorder: a meta-analysis of voxel based morphometry studies. J Affect Disord. 2012 April; 138(1–2): 9–18.CrossRefGoogle ScholarPubMed
Schmaal, L, Hibar, DP, Sämann, PG, et al. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA major depressive disorder working group. Mol Psychiatry. 2017; 22(6): 900–909.Google Scholar
Arnone, D, Job, D, Selvaraj, S, et al. Computational meta-analysis of statistical parametric maps in major depression. Hum Brain Mapp. 2016 April; 37(4): 1393–1404.CrossRefGoogle ScholarPubMed
Adolphs, R. Neural systems for recognizing emotion. Curr Opin Neurobiol. 2002 April; 12(2): 169–177.CrossRefGoogle ScholarPubMed
Phillips, ML, Ladouceur, CD, Drevets, WC. A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Mol Psychiatry. 2008 September; 13(9): 829, 833–857.Google Scholar
Kempton, MJ, Salvador, Z, Munafò, MR, et al. Structural neuroimaging studies in major depressive disorder: meta-analysis and comparison with bipolar disorder. Arch Gen Psychiatry. 2011 July; 68(7): 675–690.Google Scholar
Wise, T, Radua, J, Nortje, G, et al. Voxel-based meta-analytical evidence of structural disconnectivity in major depression and bipolar disorder. Biol Psychiatry. 2016 February 15; 79(4): 293–302.CrossRefGoogle ScholarPubMed
Liao, Y, Huang, X, Wu, Q, et al. Is depression a disconnection syndrome? Meta-analysis of diffusion tensor imaging studies in patients with MDD. J Psychiatry Neurosci JPN. 2013 January; 38(1): 49–56.CrossRefGoogle ScholarPubMed
Arnone, D, McIntosh, AM, Chandra, P, Ebmeier, KP. Meta-analysis of magnetic resonance imaging studies of the corpus callosum in bipolar disorder. Acta Psychiatr Scand. 2008 November; 118(5): 357–362.Google Scholar
Ongür, D, Drevets, WC, Price, JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci U S A. 1998 October 27; 95(22): 13290–13295.CrossRefGoogle ScholarPubMed
Cotter, D, Mackay, D, Chana, G, et al. Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. Cereb Cortex N Y N 1991. 2002 April; 12(4): 386–394.Google Scholar
Uranova, NA, Vostrikov, VM, Orlovskaya, DD, Rachmanova, VI. Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophr Res. 2004 April 1; 67(2–3): 269–275.CrossRefGoogle ScholarPubMed
Rajkowska, G, Miguel-Hidalgo, JJ, Wei, J, et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry. 1999 May 1; 45(9): 1085–1098.Google Scholar
Cotter, D, Mackay, D, Landau, S, Kerwin, R, Everall, I. Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry. 2001 June; 58(6): 545–553.Google Scholar
Stockmeier, CA, Mahajan, GJ, Konick, LC, et al. Cellular changes in the postmortem hippocampus in major depression. Biol Psychiatry. 2004 November 1; 56(9): 640–650.CrossRefGoogle ScholarPubMed
Tsopelas, C, Stewart, R, Savva, GM, et al. Neuropathological correlates of late-life depression in older people. Br J Psychiatry J Ment Sci. 2011 February; 198(2): 109–114.CrossRefGoogle ScholarPubMed
Bowley, MP, Drevets, WC, Ongür, D, Price, JL. Low glial numbers in the amygdala in major depressive disorder. Biol Psychiatry. 2002 September 1; 52(5): 404–412.CrossRefGoogle ScholarPubMed
Bielau, H, Brisch, R, Gos, T, et al. Volumetric analysis of the hypothalamus, amygdala and hippocampus in non-suicidal and suicidal mood disorder patients–a post-mortem study. CNS Neurol Disord Drug Targets. 2013 November; 12(7): 914–920.Google Scholar
Baumann, B, Bielau, H, Krell, D, et al. Circumscribed numerical deficit of dorsal raphe neurons in mood disorders. Psychol Med. 2002 January; 32(1): 93–103.Google Scholar
Oh, DH, Son, H, Hwang, S, Kim, SH. Neuropathological abnormalities of astrocytes, GABAergic neurons, and pyramidal neurons in the dorsolateral prefrontal cortices of patients with major depressive disorder. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol. 2012 May; 22(5): 330–338.CrossRefGoogle ScholarPubMed
Bernard, R, Kerman, IA, Thompson, RC, et al. Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression. Mol Psychiatry. 2011 June; 16(6): 634–646.CrossRefGoogle ScholarPubMed
Cowen, PJ. Not fade away: the HPA axis and depression. Psychol Med. 2010 January; 40(1): 1–4.CrossRefGoogle ScholarPubMed
Duman, RS, Monteggia, LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006 June 15; 59(12): 1116–1127.Google Scholar
Lanfumey, L, Mongeau, R, Cohen-Salmon, C, Hamon, M. Corticosteroid-serotonin interactions in the neurobiological mechanisms of stress-related disorders. Neurosci Biobehav Rev. 2008 August; 32(6): 1174–1184.Google Scholar
Manji, HK, Drevets, WC, Charney, DS. The cellular neurobiology of depression. Nat Med. 2001 May; 7(5): 541–547.Google Scholar
Sapolsky, RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry. 2000 October; 57(10): 925–935.Google Scholar
Young, LT, Bakish, D, Beaulieu, S. The neurobiology of treatment response to antidepressants and mood stabilizing medications. J Psychiatry Neurosci JPN. 2002 July; 27(4): 260–265.Google Scholar
Campbell, S, Macqueen, G. The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci JPN. 2004 November; 29(6): 417–426.Google ScholarPubMed
Leal, G, Comprido, D, de Luca, P, et al. The RNA-binding protein hnRNP K mediates the effect of BDNF on dendritic mRNA metabolism and regulates synaptic NMDA receptors in hippocampal neurons. eNeuro. 2017 December 12; 4(6): ENEURO.0268–17.2017.CrossRefGoogle ScholarPubMed
Arnone, D, Mumuni, AN, Jauhar, S, Condon, B, Cavanagh, J. Indirect evidence of selective glial involvement in glutamate-based mechanisms of mood regulation in depression: meta-analysis of absolute prefrontal neuro-metabolic concentrations. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol. 2015 August; 25(8): 1109–1117.CrossRefGoogle ScholarPubMed
MacQueen, GM, Campbell, S, McEwen, BS, et al. Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci U S A. 2003 February 4; 100(3): 1387–1392.CrossRefGoogle ScholarPubMed
Stewart, RJ, Chen, B, Dowlatshahi, D, MacQueen, GM, Young, LT. Abnormalities in the cAMP signaling pathway in post-mortem brain tissue from the Stanley Neuropathology Consortium. Brain Res Bull. 2001 July 15; 55(5): 625–629.Google Scholar
Dowlatshahi, D, MacQueen, GM, Wang, JF, Young, LT. Increased temporal cortex CREB concentrations and antidepressant treatment in major depression. Lancet Lond Engl. 1998 November 28; 352(9142): 1754–1755.Google ScholarPubMed
Eker, C, Kitis, O, Taneli, F, et al. Correlation of serum BDNF levels with hippocampal volumes in first episode, medication-free depressed patients. Eur Arch Psychiatry Clin Neurosci. 2010 October; 260(7): 527–533.CrossRefGoogle ScholarPubMed
Aydemir, O, Deveci, A, Taneli, F. The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry. 2005 February; 29(2): 261–265.CrossRefGoogle ScholarPubMed
Frodl, T, Meisenzahl, EM, Zill, P, et al. Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression. Arch Gen Psychiatry. 2004 February; 61(2): 177–183.Google Scholar
Lai, C-H, Hsu, Y-Y. A subtle grey-matter increase in first-episode, drug-naive major depressive disorder with panic disorder after 6 weeks’ duloxetine therapy. Int J Neuropsychopharmacol. 2011 March; 14(2): 225–235.Google Scholar
Vakili, K, Pillay, SS, Lafer, B, et al. Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study. Biol Psychiatry. 2000 June 15; 47(12): 1087–1090.Google Scholar
Hsieh, M-H, McQuoid, DR, Levy, RM, et al. Hippocampal volume and antidepressant response in geriatric depression. Int J Geriatr Psychiatry. 2002 June; 17(6): 519–525.Google Scholar
MacQueen, GM, Yucel, K, Taylor, VH, Macdonald, K, Joffe, R. Posterior hippocampal volumes are associated with remission rates in patients with major depressive disorder. Biol Psychiatry. 2008 November 15; 64(10): 880–883.CrossRefGoogle ScholarPubMed
Chen, RW, Chuang, DM. Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression. A prominent role in neuroprotection against excitotoxicity.J Biol Chem. 1999 March 5; 274(10): 6039–6042.Google Scholar
Manji, HK, Moore, GJ, Chen, G. Lithium at 50: have the neuroprotective effects of this unique cation been overlooked? Biol Psychiatry. 1999 October 1; 46(7): 929–940.Google Scholar
Goodwin, GM, Haddad, PM, Ferrier, IN, et al. Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol Oxf Engl. 2016; 30(6): 495–553.CrossRefGoogle ScholarPubMed
Manji, HK, Bebchuk, JM, Moore, GJ, et al. Modulation of CNS signal transduction pathways and gene expression by mood-stabilizing agents: therapeutic implications. J Clin Psychiatry. 1999; 60(Suppl. 2): 27–39;discussion 40–41, 113–116.Google ScholarPubMed
Chen, G, Hasanat, KA, Bebchuk, JM, et al. Regulation of signal transduction pathways and gene expression by mood stabilizers and antidepressants. Psychosom Med. 1999 October; 61(5): 599–617.CrossRefGoogle ScholarPubMed
Abe, O, Yamasue, H, Kasai, K, et al. Voxel-based analyses of gray/white matter volume and diffusion tensor data in major depression. Psychiatry Res. 2010 January 30; 181(1): 64–70.CrossRefGoogle ScholarPubMed
Bell-McGinty, S, Butters, MA, Meltzer, CC, et al. Brain morphometric abnormalities in geriatric depression: long-term neurobiological effects of illness duration. Am J Psychiatry. 2002 August; 159(8): 1424–1427.CrossRefGoogle ScholarPubMed
Bergouignan, L, Chupin, M, Czechowska, Y, Kinkingnéhun, S, Lemogne, C, Le Bastard, G, et al. Can voxel based morphometry, manual segmentation and automated segmentation equally detect hippocampal volume differences in acute depression? NeuroImage. 2009 March 1; 45(1): 29–37.Google Scholar
Kim, MJ, Hamilton, JP, Gotlib, IH. Reduced caudate gray matter volume in women with major depressive disorder. Psychiatry Res. 2008 November 30; 164(2): 114–122.CrossRefGoogle ScholarPubMed
Mak, AKY, Wong, MMC, Han, S-H, Lee, TMC. Gray matter reduction associated with emotion regulation in female outpatients with major depressive disorder: A voxel-based morphometry study. Prog Neuropsychopharmacol Biol Psychiatry. 2009 October 1; 33(7): 1184–1190.Google Scholar
Peng, J, Liu, J, Nie, B, et al. Cerebral and cerebellar gray matter reduction in first-episode patients with major depressive disorder: A voxel-based morphometry study. Eur J Radiol. 2011 November; 80(2): 395–399.Google Scholar
Shah, PJ, Ebmeier, KP, Glabus, MF, Goodwin, GM. Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression. Controlled magnetic resonance imaging study. Br J Psychiatry J Ment Sci. 1998 June; 172: 527–532.Google Scholar
Wagner, G, Koch, K, Schachtzabel, C, et al. Structural brain alterations in patients with major depressive disorder and high risk for suicide: Evidence for a distinct neurobiological entity? NeuroImage. 2011 January 15; 54(2): 1607–1614.CrossRefGoogle ScholarPubMed
Cheng, Y-Q, Xu, J, Chai, P, et al. Brain volume alteration and the correlations with the clinical characteristics in drug-naïve first-episode MDD patients: A voxel-based morphometry study. Neurosci Lett. 2010 August 9; 480(1): 30–34.Google Scholar
Lai, C-H, Hsu, Y-Y, Wu, Y-T. First episode drug-naïve major depressive disorder with panic disorder: Gray matter deficits in limbic and default network structures. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol. 2010 October; 20(10): 676–682.Google Scholar
Zou, K, Deng, W, Li, T, et al. Changes of brain morphometry in first-episode, drug-naïve, non-late-life adult patients with major depression: An optimized voxel-based morphometry study. Biol Psychiatry. 2010 January 15; 67(2): 186–188.CrossRefGoogle ScholarPubMed
Arnone, D, et al. State-dependent changes in hippocampal grey matter in depression. 2013; Available from: http://doi.org/10.1038/mp.2012.150Google Scholar
McKinnon, MC, Yucel, K, Nazarov, A, MacQueen, GM. A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. J Psychiatry Neurosci JPN. 2009 January; 34(1): 41–54.Google ScholarPubMed
Gerritsen, L, Comijs, HC, van der Graaf, Y, et al. Depression, hypothalamic pituitary adrenal axis, and hippocampal and entorhinal cortex volumes–the SMART Medea study. Biol Psychiatry. 2011 August 15; 70(4): 373–380.Google Scholar
Hickie, I, Naismith, S, Ward, PB, et al. Reduced hippocampal volumes and memory loss in patients with early- and late-onset depression. Br J Psychiatry J Ment Sci. 2005 March; 186: 197–202.CrossRefGoogle ScholarPubMed
Videbech, P, Ravnkilde, B. Hippocampal volume and depression: A meta-analysis of MRI studies. Am J Psychiatry. 2004 November; 161(11): 1957–1966.CrossRefGoogle ScholarPubMed
Salvadore, G, Nugent, AC, Lemaitre, H, et al. Prefrontal cortical abnormalities in currently depressed versus currently remitted patients with major depressive disorder. NeuroImage. 2011 February 14; 54(4): 2643–2651.Google Scholar
Wise, T, Radua, J, Via, E, et al. Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: Evidence from voxel-based meta-analysis. Mol Psychiatry. 2017 October; 22(10): 1455–1463.Google Scholar
Rao, U, Chen, L-A, Bidesi, AS, et al. Hippocampal changes associated with early-life adversity and vulnerability to depression. Biol Psychiatry. 2010 February 15; 67(4): 357–364.CrossRefGoogle ScholarPubMed
Amico, F, Meisenzahl, E, Koutsouleris, N, et al. Structural MRI correlates for vulnerability and resilience to major depressive disorder. J Psychiatry Neurosci JPN. 2011 January; 36(1): 15–22.CrossRefGoogle ScholarPubMed
Vythilingam, M, Vermetten, E, Anderson, GM, et al. Hippocampal volume, memory, and cortisol status in major depressive disorder: Effects of treatment. Biol Psychiatry. 2004 July 15; 56(2): 101–112.CrossRefGoogle ScholarPubMed
Kaufman, J, Yang, B-Z, Douglas-Palumberi, H, et al. Brain-derived neurotrophic factor-5-HTTLPR gene interactions and environmental modifiers of depression in children. Biol Psychiatry. 2006 April 15; 59(8): 673–680.CrossRefGoogle ScholarPubMed
Soetanto, A, Wilson, RS, Talbot, K, et al. Association of anxiety and depression with microtubule-associated protein 2- and synaptopodin-immunolabeled dendrite and spine densities in hippocampal CA3 of older humans. Arch Gen Psychiatry. 2010 May; 67(5): 448–457.CrossRefGoogle ScholarPubMed
Wise, T, Cleare, AJ, Herane, A, Young, AH, Arnone, D. Diagnostic and therapeutic utility of neuroimaging in depression: An overview. Neuropsychiatr Dis Treat. 2014; 10: 1509–1522.Google ScholarPubMed
Antonio, Damasio. Descartes’ Error: Emotion, Reason and the Human Brain. Random House; 2008.Google Scholar
Damasio, AR, Tranel, D, Damasio, H. Individuals with sociopathic behavior caused by frontal damage fail to respond autonomically to social stimuli. Behav Brain Res. 1990 December 14; 41(2): 81–94.Google Scholar
Bechara, A, Damasio, H, Damasio, AR. Emotion, decision making and the orbitofrontal cortex. Cereb Cortex N Y N 1991. 2000 March; 10(3): 295–307.Google Scholar
Saleem, KS, Kondo, H, Price, JL. Complementary circuits connecting the orbital and medial prefrontal networks with the temporal, insular, and opercular cortex in the macaque monkey. J Comp Neurol. 2008 February 1; 506(4): 659–693.CrossRefGoogle ScholarPubMed
Price, JL, Drevets, WC. Neurocircuitry of mood disorders. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2010 January; 35(1): 192–216.Google Scholar
Spencer, SJ, Fox, JC, Day, TA. Thalamic paraventricular nucleus lesions facilitate central amygdala neuronal responses to acute psychological stress. Brain Res. 2004 February 6; 997(2): 234–237.Google Scholar
Mayberg, HS. Limbic-cortical dysregulation: A proposed model of depression. J Neuropsychiatry Clin Neurosci. 1997; 9(3): 471–481.Google ScholarPubMed
Mayberg, HS. Targeted electrode-based modulation of neural circuits for depression. J Clin Invest. 2009 April; 119(4): 717–725.CrossRefGoogle ScholarPubMed
Adolphs, R. Neural systems for recognizing emotion. Curr Opin Neurobiol. 2002 April; 12(2): 169–177.Google Scholar

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