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Low left amygdala volume is associated with a longer duration of unipolar depression

  • Translational Neurosciences - Original Article
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Abstract

The amygdala plays a crucial role in the pathogenesis of major depressive disorder (MDD). While robust findings support a negative impact of illness duration on hippocampal volume in MDD, morphometric studies of the amygdala have yielded inhomogeneous results. Considering the methodical problems of automatic segmentation methods, a standardized segmentation protocol with proven inter- and intra-rater reliability was employed using high-resolution magnetic resonance imaging. To identify the effect of MDD on amygdala morphometry, 23 unipolar depressed patients who responded to antidepressant medication and 30 age-matched healthy controls (HC) were enrolled. First, gray matter volumes (GMV) of the bilateral amygdala were delineated manually in 3D by three blinded experts using the MultiTracer. The whole brain GMV was determined by using voxel-based morphometry. Second, the differences of the whole brain and the bilateral amygdala GMV values between MDD and HC were calculated with t-statistics. The GMV of the whole brain and the amygdala did not differ between HC and MDD patients. Third, MDD characteristics were correlated with amygdala GMV. Within the normal range, the left amygdala GMV was larger in patients with later onset and smaller in cases of prolonged depression. In line with prior reports of depressed patients responding to antidepressant treatment, amygdala GMV was negatively related to illness duration, suggesting volume loss with disease progression. It remains unclear as to whether the association between illness duration and GMV reduced left amygdala volume indicates a neurotoxic effect of prolonged MDD or is rather a negative predictor of chronic depression.

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References

  • Abercrombie HC, Schaefer SM, Larson CL, Oakes TR, Lindgren KA, Holden JE, Perlman SB, Turski PA, Krahn DD, Benca RM, Davidson RJ (1998) Metabolic rate in the right amygdala predicts negative affect in depressed patients. NeuroReport 9:3301–3307

    Article  CAS  PubMed  Google Scholar 

  • Aghamohammadi-Sereshki A, Huang Y, Olsen F, Malykhin NV (2017) In vivo quantification of amygdala subnuclei using 4.7 T fast spin echo imaging. Neuroimage. https://dx.doi.org/10.1016/j.neuroimage.2017.03.01

  • Ashburner J, Friston KJ (2005) Unified segmentation. Neuroimage 26(3):839–851

    Article  PubMed  Google Scholar 

  • Ashtari M, Greenwald BS, Kramer-Ginsberg E, Hu J, Wu H, Patel M, Aupperle P, Pollack S (1999) Hippocampal/amygdala volumes in geriatric depression. Psychol Med 29:629–638

    Article  CAS  PubMed  Google Scholar 

  • Baas D, Aleman A, Kahn RS (2004) Lateralization of amygdala activation: a systematic review of functional neuroimaging studies. Brain Res Brain Res Rev 45(2):96–103

    Article  PubMed  Google Scholar 

  • Bora E, Fornito A, Pantelis C, Yücel M (2012) Gray matter abnormalities in major depressive disorder: a meta-analysis of voxel based morphometry studies. J Affect Disord 138:9–18

    Article  PubMed  Google Scholar 

  • Bowley MP, Drevets WC, Ongür D, Price JL (2002) Low glial numbers in the amygdala in major depressive disorder. Biol Psychiatry 52:404–412

    Article  PubMed  Google Scholar 

  • Brown ES, Woolston DJ, Frol AB (2008) Amygdala volume in patients receiving chronic corticosteroid therapy. Biol Psychiatry 63:705–709

    Article  CAS  PubMed  Google Scholar 

  • Caetano SC, Fonseca M, Hatch JP, Olvera RL, Nicoletti M, Hunter K, Lafer B, Pliszka SR, Soares JC (2007) Medial temporal lobe abnormalities in pediatric unipolar depression. Neurosci Lett 427:142–147

    Article  CAS  PubMed  Google Scholar 

  • Campbell S, Marriott M, Nahmias C, MacQueen GM (2004) Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry 161:598–607

    Article  PubMed  Google Scholar 

  • Dannlowski U, Kersting A, Donges US, Lalee-Mentzel J, Arolt V, Suslow T (2006) Masked facial affect priming is associated with therapy response in clinical depression. Eur Arch Psychiatry Clin Neurosci 256(4):215–221

    Article  PubMed  Google Scholar 

  • Depping MS, Wolf ND, Vasic N, Sambataro F, Thomann PA, Christian Wolf R (2015) Specificity of abnormal brain volume in major depressive disorder: a comparison with borderline personality disorder. J Affect Disord 174:650–657

    Article  PubMed  Google Scholar 

  • Dickstein DP, Milham MP, Nugent AC, Drevets WC, Charney DS, Pine DS, Leibenluft E (2005) Frontotemporal alterations in pediatric bipolar disorder: results of a voxel-based morphometry study. Arch Gen Psychiatry 62:734–741

    Article  PubMed  Google Scholar 

  • Drevets WC, Videen TO, Price JL, Preskorn SH, Carmichael ST, Raichle ME (1992) A functional anatomical study of unipolar depression. J Neurosci 12:3628–3641

    CAS  PubMed  Google Scholar 

  • Drevets WC, Price JL, Bardgett ME, Reich T, Todd RD, Raichle ME (2002) Glucose metabolism in the amygdala in depression: relationship to diagnostic subtype and plasma cortisol levels. Pharmacol Biochem Behav 71:431–447

    Article  CAS  PubMed  Google Scholar 

  • Du MY, Wu QZ, Yue Q, Li J, Liao Y, Kuang WH, Huang XQ, Chan RC, Mechelli A, Gong QY (2012) Voxelwise meta-analysis of gray matter reduction in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 36:11–16

    Article  PubMed  Google Scholar 

  • Fakhoury M (2015) New insights into the neurobiological mechanisms of major depressive disorders. Gen Hosp Psychiatry 37:172–177

    Article  PubMed  Google Scholar 

  • Fales CL, Barch DM, Rundle MM, Mintun MA, Snyder AZ, Cohen JD, Mathews J, Sheline YI (2008) Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression. Biol Psychiatry 63:377–384

    Article  PubMed  Google Scholar 

  • Frodl T, Meisenzahl E, Zetzsche T, Bottlender R, Born C, Groll C, Jäger M, Leinsinger G, Hahn K, Möller HJ (2002) Enlargement of the amygdala in patients with a first episode of major depression. Biol Psychiatry 51:708–714

    Article  PubMed  Google Scholar 

  • Frodl T, Meisenzahl EM, Zetzsche T, Born C, Jäger M, Groll C, Bottlender R, Leinsinger G, Möller HJ (2003) Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects. Biol Psychiatry 53:338–344

    Article  PubMed  Google Scholar 

  • Frodl TS, Koutsouleris N, Bottlender R, Born C, Jäger M, Scupin I, Reiser M, Möller HJ, Meisenzahl EM (2008) Depression-related variation in brain morphology over 3 years: effects of stress? Arch Gen Psychiatry 65:1156–1165

    Article  PubMed  Google Scholar 

  • Fusar-Poli P, Placentino A, Carletti F, Landi P, Allen P, Surguladze S et al (2009) Functional atlas of emotional faces processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. J Psychiatry Neurosci 34(6):418–432

    PubMed  PubMed Central  Google Scholar 

  • Gainotti G (1972) Emotional behavior and hemispheric side of the lesion. Cortex 8:41–55

    Article  CAS  PubMed  Google Scholar 

  • Groenewold NA, Opmeer EM, de Jonge P, Aleman A, Costafreda SG (2013) Emotional valence modulates brain functional abnormalities in depression: evidence from a meta-analysis of fMRI studies. Neurosci Biobehav Rev 37(2):152–163

    Article  PubMed  Google Scholar 

  • Hajek T, Kopecek M, Kozeny J, Gunde E, Alda M, Höschl C (2009) Amygdala volumes in mood disorders—meta-analysis of magnetic resonance volumetry studies. J Affect Disord 115:395–410

    Article  PubMed  Google Scholar 

  • Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

  • Hamilton JP, Siemer M, Gotlib IH (2008) Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Mol Psychiatry 13:993–1000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hastings RS, Parsey RV, Oquendo MA, Arango V, Mann JJ (2004) Volumetric analysis of the prefrontal cortex, amygdala, and hippocampus in major depression. Neuropsychopharmacology 29:952–959

    Article  PubMed  Google Scholar 

  • Holsboer F (2000) The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23:477–501

    Article  CAS  PubMed  Google Scholar 

  • House A, Dennis M, Warlow C, Hawton K, Molyneux A (1990) Mood disorders after stroke and their relation to lesion location. A CT scan study. Brain 113(Pt 4):1113–1129

    Article  PubMed  Google Scholar 

  • Johnson LR, Farb C, Morrison JH, McEwen BS, LeDoux JE (2005) Localization of glucocorticoid receptors at postsynaptic membranes in the lateral amygdala. Neuroscience 136:289–299

    Article  CAS  PubMed  Google Scholar 

  • Kolber BJ, Montana MC, Carrasquillo Y, Xu J, Heinemann SF, Muglia LJ, Gereau RW (2010) Activation of metabotropic glutamate receptor 5 in the amygdala modulates pain-like behavior. J Neurosci 30:8203–8213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Konrad C, Ukas T, Nebel C, Arolt V, Toga AW, Narr KL (2009) Defining the human hippocampus in cerebral magnetic resonance images—an overview of current segmentation protocols. Neuroimage 47:1185–1195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lange C, Irle E (2004) Enlarged amygdala volume and reduced hippocampal volume in young women with major depression. Psychol Med 34:1059–1064

    Article  CAS  PubMed  Google Scholar 

  • Li J, Chen C, Wu K, Zhang M, Zhu B, Moyzis RK, Dong Q (2015) Genetic variations in the serotonergic system contribute to amygdala volume in humans. Front Neuroanat 9:129

    PubMed  PubMed Central  Google Scholar 

  • Liu W, Ge T, Leng Y, Pan Z, Fan J, Yang W, Cui R (2017) The role of neural plasticity in depression: from hippocampus to prefrontal cortex. Neural Plast 2017:6871089

    PubMed  PubMed Central  Google Scholar 

  • Lorenzetti V, Allen NB, Fornito A, Yücel M (2009) Structural brain abnormalities in major depressive disorder: a selective review of recent MRI studies. J Affect Disord 117:1–17

    Article  PubMed  Google Scholar 

  • MacMaster FP, Mirza Y, Szeszko PR, Kmiecik LE, Easter PC, Taormina SP, Lynch M, Rose M, Moore GJ, Rosenberg DR (2008) Amygdala and hippocampal volumes in familial early onset major depressive disorder. Biol Psychiatry 63:385–390

    Article  PubMed  Google Scholar 

  • MacMillan S, Szeszko PR, Moore GJ, Madden R, Lorch E, Ivey J, Banerjee SP, Rosenberg DR (2003) Increased amygdala: hippocampal volume ratios associated with severity of anxiety in pediatric major depression. J Child Adolesc Psychopharmacol 13:65–73

    Article  PubMed  Google Scholar 

  • Merke DP, Fields JD, Keil MF, Vaituzis AC, Chrousos GP, Giedd JN (2003) Children with classic congenital adrenal hyperplasia have decreased amygdala volume: potential prenatal and postnatal hormonal effects. J Clin Endocrinol Metab 88:1760–1765

    Article  CAS  PubMed  Google Scholar 

  • Merke DP, Giedd JN, Keil MF, Mehlinger SL, Wiggs EA, Holzer S, Rawson E, Vaituzis AC, Stratakis CA, Chrousos GP (2005) Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome. J Clin Endocrinol Metab 90:2531–2536

    Article  CAS  PubMed  Google Scholar 

  • Mervaala E, Föhr J, Könönen M, Valkonen-Korhonen M, Vainio P, Partanen K, Partanen J, Tiihonen J, Viinamäki H, Karjalainen AK, Lehtonen J (2000) Quantitative MRI of the hippocampus and amygdala in severe depression. Psychol Med 30:117–125

    Article  CAS  PubMed  Google Scholar 

  • Munn MA, Alexopoulos J, Nishino T, Babb CM, Flake LA, Singer T, Ratnanather JT, Huang H, Todd RD, Miller MI, Botteron KN (2007) Amygdala volume analysis in female twins with major depression. Biol Psychiatry 62:415–422

    Article  PubMed  PubMed Central  Google Scholar 

  • Musazzi L, Racagni G, Popoli M (2011) Stress, glucocorticoids and glutamate release: effects of antidepressant drugs. Neurochem Int 59:138–149

    Article  CAS  PubMed  Google Scholar 

  • Musazzi L, Treccani G, Mallei A, Popoli M (2013) The action of antidepressants on the glutamate system: regulation of glutamate release and glutamate receptors. Biol Psychiatry 73:1180–1188

    Article  CAS  PubMed  Google Scholar 

  • Neveu PJ, Liège S, Sarrieau A (1998) Asymmetrical distribution of hippocampal mineralocorticoid receptors depends on lateralization in mice. NeuroImmunoModulation 5:16–21

    Article  CAS  PubMed  Google Scholar 

  • Ota KT, Duman RS (2013) Environmental and pharmacological modulations of cellular plasticity: role in the pathophysiology and treatment of depression. Neurobiol Dis 57:28–37. https://doi.org/10.1016/j.nbd.2012.05.022

    Article  CAS  PubMed  Google Scholar 

  • Palmer SM, Crewther SG, Carey LM, Team SP (2014) A meta-analysis of changes in brain activity in clinical depression. Front Hum Neurosci 8:1045

    Article  PubMed  Google Scholar 

  • Pantel J, Schröder J, Essig M, Schad LR, Popp D, Eysenbach K, Jauss M, Knopp MV (1998) Volumetric brain findings in late depression. A study with quantified magnetic resonance tomography. Nervenarzt 69:968–974

    Article  CAS  PubMed  Google Scholar 

  • Phillips ML, Drevets WC, Rauch SL, Lane R (2003a) Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biol Psychiatry 54:504–514

    Article  PubMed  Google Scholar 

  • Phillips ML, Drevets WC, Rauch SL, Lane R (2003b) Neurobiology of emotion perception II: implications for major psychiatric disorders. Biol Psychiatry 54:515–528

    Article  PubMed  Google Scholar 

  • Roshchupkin GV, Gutman BA, Vernooij MW, Jahanshad N, Martin NG, Hofman A, McMahon KL, van der Lee SJ, van Duijn CM, de Zubicaray GI, Uitterlinden AG, Wright MJ, Niessen WJ, Thompson PM, Ikram MA, Adams HH (2016) Heritability of the shape of subcortical brain structures in the general population. Nat Commun 7:13738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosso IM, Cintron CM, Steingard RJ, Renshaw PF, Young AD, Yurgelun-Todd DA (2005) Amygdala and hippocampus volumes in pediatric major depression. Biol Psychiatry 57:21–26

    Article  PubMed  Google Scholar 

  • Salvatore C, Battista P, Castiglioni I (2016) Frontiers for the early diagnosis of AD by means of MRI brain imaging and support vector machines. Curr Alzheimer Res 13(5):509–533

    Article  CAS  PubMed  Google Scholar 

  • Savitz J, Nugent AC, Bogers W, Liu A, Sills R, Luckenbaugh DA, Bain EE, Price JL, Zarate C, Manji HK, Cannon DM, Marrett S, Charney DS, Drevets WC (2010) Amygdala volume in depressed patients with bipolar disorder assessed using high resolution 3T MRI: the impact of medication. Neuroimage 49:2966–2976

    Article  PubMed  Google Scholar 

  • Sheline YI, Gado MH, Price JL (1998) Amygdala core nuclei volumes are decreased in recurrent major depression. NeuroReport 9:2023–2028

    Article  CAS  PubMed  Google Scholar 

  • Sheline YI, Barch DM, Donnelly JM, Ollinger JM, Snyder AZ, Mintun MA (2001) Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry 50:651–658

    Article  CAS  PubMed  Google Scholar 

  • Siegle GJ, Steinhauer SR, Thase ME, Stenger VA, Carter CS (2002) Can’t shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals. Biol Psychiatry 51:693–707

    Article  PubMed  Google Scholar 

  • Stratmann M, Konrad C, Kugel H, Krug A, Schöning S, Ohrmann P, Uhlmann C, Postert C, Suslow T, Heindel W, Arolt V, Kircher T, Dannlowski U (2014) Insular and hippocampal gray matter volume reductions in patients with major depressive disorder. PLoS One 9:e102692

    Article  PubMed  PubMed Central  Google Scholar 

  • Tamburo RJ, Siegle GJ, Stetten GD, Cois CA, Butters MA, Reynolds CF, Aizenstein HJ (2009) Amygdalae morphometry in late-life depression. Int J Geriatr Psychiatry 24:837–846

    Article  PubMed  PubMed Central  Google Scholar 

  • Tang Y, Wang F, Xie G, Liu J, Li L, Su L, Liu Y, Hu X, He Z, Blumberg HP (2007) Reduced ventral anterior cingulate and amygdala volumes in medication-naïve females with major depressive disorder: a voxel-based morphometric magnetic resonance imaging study. Psychiatry Res 156:83–86

    Article  PubMed  Google Scholar 

  • van Eijndhoven P, van Wingen G, van Oijen K, Rijpkema M, Goraj B, Jan Verkes R, Oude Voshaar R, Fernández G, Buitelaar J, Tendolkar I (2009) Amygdala volume marks the acute state in the early course of depression. Biol Psychiatry 65:812–818

    Article  PubMed  Google Scholar 

  • von Gunten A, Fox NC, Cipolotti L, Ron MA (2000) A volumetric study of hippocampus and amygdala in depressed patients with subjective memory problems. J Neuropsychiatry Clin Neurosci 12:493–498

    Article  Google Scholar 

  • Weniger G, Lange C, Irle E (2006) Abnormal size of the amygdala predicts impaired emotional memory in major depressive disorder. J Affect Disord 94:219–229

    Article  PubMed  Google Scholar 

  • Wittchen H-U, Wunderlich U, Gruschwitz S, Zaudig M (1996) Strukturiertes Klinisches Interview für DSM-IV (SKID): Göttingen: Beltz-Test

  • Woods RP (2003) Multitracer: a Java-based tool for anatomic delineation of grayscale volumetric images. Neuroimage 19:1829–1834

    Article  PubMed  Google Scholar 

  • Xia J, Chen J, Zhou Y, Zhang J, Yang B, Xia L, Wang C (2004) Volumetric MRI analysis of the amygdala and hippocampus in subjects with major depression. J Huazhong Univ Sci Technol Med Sci 24(500–502):506

    Google Scholar 

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Acknowledgements

This work was a part of the doctoral thesis of LRSG.

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  1. Maxim Zavorotnyy and Rebecca Zöllner contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University of Marburg, Rudolf-Bultmann-Strasse 8, 35037, Marburg, Germany

    Maxim Zavorotnyy, Rebecca Zöllner & C. Konrad

  2. Department of Psychiatry and Psychotherapy, University of Muenster, Albert-Schweitzer-Campus 1, Building A9, 48149, Münster, Germany

    L. R. Schulte-Güstenberg, L. Wulff, S. Schöning, U. Dannlowski & V. Arolt

  3. Department of Clinical Radiology, University of Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149, Marburg, Germany

    H. Kugel

  4. Department of Psychiatry and Psychotherapy, Agaplesion Diakonieklinikum Rotenburg (Wümme), Rotenburg an der Wümme, Germany

    C. Konrad

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  1. Maxim Zavorotnyy
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  2. Rebecca Zöllner
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Correspondence to Maxim Zavorotnyy.

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The work was supported by the Interdisciplinary Centre for Clinical Research of the University of Muenster, Germany (Grant number IZKF FG4), the University Medical Center Giessen and Marburg (Grant number UKGM, 27/2015 MR), the Rhoen-Klinikum AG (Grant number RKA, FI22/2015), and the von Behring-Roentgen-Foundation (Grant number BRS, 64-0016).

Conflict of interest

MZ received financial support for educational program from Lundbeck, Servier, Actelion, MagVenture, Mag and More, Localite, Inomed, Sooma Oy, Brainsway/Tolko and NeuroConn. CK received fees for an educational program from esparma GmbH/Aristo Pharma GmbH, Lilly Deutschland GmbH, Servier Deutschland GmbH, and MagVenture GmbH, as well as travel support and speaker honoraria from Lundbeck. However, these relationships did not influence the content of this manuscript. The other authors report no financial or other relationships relevant to the subject of this article.

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Zavorotnyy, M., Zöllner, R., Schulte-Güstenberg, L.R. et al. Low left amygdala volume is associated with a longer duration of unipolar depression. J Neural Transm 125, 229–238 (2018). https://doi.org/10.1007/s00702-017-1811-y

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