Hostname: page-component-8448b6f56d-gtxcr Total loading time: 0 Render date: 2024-04-23T07:13:57.030Z Has data issue: false hasContentIssue false
  • English
  • Français

Brain anatomy of major depression II. Focus on amygdala

Published online by Cambridge University Press:  28 March 2011

M. Bellani ,
M. Baiano  and
P. Brambilla
M. Bellani*
Affiliation:
Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, Inter-University Center for Behavioural Neurosciences (ICBN), University of Verona, Verona, Italy
M. Baiano
Affiliation:
Center for Weight and Eating Disorders, Portogruaro, Venice, Italy
P. Brambilla
Affiliation:
DISM, Section of Psychiatry, Inter-University Center for Behavioural Neurosciences (ICBN), University of Udine, Udine, Italy IRCSS “E. Medea” Scientific Institute, Udine, Italy
*
*Address for correspondence: Dr. M. Bellani, Department of Public Health and Community Medicine, Section of Psychiatry and Clinical Psychology, University of Verona, Piazzale L.A. Scuro, 10 - 37134 Verona, Italy. (Email: marcella.bellani@univr.it, paolo.brambilla@uniud.it)
Rights & Permissions [Opens in a new window]

Abstract

Here, we briefly summarize the most consistent structural magnetic resonance imaging (MRI) studies on amygdala in major depression and debate the effects of clinical variables on amygdalar morphology.

Keywords

Major depressive disordermagnetic resonance imaging (MRI)volumes
Type
Neurobiology of Psychosis
Information
Epidemiology and Psychiatric Sciences , Volume 20 , Issue 1 , March 2011 , pp. 33 - 36
Copyright
Copyright © Cambridge University Press 2011

Major depressive disorder (MDD) has been associated with morphological changes of medial temporal lobe's structures, particularly of the amygdala, possibly being part of an altered limbic–thalamic–cortical circuitry (Zou et al. Reference Zou, Deng, Li, Zhang, Jiang, Huang, Sun and Sun2010; Bellani et al. Reference Bellani, Baiano and Brambilla2010). This structure is part of the ventral limbic system and is functionally connected to the prefrontal cortex, cingulate gyrus and hypothalamus. It is a key component for affective modulation (such as negative emotions and fear), memory encoding and social behaviour (Baxter & Murray, Reference Baxter and Murray2002). Several magnetic resonance imaging (MRI) studies have found reduced amygdala volumes in patients suffering from depression (Sheline et al. Reference Sheline, Gado and Price1998, Reference Sheline, Sanghavi, Mintun and Gado1999; Campbell et al. Reference Campbell, Marriott, Nahmias and MacQueen2004; Hickie et al. Reference Hickie, Naismith, Ward, Scott, Mitchell, Schofield, Scimone, Wilhelm and Parker2007), specifically in children (Rosso et al. Reference Rosso, Cintron, Steingard, Renshaw, Young and Yurgelun-Todd2005), unmedicated (Caetano et al. Reference Caetano, Hatch, Brambilla, Sassi, Nicoletti, Mallinger, Frank, Kupfer, Keshavan and Soares2004; Tang et al. Reference Tang, Wang, Xie, Liu, Li, Su, Liu, Hu, He and Blumberg2007; Kronenberg et al. Reference Kronenberg, Tebartz van Elst, Regen, Deuschle, Heuser and Colla2009), multiple episode (Bremner et al. Reference Bremner, Narayan, Anderson, Staib, Miller and Charney2000; Caetano et al. Reference Caetano, Hatch, Brambilla, Sassi, Nicoletti, Mallinger, Frank, Kupfer, Keshavan and Soares2004; Hastings et al. Reference Hastings, Parsey, Oquendo, Arango and Mann2004; Monkul et al. Reference Monkul, Hatch, Nicoletti, Spence, Brambilla, Lacerda, Sassi, Mallinger, Keshavan and Soares2007), psychotic and female patients (Sheline et al. Reference Sheline, Sanghavi, Mintun and Gado1999; Hastings et al. Reference Hastings, Parsey, Oquendo, Arango and Mann2004; Tang et al. Reference Tang, Wang, Xie, Liu, Li, Su, Liu, Hu, He and Blumberg2007; Keller et al. Reference Keller, Shen, Gomez, Garrett, Brent Solvason, Reiss and Schatzberg2008; Lorenzetti et al. Reference Lorenzetti, Allen, Fornito and Yücel2009). In this regard, chronic or recurrent MDD patients are persistently exposed to stress-induced glucocorticoids, which may have neurotoxic effects, potentially leading to amygdala shrinkage (Hamidi et al. Reference Hamidi, Drevets and Price2004). Interestingly, slight volume reductions of amygdalar grey matter have been shown over time without significant gross abnormalities (Frodl et al. Reference Frodl, Jäger, Smajstrlova, Born, Bottlender, Palladino, Reiser, Möller and Meisentzhal2008a, b), suggesting the presence of subtle microstructural processes occurring during a depression episode and after recovery. However, other structural investigations have shown preserved volumes (Mervaala et al. Reference Mervaala, Föhr, Könönen, Valkonen-Korhonen, Vainio, Partanen, Partanen, Tiihonen, Viinamäki, Karjalainen and Lethonen2000; Munn et al. Reference Munn, Alexopoulos, Nishino, Babb, Flake, Singer, Ratnanather, Huang, Todd, Miller and Botteron2007; MacMaster et al. Reference MacMaster, Mirza, Szeszko, Kmiecik, Easter, Taormina, Lynch, Rose, Moore and Rosenberg2008), mainly in current non-suicidal patients (Monkul et al. Reference Monkul, Hatch, Nicoletti, Spence, Brambilla, Lacerda, Sassi, Mallinger, Keshavan and Soares2007), in non-psychotic depressed patients (Keller et al. Reference Keller, Shen, Gomez, Garrett, Brent Solvason, Reiss and Schatzberg2008) or in recovered patients (van Eijndhoven et al. Reference van Eijndhoven, van Wingen, van Oijen, Rijpkema, Goraj, Jan Verkes, Oude Voshaar, Fernández, Buitelaar and Tendolkar2009; Lorenzetti et al. Reference Lorenzetti, Allen, Whittle and Yücel2010). Moreover, enlarged amygdalar volumes have also been reported (van Elst et al. Reference van Elst, Woermann, Lemieux and Trimble2000), particularly in subjects using antidepressants (Frodl et al. Reference Frodl, Meisenzahl, Zetzsche, Born, Jäger, Groll, Bottlender, Leinsinger and Möller2003; Weniger et al. Reference Weniger, Lange and Irle2006) and in those with severe illness or at the early stage of the disease (Frodl et al. Reference Frodl, Meisenzahl, Zetzsche, Born, Jäger, Groll, Bottlender, Leinsinger and Möller2003, Reference Frodl, Jäger, Smajstrlova, Born, Bottlender, Palladino, Reiser, Möller and Meisentzhal2008a; Lange & Irle, Reference Lange and Irle2004; Lorenzetti et al. Reference Lorenzetti, Allen, Whittle and Yücel2010; Weniger et al. Reference Weniger, Lange and Irle2006).

In summary, although there is some evidence that amygdalar size is reduced in MDD patients, particularly in those with recurrent episodes (Hamilton et al. Reference Hamilton, Siemer and Gotlib2008; Lorenzetti et al. Reference Lorenzetti, Allen, Fornito and Yücel2009), preserved and increased volumes have also been reported. The heterogeneity of the results summarized here (see Table 1) may in part be due to socio-demographical and clinical differences of the samples (age of onset, single or multiple episodes, familiar history of MDD, medication, psychotic symptoms and phases of the illness) (Hajek et al. Reference Hajek, Kopececk, Kozeni, Gunde, Martin and Höschl2009). Furthermore, the proximity of the amygdala to the head of the hippocampus makes the anatomical delineation of this structure difficult. Indeed, as reported in the meta-analysis by Campbell et al. (Reference Campbell, Marriott, Nahmias and MacQueen2004), MRI studies considering the amygdala–hippocampus complex revealed no significant differences between depressed and control subjects. In order to better clarify the role of amygdala for the pathophysiology of MDD, future MRI studies should explore amygdalar morphology in large sample of drug-naïve patients at their first episode of depression in comparison with matched healthy individuals, longitudinally following them after recovery.

Table 1. Cross-sectional and follow-up studies investigating amygdalar volumetry in adult patients with MDD compared with healthy control subjects

*Follow-up studies: AD, patients on antidepressants at the time of the MRI scanning; HC, healthy control subjects; HR, high risk; L, left; R, right; ROI, region of interest; T, twins; VBM, voxel-based-morphometry; M, male; F, female.

Footnotes

This Section of Epidemiology and Psychiatric Sciences regularly appears in each issue of the Journal to describe relevant studies investigating the relationship between neurobiology and psychosocial psychiatry in major psychoses. The aim of these Editorials is to provide a better understanding of the neural basis of psychopathology and clinical features of these disorders, in order to raise new perspectives in every-day clinical practice.

Paolo Brambilla, Section Editor and Michele Tansella, Editor EPS

References

Baxter, MG, Murray, EA (2002). The amygdala and reward. Nature Reviews Neuroscience 3, 563–573.CrossRefGoogle ScholarPubMed
Bellani, M, Baiano, M, Brambilla, P (2010). Brain anatomy of major depression I. Focus on hippocampus. Epidemiologia e Psichiatria Sociale 19, 298–301.CrossRefGoogle ScholarPubMed
Bremner, JD, Narayan, M, Anderson, ER, Staib, LH, Miller, HL, Charney, DS (2000). Hippocampal volume reduction in major depression. American Journal of Psychiatry 157, 115–117.CrossRefGoogle ScholarPubMed
Caetano, SC, Hatch, JP, Brambilla, P, Sassi, RB, Nicoletti, M, Mallinger, AG, Frank, E, Kupfer, DJ, Keshavan, MS, Soares, JC (2004). Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression. Psychiatry Research: Neuroimaging 132, 141–147.CrossRefGoogle ScholarPubMed
Campbell, S, Marriott, M, Nahmias, C, MacQueen, GM (2004). Lower hippocampal volume in patients suffering from depression: a meta-analysis. American Journal of Psychiatry 161, 598–607.CrossRefGoogle ScholarPubMed
Frodl, T, Jäger, M, Smajstrlova, I, Born, C, Bottlender, R, Palladino, T, Reiser, M, Möller, HJ, Meisentzhal, E (2008 a). Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3 year prospective magnetic resonance imaging study. Journal of Psychiatry and Neuroscience 33, 423–430.Google ScholarPubMed
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. Biological Psychiatry 53, 338–344.CrossRefGoogle ScholarPubMed
Frodl, TS, Koutsouleris, N, Bottlender, R, Born, C, Jager, M, Scupin, I, Reiser, M, Möller, HJ, Meisenzahl, EM (2008 b). Depression related variation in brain morphology over 3 years. Effects of stress? Archives of General Psychiatry 65, 1156–1165.CrossRefGoogle ScholarPubMed
Hajek, T, Kopececk, M, Kozeni, J, Gunde, E, Martin, A, Höschl, C (2009). Amygdala volumes in mood disorders. A meta-analysis of magnetic resonance volumetry studies. Journal of Affective Disorders 115, 395–410.CrossRefGoogle ScholarPubMed
Hamidi, M, Drevets, WC, Price, JL (2004). Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes. Biological Psychiatry 55, 63–59.CrossRefGoogle ScholarPubMed
Hamilton, JP, Siemer, M, Gotlib, IH (2008). Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Molecular Psychiatry 13, 993–1000.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Hickie, IB, Naismith, SL, Ward, PB, Scott, EM, Mitchell, PB, Schofield, PR, Scimone, A, Wilhelm, K, Parker, G (2007). Serotonin transporter gene status predicts caudate nucleus but not amygdala or hippocampal volumes in older persons with major depression. Journal of Affective Disorders 98, 137–142.CrossRefGoogle ScholarPubMed
Keller, J, Shen, L, Gomez, RG, Garrett, A, Brent Solvason, H, Reiss, A, Schatzberg, AF (2008). Hippocampal and amygdalar volumes in psychotic and nonpsychotic unipolar depression. American Journal of Psychiatry 165, 872–880.CrossRefGoogle ScholarPubMed
Kronenberg, G, Tebartz van Elst, L, Regen, F, Deuschle, M, Heuser, I, Colla, M (2009). Reduced amygdala volume in newly admitted psychiatric in-patients with unipolar major depression. Journal of Psychiatric Research 43, 1112–1117.CrossRefGoogle ScholarPubMed
Lange, C, Irle, E (2004). Enlarged amygdala volume and reduced hippocampal volume in young women with major depression. Psychological Medicine 34, 1059–1064.CrossRefGoogle ScholarPubMed
Lorenzetti, V, Allen, NB, Fornito, A, Yücel, M (2009). Structural brain abnormalities in major depressive disorder: a selective review of recent MRI studies. Journal of Affective Disorder 117, 1–17.CrossRefGoogle ScholarPubMed
Lorenzetti, V, Allen, NB, Whittle, S, Yücel, M (2010). Amygdala volumes in a sample of current depressed and remitted depressed patients and healthy controls. Journal of Affective Disorders 120, 112–119.CrossRefGoogle Scholar
MacMaster, FP, Mirza, Y, Szeszko, PR, Kmiecik, LE, Easter, P, Taormina, SP, Lynch, M, Rose, M, Moore, GJ, Rosenberg, DR (2008). Amygdala and hippocampal volumes in familial early onset major depressive disorder. Biological Psychiatry 63, 385–390.CrossRefGoogle ScholarPubMed
Mervaala, E, Föhr, J, Könönen, M, Valkonen-Korhonen, M, Vainio, P, Partanen, K, Partanen, J, Tiihonen, J, Viinamäki, H, Karjalainen, AK, Lethonen, J (2000). Quantitative MRI of the hippocampus and amygdala in severe depression. Psychological Medicine 30, 117–125.CrossRefGoogle ScholarPubMed
Monkul, ES, Hatch, JP, Nicoletti, MA, Spence, S, Brambilla, P, Lacerda, ALT, Sassi, RB, Mallinger, AG, Keshavan, MS, Soares, JC (2007). Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder. Molecular Psychiatry 62, 360–366.CrossRefGoogle 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. Biological Psychiatry 62, 415–422.CrossRefGoogle ScholarPubMed
Rosso, IM, Cintron, CM, Steingard, RJ, Renshaw, PF, Young, AD, Yurgelun-Todd, DA (2005). Amygdala and hippocampus volumes in pediatric major depression. Biological Psychiatry 57, 21–26.CrossRefGoogle ScholarPubMed
Sheline, YI, Gado, MH, Price, JL (1998). Amygdala core nuclei volumes are decreased in recurrent major depression. Neuroreport 9, 2023–2028.CrossRefGoogle ScholarPubMed
Sheline, YI, Sanghavi, M, Mintun, MA, Gado, MH (1999). Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. Journal of Neuroscience 19, 5034–5043.CrossRefGoogle 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 Research: Neuroimaging 156, 83–86.CrossRefGoogle ScholarPubMed
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. Biological Psychiatry 65, 812–818.CrossRefGoogle Scholar
van Elst, LT, Woermann, F, Lemieux, L, Trimble, MR (2000). Increased amygdala volumes in female and depressed humans. A quantitative magnetic resonance imaging study. Neuroscience Letters 281, 103–106.CrossRefGoogle Scholar
Von Gunten, A, Fox, NC, Cipolotti, L, Ron, MA (2000). A volumetric study of hippocampus and amygdalagdale in depressed patients with subjective memory problems. Journal of Neuropsychiatry and Clinical Neurosciences 12, 493–498.CrossRefGoogle ScholarPubMed
Weniger, G, Lange, C, Irle, E (2006). Abnormal size of the amygdala predicts impaired emotional memory in major depressive disorder. Journal of Affective Disorders 94, 219–229.CrossRefGoogle ScholarPubMed
Zou, K, Deng, W, Li, T, Zhang, B, Jiang, L, Huang, C, Sun, X, Sun, X (2010). Changes of brain morphometry in first-episode, drug-naïve, non-late-life adult patients with major depression: an optimized voxel-based morphometry study. Biological Psychiatry 67, 186–188.CrossRefGoogle ScholarPubMed
Figure 0

Table 1. Cross-sectional and follow-up studies investigating amygdalar volumetry in adult patients with MDD compared with healthy control subjects