Skip to main content
×
Home
    • Aa
    • Aa
  • The International Journal of Neuropsychopharmacology, Volume 12, Issue 1
  • February 2009, pp. 11-22

Reduced amygdala–prefrontal coupling in major depression: association with MAOA genotype and illness severity

Abstract
Abstract

The amygdala plays a pivotal role in a cortico-limbic circuitry implicated in emotion processing and regulation. In the present study, functional connectivity of the amygdala with prefrontal areas involved in emotion regulation was investigated during a facial expression processing task in a sample of 34 depressed inpatients and 31 healthy controls. All patients were genotyped for a common functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the monoamine oxidase A gene (MAOA u-VNTR) which has been previously associated with major depression as well as reduced cortico-limbic connectivity in healthy subjects. In our control group, we observed tight coupling of the amygdala and dorsal prefrontal areas comprising the dorsolateral prefrontal cortex (DLPFC), dorsal parts of the anterior cingulate cortex (dACC), and lateral orbitofrontal cortex. Amygdala–prefrontal connectivity was significantly reduced in depressed patients and carriers of the higher active MAOA risk alleles (MAOA-H). Hence, depressed MAOA-H carriers showed the weakest amygdala–prefrontal coupling of the investigated subgroups. Furthermore, reduced coupling of this circuitry predicted more than 40% variance of clinical variables characterizing a longer and more severe course of disease. We conclude that genetic variation in the MAOA gene may affect the course of major depression by disrupting cortico-limbic connectivity.

Copyright
Corresponding author
Address for correspondence: Prof. Dr. T. Suslow, Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, 48149 Münster, Germany. Tel.: +49-251-8356601Fax: +49-251-8356612E-mail: suslow@uni-muenster.de
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

A Anand , Y Li , Y Wang , K Gardner , MJ Lowe (2007). Reciprocal effects of antidepressant treatment on activity and connectivity of the mood regulating circuit: an FMRI study. Journal of Neuropsychiatry and Clinical Neuroscience 19, 274282.

A Anand , Y Li , Y Wang , J Wu , S Gao , L Bukhari , VP Mathews , A Kalnin , MJ Lowe (2005a). Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study. Biological Psychiatry 57, 10791088.

LR Baxter Jr., JM Schwartz , ME Phelps , JC Mazziotta , BH Guze , CE Selin , RH Gerner , RM Sumida (1989). Reduction of prefrontal glucose metabolism common to three types of depression. Archives of General Psychiatry 46, 243250.

M Beauregard , V Paquette , J Levesque (2006). Dysfunction in the neural circuitry of emotional self-regulation in major depressive disorder. Neuroreport 17, 843846.

A Bertolino , G Arciero , V Rubino , V Latorre , M De Candia , V Mazzola , G Blasi , G Caforio , A Hariri , B Kolachana , (2005). Variation of human amygdala response during threatening stimuli as a function of 5′HTTLPR genotype and personality style. Biological Psychiatry 57, 15171525.

BH Brummett , AD Krystal , IC Siegler , C Kuhn , RS Surwit , S Züchner , A Ashley-Koch , JC Barefoot , RB Williams (2007). Associations of a regulatory polymorphism of monoamine oxidase-A gene promoter (MAOA-uVNTR) with symptoms of depression and sleep quality. Psychosomatic Medicine 69, 396401.

SM Brown , E Peet , SB Manuck , DE Williamson , RE Dahl , RE Ferrell , AR Hariri (2005). A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity. Molecular Psychiatry 10, 884–808.

JW Buckholtz , JH Callicott , B Kolachana , AR Hariri , TE Goldberg , M Genderson , MF Egan , VS Mattay , DR Weinberger , A Meyer-Lindenberg (2008). Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality. Molecular Psychiatry 13, 313324.

U Dannlowski , P Ohrmann , J Bauer , J Deckert , C Hohoff , H Kugel , V Arolt , W Heindel , BT Baune , A Kersting , T Suslow (2008). 5-HTTLPR biases amygdala activity in response to masked facial expressions in major depression. Neuropsychopharmacology 33, 418424.

U Dannlowski , P Ohrmann , J Bauer , H Kugel , BT Baune , C Hohoff , A Kersting , V Arolt , W Heindel , J Deckert , T Suslow (2007). Serotonergic genes modulate amygdala activity in major depression. Genes, Brain, and Behavior 6, 672676.

J Deckert , M Catalano , YV Syagailo , M Bosi , O Okladnova , D Di Bella , MM Nöthen , P Maffei , P Franke , J Fritze , (1999). Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. Human Molecular Genetics 8, 621624.

K Domschke , M Braun , P Ohrmann , T Suslow , H Kugel , J Bauer , C Hohoff , A Kersting , A Engelien , V Arolt , (2006). Association of the functional -1019C/G 5-HT1A polymorphism with prefrontal cortex and amygdala activation measured with 3 T fMRI in panic disorder. International Journal of Neuropsychopharmacology 9, 349355.

WC Drevets (1999). Prefrontal cortical amygdalar metabolism in major depression. Annals of the New York Academy of Science 877, 614637.

DL Evans , DS Charney (2003). Mood disorders and medical illness: a major public health problem. Biological Psychiatry 54, 177180.

F Faul , E Erdfelder , AG Lang , A Buchner (2007). G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior Research Methods 39, 175191.

KJ Friston (1994). Functional and effective connectivity in neuroimaging: a synthesis. Human Brain Mapping 2, 5678.

M Hamilton (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.

AR Hariri , EM Drabant , KE Munoz , BS Kolachana , VS Mattay , MF Egan , DR Weinberger (2005). A susceptibility gene for affective disorders and the response of the human amygdala. Archives of General Psychiatry 62, 146152.

AR Hariri , EM Drabant , DR Weinberger (2006). Imaging genetics: perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing. Biological Psychiatry 59, 888897.

AR Hariri , VS Mattay , A Tessitore , B Kolachana , F Fera , D Goldman , MF Egan , DR Weinberger (2002). Serotonin transporter genetic variation and the response of the human amygdala. Science 297, 400403.

G Hasler , WC Drevets , HK Manji , DS Charney (2004). Discovering endophenotypes for major depression. Neuropsychopharmacology 29, 17651781.

A Heinz , DF Braus , MN Smolka , J Wrase , I Puls , D Hermann , S Klein , SM Grusser , H Flor , G Schumann , (2005). Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nature Neuroscience 8, 2021.

T Johnstone , CM van Reekum , HL Urry , NH Kalin , RJ Davidson (2007). Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression. Journal of Neuroscience 27, 88778884.

A Kersting , K Kroker , J Horstmann , BT Baune , C Hohoff , LS Mortensen , LC Neumann , V Arolt , K Domschke (2008). Association of MAO-A variant with complicated grief in major depression. Neuropsychobiology 56, 191196.

SH Kim , S Hamann (2007). Neural correlates of positive and negative emotion regulation. Journal of Cognitive Neuroscience 19, 776798.

J Lévesque , F Eugène , Y Joanette , V Paquette , B Mensour , G Beaudoin , JM Leroux , P Bourgouin , M Beauregard (2003). Neural circuitry underlying voluntary suppression of sadness. Biological Psychiatry 53, 502510.

JA Maldjian , PJ Laurienti , RA Kraft , JH Burdette (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 19, 12331239.

AK Malhotra , D Goldman (1999). Benefits and pitfalls encountered in psychiatric genetic association studies. Biological Psychiatry 45, 544550.

HS Mayberg , SK Brannan , JL Tekell , JA Silva , RK Mahurin , S McGinnis , PA Jerabek (2000). Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biological Psychiatry 48, 830843.

JH Meyer , N Ginovart , A Boovariwala , S Sagrati , D Hussey , A Garcia , T Young , N Praschak-Rieder , AA Wilson , S Houle (2006). Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression. Archives of General Psychiatry 63, 12091216.

A Meyer-Lindenberg , JW Buckholtz , B Kolachana , AR Hariri , L Pezawas , G Blasi , A Wabnitz , R Honea , B Verchinski , JH Callicott , (2006). Neural mechanisms of genetic risk for impulsivity and violence in humans. Proceedings of the National Academy of Sciences USA 103, 62696274.

X Ni , T Sicard , N Bulgin , R Bismil , K Chan , S McMain , JL Kennedy (2007). Monoamine oxidase a gene is associated with borderline personality disorder. Psychiatric Genetics 17, 153157.

KN Ochsner , JJ Gross (2005). The cognitive control of emotion. Trends in Cognitive Sciences 9, 242249.

KN Ochsner , RD Ray , JC Cooper , ER Robertson , S Chopra , JD Gabrieli , JJ Gross (2004). For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion. Neuroimage 23, 483499.

H Ohira , M Nomura , N Ichikawa , T Isowa , T Iidaka , A Sato , S Fukuyama , T Nakajima , J Yamada (2006). Association of neural and physiological responses during voluntary emotion suppression. Neuroimage 29, 721733.

L Pezawas , A Meyer-Lindenberg , EM Drabant , BA Verchinski , KE Munoz , BS Kolachana , MF Egan , VS Mattay , AR Hariri , DR Weinberger (2005). 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nature Neuroscience 8, 828834.

KL Phan , DA Fitzgerald , PJ Nathan , GJ Moore , TW Uhde , ME Tancer (2005). Neural substrates for voluntary suppression of negative affect: a functional magnetic resonance imaging study. Biological Psychiatry 57, 210219.

ML Phillips , WC Drevets , SL Rauch , R Lane (2003). Neurobiology of emotion perception II: Implications for major psychiatric disorders. Biological Psychiatry 54, 515528.

N Ramnani , TE Behrens , W Penny , PM Matthews (2004). New approaches for exploring anatomical and functional connectivity in the human brain. Biological Psychiatry 56, 613619.

AV Rauch , P Ohrmann , J Bauer , H Kugel , A Engelien , V Arolt , W Heindel , T Suslow (2007). Cognitive coping style modulates neural responses to emotional faces in healthy humans: a 3-T fMRI study. Cerebral Cortex 17, 25262535.

S Robinson , C Windischberger , A Rauscher , E Moser (2004). Optimized 3 T EPI of the amygdalae. Neuroimage 22, 203210.

SZ Sabol , S Hu , D Hamer (1998). A functional polymorphism in the monoamine oxidase A gene promoter. Human Genetics 103, 273279.

TG Schulze , DJ Müller , H Krauss , H Scherk , S Ohlraun , YV Syagailo , C Windemuth , H Neidt , M Grässle , A Papassotiropoulos , (2000). Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder. American Journal of Medical Genetics 96, 801803.

GJ Siegle , SR Steinhauer , ME Thase , VA Stenger , CS Carter (2002). Can't shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals. Biological Psychiatry 51, 693707.

GJ Siegle , W Thompson , CS Carter , SR Steinhauer , ME Thase (2007). Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression. related and independent features. Biological Psychiatry 61, 198209.

S Surguladze , MJ Brammer , P Keedwell , V Giampietro , AW Young , MJ Travis , SC Williams , ML Phillips (2005). A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biological Psychiatry 57, 201209.

N Tzourio-Mazoyer , B Landeau , D Papathanassiou , F Crivello , O Etard , N Delcroix , B Mazoyer , M Joliot (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15, 273289.

ML Wong , J Licinio (2001). Research and treatment approaches to depression. Nature Reviews Neuroscience 2, 343351.

YW Yu , SJ Tsai , CJ Hong , TJ Chen , MC Chen , CW Yang (2005). Association study of a monoamine oxidase a gene promoter polymorphism with major depressive disorder and antidepressant response. Neuropsychopharmacology 30, 17191723.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The The International Journal of Neuropsychopharmacology
  • ISSN: 1461-1457
  • EISSN: 1469-5111
  • URL: /core/journals/the-international-journal-of-neuropsychopharmacology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords: