Limbic-cortical dysregulation: a proposed model of depression



	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted
	Citation Map



	Email this article to a Colleague
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Add to My Articles & Searches
	Download to citation manager



	Citing Articles via HighWire
	Citing Articles via Google Scholar



	Articles by Mayberg, H. S.
	Search for Related Content



	PubMed Citation
	Articles by Mayberg, H. S.

REGULAR ARTICLES

Limbic-cortical dysregulation: a proposed model of depression

HS Mayberg
Department of Medicine (Neurology), University of Texas Health Science Center at San Antonio 78284-6240, USA. mayberg@uthscsa.edu

A working model of depression implicating failure of the coordinated interactions of a distributed network of limbic-cortical pathways is proposed. Resting state patterns of regional glucose metabolism in idiopathic depressed patients, changes in metabolism with antidepressant treatment, and blood flow changes with induced sadness in healthy subjects were used to test and refine this hypothesis. Dorsal neocortical decreases and ventral paralimbic increases characterize both healthy sadness and depressive illness; concurrent inhibition of overactive paralimbic regions and normalization of hypofunctioning dorsal cortical sites characterize disease remission. Normal functioning of the rostral anterior cingulate, with its direct connections to these dorsal and ventral areas, is postulated to be additionally required for the observed reciprocal compensatory changes, since pretreatment metabolism in this region uniquely predicts antidepressant treatment response. This model is offered as an adaptable framework to facilitate continued integration of clinical imaging findings with complementary neuroanatomical, neurochemical, and electrophysiological studies in the investigation of the pathogenesis of affective disorders.

This article has been cited by other articles:

T. S. Frodl, N. Koutsouleris, R. Bottlender, C. Born, M. Jager, I. Scupin, M. Reiser, H.-J. Moller, and E. M. Meisenzahl
Depression-Related Variation in Brain Morphology Over 3 Years: Effects of Stress?
Arch Gen Psychiatry, October 1, 2008; 65(10): 1156 - 1165.
[Abstract] [Full Text] [PDF]

A. Lothe, A. Didelot, A. Hammers, N. Costes, M. Saoud, F. Gilliam, and P. Ryvlin
Comorbidity between temporal lobe epilepsy and depression: a [18F]MPPF PET study
Brain, September 2, 2008; (2008) awn194v1.
[Abstract] [Full Text] [PDF]

L. Wang, K. R. Krishnan, D. C. Steffens, G. G. Potter, F. Dolcos, and G. McCarthy
Depressive State- and Disease-Related Alterations in Neural Responses to Affective and Executive Challenges in Geriatric Depression
Am J Psychiatry, July 1, 2008; 165(7): 863 - 871.
[Abstract] [Full Text] [PDF]

H. Johansen-Berg, D. A. Gutman, T. E. J. Behrens, P. M. Matthews, M. F. S. Rushworth, E. Katz, A. M. Lozano, and H. S. Mayberg
Anatomical Connectivity of the Subgenual Cingulate Region Targeted with Deep Brain Stimulation for Treatment-Resistant Depression
Cereb Cortex, June 1, 2008; 18(6): 1374 - 1383.
[Abstract] [Full Text] [PDF]

J. Jogia, M. Haldane, A. Cobb, V. Kumari, and S. Frangou
Pilot investigation of the changes in cortical activation during facial affect recognition with lamotrigine monotherapy in bipolar disorder
The British Journal of Psychiatry, March 1, 2008; 192(3): 197 - 201.
[Abstract] [Full Text] [PDF]

P. J. Gianaros, L. K. Sheu, K. A. Matthews, J. R. Jennings, S. B. Manuck, and A. R. Hariri
Individual Differences in Stressor-Evoked Blood Pressure Reactivity Vary with Activation, Volume, and Functional Connectivity of the Amygdala
J. Neurosci., January 23, 2008; 28(4): 990 - 999.
[Abstract] [Full Text] [PDF]

H. S. Mayberg, A. M. Lozano, V. Voon, H. E. McNeely, D. Seminowicz, C. Hamani, J. M. Schwalb, and S. H. Kennedy
Deep Brain Stimulation for Treatment-Resistant Depression
Focus, January 1, 2008; 6(1): 143 - 154.
[Abstract] [Full Text] [PDF]

J.-K. Chen, K. M. Johnston, M. Petrides, and A. Ptito
Neural Substrates of Symptoms of Depression Following Concussion in Male Athletes With Persisting Postconcussion Symptoms
Arch Gen Psychiatry, January 1, 2008; 65(1): 81 - 89.
[Abstract] [Full Text] [PDF]

V. Gabbay, D. A. Hess, S. Liu, J. S. Babb, R. G. Klein, and O. Gonen
Lateralized Caudate Metabolic Abnormalities in Adolescent Major Depressive Disorder: A Proton MR Spectroscopy Study
Am J Psychiatry, December 1, 2007; 164(12): 1881 - 1889.
[Abstract] [Full Text] [PDF]

S. J. Banks, K. T. Eddy, M. Angstadt, P. J. Nathan, and K. L. Phan
Amygdala frontal connectivity during emotion regulation
Soc Cogn Affect Neurosci, December 1, 2007; 2(4): 303 - 312.
[Abstract] [Full Text] [PDF]

L. M. Williams, A. H. Kemp, K. Felmingham, B. J. Liddell, D. M. Palmer, and R. A. Bryant
Neural biases to covert and overt signals of fear: dissociation by trait anxiety and depression.
J. Cogn. Neurosci., October 1, 2007; 19(10): 1595 - 1608.
[Abstract] [Full Text] [PDF]

Y. Moriguchi, J. Decety, T. Ohnishi, M. Maeda, T. Mori, K. Nemoto, H. Matsuda, and G. Komaki
Empathy and Judging Other's Pain: An fMRI Study of Alexithymia
Cereb Cortex, September 1, 2007; 17(9): 2223 - 2234.
[Abstract] [Full Text] [PDF]

B. Yulug, M. Bakar, I. Karapolat, O. Guzel, and W. R. Schabitz
Topiramate Improves Glucose Metabolism in Choreatic and Depressive Patient: PET Findings
J Neuropsychiatry Clin Neurosci, August 1, 2007; 19(3): 346 - 347.
[Full Text] [PDF]

S. H. Kennedy, J. Z. Konarski, Z. V. Segal, M. A. Lau, P. J. Bieling, R. S. McIntyre, and H. S. Mayberg
Differences in Brain Glucose Metabolism Between Responders to CBT and Venlafaxine in a 16-Week Randomized Controlled Trial
Am J Psychiatry, May 1, 2007; 164(5): 778 - 788.
[Abstract] [Full Text] [PDF]

N. Ma, L. Li, N. Shu, J. Liu, G. Gong, Z. He, Z. Li, L. Tan, W. S. Stone, Z. Zhang, et al.
White Matter Abnormalities in First-Episode, Treatment-Naive Young Adults With Major Depressive Disorder
Am J Psychiatry, May 1, 2007; 164(5): 823 - 826.
[Abstract] [Full Text] [PDF]

C. H.Y. Fu, S. C.R. Williams, M. J. Brammer, J. Suckling, J. Kim, A. J. Cleare, N. D. Walsh, M. T. Mitterschiffthaler, C. M. Andrew, E. M. Pich, et al.
Neural Responses to Happy Facial Expressions in Major Depression Following Antidepressant Treatment
Am J Psychiatry, April 1, 2007; 164(4): 599 - 607.
[Abstract] [Full Text] [PDF]

M. Wessa, J. Houenou, M.-L. Paillere-Martinot, S. Berthoz, E. Artiges, M. Leboyer, and J.-L. Martinot
Fronto-Striatal Overactivation in Euthymic Bipolar Patients During an Emotional Go/NoGo Task
Am J Psychiatry, April 1, 2007; 164(4): 638 - 646.
[Abstract] [Full Text] [PDF]

C. M. van Reekum, H. L. Urry, T. Johnstone, M. E. Thurow, C. J. Frye, C. A. Jackson, H. S. Schaefer, A. L. Alexander, and R. J. Davidson
Individual Differences in Amygdala and Ventromedial Prefrontal Cortex Activity are Associated with Evaluation Speed and Psychological Well-being.
J. Cogn. Neurosci., February 1, 2007; 19(2): 237 - 248.
[Abstract] [Full Text] [PDF]

M. A. Oquendo, R. S. Hastings, Y.-y. Huang, N. Simpson, R. T. Ogden, X.-z. Hu, D. Goldman, V. Arango, R. L. Van Heertum, J. J. Mann, et al.
Brain Serotonin Transporter Binding in Depressed Patients With Bipolar Disorder Using Positron Emission Tomography
Arch Gen Psychiatry, February 1, 2007; 64(2): 201 - 208.
[Abstract] [Full Text] [PDF]

J. E. Max, H. S. Levin, R. J. Schachar, J. Landis, A. E. Saunders, L. Ewing-Cobbs, S. B. Chapman, and M. Dennis
Predictors of Personality Change Due to Traumatic Brain Injury in Children and Adolescents Six to Twenty-Four Months After Injury.
J Neuropsychiatry Clin Neurosci, December 1, 2006; 18(1): 21 - 32.
[Abstract] [Full Text] [PDF]

A. M. Hunter, A. F. Leuchter, M. L. Morgan, and I. A. Cook
Changes in Brain Function (Quantitative EEG Cordance) During Placebo Lead-In and Treatment Outcomes in Clinical Trials for Major Depression
Am J Psychiatry, August 1, 2006; 163(8): 1426 - 1432.
[Abstract] [Full Text] [PDF]

L. J. Julian and D. C. Mohr
Cognitive Predictors of Response to Treatment for Depression in Multiple Sclerosis
J Neuropsychiatry Clin Neurosci, August 1, 2006; 18(3): 356 - 363.
[Abstract] [Full Text] [PDF]

F. Dolcos and G. McCarthy
Brain Systems Mediating Cognitive Interference by Emotional Distraction
J. Neurosci., February 15, 2006; 26(7): 2072 - 2079.
[Abstract] [Full Text] [PDF]

R. V. Parsey, R. S. Hastings, M. A. Oquendo, Y.-y. Huang, N. Simpson, J. Arcement, Y. Huang, R. T. Ogden, R. L. Van Heertum, V. Arango, et al.
Lower Serotonin Transporter Binding Potential in the Human Brain During Major Depressive Episodes
Am J Psychiatry, January 1, 2006; 163(1): 52 - 58.
[Abstract] [Full Text] [PDF]

S. M. Brown, S. Henning, and C. L. Wellman
Mild, Short-term Stress Alters Dendritic Morphology in Rat Medial Prefrontal Cortex
Cereb Cortex, November 1, 2005; 15(11): 1714 - 1722.
[Abstract] [Full Text] [PDF]

D. C. Steffens
Research in Geriatric Depression: A Model for Mental Health Research in the 21st Century?
Am J Geriatr Psychiatry, October 1, 2005; 13(10): 829 - 833.
[Full Text] [PDF]

T. Canli, K. Omura, B. W. Haas, A. Fallgatter, R. T. Constable, and K. P. Lesch
Beyond affect: A role for genetic variation of the serotonin transporter in neural activation during a cognitive attention task
PNAS, August 23, 2005; 102(34): 12224 - 12229.
[Abstract] [Full Text] [PDF]

A. Etkin, C. Pittenger, H. J. Polan, and E. R. Kandel
Toward a Neurobiology of Psychotherapy: Basic Science and Clinical Applications
J Neuropsychiatry Clin Neurosci, May 1, 2005; 17(2): 145 - 158.
[Abstract] [Full Text] [PDF]

M. S. Milak, R. V. Parsey, J. Keilp, M. A. Oquendo, K. M. Malone, and J. J. Mann
Neuroanatomic Correlates of Psychopathologic Components of Major Depressive Disorder
Arch Gen Psychiatry, April 1, 2005; 62(4): 397 - 408.
[Abstract] [Full Text] [PDF]

H. Kim, L. H. Somerville, T. Johnstone, S. Polis, A. L. Alexander, L. M. Shin, and P. J. Whalen
Contextual Modulation of Amygdala Responsivity to Surprised Faces
J. Cogn. Neurosci., December 1, 2004; 16(10): 1730 - 1745.
[Abstract] [Full Text] [PDF]

B. Levine, G. R. Turner, D. Tisserand, S. J. Hevenor, S. J. Graham, and A. R. McIntosh
The Functional Neuroanatomy of Episodic and Semantic Autobiographical Remembering: A Prospective Functional MRI Study
J. Cogn. Neurosci., November 1, 2004; 16(9): 1633 - 1646.
[Abstract] [Full Text] [PDF]

P. Weikop, J. Kehr, and J. Scheel-Kruger
The Role of {alpha}1- and {alpha}2-Adrenoreceptors on Venlafaxineinduced Elevation of Extracellular Serotonin, Noradrenaline and Dopamine Levels in the Rat Prefrontal Cortex and Hippocampus
J Psychopharmacol, September 1, 2004; 18(3): 395 - 403.
[Abstract] [PDF]

K. Chang, N. E. Adleman, K. Dienes, D. I. Simeonova, V. Menon, and A. Reiss
Anomalous Prefrontal-Subcortical Activation in Familial Pediatric Bipolar Disorder: A Functional Magnetic Resonance Imaging Investigation
Arch Gen Psychiatry, August 1, 2004; 61(8): 781 - 792.
[Abstract] [Full Text] [PDF]

D. D. Dougherty, S. L. Rauch, T. Deckersbach, C. Marci, R. Loh, L. M. Shin, N. M. Alpert, A. J. Fischman, and M. Fava
Ventromedial Prefrontal Cortex and Amygdala Dysfunction During an Anger Induction Positron Emission Tomography Study in Patients With Major Depressive Disorder With Anger Attacks
Arch Gen Psychiatry, August 1, 2004; 61(8): 795 - 804.
[Abstract] [Full Text] [PDF]

W. D. Taylor, J. R. MacFall, M. E. Payne, D. R. McQuoid, J. M. Provenzale, D. C. Steffens, and K. R. R. Krishnan
Late-Life Depression and Microstructural Abnormalities in Dorsolateral Prefrontal Cortex White Matter
Am J Psychiatry, July 1, 2004; 161(7): 1293 - 1296.
[Abstract] [Full Text] [PDF]

C. Rocher, M. Spedding, C. Munoz, and T. M. Jay
Acute Stress-induced Changes in Hippocampal/Prefrontal Circuits in Rats: Effects of Antidepressants
Cereb Cortex, February 1, 2004; 14(2): 224 - 229.
[Abstract] [Full Text] [PDF]

K. Goldapple, Z. Segal, C. Garson, M. Lau, P. Bieling, S. Kennedy, and H. Mayberg
Modulation of Cortical-Limbic Pathways in Major Depression: Treatment-Specific Effects of Cognitive Behavior Therapy
Arch Gen Psychiatry, January 1, 2004; 61(1): 34 - 41.
[Abstract] [Full Text] [PDF]

J.-K. Zubieta, T. A. Ketter, J. A. Bueller, Y. Xu, M. R. Kilbourn, E. A. Young, and R. A. Koeppe
Regulation of Human Affective Responses by Anterior Cingulate and Limbic {micro}-Opioid Neurotransmission
Arch Gen Psychiatry, November 1, 2003; 60(11): 1145 - 1153.
[Abstract] [Full Text] [PDF]

C. E. Coffey
Pursuing Perfect Care in Neuropsychiatry: Implications of the Institute of Medicine's "Quality Chasm" Report for Neuropsychiatry
J Neuropsychiatry Clin Neurosci, November 1, 2003; 15(4): 403 - 406.
[Full Text] [PDF]

J. Shumake and F. Gonzalez-Lima
Brain Systems Underlying Susceptibility to Helplessness and Depression
Behav Cogn Neurosci Rev, September 1, 2003; 2(3): 198 - 221.
[Abstract] [PDF]

E. T. Rolls, K. Inoue, and A. Browning
Activity of Primate Subgenual Cingulate Cortex Neurons Is Related to Sleep
J Neurophysiol, July 1, 2003; 90(1): 134 - 142.
[Abstract] [Full Text] [PDF]

J. Hornak, J. Bramham, E. T. Rolls, R. G. Morris, J. O'Doherty, P. R. Bullock, and C. E. Polkey
Changes in emotion after circumscribed surgical lesions of the orbitofrontal and cingulate cortices
Brain, July 1, 2003; 126(7): 1691 - 1712.
[Abstract] [Full Text] [PDF]

W. E. Bunney, B. G. Bunney, M. P. Vawter, H. Tomita, J. Li, S. J. Evans, P. V. Choudary, R. M. Myers, E. G. Jones, S. J. Watson, et al.
Microarray Technology: A Review of New Strategies to Discover Candidate Vulnerability Genes in Psychiatric Disorders
Am J Psychiatry, April 1, 2003; 160(4): 657 - 666.
[Abstract] [Full Text] [PDF]

H. S Mayberg
Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment
Br. Med. Bull., March 1, 2003; 65(1): 193 - 207.
[Abstract] [Full Text] [PDF]

M. D. Greicius, B. Krasnow, A. L. Reiss, and V. Menon
Functional connectivity in the resting brain: A network analysis of the default mode hypothesis
PNAS, January 7, 2003; 100(1): 253 - 258.
[Abstract] [Full Text] [PDF]

A. L. Brody, M. A. Mandelkern, E. D. London, A. R. Childress, G. S. Lee, R. G. Bota, M. L. Ho, S. Saxena, L. R. Baxter Jr, D. Madsen, et al.
Brain Metabolic Changes During Cigarette Craving
Arch Gen Psychiatry, December 1, 2002; 59(12): 1162 - 1172.
[Abstract] [Full Text] [PDF]

H. S. Mayberg and A. M. Lozano
Penfield revisited?: Understanding and modifying behavior by deep brain stimulation for PD
Neurology, November 12, 2002; 59(9): 1298 - 1299.
[Full Text] [PDF]

S. Bell-McGinty, M. A. Butters, C. C. Meltzer, P. J. Greer, C. F. Reynolds III, and J. T. Becker
Brain Morphometric Abnormalities in Geriatric Depression: Long-Term Neurobiological Effects of Illness Duration
Am J Psychiatry, August 1, 2002; 159(8): 1424 - 1427.
[Abstract] [Full Text] [PDF]

P. J. Harrison
The neuropathology of primary mood disorder
Brain, July 1, 2002; 125(7): 1428 - 1449.
[Abstract] [Full Text] [PDF]

H Mertz
Role of the brain and sensory pathways in gastrointestinal sensory disorders in humans
Gut, July 1, 2002; 51(90001): i29 - 33.
[Abstract] [Full Text]

H. S. Mayberg, J. A. Silva, S. K. Brannan, J. L. Tekell, R. K. Mahurin, S. McGinnis, and P. A. Jerabek
The Functional Neuroanatomy of the Placebo Effect
Am J Psychiatry, May 1, 2002; 159(5): 728 - 737.
[Abstract] [Full Text] [PDF]

P. J. SHAH, M. F. GLABUS, G. M. GOODWIN, and K. P. EBMEIER
Chronic, treatment-resistant depression and right fronto-striatal atrophy
The British Journal of Psychiatry, May 1, 2002; 180(5): 434 - 440.
[Abstract] [Full Text] [PDF]

S. Saxena, A. L. Brody, M. L. Ho, S. Alborzian, K. M. Maidment, N. Zohrabi, M. K. Ho, S.-C. Huang, H.-M. Wu, and L. R. Baxter Jr
Differential Cerebral Metabolic Changes With Paroxetine Treatment of Obsessive-Compulsive Disorder vs Major Depression
Arch Gen Psychiatry, March 1, 2002; 59(3): 250 - 261.
[Abstract] [Full Text] [PDF]

W. M. Perlstein, T. Elbert, and V. A. Stenger
Dissociation in human prefrontal cortex of affective influences on working memory-related activity
PNAS, January 24, 2002; (2002) 241650598.
[Abstract] [Full Text] [PDF]