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Decreased functional connectivity between the amygdala and the left ventral prefrontal cortex in treatment-naive patients with major depressive disorder: a resting-state functional magnetic resonance imaging study

Published online by Cambridge University Press:  30 November 2012

Y. Tang ,
L. Kong ,
F. Wu ,
F. Womer ,
W. Jiang ,
Y. Cao ,
L. Ren ,
J. Wang ,
G. Fan  and
H. P. Blumberg
...Show all authors
Y. Tang
Affiliation:
Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
L. Kong
Affiliation:
Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
F. Wu
Affiliation:
Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
F. Womer
Affiliation:
Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
W. Jiang
Affiliation:
Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
Y. Cao
Affiliation:
Shenyang Mental Health Center, Shenyang, Liaoning, PR China
L. Ren
Affiliation:
Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
J. Wang
Affiliation:
Center for Cognition and Brain Disorders, Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, PR China
G. Fan
Affiliation:
Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
H. P. Blumberg
Affiliation:
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
K. Xu*
Affiliation:
Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
F. Wang*
Affiliation:
Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
*
*Author for correspondence: K. Xu, M.D., Ph.D., Department of Radiology, First Affiliated Hospital, China Medical University, 155 Nanjing North Street, Shenyang 110001, Liaoning, PR China. (Email: kexu@vip.sina.com) [K. Xu] (Email:fei.wang@yale.edu) [F. Wang]
*Author for correspondence: K. Xu, M.D., Ph.D., Department of Radiology, First Affiliated Hospital, China Medical University, 155 Nanjing North Street, Shenyang 110001, Liaoning, PR China. (Email: kexu@vip.sina.com) [K. Xu] (Email:fei.wang@yale.edu) [F. Wang]
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Abstract

Background

Convergent studies provide support for abnormalities in the structure and functioning of the prefrontal cortex (PFC) and the amygdala, the key components of the neural system that subserves emotional processing in major depressive disorder (MDD). We used resting-state functional magnetic resonance imaging (fMRI) to examine potential amygdala–PFC functional connectivity abnormalities in treatment-naive subjects with MDD.

Methods

Resting-state fMRI data were acquired from 28 individuals with MDD and 30 healthy control (HC) subjects. Amygdala–PFC functional connectivity was compared between the MDD and HC groups.

Results

Decreased functional connectivity to the left ventral PFC (VPFC) from the left and right amygdala was observed in the MDD group, compared with the HC group (p < 0.05, corrected).

Conclusions

The treatment-naive subjects with MDD showed decreased functional connectivity from the amygdala to the VPFC, especially to the left VPFC. This suggests that these connections may play an important role in the neuropathophysiology of MDD at its onset.

Keywords

Amygdalafunctional connectivityfunctional magnetic resonancemajor depressive disorderresting stateventral prefrontal cortex
Type
Original Articles
Information
Psychological Medicine , Volume 43 , Issue 9 , September 2013 , pp. 1921 - 1927
Copyright
Copyright © Cambridge University Press 2012 

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References

Amaral, DG, Price, JL (1984). Amygdalo-cortical projections in the monkey (Macaca fascicularis). Journal of Comparative Neurology 230, 465–496.CrossRefGoogle ScholarPubMed
Anand, A, Li, Y, Wang, Y, Wu, J, Gao, S, Bukhari, L, Mathews, VP, Kalnin, A, Lowe, MJ (2005 a). Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study. Biological Psychiatry 57, 1079–1088.CrossRefGoogle ScholarPubMed
Anand, A, Li, Y, Wang, Y, Wu, J, Gao, S, Bukhari, L, Mathews, VP, Kalnin, A, Lowe, MJ (2005 b). Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study. Neuropsychopharmacology 30, 1334–1344.CrossRefGoogle ScholarPubMed
Bajwa, S, Bermpohl, F, Rigonatti, SP, Pascual-Leone, A, Boggio, PS, Fregni, F (2008). Impaired interhemispheric interactions in patients with major depression. Journal of Nervous and Mental Disease 196, 671–677.CrossRefGoogle ScholarPubMed
Chen, CH, Suckling, J, Ooi, C, Fu, CH, Williams, SC, Walsh, ND, Mitterschiffthaler, MT, Pich, EM, Bullmore, E (2008). Functional coupling of the amygdala in depressed patients treated with antidepressant medication. Neuropsychopharmacology 33, 1909–1918.CrossRefGoogle ScholarPubMed
Cordes, D, Haughton, VM, Arfanakis, K, Carew, JD, Turski, PA, Moritz, CH, Quigley, MA, Meyerand, ME (2001). Frequencies contributing to functional connectivity in the cerebral cortex in ‘resting-state’ data. American Journal of Neuroradiology 22, 1326–1333.Google ScholarPubMed
Costafreda, SG, Brammer, MJ, David, AS, Fu, CH (2008). Predictors of amygdala activation during the processing of emotional stimuli: a meta-analysis of 385 PET and fMRI studies. Brain Research Reviews 58, 57–70.CrossRefGoogle ScholarPubMed
Davidson, RJ (2002). Anxiety and affective style: role of prefrontal cortex and amygdala. Biological Psychiatry 51, 68–80.CrossRefGoogle ScholarPubMed
Davidson, RJ, Irwin, W (1999). The functional neuroanatomy of emotion and affective style. Trends in Cognitive Sciences 3, 11–21.CrossRefGoogle ScholarPubMed
Dougherty, DD, Rauch, SL, Deckersbach, T, Marci, C, Loh, R, Shin, LM, Alpert, NM, Fischman, AJ, Fava, M (2004). Ventromedial prefrontal cortex and amygdala dysfunction during an anger induction positron emission tomography study in patients with major depressive disorder with anger attacks. Archives of General Psychiatry 61, 795–804.CrossRefGoogle ScholarPubMed
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. Pharmacology, Biochemistry and Behavior 71, 431–447.CrossRefGoogle ScholarPubMed
Drevets, WC, Price, JL, Furey, ML (2008). Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Structure and Function 213, 93–118.CrossRefGoogle ScholarPubMed
Fox, MD, Zhang, D, Snyder, AZ, Raichle, ME (2009). The global signal and observed anticorrelated resting state brain networks. Journal of Neurophysiology 101, 3270–3283.CrossRefGoogle ScholarPubMed
Frodl, T, Bokde, AL, Scheuerecker, J, Lisiecka, D, Schoepf, V, Hampel, H, Moller, HJ, Bruckmann, H, Wiesmann, M, Meisenzahl, E (2010). Functional connectivity bias of the orbitofrontal cortex in drug-free patients with major depression. Biological Psychiatry 67, 161–167.CrossRefGoogle ScholarPubMed
Ghashghaei, HT, Hilgetag, CC, Barbas, H (2007). Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala. NeuroImage 34, 905–923.CrossRefGoogle ScholarPubMed
Greicius, M (2008). Resting-state functional connectivity in neuropsychiatric disorders. Current Opinion in Neurology 21, 424–430.CrossRefGoogle ScholarPubMed
Greicius, MD, Flores, BH, Menon, V, Glover, GH, Solvason, HB, Kenna, H, Reiss, AL, Schatzberg, AF (2007). Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biological Psychiatry 62, 429–437.CrossRefGoogle ScholarPubMed
Grimm, S, Beck, J, Schuepbach, D, Hell, D, Boesiger, P, Bermpohl, F, Niehaus, L, Boeker, H, Northoff, G (2008). Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment: an fMRI study in severe major depressive disorder. Biological Psychiatry 63, 369–376.CrossRefGoogle ScholarPubMed
Hercher, C, Turecki, G, Mechawar, N (2009). Through the looking glass: examining neuroanatomical evidence for cellular alterations in major depression. Journal of Psychiatric Research 43, 947–961.CrossRefGoogle ScholarPubMed
Horn, DI, Yu, C, Steiner, J, Buchmann, J, Kaufmann, J, Osoba, A, Eckert, U, Zierhut, KC, Schiltz, K, He, H, Biswal, B, Bogerts, B, Walter, M (2010). Glutamatergic and resting-state functional connectivity correlates of severity in major depression – the role of pregenual anterior cingulate cortex and anterior insula. Frontiers in Systems Neuroscience 4, 33.Google ScholarPubMed
Jackson, DC, Mueller, CJ, Dolski, I, Dalton, KM, Nitschke, JB, Urry, HL, Rosenkranz, MA, Ryff, CD, Singer, BH, Davidson, RJ (2003). Now you feel it, now you don't: frontal brain electrical asymmetry and individual differences in emotion regulation. Psychological Science 14, 612–617.CrossRefGoogle ScholarPubMed
Johnstone, T, van Reekum, CM, Urry, HL, Kalin, NH, Davidson, RJ (2007). Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression. Journal of Neuroscience 27, 8877–8884.CrossRefGoogle ScholarPubMed
Keedwell, PA, Andrew, C, Williams, SC, Brammer, MJ, Phillips, ML (2005). A double dissociation of ventromedial prefrontal cortical responses to sad and happy stimuli in depressed and healthy individuals. Biological Psychiatry 58, 495–503.CrossRefGoogle ScholarPubMed
Lebowitz, BD, Pearson, JL, Schneider, LS, Reynolds, CF 3rd, Alexopoulos, GS, Bruce, ML, Conwell, Y, Katz, IR, Meyers, BS, Morrison, MF, Mossey, J, Niederehe, G, Parmelee, P (1997). Diagnosis and treatment of depression in late life. Consensus statement update. Journal of the American Medical Association 278, 1186–1190.CrossRefGoogle ScholarPubMed
LeDoux, JE (1992). Brain mechanisms of emotion and emotional learning. Current Opinion in Neurobiology 2, 191–197.CrossRefGoogle ScholarPubMed
Lee, BT, Seok, JH, Lee, BC, Cho, SW, Yoon, BJ, Lee, KU, Chae, JH, Choi, IG, Ham, BJ (2008). Neural correlates of affective processing in response to sad and angry facial stimuli in patients with major depressive disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry 32, 778–785.CrossRefGoogle ScholarPubMed
Liu, Y, Hu, D, Zhou, Z, Shen, H, Wang, X (2008). fMRI noise reduction based on canonical correlation analysis and surrogate test. IEEE Journal of Selected Topics in Signal Processing 2, 870–878.CrossRefGoogle Scholar
Liu, Z, Xu, C, Xu, Y, Wang, Y, Zhao, B, Lv, Y, Cao, X, Zhang, K, Du, C (2010). Decreased regional homogeneity in insula and cerebellum: a resting-state fMRI study in patients with major depression and subjects at high risk for major depression. Psychiatry Research 182, 211–215.CrossRefGoogle ScholarPubMed
Lowe, MJ, Dzemidzic, M, Lurito, JT, Mathews, VP, Phillips, MD (2000). Correlations in low-frequency BOLD fluctuations reflect cortico-cortical connections. NeuroImage 12, 582–587.CrossRefGoogle ScholarPubMed
MacQueen, GM (2009). Magnetic resonance imaging and prediction of outcome in patients with major depressive disorder. Journal of Psychiatry and Neuroscience 34, 343–349.Google ScholarPubMed
Martinot, JL, Hardy, P, Feline, A, Huret, JD, Mazoyer, B, Attar-Levy, D, Pappata, S, Syrota, A (1990). Left prefrontal glucose hypometabolism in the depressed state: a confirmation. American Journal of Psychiatry 147, 1313–1317.Google ScholarPubMed
Mayberg, HS, Liotti, M, Brannan, SK, McGinnis, S, Mahurin, RK, Jerabek, PA, Silva, JA, Tekell, JL, Martin, CC, Lancaster, JL, Fox, PT (1999). Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. American Journal of Psychiatry 156, 675–682.CrossRefGoogle ScholarPubMed
Nitschke, JB, Heller, W, Etienne, MA, Miller, GA (2004). Prefrontal cortex activity differentiates processes affecting memory in depression. Biological Psychology 67, 125–143.CrossRefGoogle ScholarPubMed
Ochsner, KN, Gross, JJ (2007). The neural architecture of emotion regulation. In Handbook of Emotion Regulation (ed. Gross, J. J.), pp. 87–109. Guilford Press: New York.Google Scholar
Peng, J, Liu, J, Nie, B, Li, Y, Shan, B, Wang, G, Li, K (2011). Cerebral and cerebellar gray matter reduction in first-episode patients with major depressive disorder: a voxel-based morphometry study. European Journal of Radiology 80, 395–399.CrossRefGoogle ScholarPubMed
Pessoa, L (2008). On the relationship between emotion and cognition. Nature Reviews. Neuroscience 9, 148–158.CrossRefGoogle ScholarPubMed
Pillai, JJ, Friedman, L, Stuve, TA, Trinidad, S, Jesberger, JA, Lewin, JS, Findling, RL, Swales, TP, Schulz, SC (2002). Increased presence of white matter hyperintensities in adolescent patients with bipolar disorder. Psychiatry Research 114, 51–56.CrossRefGoogle ScholarPubMed
Quirk, GJ, Beer, JS (2006). Prefrontal involvement in the regulation of emotion: convergence of rat and human studies. Current Opinion in Neurobiology 16, 723–727.CrossRefGoogle ScholarPubMed
Quirk, GJ, Likhtik, E, Pelletier, JG, Pare, D (2003). Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. Journal of Neuroscience 23, 8800–8807.CrossRefGoogle ScholarPubMed
Raichle, ME, MacLeod, AM, Snyder, AZ, Powers, WJ, Gusnard, DA, Shulman, GL (2001). A default mode of brain function. Proceedings of the National Academy of Sciences USA 98, 676–682.CrossRefGoogle ScholarPubMed
Sackeim, HA, Greenberg, MS, Weiman, AL, Gur, RC, Hungerbuhler, JP, Geschwind, N (1982). Hemispheric asymmetry in the expression of positive and negative emotions. Neurologic evidence. Archives of Neurology 39, 210–218.CrossRefGoogle ScholarPubMed
Sackeim, HA, Prohovnik, I, Moeller, JR, Brown, RP, Apter, S, Prudic, J, Devanand, DP, Mukherjee, S (1990). Regional cerebral blood flow in mood disorders. I. Comparison of major depressives and normal controls at rest. Archives of General Psychiatry 47, 60–70.CrossRefGoogle ScholarPubMed
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. Biological Psychiatry 50, 651–658.CrossRefGoogle ScholarPubMed
Siegle, GJ, Thompson, W, Carter, CS, Steinhauer, SR, Thase, ME (2007). Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features. Biological Psychiatry 61, 198–209.CrossRefGoogle ScholarPubMed
Tomarken, AJ, Davidson, RJ, Wheeler, RE, Doss, RC (1992). Individual differences in anterior brain asymmetry and fundamental dimensions of emotion. Journal of Personality and Social Psychology 62, 676–687.CrossRefGoogle ScholarPubMed
Urry, HL, van Reekum, CM, Johnstone, T, Kalin, NH, Thurow, ME, Schaefer, HS, Jackson, CA, Frye, CJ, Greischar, LL, Alexander, AL, Davidson, RJ (2006). Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults. Journal of Neuroscience 26, 4415–4425.CrossRefGoogle ScholarPubMed
van Tol, MJ, Demenescu, LR, van der Wee, NJ, Kortekaas, R, Marjan, MAN, Boer, JA, Renken, RJ, van Buchem, MA, Zitman, FG, Aleman, A, Veltman, DJ (2012). Functional magnetic resonance imaging correlates of emotional word encoding and recognition in depression and anxiety disorders. Biological Psychiatry 71, 593–602.CrossRefGoogle ScholarPubMed
Veer, IM, Beckmann, CF, van Tol, MJ, Ferrarini, L, Milles, J, Veltman, DJ, Aleman, A, van Buchem, MA, van der Wee, NJ, Rombouts, SA (2010). Whole brain resting-state analysis reveals decreased functional connectivity in major depression. Frontiers in Systems Neuroscience 4, 41.CrossRefGoogle ScholarPubMed