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Increased neural response to fear in patients recovered from depression: a 3T functional magnetic resonance imaging study

Published online by Cambridge University Press:  23 July 2009

R. Norbury ,
S. Selvaraj ,
M. J. Taylor ,
C. Harmer  and
P. J. Cowen
R. Norbury*
Affiliation:
Psychopharmacology Research Unit (PPRU), University of Oxford, Department of Psychiatry, Oxford, UK
S. Selvaraj
Affiliation:
Psychopharmacology Research Unit (PPRU), University of Oxford, Department of Psychiatry, Oxford, UK
M. J. Taylor
Affiliation:
Psychopharmacology Research Unit (PPRU), University of Oxford, Department of Psychiatry, Oxford, UK
C. Harmer
Affiliation:
Psychopharmacology and Emotion Research Laboratory (PERL), University of Oxford, Department of Psychiatry, Oxford, UK
P. J. Cowen
Affiliation:
Psychopharmacology Research Unit (PPRU), University of Oxford, Department of Psychiatry, Oxford, UK
*
*Address for correspondence: Dr R. Norbury, Psychopharmacology Research Unit (PPRU), University of Oxford, Department of Psychiatry, Neurosciences Building, Warneford Hospital, Headington, OxfordOX3 7JX, UK. (Email: [email protected])
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Abstract

Background

Previous imaging studies have revealed that acute major depression is characterized by altered neural responses to negative emotional stimuli. Typically, responses in limbic regions such as the amygdala are increased while activity in cortical regulatory regions such as the dorsolateral prefrontal cortex (DLPFC) is diminished. Whether these changes persist in unmedicated recovered patients is unclear.

Method

We used functional magnetic resonance imaging to examine neural responses to emotional faces in a facial expression-matching task in 16 unmedicated recovered depressed patients and 21 healthy controls.

Results

Compared with controls, recovered depressed patients had increased responses bilaterally to fearful faces in the DLPFC and right caudate. Responses in the amygdala did not distinguish the groups.

Conclusions

Our findings indicate that clinical recovery from depression is associated with increased activity in the DLPFC to negative emotional stimuli. We suggest that this increase may reflect a compensatory cortical control mechanism with the effect of limiting emotional dysregulation in limbic regions such as the amygdala.

Keywords

AmygdaladepressionfMRI
Type
Original Articles
Information
Psychological Medicine , Volume 40 , Issue 3 , March 2010 , pp. 425 - 432
Copyright
Copyright © Cambridge University Press 2009

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References

Baxter, LR Jr., Phelps, ME, Mazziotta, JC, Guze, BH, Schwartz, JM, Selin, CE (1987). Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls. Archives of General Psychiatry 44, 211–218.CrossRefGoogle ScholarPubMed
Bhagwagar, Z, Cowen, PJ (2008). ‘It's not over when it's over’: persistent neurobiological abnormalities in recovered depressed patients. Psychological Medicine 38, 307–313.CrossRefGoogle Scholar
Bhagwagar, Z, Cowen, PJ, Goodwin, GM, Harmer, CJ (2004). Normalization of enhanced fear recognition by acute SSRI treatment in subjects with a previous history of depression. American Journal of Psychiatry 161, 166–168.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, 115–118.CrossRefGoogle ScholarPubMed
Brody, AL, Saxena, S, Stoessel, P, Gillies, LA, Fairbanks, LA, Alborzian, S, Phelps, ME, Huang, SC, Wu, HM, Ho, ML, Ho, MK, Au, SC, Maidment, K, Baxter, LR Jr. (2001). Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings. Archives of General Psychiatry 58, 631–640.CrossRefGoogle ScholarPubMed
Chen, CH, Ridler, K, Suckling, J, Williams, S, Fu, CH, Merlo-Pich, E, Bullmore, E (2007). Brain imaging correlates of depressive symptom severity and predictors of symptom improvement after antidepressant treatment. Biological Psychiatry 62, 407–414.CrossRefGoogle ScholarPubMed
DeRubeis, RJ, Siegle, GJ, Hollon, SD (2008). Cognitive therapy versus medication for depression: treatment outcomes and neural mechanisms. Nature Reviews Neuroscience 9, 788–796.CrossRefGoogle ScholarPubMed
Drabant, EM, McRae, K, Manuck, SB, Hariri, AR, Gross, JJ (2009). Individual differences in typical reappraisal use predict amygdala and prefrontal responses. Biological Psychiatry 65, 367–373.CrossRefGoogle ScholarPubMed
Fales, CL, Barch, DM, Rundle, MM, Mintun, MA, Mathews, J, Snyder, AZ, Sheline, YI (2009). Antidepressant treatment normalizes hypoactivity in dorsolateral prefrontal cortex during emotional interference processing in major depression. Journal of Affective Disorders 112, 206–211.CrossRefGoogle ScholarPubMed
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. Biological Psychiatry 63, 377–384.CrossRefGoogle ScholarPubMed
Forman, SD, Cohen, JD, Fitzgerald, M, Eddy, WF, Mintun, MA, Noll, DC (1995). Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold. Magnetic Resonance Imaging in Medicine 33, 636–647.CrossRefGoogle ScholarPubMed
Friston, KJ, Worsley, KJ, Frackowiak, RSJ, Mazziotta, JC, Evans, AC (1994). Assessing the significance of focal activations using their spatial extent. Human Brain Mapping 1, 214–220.CrossRefGoogle ScholarPubMed
Fu, CH, Williams, SC, Cleare, AJ, Brammer, MJ, Walsh, ND, Kim, J, Andrew, CM, Pich, EM, Williams, PM, Reed, LJ, Mitterschiffthaler, MT, Suckling, J, Bullmore, ET (2004). Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. Archives of General Psychiatry 61, 877–889.CrossRefGoogle ScholarPubMed
Fu, CH, Williams, SC, Cleare, AJ, Scott, J, Mitterschiffthaler, MT, Walsh, ND, Donaldson, C, Suckling, J, Andrew, C, Steiner, H, Murray, RM (2008). Neural responses to sad facial expressions in major depression following cognitive behavioral therapy. Biological Psychiatry 64, 505–512.CrossRefGoogle ScholarPubMed
Ghashghaei, HT, Barbas, H (2002). Pathways for emotion: interactions of prefrontal and anterior temporal pathways in the amygdala of the rhesus monkey. Neuroscience 115, 1261–1279.CrossRefGoogle ScholarPubMed
Gross, JJ, John, OP (2003). Individual differences in two emotion regulation processes: implications for affect, relationships, and well-being. Journal of Personality and Social Psychology 85, 348–362.CrossRefGoogle ScholarPubMed
Hamilton, JP, Gotlib, IH (2008). Neural substrates of increased memory sensitivity for negative stimuli in major depression. Biological Psychiatry 63, 1155–1162.CrossRefGoogle ScholarPubMed
Hannestad, J, Taylor, WD, McQuoid, DR, Payne, ME, Krishnan, KR, Steffens, DC, Macfall, JR (2006). White matter lesion volumes and caudate volumes in late-life depression. International Journal of Geriatric Psychiatry 21, 1193–1198.CrossRefGoogle ScholarPubMed
Hariri, AR, Drabant, EM, Munoz, KE, Kolachana, BS, Mattay, VS, Egan, MF, Weinberger, DR (2005). A susceptibility gene for affective disorders and the response of the human amygdala. Archives of General Psychiatry 62, 146–152.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
Jenkinson, M, Bannister, P, Brady, M, Smith, S (2002). Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 17, 825–841.CrossRefGoogle ScholarPubMed
Jenkinson, M, Smith, S (2001). A global optimisation method for robust affine registration of brain images. Medical Image Analysis 5, 143–156.CrossRefGoogle ScholarPubMed
Johnstone, T, Somerville, LH, Alexander, AL, Oakes, TR, Davidson, RJ, Kalin, NH, Whalen, PJ (2005). Stability of amygdala BOLD response to fearful faces over multiple scan sessions. Neuroimage 25, 1112–1123.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
Krishnan, KR, McDonald, WM, Escalona, PR, Doraiswamy, PM, Na, C, Husain, MM, Figiel, GS, Boyko, OB, Ellinwood, EH, Nemeroff, CB (1992). Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations. Archives of General Psychiatry 49, 553–557.CrossRefGoogle ScholarPubMed
Maldjian, JA, Laurienti, PJ, Kraft, RA, Burdette, JH (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 19, 1233–1239.CrossRefGoogle ScholarPubMed
Matsumoto, J, Eckman, P (1988). Japanese and Caucasian Facial Expressions of Emotion (JACFEE) and Neutral Faces (JACNeuF). Human Interaction Laboratory: San Francisco.Google Scholar
Mayberg, HS, Lozano, AM, Voon, V, McNeely, HE, Seminowicz, D, Hamani, C, Schwalb, JM, Kennedy, SH (2005). Deep brain stimulation for treatment-resistant depression. Neuron 45, 651–660.CrossRefGoogle ScholarPubMed
Neumeister, A, Drevets, WC, Belfer, I, Luckenbaugh, DA, Henry, S, Bonne, O, Herscovitch, P, Goldman, D, Charney, DS (2006). Effects of a α2C-adrenoreceptor gene polymorphism on neural responses to facial expressions in depression. Neuropsychopharmacology 31, 1750–1756.CrossRefGoogle Scholar
Paulus, MP, Feinstein, JS, Castillo, G, Simmons, AN, Stein, MB (2005). Dose-dependent decrease of activation in bilateral amygdala and insula by lorazepam during emotion processing. Archives of General Psychiatry 62, 282–288.CrossRefGoogle ScholarPubMed
Phillips, ML, Ladouceur, CD, Drevets, WC (2008). Neural systems underlying voluntary and automatic emotion regulation: toward a neural model of bipolar disorder. Molecular Psychiatry 13, 829.CrossRefGoogle Scholar
Pittenger, C, Duman, RS (2008). Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33, 88–109.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
Smith, S (2002). Fast robust automated brain extraction. Human Brain Mapping 17, 143–155.CrossRefGoogle ScholarPubMed
Smith, SM, Jenkinson, M, Woolrich, MW, Beckman, CF, Behrens, TE, Johansen-Berg, H, Bannister, PR, De Luca, M, Drobnjak, I, Flitney, DE, Niazy, RK, Saunders, J, Vickers, J, Zhang, Y, De Stefano, N, Brady, JM, Mathews, PM (2004). Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23, S208–S219.CrossRefGoogle ScholarPubMed
Stein, MB, Simmons, AN, Feinstein, JS, Paulus, MP (2007). Increased amygdala and insula activation during emotion processing in anxiety-prone subjects. American Journal of Psychiatry 164, 318–327.CrossRefGoogle ScholarPubMed
Whalen, PJ, Johnstone, T, Somerville, LH, Nitschke, JB, Polis, S, Alexander, AL, Davidson, RJ, Kalin, NH (2008). A functional magnetic resonance imaging predictor of treatment response to venlafaxine in generalized anxiety disorder. Biological Psychiatry 63, 858–863.CrossRefGoogle ScholarPubMed
Woolrich, MW, Behrens, TE, Beckmann, CF, Jenkinson, M, Smith, SM (2004). Multilevel linear modelling for FMRI group analysis using Bayesian inference. Neuroimage 21, 1732–1747.CrossRefGoogle ScholarPubMed
Woolrich, MW, Ripley, BD, Brady, M, Smith, SM (2001). Temporal autocorrelation in univariate linear modeling of FMRI data. Neuroimage 14, 1370–1386.CrossRefGoogle ScholarPubMed