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

  • R. Norbury (a1), S. Selvaraj (a1), M. J. Taylor (a1), C. Harmer (a2) and P. J. Cowen (a1)...
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.

Copyright
Corresponding author
*Address for correspondence: Dr R. Norbury, Psychopharmacology Research Unit (PPRU), University of Oxford, Department of Psychiatry, Neurosciences Building, Warneford Hospital, Headington, Oxford OX3 7JX, UK. (Email: raymond.norbury@psych.ox.ac.uk)
References
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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, 211218.
Bhagwagar Z, Cowen PJ (2008). ‘It's not over when it's over’: persistent neurobiological abnormalities in recovered depressed patients. Psychological Medicine 38, 307313.
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, 166168.
Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS (2000). Hippocampal volume reduction in major depression. American Journal of Psychiatry 157, 115118.
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, 631640.
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, 407414.
DeRubeis RJ, Siegle GJ, Hollon SD (2008). Cognitive therapy versus medication for depression: treatment outcomes and neural mechanisms. Nature Reviews Neuroscience 9, 788796.
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, 367373.
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, 206211.
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, 377384.
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, 636647.
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, 214220.
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, 877889.
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, 505512.
Ghashghaei HT, Barbas H (2002). Pathways for emotion: interactions of prefrontal and anterior temporal pathways in the amygdala of the rhesus monkey. Neuroscience 115, 12611279.
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, 348362.
Hamilton JP, Gotlib IH (2008). Neural substrates of increased memory sensitivity for negative stimuli in major depression. Biological Psychiatry 63, 11551162.
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, 11931198.
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, 146152.
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, 137142.
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, 825841.
Jenkinson M, Smith S (2001). A global optimisation method for robust affine registration of brain images. Medical Image Analysis 5, 143156.
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, 11121123.
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, 88778884.
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, 553557.
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, 12331239.
Matsumoto J, Eckman P (1988). Japanese and Caucasian Facial Expressions of Emotion (JACFEE) and Neutral Faces (JACNeuF). Human Interaction Laboratory: San Francisco.
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, 651660.
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, 17501756.
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, 282288.
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.
Pittenger C, Duman RS (2008). Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology 33, 88–109.
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, 651658.
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, 198209.
Smith S (2002). Fast robust automated brain extraction. Human Brain Mapping 17, 143155.
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, S208S219.
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, 318327.
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, 858863.
Woolrich MW, Behrens TE, Beckmann CF, Jenkinson M, Smith SM (2004). Multilevel linear modelling for FMRI group analysis using Bayesian inference. Neuroimage 21, 17321747.
Woolrich MW, Ripley BD, Brady M, Smith SM (2001). Temporal autocorrelation in univariate linear modeling of FMRI data. Neuroimage 14, 13701386.
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Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
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