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Paradoxical effects of short-term antidepressant treatment in fMRI emotional processing models in volunteers with high neuroticism

Published online by Cambridge University Press:  19 April 2013

M. Di Simplicio ,
R. Norbury ,
A. Reinecke  and
C. J. Harmer
M. Di Simplicio*
Affiliation:
MRC Brain and Cognition Sciences Unit, Cambridge, UK University Department of Psychiatry, Warneford Hospital, Oxford, UK
R. Norbury
Affiliation:
University Department of Psychiatry, Warneford Hospital, Oxford, UK Oxford Centre for Clinical Magnetic Resonance Research (OCMR), John Radcliffe Hospital, Oxford, UK
A. Reinecke
Affiliation:
University Department of Psychiatry, Warneford Hospital, Oxford, UK
C. J. Harmer
Affiliation:
University Department of Psychiatry, Warneford Hospital, Oxford, UK
*
*Address for correspondence: Dr M. Di Simplicio, MRC Brain and Cognition Sciences Unit, 15 Chaucer Road, Cambridge CB2 7EF, UK. (Email: [email protected])
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Abstract

Background

Short-term antidepressant administration has been reported to decrease amygdala response to threat in healthy volunteers and depressed patients. Neuroticism (N) is a risk factor for depression but has also been associated with slow or incomplete remission with antidepressant drug treatment. Our aim was to investigate early selective serotonin reuptake inhibitor (SSRI) administration neural effects on implicit processing of fearful facial expressions in volunteers with high levels of N.

Method

Highly neurotic subjects received 20 mg/day citalopram versus placebo for 7 days in a double-blind, between-groups design. On the last day haemoperfusion and functional magnetic resonance imaging (fMRI) data during a gender discrimination task with fearful and happy faces were acquired. A control group of non-neurotic volunteers was also tested.

Results

High-N volunteers had reduced responses to threatening facial expressions across key neural circuits compared to low-N volunteers. SSRI treatment was found to elevate resting perfusion in the right amygdala, increase bilateral amygdalae activation to positive and negative facial expressions and increase activation to fearful versus happy facial expressions in occipital, parietal, temporal and prefrontal cortical areas.

Conclusions

These results suggest that 7 days of SSRI administration can increase neural markers of fear reactivity in subjects at the high end of the N dimension and may be related to early increases in anxiety and agitation seen early in treatment. Such processes may be involved in the later therapeutic effects through decreased avoidance and increased learning about social ‘threat’ cues.

Keywords

AntidepressantsanxiogenicemotionfMRIneuroticism
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 2 , January 2014 , pp. 241 - 252
Copyright
Copyright © Cambridge University Press 2013 

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References

Adolphs, R (2008). Fear, faces, and the human amygdala. Current Opinion in Neurobiology 18, 166–172.CrossRefGoogle ScholarPubMed
Adolphs, R, Gosselin, F, Buchanan, TW, Tranel, D, Schyns, P, Damasio, AR (2005). A mechanism for impaired fear recognition after amygdala damage. Nature 433, 68–72.Google Scholar
Beckmann, C, Smith, SM (2004). Probabilistic independent component analysis for functional magnetic resonance imaging. IEEE Transactions of Medical Imaging 23, 137–152.CrossRefGoogle ScholarPubMed
Bigos, KL, Pollock, BG, Aizenstein, HJ, Fisher, PM, Bies, RR, Hariri, AR (2008). Acute 5-HT reuptake blockade potentiates human amygdala reactivity. Neuropsychopharmacology 33, 3221–3225.Google Scholar
Bishop, SJ (2007). Neurocognitive mechanisms of anxiety: an integrative account. Trends in Cognitive Sciences 11, 307–216.CrossRefGoogle ScholarPubMed
Browning, M, Reid, C, Cowen, PJ, Goodwin, GM, Harmer, CJ (2007). A single dose of citalopram increases fear recognition in healthy subjects. Journal of Psychopharmacology 21, 684–690.CrossRefGoogle ScholarPubMed
Butler, G, Fennell, M, Hackman, A (2008). Avoidance of affect. In Cognitive-Behavioural Therapy for Anxiety Disorders: Mastering Clinical Challenges, pp. 133–151. Guilford Press: New York.Google Scholar
Carver, CS, Johnson, SL, Joormann, J (2008). Serotonergic function, two-mode models of self-regulation, and vulnerability to depression: what depression has in common with impulsive aggression. Psychological Bulletin 134, 912–943.CrossRefGoogle ScholarPubMed
Chan, SW, Goodwin, GM, Harmer, CJ (2007). Highly neurotic never-depressed students have negative biases in information processing. Psychological Medicine 37, 1281–1291.CrossRefGoogle ScholarPubMed
Chan, SW, Norbury, R, Goodwin, GM, Harmer, CJ (2009). Risk for depression and neural responses to fearful facial expressions of emotion. British Journal of Psychiatry 194, 139–145.Google Scholar
Chappell, MA, Okell, TW, Jezzard, P, Woolrich, MW (2009). Vascular territory image analysis using vessel encoded arterial spin labeling. Medical Image Computing and Computer-Assisted Intervention 12, 514–521.Google Scholar
Chen, Y, Wan, HI, O'Reardon, JP, Wang, DJ, Wang, Z, Korczykowski, M, Detre, JA (2011). Quantification of cerebral blood flow as biomarker of drug effect: arterial spin labeling phMRI after a single dose of oral citalopram. Clinical Pharmacology and Therapeutics 89, 251–258.Google Scholar
Clark, DA, Beck, AT (2010). Cognitive theory and therapy of anxiety and depression: convergence with neurobiological findings. Trends in Cognitive Sciences 14, 418–424.Google Scholar
Cunningham, WA, Arbuckle, NL, Jahn, A, Mowrer, SM, Abduljalil, AM (2011). Reprint of: Aspects of neuroticism and the amygdala: chronic tuning from motivational styles. Neuropsychologia 49, 657–662.Google Scholar
Davidson, RJ, Irwin, W, Anderle, MJ, Kalin, NH (2003). The neural substrates of affective processing in depressed patients treated with venlafaxine. American Journal of Psychiatry 160, 64–75.CrossRefGoogle ScholarPubMed
Davis, M, Whalen, PJ (2001). The amygdala: vigilance and emotion. Molecular Psychiatry 6, 13–34.Google Scholar
Del-Ben, CM, Deakin, JF, McKie, S, Delvai, NA, Williams, SR, Elliott, R, Dolan, M, Anderson, IM (2005). The effect of citalopram pretreatment on neuronal responses to neuropsychological tasks in normal volunteers: an fMRI study. Neuropsychopharmacology 30, 1724–1734.CrossRefGoogle ScholarPubMed
Di Simplicio, M, Doallo, S, Costoloni, G, Rohenkohl, G, Nobre, AC, Harmer, CJ (2012). ‘Can you look me in the eyes?’ Short-term SSRI administration reverts avoidant ocular face exploration in subjects at risk for psychopathology. Poster presented at the 25th ECNP Congress, 13–17 October 2012, Vienna, Austria.Google Scholar
DeYoung, CG, Quilty, LC, Peterson, JB (2007). Between facets and domains: 10 aspects of the Big Five. Journal of Personality and Social Psychology 93, 880–896.Google Scholar
Di Simplicio, M, Norbury, R, Harmer, CJ (2012). Short-term antidepressant administration reduces negative self-referential processing in the medial prefrontal cortex in subjects at risk for depression. Molecular Psychiatry 17, 503–510.Google Scholar
Ekman, PF (1976). Pictures of Facial Affect. Consulting Psychologists Press: Palo Alto, CA.Google Scholar
Etkin, A, Egner, T, Kalisch, R (2011). Emotional processing in anterior cingulate and medial prefrontal cortex. Trends in Cognitive Sciences 15, 85–93.CrossRefGoogle ScholarPubMed
Eysenck, SBG, Eysenck, HJ (1975). Manual of the EPQ (Eysenck Personality Questionnaire). University of London Press: London.Google Scholar
Eysenck, SBG, Eysenck, HJ, Barret, P (1985). A revised version of the psychoticism scale. Personality and Individual Differences 6, 21–29.CrossRefGoogle Scholar
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (1998). Structured Clinical Interview for DSM-IV Axis I Disorders, Research Version, Patient Edition (SCID-I/P). New York: Biometrics Research, New York State Psychiatric Institute.Google Scholar
Friston, K, Worsley, KJ, Farckowiak, RSJ, Mazziotta, JC, Evans, AC (1994). Assessing the significance of focal activations using their spatial extent. Human Brain Mapping 1, 210–220.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
Godlewska, BR, Norbury, R, Selvaraj, S, Cowen, PJ, Harmer, CJ (2012). Short-term SSRI treatment normalises amygdala hyperactivity in depressed patients. Psychological Medicine 42, 2609–2617.CrossRefGoogle ScholarPubMed
Haas, BW, Constable, RT, Canli, T (2008). Stop the sadness: neuroticism is associated with sustained medial prefrontal cortex response to emotional facial expressions. NeuroImage 42, 385–392.CrossRefGoogle ScholarPubMed
Haas, BW, Omura, K, Constable, RT, Canli, T (2007). Emotional conflict and neuroticism: personality-dependent activation in the amygdala and subgenual anterior cingulate. Behavioral Neuroscience 121, 249–256.Google Scholar
Hamilton, M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry 23, 56–62.Google Scholar
Harmer, CJ (2008). Serotonin and emotional processing: does it help explain antidepressant drug action? Neuropharmacology 55, 1023–1028.CrossRefGoogle ScholarPubMed
Harmer, CJ, Goodwin, GM, Cowen, PJ (2009). Why do antidepressants take so long to work? A cognitive neuropsychological model of antidepressant drug action. British Journal of Psychiatry 195, 102–108.Google Scholar
Harmer, CJ, Mackay, CE, Reid, CB, Cowen, PJ, Goodwin, GM (2006). Antidepressant drug treatment modifies the neural processing of nonconscious threat cues. Biological Psychiatry 59, 816–820.CrossRefGoogle ScholarPubMed
Harmer, CJ, Shelley, NC, Cowen, PJ, Goodwin, GM (2004). Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. American Journal of Psychiatry 161, 1256–1263.Google Scholar
Jenkinson, MBP, Brady, M, Smith, SM (2002). Improved optimization for the robust and accurate linear registration and motion correction of brain images. NeuroImage 17, 825–841.CrossRefGoogle ScholarPubMed
Katon, W, Unutzer, J, Russo, J (2010). Major depression: the importance of clinical characteristics and treatment response to prognosis. Depression and Anxiety 27, 19–26.Google Scholar
Kendler, KS, Neale, MC, Kessler, RC, Heath, AC, Eaves, LJ (1993). A longitudinal twin study of personality and major depression in women. Archives of General Psychiatry 50, 853–862.CrossRefGoogle ScholarPubMed
Lahey, B (2009). Public health significance of neuroticism. American Psychologist 64, 241–256.Google Scholar
MacIntosh, BJ, Pattinson, KT, Gallichan, D, Ahmad, I, Miller, KL, Feinberg, DA, Wise, RG, Jezzard, P (2008). Measuring the effects of remifentanil on cerebral blood flow and arterial arrival time using 3D GRASE MRI with pulsed arterial spin labelling. Journal of Cerebral Blood Flow and Metabolism 28, 1514–1522.Google Scholar
Mogg, K, Garner, M, Bradley, BP (2007). Anxiety and orienting of gaze to angry and fearful faces. Biological Psychology 76, 163–169.Google Scholar
Morris, JS, Friston, KJ, Büchel, C, Frith, CD, Young, AW, Calder, AJ, Dolan, RJ (1998). A neuromodulatory role for the human amygdala in processing emotional facial expressions. Brain 121, 47–57.Google Scholar
Murphy, SE (2010). Using functional neuroimaging to investigate the mechanisms of action of selective serotonin reuptake inhibitors (SSRIs). Current Pharmaceutical Design 16, 1990–1997.CrossRefGoogle ScholarPubMed
Murphy, SE, Norbury, R, O'Sullivan, U, Cowen, PJ, Harmer, CJ (2009). Effect of a single dose of citalopram on amygdala response to emotional faces. British Journal of Psychiatry 194, 535–540.Google Scholar
Nichols, TE, Holmes, AP (2002). Nonparametric permutation tests for functional neuroimaging: a primer with examples. Human Brain Mapping 15, 1–25.CrossRefGoogle ScholarPubMed
Norbury, R, Taylor, MJ, Selvaraj, S, Murphy, SE, Harmer, CJ, Cowen, PJ (2009). Short-term antidepressant treatment modulates amygdala response to happy faces. Psychopharmacology (Berlin) 206, 197–204.CrossRefGoogle ScholarPubMed
Ochsner, KN, Gross, JJ (2005). The cognitive control of emotion. Trends in Cognitive Sciences 9, 242–249.Google 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.Google Scholar
Phan, KL, Wager, TD, Taylor, SF, Liberzon, I (2002). Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. NeuroImage 16, 331–348.Google Scholar
Pourtois, G, Schettino, A, Vuilleumier, P (2013). Brain mechanisms for emotional influences on perception and attention: what is magic and what is not. Biological Psychology 92, 492–512.Google Scholar
Rawlings, NB, Norbury, R, Cowen, PJ, Harmer, CJ (2010). A single dose of mirtazapine modulates neural responses to emotional faces in healthy people. Psychopharmacology (Berlin) 212, 625–634.Google Scholar
Robinson, OJ, Charney, DR, Overstreet, C, Vytal, K, Grillon, C (2012). The adaptive threat bias in anxiety: amygdala-dorsomedial prefrontal cortex coupling and aversive amplification. NeuroImage 60, 523–529.Google Scholar
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
Sinclair, LI, Christmas, DM, Hood, SD, Potokar, JP, Robertson, A, Isaac, A, Srivastava, S, Nutt, DJ, Davies, SJ (2009). Antidepressant-induced jitteriness/anxiety syndrome: systematic review. British Journal of Psychiatry 194, 483–490.Google Scholar
Smith, S (2002). Fast and robust automated brain extraction. Human Brain Mapping 17, 143–155.Google Scholar
Smith, SM, Jenkinson, M, Woolrich, MW, Beckmann, 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, Matthews, PM (2004). Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 23 (Suppl. 1), S208–S219.Google Scholar
Spielberger, CD, Gorsuch, RL, Lushene, RD (1983). Manual for the State-Trait Anxiety Inventory (STAI). Consulting Psychologists Press: Palo Alto, CA.Google Scholar
Straube, T, Schmidt, S, Weiss, T, Mentzel, HJ, Miltner, WH (2009). Dynamic activation of the anterior cingulate cortex during anticipatory anxiety. NeuroImage 44, 975–981.Google Scholar
Surguladze, S, Brammer, MJ, Keedwell, P, Giampietro, V, Young, AW, Travis, MJ, Williams, SC, Phillips, ML (2005). A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biological Psychiatry 57, 201–209.Google Scholar
Talaraich, J, Tournoux, P (1988). Co-planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System. Thieme Medical: New York.Google Scholar
Tranter, R, Bell, D, Gutting, P, Harmer, C, Healy, D, Anderson, IM (2009). The effect of serotonergic and noradrenergic antidepressants on face emotion processing in depressed patients. Journal of Affective Disorders 118, 87–93.CrossRefGoogle ScholarPubMed
von Zerssen, DSF, Schwarz, D (1974). Evaluation of depressive states, especially in longitudinal studies. Modern Problems of Pharmacopsychiatry 7, 189–202.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, Jbabdi, S, Patenaude, B, Chappell, M, Makni, S, Behrens, T, Beckmann, C, Jenkinson, M, Smith, SM (2009). Bayesian analysis of neuroimaging data in FSL. NeuroImage 45, S173–S186.Google Scholar
Woolrich, MW, Ripley, BD, Brady, M, Smith, SM (2001). Temporal autocorrelation in univariate linear modeling of FMRI data. NeuroImage 14, 1370–1386.Google Scholar
Young, AW, Rowland, D, Calder, AJ, Etcoff, NL, Seth, A, Perrett, DI (1997). Facial expression megamix: tests of dimensional and category accounts of emotion recognition. Cognition 63, 271–313.Google Scholar
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