Advertisement

Induction of Depressed Mood Disrupts Emotion Regulation Neurocircuitry and Enhances Pain Unpleasantness

  • Chantal Berna
    Correspondence
    Address correspondence to Chantal Berna, M.D., Centre for Functional Magnetic Resonance Imaging of the Brain, Departments of Clinical Neurology and Anaesthetics, University of Oxford, Oxford OX3 9DU, United Kingdom
    Affiliations
    Centre for Functional Magnetic Resonance Imaging of the Brain, Department of Clinical Neurology and Nuffield Department of Anaesthetics, University of Oxford, Oxford, United Kingdom

    Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom
    Search for articles by this author
  • Siri Leknes
    Affiliations
    Centre for Functional Magnetic Resonance Imaging of the Brain, Department of Clinical Neurology and Nuffield Department of Anaesthetics, University of Oxford, Oxford, United Kingdom
    Search for articles by this author
  • Emily A. Holmes
    Affiliations
    Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom
    Search for articles by this author
  • Robert R. Edwards
    Affiliations
    Department of Anesthesiology, Harvard Medical School, Brigham & Women's Hospital, Chestnut Hill, Massachusetts
    Search for articles by this author
  • Guy M. Goodwin
    Affiliations
    Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom
    Search for articles by this author
  • Irene Tracey
    Affiliations
    Centre for Functional Magnetic Resonance Imaging of the Brain, Department of Clinical Neurology and Nuffield Department of Anaesthetics, University of Oxford, Oxford, United Kingdom
    Search for articles by this author

      Background

      Depressed mood alters the pain experience. Yet, despite its clear clinical relevance, little is known about the cognitive and neural mechanisms underlying this phenomenon. We tested an experimental manipulation to unravel the interaction between depressed mood and pain. We hypothesized that dysregulation of the neural circuitry underlying emotion regulation is the mechanism whereby pain processing is affected during depressed mood.

      Methods

      Using functional magnetic resonance imaging, we compared the effects of sad and neutral cognitive mood inductions on affective pain ratings, pain-specific cognitions, and central pain processing of a tonic noxious heat stimulus in 20 healthy volunteers.

      Results

      The increase in negative pain-specific cognitions during depressed mood predicted the perceived increase in pain unpleasantness. Following depressed mood induction, brain responses to noxious thermal stimuli were characterized by increased activity in a broad network including prefrontal areas, subgenual anterior cingulate cortex, and hippocampus, as well as significantly less deactivation when compared with pain responses in a neutral mood. The participants who reported the largest increase in pain unpleasantness after the sad mood induction showed greater inferior frontal gyrus and amygdala activation, linking changes in emotion regulation mechanisms with enhancement of pain affect.

      Conclusions

      Our results inform how depressed mood and chronic pain co-occur clinically and may serve to develop and translate effective interventions using pharmacological or psychological treatment.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bair M.J.
        • Robinson R.L.
        • Katon W.
        • Kroenke K.
        Depression and pain comorbidity: A literature review.
        Arch Intern Med. 2003; 163: 2433-2445
        • Geisser M.E.
        • Roth R.S.
        • Theisen M.E.
        • Robinson M.E.
        • Riley 3rd, J.L.
        Negative affect, self-report of depressive symptoms, and clinical depression: Relation to the experience of chronic pain.
        Clin J Pain. 2000; 16: 110-120
        • Bar K.J.
        • Wagner G.
        • Koschke M.
        • Boettger S.
        • Boettger M.K.
        • Schlosser R.
        • et al.
        Increased prefrontal activation during pain perception in major depression.
        Biol Psychiatry. 2007; 62: 1281-1287
        • Strigo I.A.
        • Simmons A.N.
        • Matthews S.C.
        • Craig A.D.
        • Paulus M.P.
        Association of major depressive disorder with altered functional brain response during anticipation and processing of heat pain.
        Arch Gen Psychiatry. 2008; 65: 1275-1284
        • Giesecke T.
        • Gracely R.H.
        • Williams D.A.
        • Geisser M.E.
        • Petzke F.W.
        • Clauw D.J.
        The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort.
        Arthritis Rheum. 2005; 52: 1577-1584
        • Schweinhardt P.
        • Kalk N.
        • Wartolowska K.
        • Chessell I.
        • Wordsworth P.
        • Tracey I.
        Investigation into the neural correlates of emotional augmentation of clinical pain.
        Neuroimage. 2008; 40: 759-766
        • Apkarian A.V.
        • Sosa Y.
        • Sonty S.
        • Levy R.M.
        • Harden R.N.
        • Parrish T.B.
        • et al.
        Chronic back pain is associated with decreased prefrontal and thalamic gray matter density.
        J Neurosci. 2004; 24: 10410-10415
        • Campbell S.
        • MacQueen G.
        An update on regional brain volume differences associated with mood disorders.
        Curr Opin Psychiatry. 2006; 19: 25-33
        • Williams J.M.
        • Barnhofer T.
        • Crane C.
        • Beck A.T.
        Problem solving deteriorates following mood challenge in formerly depressed patients with a history of suicidal ideation.
        J Abnorm Psychol. 2005; 114: 421-431
        • Goodwin A.M.
        • Williams J.M.G.
        Mood-induction research—its implications for clinical depression.
        Behav Res Ther. 1982; 20: 373-382
        • Loggia M.L.
        • Mogil J.S.
        • Bushnell M.C.
        Experimentally induced mood changes preferentially affect pain unpleasantness.
        J Pain. 2008; 9: 784-791
        • Villemure C.
        • Slotnick B.M.
        • Bushnell M.C.
        Effects of odors on pain perception: Deciphering the roles of emotion and attention.
        Pain. 2003; 106: 101-108
        • Rainville P.
        • Bao Q.V.H.
        • Chretien P.
        Pain-related emotions modulate experimental pain perception and autonomic responses.
        Pain. 2005; 118: 306-318
        • Zelman D.C.
        • Howland E.W.
        • Nichols S.N.
        • Cleeland C.S.
        The effects of induced mood on laboratory pain.
        Pain. 1991; 46: 105-111
        • Sharp T.J.
        Chronic pain: A reformulation of the cognitive-behavioural model.
        Behav Res Ther. 2001; 39: 787-800
        • Geisser M.E.
        • Robinson M.E.
        • Keefe F.J.
        • Weiner M.L.
        Catastrophizing, depression and the sensory, affective and evaluative aspects of chronic pain.
        Pain. 1994; 59: 79-83
        • Johnstone T.
        • van Reekum C.M.
        • Urry H.L.
        • Kalin N.H.
        • Davidson R.J.
        Failure to regulate: Counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression.
        J Neurosci. 2007; 27: 8877-8884
        • Beauregard M.
        • Paquette V.
        • Levesque J.
        Dysfunction in the neural circuitry of emotional self-regulation in major depressive disorder.
        Neuroreport. 2006; 17: 843-846
        • Clark D.M.
        On the induction of depressed mood in the laboratory: Evaluation and comparison of the Velten and musical procedures.
        Adv Behav Res Ther. 1983; 5: 27-49
        • Edwards R.R.
        • Smith M.T.
        • Stonerock G.
        • Haythornthwaite J.A.
        Pain-related catastrophizing in healthy women is associated with greater temporal summation of and reduced habituation to thermal pain.
        Clin J Pain. 2006; 22: 730-737
        • Beck A.T.
        • Steer R.A.
        • Brown G.K.
        Manual for the Back Depression Inventory-II.
        Psychological Corporation, San Antonio, TX1996
        • Sheehan D.V.
        • Lecrubier Y.
        • Sheehan K.H.
        • Amorim P.
        • Janavs J.
        • Weiller E.
        • et al.
        The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.
        J Clin Psychiatry. 1998; 59 (quiz 34–57): 22-33
        • Eysenck S.B.G.
        • Eysenck H.J.
        • Barrett P.
        A revised version of the psychoticism scale.
        Pers Individ Dif. 1985; 6: 21-29
        • Velten Jr, E.
        A laboratory task for induction of mood states.
        Behav Res Ther. 1968; 6: 473-482
        • Richell R.A.
        • Anderson M.
        Reproducibility of negative mood induction: A self-referent plus musical mood induction procedure and a controllable/uncontrollable stress paradigm.
        J Psychopharmacol. 2004; 18: 94-101
        • Clark D.M.
        • Teasdale J.D.
        Constraints on the effects of mood on memory.
        J Pers Soc Psychol. 1985; 6: 1595-1608
        • Au Yeung C.
        • Dalgleish T.
        • Golden A.-M.
        • Schartau P.
        Reduced specificity of autobiographical memories following a negative mood induction.
        Behav Res Ther. 2006; 44: 1481-1490
        • Seibert P.S.
        • Ellis H.C.
        A convenient self-referencing mood induction procedure.
        Bull Psychon Soc. 1991; 29: 121-124
        • Price D.D.
        • McGrath P.A.
        • Rafii A.
        • Buckingham B.
        The validation of visual analogue scales as ratio scale measures for chronic and experimental pain.
        Pain. 1983; 17: 45-56
        • Beckmann C.F.
        • Jenkinson M.
        • Smith S.M.
        General multilevel linear modeling for group analysis in fMRI.
        Neuroimage. 2003; 20: 1052-1063
        • Phan K.L.
        • Wager T.
        • Taylor S.F.
        • Liberzon I.
        Functional neuroanatomy of emotion: A meta-analysis of emotion activation studies in PET and fMRI.
        Neuroimage. 2002; 16: 331-348
        • Rhudy J.L.
        • Williams A.E.
        • McCabe K.M.
        • Russell J.L.
        • Maynard L.J.
        Emotional control of nociceptive reactions (ECON): Do affective valence and arousal play a role?.
        Pain. 2008; 136: 250-261
        • Vlaeyen J.W.S.
        • Linton S.J.
        Fear-avoidance and its consequences in chronic musculoskeletal pain: A state of the art.
        Pain. 2000; 85: 317-332
        • Nolen-Hoeksema S.
        The role of rumination in depressive disorders and mixed anxiety/depressive symptoms.
        J Abnorm Psychol. 2000; 109: 504-511
        • Eccleston C.
        • Crombez G.
        Worry and chronic pain: A misdirected problem solving model.
        Pain. 2007; 132: 233-236
        • Tracey I.
        • Mantyh P.W.
        The cerebral signature for pain perception and its modulation.
        Neuron. 2007; 55: 377-391
        • Mayberg H.S.
        • Liotti M.
        • Brannan S.K.
        • McGinnis S.
        • Mahurin R.K.
        • Jerabek P.A.
        • et al.
        Reciprocal limbic-cortical function and negative mood: Converging PET findings in depression and normal sadness.
        Am J Psychiatry. 1999; 156: 675-682
        • Bingel U.
        • Schoell E.
        • Herken W.
        • Buchel C.
        • May A.
        Habituation to painful stimulation involves the antinociceptive system.
        Pain. 2007; 131: 21-30
        • Vogt B.A.
        Pain and emotion interactions in subregions of the cingulate gyrus.
        Nat Rev Neurosci. 2005; 6: 533-544
        • Ploghaus A.
        • Narain C.
        • Beckmann C.F.
        • Clare S.
        • Bantick S.
        • Wise R.
        • et al.
        Exacerbation of pain by anxiety is associated with activity in a hippocampal network.
        J Neurosci. 2001; 21: 9896-9903
        • Kong J.
        • Gollub R.L.
        • Polich G.
        • Kirsch I.
        • Laviolette P.
        • Vangel M.
        • et al.
        A functional magnetic resonance imaging study on the neural mechanisms of hyperalgesic nocebo effect.
        J Neurosci. 2008; 28: 13354-13362
        • Johansen-Berg H.
        • Gutman D.A.
        • Behrens T.E.J.
        • Matthews P.M.
        • Rushworth M.F.S.
        • Katz E.
        • et al.
        Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression.
        Cereb Cortex. 2008; 18: 1374-1383
        • Seminowicz D.A.
        • Mayberg H.S.
        • McIntosh A.R.
        • Goldapple K.
        • Kennedy S.
        • Segal Z.
        • et al.
        Limbic-frontal circuitry in major depression: A path modeling metanalysis.
        Neuroimage. 2004; 22: 409-418
        • Tucker D.M.
        • Luu P.
        • Pribram K.H.
        Social and emotional self-regulationa.
        Ann N Y Acad Sci. 1995; 769: 213-240
        • Phillips M.L.
        • Ladouceur C.D.
        • Drevets W.C.
        A neural model of voluntary and automatic emotion regulation: Implications for understanding the pathophysiology and neurodevelopment of bipolar disorder.
        Mol Psychiatry. 2008; 13: 833-857
        • Kalisch R.
        • Wiech K.
        • Critchley H.D.
        • Seymour B.
        • O'Doherty J.P.
        • Oakley D.A.
        • et al.
        Anxiety reduction through detachment: Subjective, physiological, and neural effects.
        J Cogn Neurosci. 2005; 17: 874
        • Wiech K.
        • Kalisch R.
        • Weiskopf N.
        • Pleger B.
        • Stephan K.E.
        • Dolan R.J.
        Anterolateral prefrontal cortex mediates the analgesic effect of expected and perceived control over pain.
        J Neurosci. 2006; 26: 11501-11509
        • Dolcos F.
        • McCarthy G.
        Brain systems mediating cognitive interference by emotional distraction.
        J Neurosci. 2006; 26: 2072-2079
        • Wager T.D.
        • Davidson M.L.
        • Hughes B.L.
        • Lindquist M.A.
        • Ochsner K.N.
        Prefrontal-subcortical pathways mediating successful emotion regulation.
        Neuron. 2008; 59: 1037-1050
        • Ochsner K.N.
        • Ray R.D.
        • Cooper J.C.
        • Robertson E.R.
        • Chopra S.
        • Gabrieli J.D.E.
        • et al.
        For better or for worse: Neural systems supporting the cognitive down- and up-regulation of negative emotion.
        Neuroimage. 2004; 23: 483-499
        • Phan K.L.
        • Fitzgerald D.A.
        • Nathan P.J.
        • Moore G.J.
        • Uhde T.W.
        • Tancer M.E.
        Neural substrates for voluntary suppression of negative affect: A functional magnetic resonance imaging study.
        Biol Psychiatry. 2005; 57: 210-219
        • Villemure C.
        • Bushnell M.C.
        Mood influences supraspinal pain processing separately from attention.
        J Neurosci. 2009; 29: 705-715
        • Wager T.D.
        • Phan K.L.
        • Liberzon I.
        • Taylor S.F.
        Valence, gender, and lateralization of functional brain anatomy in emotion: A meta-analysis of findings from neuroimaging.
        Neuroimage. 2003; 19: 513-531
        • Mazoyer B.
        • Zago L.
        • Mellet E.
        • Bricogne S.
        • Etard O.
        • Houdé O.
        • et al.
        Cortical networks for working memory and executive functions sustain the conscious resting state in man.
        Brain Res Bull. 2001; 54: 287-298
        • McKiernan K.A.
        • Kaufman J.N.
        • Kucera-Thompson J.
        • Binder J.R.
        A parametric manipulation of factors affecting task-induced deactivation in functional neuroimaging.
        J Cogn Neurosci. 2003; 15: 394-408
        • Shulman G.L.
        • Fiez J.A.
        • Corbetta M.
        • Buckner R.L.
        • Miezin F.M.
        • Raichle M.E.
        • et al.
        Common blood flow changes across visual tasks.
        J Cogn Neurosci. 1997; 9: 648-663
        • Harrison B.J.
        • Pujol J.
        • Ortiz H.
        • Fornito A.
        • Pantelis C.
        • Yucel M.
        Modulation of brain resting-state networks by sad mood induction.
        PLoS ONE. 2008; 3: e1794
        • Wegner D.M.
        • Erber R.
        • Zanakos S.
        Ironic processes in the mental control of mood and mood-related thought.
        J Pers Soc Psychol. 1993; 65: 1093-1104