Increased amygdala responses to sad but not fearful faces in major depression: relation to mood state and pharmacological treatment
Abstract
OBJECTIVE: Increased amygdala response to negative emotions seen in functional MRI (fMRI) has been proposed as a biomarker for negative emotion processing bias underlying depressive symptoms and vulnerability to depressive relapse that are normalized by antidepressant drug treatment. The purpose of this study was to determine whether abnormal amygdala responses to face emotions in depression are related to specific emotions or change in response to antidepressant treatment and whether they are present as a stable trait in medication-free patients in remission. METHOD: Sixty-two medication-free unipolar depressed patients (38 were currently depressed, and 24 were in remission) and 54 healthy comparison subjects underwent an indirect face-emotion processing task during fMRI. Thirty-two currently depressed patients were treated with the antidepressant citalopram for 8 weeks. Adherence to treatment was evaluated by measuring citalopram plasma concentrations. RESULTS: Patients with current depression had increased bilateral amygdala responses specific to sad faces relative to healthy comparison subjects and nonmedicated patients in stable remission. Treatment with citalopram abolished the abnormal amygdala responses to sad faces in currently depressed patients but did not alter responses to fearful faces. CONCLUSIONS: Aberrant amygdala activation in response to sad facial emotions is specific to the depressed state and is a potential biomarker for a negative affective bias during a depressive episode.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Enhanced responsiveness to negative emotions, mediated by enhanced amygdala response, has been observed in non-parent depression.
“Notably, enhanced responsiveness to negative emotions, (mediated by enhanced amygdala response), has been observed in non-parent depression (Arnone et al., 2012).”
From Approaching the biology of human parental attachment: Brain imaging, oxytocin and coordinated assessments of mothers and fathers (2014) · cites this paper as Arnone et al., 2012
Cited by
Sorted by citations
Examining emotion regulation in depression: A review and future directions
Joormann, J., & Stanton, C. H. (2016) · Behaviour Research and Therapy · doi:10.1016/j.brat.2016.07.007 · Cited by 749 · see citing works
Serotonin and brain function: a tale of two receptors
Carhart-Harris, R., & Nutt, D. (2017) · Journal of Psychopharmacology · doi:10.1177/0269881117725915 · Cited by 739 · see citing works
“5-HT availability (e.g. through chronic selective serotonin reuptake inhibitors (SSRIs)) but postsynaptic 5-HT1ARs do not (Lanfumey and Hamon, 2000), although they do appear to downregulate in response to stress (Berton et al., 1998; Lopez et al., 1999) – and perhaps relatedly, to electroconvulsive shock (Burnet et al…”
BackgroundInfluentialPrecision psychiatry: a neural circuit taxonomy for depression and anxiety
Williams, L. M. (2016) · The Lancet Psychiatry · doi:10.1016/s2215-0366(15)00579-9 · Cited by 641 · see citing works
Cognitive function following a major depressive episode: a systematic review and meta-analysis
Semkovska, M., Quinlivan, L., O'Grady, T., Johnson, R., Collins, A., O'Connor, J., Knittle, H., Ahern, E., & Gload, T. (2019) · The Lancet Psychiatry · doi:10.1016/s2215-0366(19)30291-3 · Cited by 631 · see citing works
Rive, M. M., van Rooijen, G., Veltman, D. J., .Phillips, M. L., Schene, A. H., & Ruhé, H. G. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.07.018 · Cited by 481 · see citing works
“Nevertheless, medication is thought to diminish amygdala activity during passive exposure as well as during regulation of negative emotional stimuli (Anand et al., 2007; Arce et al., 2008; Arnone et al., 2012; de Almeida et al., 2010; Fu et al., 2004; Godlewska et al., 2012; Harmer et al., 2006; Sheline et al., 2001;…”
BackgroundEstrogen, Stress, and Depression: Cognitive and Biological Interactions
Albert, K. M., & NEWHOUSE, P. A. (2019) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-050718-095557 · Cited by 355 · see citing works
Wise, T., Raduà, J., Nortje, G., Cleare, A. J., Young, A. H., & Arnone, D. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.03.004 · Cited by 304 · see citing works
“Nevertheless further research investigating the contribution of mood state to neuroimaging findings is warranted as there is very little data available in the literature (46,47).”
BackgroundSelf-citationWilliams, L. M. (2016) · Depression and Anxiety · doi:10.1002/da.22556 · Cited by 290 · see citing works
“In addition to the findings for threat, MDD has also beenassociatedwithmood-congruent hyperreactivity of the amygdala evoked by sad faces (Arnone et al., 2012; Fu et al., 2004; Victor et al., 2010).”
BackgroundSwain, J. E., Kim, P., Spicer, J., Ho, S. S., Dayton, C. J., Elmadih, A., & Abel, K. M. (2014) · Brain Research · doi:10.1016/j.brainres.2014.03.007 · Cited by 290 · see citing works
“Notably, enhanced responsiveness to negative emotions, (mediated by enhanced amygdala response), has been observed in non-parent depression (Arnone et al., 2012).”
State-dependent changes in hippocampal grey matter in depression
Arnone, D., McKie, S., Elliott, R., Juhasz, G., Thomas, E. J., Downey, D., Williams, S., Deakin, J. F. W., & Anderson, I. M. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.150 · Cited by 287 · see citing works
Self-citationPhillips, M. L., Chase, H. W., Sheline, Y. I., Etkin, A., Almeida, J. R. C., Deckersbach, T., & Trivedi, M. H. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.14010076 · Cited by 267 · see citing works
Neuropsychological mechanism underlying antidepressant effect: a systematic meta-analysis
Ma, Y. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.24 · Cited by 270 · see citing works
Williams, L. M., Korgaonkar, M. S., Song, Y. C., Paton, R., Eagles, S., Goldstein-Piekarski, A., Grieve, S. M., Harris, A. W. F., Usherwood, T., & Etkin, A. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.89 · Cited by 195 · see citing works
“This suggestion is consistent with previous evidence that amygdala activation for subliminal sadness in MDD changes following treatment (Victor et al, 2010; Arnone et al, 2012).”
BackgroundMethodResultInfluentialComputational meta‐analysis of statistical parametric maps in major depression
Arnone, D., Job, D. E., Selvaraj, S., Abe, O., Amico, F., Cheng, Y., Colloby, S. J., O'Brien, J. T., Frodl, T., Gotlib, I. H., et al. (2016) · Human Brain Mapping · doi:10.1002/hbm.23108 · Cited by 184 · see citing works
“Our finding of grey matter loss in hippocampus and parahippocampal gyrus is consistent with Du et al.’s [2012] results and represents the most frequently replicated morphometric abnormality in major depression [Arnone et al., 2012a; Koolschijn et al., 2009; Schmaal et al., 2015].”
BackgroundMethodResultInfluentialSelf-citationConnolly, C. G., Ho, T. C., Blom, E. H., LeWinn, K. Z., Sacchet, M. D., Tymofiyeva, O., Simmons, A. N., & Yang, T. T. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.09.026 · Cited by 177 · see citing works
“…activation to emotional stimuli has also been associated with successful pharmacological and psychotherapeutic interventions for depression in both adults (Arnone et al., 2012; Fu et al., 2008; Godlewska et al., 2012; Sheline et al., 2001) and adolescents (Straub et al., 2015; Tao et al., 2012).”
BackgroundNeuropsychiatric syndromes of multiple sclerosis
Murphy, R., O’Donoghue, S., Counihan, T. J., McDonald, C., Calabresi, P. A., Ahmed, M. A., Kaplin, A. I., & Hallahan, B. P. (2017) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2016-315367 · Cited by 170 · see citing works
Insomnia Disorder is Associated with Increased Amygdala Reactivity to Insomnia-Related Stimuli
Baglioni, C., Spiegelhalder, K., Regen, W., Feige, B., Nissen, C., Lombardo, C., Violani, C., Hennig, J., & Riemann, D. W. (2014) · SLEEP · doi:10.5665/sleep.4240 · Cited by 175 · see citing works
Neuronal connectivity in major depressive disorder: a systematic review
Helm, K., Viol, K., Weiger, T. M., Tass, P. A., Grefkes, C., del Monte, D., & Schiepek, G. (2018) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s170989 · Cited by 164 · see citing works
Diffusion tensor imaging predictors of treatment outcomes in major depressive disorder
Korgaonkar, M. S., Williams, L. M., Song, Y. J. C., Usherwood, T. P., & Grieve, S. M. (2014) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.113.140376 · Cited by 145 · see citing works
Jung, J., Kang, J. C., Won, E., Nam, K., Lee, M.-S., Tae, W., & Ham, B. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.08.018 · Cited by 133 · see citing works
“The pathology of MDD is still unclear but it has been agreed that a distributed brain network involved in mood regulation is structurally and functionally impaired by MDD (Mayberg, 1997; Drevets et al., 2007, 2008; Arnone et al., 2012a; Lai and Wu, 2014).”
BackgroundJust, S., Chenard, B. L., Ceci, A., Strassmaier, T., Chong, J. A., Blair, N. T., Gallaschun, R. J., del Camino, D., Cantin, S., D’Amours, M., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0191225 · Cited by 135 · see citing works
In Search of Neural Endophenotypes of Postpartum Psychopathology and Disrupted Maternal Caregiving
Moses‐Kolko, E. L., Horner, M. S., Phillips, M. L., Hipwell, A. E., & Swain, J. E. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12183 · Cited by 129 · see citing works
Sankar, A., Melin, A., Lorenzetti, V., Horton, P., Costafreda, S. G., & Fu, C. H. Y. (2018) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2018.07.002 · Cited by 114 · see citing works
Redlich, R., Opel, N., Bürger, C., Dohm, K., Grotegerd, D., Förster, K., Zaremba, D., Meinert, S. L., Repple, J., Enneking, V., et al. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.246 · Cited by 111 · see citing works
Biomarkers for major depressive disorder
Hacımusalar, Y., & Eşel, E. (2017) · Nöro Psikiyatri Arşivi · doi:10.5152/npa.2017.19482 · Cited by 120 · see citing works
Schulze, L., Schulze, A., Renneberg, B., Schmahl, C., & Niedtfeld, I. (2019) · Biological Psychiatry: Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2018.11.004 · Cited by 102 · see citing works
Diagnostic and therapeutic utility of neuroimaging in depression: an overview
Arnone, D., Wise, T., Cleare, A. J., Young, A. H., & Herane-Vives, A. (2014) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s50156 · Cited by 104 · see citing works
“Amygdala hyperactivity in response to negative emotions has been demonstrated to be characteristic of a depressed state and is sensitive to clinical improvement after a course of antidepressant treatment.(46) These findings suggest that structural and functional neuroimaging could contribute to the prediction of treat…”
Self-citationAn affective neuroscience model of boosting resilience in adults
Tabibnia, G. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.05.005 · Cited by 109 · see citing works
Functional MRI findings, pharmacological treatment in major depression and clinical response
Arnone, D. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.08.004 · Cited by 98 · see citing works
Self-citationZisner, A. R., & Beauchaine, T. P. (2016) · Development and Psychopathology · doi:10.1017/s0954579416000754 · Cited by 92 · see citing works
An fMRI study of emotional face processing in adolescent major depression
Hall, L. M. J., Klimes‐Dougan, B., Hunt, R. H., Thomas, K. M., Houri, A. K., Noack, E., Mueller, B. A., Lim, K. O., & Cullen, K. R. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.06.037 · Cited by 87 · see citing works
Hastings, P. D., Klimes-Dougan, B., Kendziora, K. T., Brand, A., & Zahn-Waxler, C. (2014) · Development and Psychopathology · doi:10.1017/s0954579414001084 · Cited by 87 · see citing works
“It was intriguing that a recent neuroimaging study revealed that unipolar depressed patients showed elevated bilateral amygdala response to sad faces but not fearful faces (Arnone et al., 2012), which also suggests that depression is characterized by strong neurobiological arousal specifically by sad stimuli.”
BackgroundFunctional MRI in major depressive disorder: A review of findings, limitations, and future prospects
Pilmeyer, J., Huijbers, W., Lamerichs, R. M. J. N., Jansen, J. F. A., Breeuwer, M. M., & Zinger, S. (2022) · Journal of Neuroimaging · doi:10.1111/jon.13011 · Cited by 94 · see citing works
Fu, C. H. Y., Costafreda, S. G., Sankar, A., Adams, T. M., Rasenick, M. M., Liu, P., Donati, R. J., Maglanoc, L. A., Horton, P., & Marangell, L. B. (2015) · BMC Psychiatry · doi:10.1186/s12888-015-0457-2 · Cited by 82 · see citing works
“Furthermore, most studies to date have examined the effects of the SRI class of antidepressants [3-5,34].”
BackgroundResultWang, L., Zhao, Y., Edmiston, E. K., Womer, F. Y., Zhang, R., Zhao, P., Jiang, X., Wu, F., Kong, L., Zhou, Y., et al. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00923 · Cited by 81 · see citing works
A two-factor model of relapse/recurrence vulnerability in unipolar depression
Farb, N. A. S., Irving, J. A., Anderson, A. K., & Segal, Z. V. (2015) · Journal of Abnormal Psychology · doi:10.1037/abn0000031 · Cited by 75 · see citing works
Barraclough, M. L., McKie, S., Parker, B., Jackson, A., Pemberton, P. W., Elliott, R., & Bruce, I. N. (2019) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2018-214677 · Cited by 77 · see citing works
Self-citationZhang, M., Zhou, H., Liu, L., Feng, L., Yang, J., Wang, G., & Zhong, N. (2018) · Clinical Neurophysiology · doi:10.1016/j.clinph.2018.01.017 · Cited by 75 · see citing works
Default mode network deactivation during emotion processing predicts early antidepressant response
Spies, M., Kraus, C., Geissberger, N., Auer, B., Klöbl, M., Tik, M., Stürkat, I.-L., Hahn, A., Woletz, M., Pfabigan, D. M., et al. (2017) · Translational Psychiatry · doi:10.1038/tp.2016.265 · Cited by 68 · see citing works
Wessa, M., & Lois, G. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666150416224801 · Cited by 67 · see citing works
“[24] n =32 MDD n=15 CON open-label study, longitudinal design MADRS=27 (4.”
BackgroundThe neuroscience of depression: Implications for assessment and intervention
Singh, M. K., & Gotlib, I. H. (2014) · Behaviour Research and Therapy · doi:10.1016/j.brat.2014.08.008 · Cited by 70 · see citing works
“Other studies suggest that aberrant amygdala activation in response to sad faces (Arnone et al., 2012) and memory formation and retrieval (van Wingen et al., 2010) are specific to the depressed state and are responsive to treatment.”
Outhred, T., Hawkshead, B. E., Wager, T. D., Das, P., Malhi, G. S., & Kemp, A. H. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.07.010 · Cited by 67 · see citing works
Deficits of unconscious emotional processing in patients with major depression: An ERP study
Zhang, D., He, Z., Chen, Y., & Wei, Z. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.03.056 · Cited by 65 · see citing works
Social-economical decision making in current and remitted major depression
Pulcu, E., Thomas, E. J., Trotter, P. D., McFarquhar, M., Juhasz, G., Sahakian, B. J., Deakin, J. F. W., Anderson, I. M., Zahn, R., & Elliott, R. (2015) · Psychological Medicine · doi:10.1017/s0033291714002414 · Cited by 62 · see citing works
“It is notable that combining UG offers with emotive pictures of proposers in studies of depressed individuals may be further complicated by differences in facial emotion recognition in MDD (Anderson et al. 2011; Arnone et al. 2012).”
BackgroundSelf-citationGünther, V., Dannlowski, U., Kersting, A., & Suslow, T. (2015) · BMC Psychiatry · doi:10.1186/s12888-015-0501-2 · Cited by 65 · see citing works
“Studies using neuroimaging techniques revealed a hyper-responsiveness of the amygdala to negative stimuli in patients suffering from MDD [27–31].”
MethodWeightman, M. J., Knight, M. J., & Baune, B. T. (2019) · Psychiatry Research · doi:10.1016/j.psychres.2019.02.035 · Cited by 65 · see citing works
“, 2004), citalopram (Arnone et al., 2012), sertraline (Victor et al.”
Modulation of amygdala reactivity following rapidly acting interventions for major depression
Loureiro, J. R., Leaver, A. M., Vasavada, M. M., Sahib, A. K., Kubicki, A., Joshi, S. H., Woods, R. P., Wade, B., Congdon, E. L., Espinoza, R. T., et al. (2020) · Human Brain Mapping · doi:10.1002/hbm.24895 · Cited by 63 · see citing works
Wei, S., Chang, M., Zhang, R., Jiang, X., Wang, F., & Tang, Y. (2018) · Annals of General Psychiatry · doi:10.1186/s12991-018-0208-0 · Cited by 63 · see citing works
Seymour, K. E., Jones, R. N., Cushman, G. K., Galvan, T., Puzia, M., Kim, K. L., Spirito, A., & Dickstein, D. P. (2015) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-015-0733-1 · Cited by 59 · see citing works
Chen, J., Ma, W., Zhang, Y., Wu, X., Wei, D., Liu, G., Deng, Z., Yang, L.-Q., & Zhang, Z. (2014) · PLoS ONE · doi:10.1371/journal.pone.0109176 · Cited by 58 · see citing works
“Several neuroimaging studies have also indicated that reduced amygdala activation in response to positive stimuli in depression may be linked to anhedonic symptoms caused by inappropriate salience attribution to positive information [48,49].”
BackgroundIncreased amygdala response to shame in remitted major depressive disorder
Pulcu, E., Lythe, K., Elliott, R., Green, S., Moll, J., Deakin, J. F. W., & Zahn, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086900 · Cited by 57 · see citing works
Self-citationMRI predictors of pharmacotherapy response in major depressive disorder
Gerlach, A. R., Karim, H. T., Peciña, M., Ajilore, O., Taylor, W. D., Butters, M. A., & Andreescu, C. (2022) · NeuroImage: Clinical · doi:10.1016/j.nicl.2022.103157 · Cited by 57 · see citing works
“…regardless of clinical outcome (Victor et al., 2010), similarly outcome-agnostic decreases in amygdala activation to sad but not fearful faces (Arnone, 2012), increases in amygdala activation to subliminal happy and threatening faces for responders and decreases in amygdala activation to…”
BackgroundNeural correlates of successful psychotherapy of depression in adolescents
Straub, J., Plener, P. L., Sproeber, N., Sprenger, L., Kölch, M. G., Groen, G., & Abler, B. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.05.020 · Cited by 56 · see citing works
Nikolova, Y. S., Misquitta, K. A., Rocco, B. R., Prévot, T. D., Knodt, A. R., Ellegood, J., Voineskos, A. N., Lerch, J. P., Hariri, A. R., Sibille, E. L., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-017-0083-5 · Cited by 51 · see citing works
Social cognition in major depressive disorder: A new paradigm?
Billeke, P. B., Boardman, S., & Doraiswamy, P. M. (2013) · Translational Neuroscience · doi:10.2478/s13380-013-0147-9 · Cited by 52 · see citing works
An, J., Wang, L., Li, K., Zeng, Y., Su, Y., Jin, Z., Yu, X., & Si, T. (2017) · Scientific Reports · doi:10.1038/s41598-017-10575-9 · Cited by 48 · see citing works
Diagnostic and clinical implications of functional neuroimaging in bipolar disorder
Brooks, J. O., & Vizueta, N. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.05.018 · Cited by 45 · see citing works
Ehrlich, D., Neigh, G. N., Bourke, C. H., Nemeth, C. L., Hazra, R., Ryan, S. J., Rowson, S. A., Jairam, N., Sholar, C. R., Rainnie, D. G., et al. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.05.012 · Cited by 47 · see citing works
“Given that escitalopram may help treat depression via regulation of serotonergic transmission in the amygdala (Arnone et al., 2012; Bigos et al., 2008; Lanzenberger et al., 2012; Rosenblau et al., 2012), we also measured offspring expression of two amygdala serotonin receptors linked to the treatment of depression, 5-…”
BackgroundMethodWilliams, L. M., Goldstein‐Piekarski, A. N., Chowdhry, N., Grisanzio, K. A., Haug, N. A., Samara, Z., Etkin, A., O'Hara, R. M., Schatzberg, A. F., Suppes, T. M., et al. (2016) · BMC Psychiatry · doi:10.1186/s12888-016-0771-3 · Cited by 45 · see citing works
“who go on to respond to typical first-line antidepressants [27, 29].”
BackgroundWhite Matter Indices of Medication Response in Major Depression: A Diffusion Tensor Imaging Study
Davis, A. D., Hassel, S., Arnott, S. R., Harris, J. K., Lam, R. W. M., Milev, R. V., Rotzinger, S., Zamyadi, M., Frey, B. N., Minuzzi, L., et al. (2019) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2019.05.016 · Cited by 46 · see citing works
Grieve, S. M., Korgaonkar, M. S., Etkin, A., Harris, A., Koslow, S. H., Wisniewski, S., Schatzberg, A. F., Nemeroff, C. B., Gordon, E., & Williams, L. M. (2013) · Trials · doi:10.1186/1745-6215-14-224 · Cited by 44 · see citing works
“The rationale behind the use of three treatment arms in iSPOT-D is to identify what are the unique and common brain circuits that modulate response and remission to different types of anti-depressant medications, that is, selective serotonin reuptake inhibitors (SSRIs) versus selective norepinephrine reuptake inhibito…”
BackgroundImaging predictors of remission to anti-depressant medications in major depressive disorder
Kee, F., Korgaonkar, M. S., & Grieve, S. M. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.07.002 · Cited by 43 · see citing works
Kleyn, C. E., Talbot, P. S., Mehta, N. N., Sampogna, F., Bundy, C., Ashcroft, D. M., Kimball, A. B., Kerkhof, P., Griffiths, C. E. M., Valenzuela, F., et al. (2019) · Acta Dermato Venereologica · doi:10.2340/00015555-3375 · Cited by 46 · see citing works
“Functional magnetic resonance imaging (fMRI) shows the amygdala is overly active in people with MDD when shown sad stimuli, but under-active when shown positive stimuli (18), suggesting a neural basis for the negative cognitive bias in MDD which is the therapeutic target of cognitive behavioural therapy.”
BackgroundZhang, R., Zhang, L., Wei, S., Wang, P., Jiang, X., Tang, Y., & Wang, F. (2021) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2020.585664 · Cited by 40 · see citing works
“A recent fMRI study also indicated that suicide attempters exhibited higher brain activity in multiple regions, including the right inferior parietal lobe and left precuneus (Cao et al., 2015).”
BackgroundInfluentialJenkins, L. M., Kendall, A. D., Kassel, M. T., Patrón, V. G., Gowins, J. R., Dion, C., Shankman, S. A., Weisenbach, S. L., Maki, P. M., & Langenecker, S. A. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.08.027 · Cited by 37 · see citing works
“Notably, other studies have shown that amygdala hyperactivation normalizes with antidepressant treatment (Arnone et al., 2012; Sheline et al., 2001).”
BackgroundFu, C. H. Y., Yong Fan, A., & Davatzikos, C. A. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.101997 · Cited by 39 · see citing works
“, 2008b) as well as treatment with a selective serotonin reuptake inhibitor antidepressant (Fu et al., 2004; Arnone et al., 2012) has been associated with nor-”
Depressogenic Thinking and Shame Proneness in the Development of Internalizing Problems
Mills, R. S. L., Hastings, P. D., Serbin, L. A., Stack, D. M., Abela, J. R. Z., Arbeau, K. A., & Lall, D. I. K. (2013) · Child Psychiatry & Human Development · doi:10.1007/s10578-013-0416-4 · Cited by 36 · see citing works
“For example, there is recent neurobiological evidence that depression involves an affective bias specifically involving sadness, as seen in unipolar depressed patients’ elevated bilateral amygdala response to sad faces, but not fearful faces [13].”
BackgroundNeuroimaging for precision medicine in psychiatry
Williams, L. M., & Whitfield, S. (2024) · Neuropsychopharmacology · doi:10.1038/s41386-024-01917-z · Cited by 39 · see citing works
Wu, X., Chen, J., Jia, T., Ma, W., Zhang, Y., Deng, Z., & Yang, L.-Q. (2015) · Brain Topography · doi:10.1007/s10548-015-0444-4 · Cited by 33 · see citing works
“Furthermore, evidence from neuroimaging studies in depression have also demonstrated that decreased amygdala activation in response to positive stimuli may be associated with anhedonic symptoms caused by inappropriate salience attribution to positive information (Arnone et al. 2012; Stuhrmann et al. 2013).”
BackgroundTassone, V. K., Demchenko, I., Salvo, J. J., Mahmood, R., Passa, A.-M. D., Kuburi, S., Rueda, A., & Bhat, V. (2022) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2022.111517 · Cited by 33 · see citing works
Lemke, H., Probst, S., Warneke, A., Waltemate, L., Winter, A., Thiel, K., Meinert, S. L., Enneking, V., Breuer, F., Klug, M., et al. (2021) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2021.05.008 · Cited by 30 · see citing works
Flournoy, J. C., Bryce, N. V., Dennison, M., Rodman, A. M., McNeilly, E. A., Lurie, L. A., Bitrán, D., Reid-Russell, A., Bustamante, C. M. V., Madhyastha, T. M., et al. (2023) · NeuroImage · doi:10.1016/j.neuroimage.2023.120503 · Cited by 30 · see citing works
“…each fluctuate dynamically within individuals over time and have been associated with neural responses to aversive cues in between-person studies (Arnone et al., 2012; Goldstein-Piekarski et al., 2015; Larson and Ham, 1993; Mroczek and Almeida, 2004; Sliwinski et al., 2009; Swartz et al., 2015b,…”
Neuronal Circuits for Social Decision-Making and Their Clinical Implications
Báez-Mendoza, R., Vázquez, Y., Mastrobattista, E. P., & Williams, Z. M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.720294 · Cited by 32 · see citing works
Albert, K. M., Gau, V., Taylor, W. D., & NEWHOUSE, P. A. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.12.010 · Cited by 31 · see citing works
Studies on the animal model of post-stroke depression and application of antipsychotic aripiprazole
Kim, Y. R., Kim, H. N., Pak, M. E., Ahn, S., Hong, K. H., Shin, H. K., & Choi, B. T. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.03.062 · Cited by 30 · see citing works
Zhang, Z., Huang, P., Li, S., Liu, Z., Zhang, J., Li, Y., & Liu, Z. (2022) · Psychiatry Research · doi:10.1016/j.psychres.2022.114598 · Cited by 30 · see citing works
Szczepanik, J. E., Nugent, A. C., Drevets, W. C., Khanna, A., Zarate, C. A., & Furey, M. L. (2016) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2016.06.005 · Cited by 30 · see citing works
Scopolamine and Depression: A Role for Muscarinic Antagonism?
Hasselmann, H. (2014) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527313666140618105710 · Cited by 28 · see citing works
Brain mechanisms underlying the emotion processing bias in treatment-resistant depression
Fan, X., Mocchi, M. M., Pascuzzi, B., Xiao, J., Metzger, B. A., Mathura, R. K., Hacker, C. D., Adkinson, J. A., Bartoli, E., Elhassa, S., et al. (2024) · Nature Mental Health · doi:10.1038/s44220-024-00238-w · Cited by 27 · see citing works
“The biased processing of emotional stimuli in depression has been linked to dysfunction in the amygdala 8,9 , the prefrontal cortex (PFC) 10,11 , the dorsal anterior cingulate 12,13 and their connections 14,15 .”
Tassone, V. K., Nezhad, F. G., Demchenko, I., Rueda, A., & Bhat, V. (2024) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2023.111777 · Cited by 28 · see citing works
Horáček, J., Mikoláš, P., Tintěra, J., Novák, T., Páleníček, T., Brunovský, M., Höschl, C., & Alda, M. (2015) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.140044 · Cited by 27 · see citing works
Neural origins of psychosocial functioning impairments in major depression
Pulcu, E., & Elliott, R. (2015) · The Lancet Psychiatry · doi:10.1016/s2215-0366(15)00237-0 · Cited by 27 · see citing works
Self-citationDecision-Making Dysfunctions of Counterfactuals in Depression: Who Might I have Been?
Howlett, J. R., & Paulus, M. P. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00143 · Cited by 27 · see citing works
TOMM40 rs2075650 May Represent a New Candidate Gene for Vulnerability to Major Depressive Disorder
McFarquhar, M., Elliott, R., McKie, S., Thomas, E., Downey, D., Mekli, K., Toth, Z. G., Anderson, I. M., Deakin, J. F. W., & Juhász, G. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.22 · Cited by 26 · see citing works
Self-citationLuo, L., Becker, B., Zheng, X., Zhao, Z., Xu, X., Zhou, F., Wang, J., Kou, J., Dai, J., & Kendrick, K. M. (2017) · Human Brain Mapping · doi:10.1002/hbm.23880 · Cited by 24 · see citing works
“Most previous patient-based studies showed an opposite pattern, suggesting that MDD patients are more sensitive to sad faces (Arnone et al., 2012; Surguladze et al., 2005) while SAD patients are more sensitive to fearful faces (Frick, Howner, Fischer, Kristiansson, & Furmark, 2013; Killgore and Yurgelun-Todd, 2005).”
ResultChen, Y.-T., Huang, M.-W., Hung, I.-C., Lane, H.-Y., & Hou, C.-J. (2014) · Behavioral and Brain Functions · doi:10.1186/1744-9081-10-36 · Cited by 24 · see citing works
“showed that aberrant amygdala activation in response to sad facial emotions was specific to the depressed state, making it a potential biomarker for negative affective bias during a depressive episode [30].”
BackgroundLucifora, C., Grasso, G. M., Nitsche, M. A., D'Italia, G., Sortino, M., Salehinejad, M. A., Falzone, A., Avenanti, A., & Vicario, C. M. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.05.033 · Cited by 26 · see citing works
Wei, S., Womer, F. Y., Geng, H., Jiang, X., Zhou, Q., Chang, M., Zhou, Y., Tang, Y., & Wang, F. (2017) · Scientific Reports · doi:10.1038/srep44316 · Cited by 24 · see citing works
Atkinson, L. Z., Sankar, A., Adams, T. M., & Fu, C. H. Y. (2014) · Current Treatment Options in Psychiatry · doi:10.1007/s40501-014-0022-5 · Cited by 22 · see citing works
Brain-derived neurotrophic factor association with amygdala response in major depressive disorder
Lorenzetti, V., Costafreda, S. G., Rimmer, R. M., Rasenick, M. M., Marangell, L. B., & Fu, C. H. Y. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.01.159 · Cited by 20 · see citing works
“Amygdala responsivity is a potential marker of depressive state which shows a demonstrated specificity to sad faces with increased activation during a current depressive episode that normalises following treatment (Fu et al., 2004; Arnone et al., 2012).”
BackgroundNeuroimaging in Psychiatric Pharmacogenetics Research: The Promise and Pitfalls
Falcone, M., Smith, R. M., Chenoweth, M. J., Bhattacharjee, A. K., Kelsoe, J. R., Tyndale, R. F., & Lerman, C. E. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.152 · Cited by 21 · see citing works
Neural mechanisms of expectancy-based placebo effects in antidepressant clinical trials
Zilcha-Mano, S., Wang, Z., Peterson, B. S., Wall, M. M., Chen, Y., Wager, T. D., Brown, P. J., Roose, S. P., & Rutherford, B. R. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2019.05.023 · Cited by 22 · see citing works
Changes in brain function during negative emotion processing in the long-term course of depression
Enneking, V., Klug, M., Borgers, T., Dohm, K., Grotegerd, D., Frankenberger, L. M., Hülsmann, C., Lemke, H., Meinert, S. L., Leehr, E. J., et al. (2022) · The British Journal of Psychiatry · doi:10.1192/bjp.2021.223 · Cited by 20 · see citing works
Fu, C. H. Y., Erus, G., Yong Fan, A., Antoniades, M., Arnone, D., Arnott, S. R., Chen, T., Choi, K. S., Fatt, C. C., Frey, B. N., et al. (2023) · BMC Psychiatry · doi:10.1186/s12888-022-04509-7 · Cited by 20 · see citing works
“Treatment protocol was an 8-week trial of SSRI, citalopram, with MRI scans acquired at baseline and week 8 in both MDD and healthy participants [54].”
MethodSelf-citationSpies, M., Klöbl, M., Höflich, A. S., Hummer, A., Vanicek, T., Michenthaler, P., Kranz, G. S., Hahn, A., Winkler, D., Windischberger, C., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-46702-x · Cited by 22 · see citing works
Ai, H., Opmeer, E. M., Marsman, J.-B. C., Veltman, D. J., van der Wee, N. J. A., Aleman, A., & van Tol, M. (2019) · Psychological Medicine · doi:10.1017/s0033291719001259 · Cited by 19 · see citing works
“At the same time, volumetric changes in the hippocampus have 305 been linked to symptomatic improvement following treatment (Arnone et al 2012a), suggesting state-dependency of 306 hippocampal volume.”
BackgroundGeller, W. N., Liu, K., & Warren, S. L. (2021) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2021.111349 · Cited by 18 · see citing works
Zeng, J., Wang, Z., Zhang, X., Zhao, A., Qi, H., Jiang, Y., Cai, D., & Zeng, N. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.156927 · Cited by 20 · see citing works
fMRI Response of Parietal Brain Areas to Sad Facial Stimuli in Mild Depression
Мельников, М. Е., Петровский, Е. Д., Bezmaternykh, D. D., Kozlova, L. I., Shtark, M. B., Savelov, A. A., Shubina, O. S., & Natarova, K. A. (2018) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-018-4255-y · Cited by 18 · see citing works
Ao, X., Mo, L., Wei, Z., Yu, W., Zhou, F., & Zhang, D. (2020) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2020.593010 · Cited by 18 · see citing works
“…are consistent with previous behavioral findings in depression (Gotlib et al., 1988; Mogg et al., 1991; Koster et al., 2005; Kellough et al., 2008; Atchley et al., 2012; for reviews see Peckham et al., 2010; Winer and Salem, 2016) but also restrict the attentional impairment within the P1 time…”
Result
- Authors
- Arnone, D., McKie, S., Elliott, R., Thomas, E. J., Downey, D., Juhasz, G., Williams, S. R., Deakin, J. F. W., & Anderson, I. M.
- Affiliations
- University of Manchester (GB)
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2012-08
- Volume
- 169
- Issue
- 8
- Pages
- 841-850
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2057953148
- Cited by
- 192
- References
- 0
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 13 · 2023: 3 · 2022: 11 · 2021: 34 · 2020: 9 · 2019: 15 · 2018: 15 · 2017: 12 · 2016: 14 · 2015: 20 · 2014: 19 · 2013: 11 · 2012: 3
- FWCI
- 22.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- major depressive disorder, amygdala, sad faces, fearful faces, citalopram, antidepressant treatment, remission, mood states, biomarkers, medication adherence
- MeSH terms
- Adult, Affect, Amygdala, Major Depressive Disorder, Depressive Disorder, Major, Facial Expression, Fear, Female, Humans, Magnetic Resonance Imaging, Male, Citalopram, Biomarkers, Case-Control Studies, Antidepressive Agents, Second-Generation, Functional Neuroimaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
