Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Neural mechanisms of the cognitive model of depression

Nature Reviews Neuroscience volume 12, pages 467–477 (2011)Cite this article

Subjects

Key Points

  • Beck's cognitive model of depression, which posits that depressive symptoms are generated and maintained by a combination of maladaptive cognitions, has been the predominant theory of depression dating back to its conception over 40 years ago.

  • According to the cognitive model, individuals with depression are prone to selectively attend to negative stimuli (biased attention), experience greater perception and awareness for negative stimuli (biased processing), ruminate excessively about depressive ideas (biased thought and rumination), recall depressive episodes with disproportionate frequency (biased memory) and to posses negative internal representations about the self the environment (dysfunctional attitudes and negative schemas).

  • Biased attention may stem from an inability to disengage attention from aversive stimuli, which correlates with decreased activation in the superior parietal lobe, ventrolateral prefrontal cortex (VLPFC) and dorsolateral prefrontal cortex (DLPFC). In addition, aberrant rostral anterior cingulate cortex (ACC) activity indicates that inhibition of negative items may be less efficient in individuals with depression.

  • Biased processing of emotional stimuli is associated with greater and more sustained amygdala reactivity, accompanied by left DLPFC hypoactivity and right DLPFC hyperactivity. Patients with depression also experience diminished positive affect and reward response, associated with decreased nucleus accumbens and prefrontal activity.

  • Biased thoughts and rumination, which are frequently self-referential, are associated with a functional network that includes hyperactivity in the amygdala, hippocampus, subgenual cingulate and medial prefrontal cortex (MPFC), as well as altered rostral ACC activity.

  • Biased memory is associated with amygdala hyperactivity, which is positively correlated with activity in the hippocampus, caudate and putamen. Differing levels of activation in the ventral MPFC during happy and sad self-referential memories support the idea that the depressed brain requires less cognitive effort to recall negative events.

  • Dysfunctional attitudes and negative schemas are associated with decreased connectivity between the dorsal ACC and the limbic system, which suggests impaired cognitive control. The degree of connectivity is negatively correlated with activity in the amygdala, MPFC, and rostral and ventral ACC, suggesting that attenuated regulation allows for a more salient experience of aversive situations.

  • In summary, maladaptive thoughts seem to be instigated and maintained by increased bottom-up reactivity (most notably in regions such as the amygdala, hippocampus, subgenual cingulate, and ventral and rostral ACC) combined with attenuated cognitive control as manifested by decreased top-down influence (most notably from areas such as the DLPFC, VLPFC and dorsal ACC) on these lower brain regions.

Abstract

In the 40 years since Aaron Beck first proposed his cognitive model of depression, the elements of this model — biased attention, biased processing, biased thoughts and rumination, biased memory, and dysfunctional attitudes and schemas — have been consistently linked with the onset and maintenance of depression. Although numerous studies have examined the neural mechanisms that underlie the cognitive aspects of depression, their findings have not been integrated with Beck's cognitive model. In this Review, we identify the functional and structural neurobiological architecture of Beck's cognitive model of depression. Although the mechanisms underlying each element of the model differ, in general the negative cognitive biases in depression are facilitated by increased influence from subcortical emotion processing regions combined with attenuated top-down cognitive control.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Information processing in the cognitive model of depression.
Figure 2: Putative cognitive neurobiological model of biased attention for negative stimuli in individuals with depression.
Figure 3: Putative cognitive neurobiological model of biased processing of negative stimuli in individuals with depression.
Figure 4: Putative cognitive neurobiological model of ruminative thought in individuals with depression.
Figure 5: Putative cognitive neurobiological model of biased memory for negative stimuli in individuals with depression.
Figure 6: Putative cognitive neurobiological model of self-referential schemas in individuals with depression.
Figure 7: Summary of an integrated cognitive neurobiological model of depression.

References

  1. Beck, A. T. Depression: Clinical, Experimental, and Theoretical Aspects. (Harper & Row, New York, 1967). This landmark book presented, for the first time, Beck's cognitive model of depression.

    Google Scholar 

  2. Dobson, K. S. A meta-analysis of the efficacy of cognitive therapy for depression. J. Consult. Clin. Psychol. 57, 414–419 (1989).

    Article  CAS  PubMed  Google Scholar 

  3. Beck, A. T. The evolution of the cognitive model of depression and its neurobiological correlates. Am. J. Psychiatry 165, 969–977 (2008).

    Article  PubMed  Google Scholar 

  4. Liotti, M. et al. Differential limbic–cortical correlates of sadness and anxiety in healthy subjects: implications for affective disorders. Biol. Psychiatry 48, 30–42 (2000).

    Article  CAS  PubMed  Google Scholar 

  5. Mayberg, H. S. Limbic-cortical dysregulation: a proposed model of depression. J. Neuropsychiatry Clin. Neurosci. 9, 471–481 (1997).

    Article  CAS  PubMed  Google Scholar 

  6. Mayberg, H. S. Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. Br. Med. Bull. 65, 193–207 (2003).

    Article  PubMed  Google Scholar 

  7. Phillips, M. L., Drevets, W. C., Rauch, S. L. & Lane, R. Neurobiology of emotion perception II: implications for major psychiatric disorders. Biol. Psychiatry 54, 515–528 (2003).

    Article  PubMed  Google Scholar 

  8. Phillips, M. L., Drevets, W. C., Rauch, S. L. & Lane, R. Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biol. Psychiatry 54, 504–514 (2003).

    Article  PubMed  Google Scholar 

  9. Insel, T. R. Translating scientific opportunity into public health impact: a strategic plan for research on mental illness. Arch. Gen. Psychiatry 66, 128–133 (2009).

    Article  PubMed  Google Scholar 

  10. Beck, A. T. Cognitive models of depression. J. Cogn. Psychother. 1, 5–37 (1987).

    Google Scholar 

  11. Clark, D. A., Beck, A. T. & Alford, B. A. Scientific Foundations of Cognitive Theory and Therapy of Depression. (John Wiley & Sons, New York, 1999).

    Google Scholar 

  12. Kellough, J. L., Beevers, C. G., Ellis, A. J. & Wells, T. T. Time course of selective attention in clinically depressed young adults: an eye tracking study. Behav. Res. Ther. 46, 1238–1243 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Beck, A. T. in Cognition and Psychotherapy. (eds Freeman, A., Mahoney, M. J., DeVito, P. & Martin, D.) 197–220 (Springer Publishing Co, New York, 2004).

    Google Scholar 

  14. Mathews, A. & MacLeod, C. Cognitive vulnerability to emotional disorders. Annu. Rev. Clin. Psychol. 1, 167–195 (2005).

    Article  PubMed  Google Scholar 

  15. Gotlib, I. H. & Joormann, J. Cognition and depression: current status and future directions. Annu. Rev. Clin. Psychol. 6, 285–312 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Joormann, J. The relation of rumination and inhibition: evidence from a negative priming task. Cognit. Ther. Res. 30, 149–160 (2006).

    Article  Google Scholar 

  17. Just, N. & Alloy, L. B. The response styles theory of depression: tests and an extension of the theory. J. Abnorm. Psychol. 106, 221–229 (1997).

    Article  CAS  PubMed  Google Scholar 

  18. Kuehner, C. & Weber, I. Responses to depression in unipolar depressed patients: an investigation of Nolen-Hoeksema's response styles theory. Psychol. Med. 29, 1323–1333 (1999).

    Article  CAS  PubMed  Google Scholar 

  19. Nolen-Hoeksema, S. The role of rumination in depressive disorders and mixed anxiety/depressive symptoms. J. Abnorm. Psychol. 109, 504–511 (2000).

    Article  CAS  PubMed  Google Scholar 

  20. Nolen-Hoeksema, S., Morrow, J. & Fredrickson, B. L. Response styles and the duration of episodes of depressed mood. J. Abnorm. Psychol. 102, 20–28 (1993).

    Article  CAS  PubMed  Google Scholar 

  21. Posner, M. I. & Rothbart, M. K. Developing mechanisms of self-regulation. Dev. Psychopathol. 12, 427–441 (2000).

    Article  Google Scholar 

  22. Gotlib, I. H., Krasnoperova, E., Yue, D. N. & Joormann, J. Attentional biases for negative interpersonal stimuli in clinical depression. J. Abnorm. Psychol. 113, 121–135 (2004). This study provides strong evidence that individuals with depression have attentional biases for negative, but not positive, information.

    PubMed  Google Scholar 

  23. Hasler, G., Drevets, W. C., Manji, H. K. & Charney, D. S. Discovering endophenotypes for major depression. Neuropsychopharmacology 29, 1765–1781 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. Corbetta, M. et al. A common network of functional areas for attention and eye movements. Neuron 21, 761–773 (1998).

    Article  CAS  PubMed  Google Scholar 

  25. Kastner, S., De Weerd, P., Desimone, R. & Ungerleider, L. G. Mechanisms of directed attention in the human extrastriate cortex as revealed by functional MRI. Science 282, 108–111 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. Fales, C. L. et al. Altered emotional interference processing in affective and cognitive-control brain circuitry in major depression. Biol. Psychiatry 63, 377–384 (2008).

    Article  PubMed  Google Scholar 

  27. Beevers, C. G., Clasen, P., Stice, E. & Schnyer, D. Depression symptoms and cognitive control of emotion cues: a functional magnetic resonance imaging study. Neuroscience 167, 97–103 (2010).

    Article  CAS  PubMed  Google Scholar 

  28. Passarotti, A. M., Sweeney, J. A. & Pavuluri, M. N. Neural correlates of incidental and directed facial emotion processing in adolescents and adults. Soc. Cogn. Affect Neurosci. 4, 387–398 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Cohen, J. R. & Lieberman, M. D. in Self control in society, mind, and brain. Vol. xiii (eds Hassin, R. R., Ochsner K. N. & Trope, Y.) 141–160 (Oxford Univ. Press, New York, 2010).

    Book  Google Scholar 

  30. Koster, E. H., De Raedt, R., Goeleven, E., Franck, E. & Crombez, G. Mood-congruent attentional bias in dysphoria: maintained attention to and impaired disengagement from negative information. Emotion 5, 446–455 (2005).

    Article  PubMed  Google Scholar 

  31. Gotlib, I. H. & Hamilton, J. P. Neuroimaging and depression: current status and unresolved issues. Curr. Dir. Psychol. Sci. 17, 159–163 (2008).

    Article  Google Scholar 

  32. Shafritz, K. M., Collins, S. H. & Blumberg, H. P. The interaction of emotional and cognitive neural systems in emotionally guided response inhibition. Neuroimage 31, 468–475 (2006).

    Article  PubMed  Google Scholar 

  33. Bush, G., Luu, P. & Posner, M. I. Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn. Sci. 4, 215–222 (2000).

    Article  CAS  PubMed  Google Scholar 

  34. Eugene, F., Joormann, J., Cooney, R. E., Atlas, L. Y. & Gotlib, I. H. Neural correlates of inhibitory deficits in depression. Psychiatry Res. 181, 30–35 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Elliott, R., Rubinsztein, J. S., Sahakian, B. J. & Dolan, R. J. The neural basis of mood-congruent processing biases in depression. Arch. Gen. Psychiatry 59, 597–604 (2002).

    Article  PubMed  Google Scholar 

  36. Mitterschiffthaler, M. T. et al. Neural basis of the emotional Stroop interference effect in major depression. Psychol. Med. 38, 247–256 (2008).

    Article  CAS  PubMed  Google Scholar 

  37. LeDoux, J. E. The Emotional Brain. (Simon & Schuster, New York,1996).

    Google Scholar 

  38. Santos, A., Mier, D., Kirsch, P. & Meyer-Lindenberg, A. Evidence for a general face salience signal in human amygdala. Neuroimage 54, 3111–3116 (2011).

    Article  PubMed  Google Scholar 

  39. Sander, D., Grafman, J. & Zalla, T. The human amygdala: an evolved system for relevance detection. Rev. Neurosci. 14, 303–316 (2003).

    Article  PubMed  Google Scholar 

  40. Davidson, R. J. Affective style, psychopathology, and resilience: brain mechanisms and plasticity. Am. Psychol. 55, 1196–1214 (2000).

    Article  CAS  PubMed  Google Scholar 

  41. Drevets, W. C. Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr. Opin. Neurobiol. 11, 240–249 (2001).

    Article  CAS  PubMed  Google Scholar 

  42. Costafreda, S. G., Brammer, M. J., David, A. S. & Fu, C. H. Predictors of amygdala activation during the processing of emotional stimuli: a meta-analysis of 385 PET and fMRI studies. Brain Res. Rev. 58, 57–70 (2008).

    Article  PubMed  Google Scholar 

  43. Siegle, G. J., Steinhauer, S. R., Thase, M. E., Stenger, V. A. & Carter, C. S. Can't shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals. Biol. Psychiatry 51, 693–707 (2002). This study demonstrates that individuals with depression show a stronger and more sustained amygdala response to self-relevant negative information than healthy controls.

    Article  PubMed  Google Scholar 

  44. Surguladze, S. et al. A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biol. Psychiatry 57, 201–209 (2005).

    Article  PubMed  Google Scholar 

  45. Suslow, T. et al. Attachment avoidance modulates neural response to masked facial emotion. Hum. Brain Mapp. 30, 3553–3562 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Victor, T. A., Furey, M. L., Fromm, S. J., Ohman, A. & Drevets, W. C. Relationship between amygdala responses to masked faces and mood state and treatment in major depressive disorder. Arch. Gen. Psychiatry 67, 1128–1138 (2010). This study documents that people with depression show amygdala reactivity to negative stimuli even when stimuli are presented subconsciously, and that this bias predicts the response to medication treatment.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Dannlowski, U. et al. Amygdala reactivity predicts automatic negative evaluations for facial emotions. Psychiatry Res. 154, 13–20 (2007).

    Article  PubMed  Google Scholar 

  48. van Reekum, C. M. et al. Individual differences in amygdala and ventromedial prefrontal cortex activity are associated with evaluation speed and psychological well-being. J. Cogn. Neurosci. 19, 237–248 (2007).

    Article  PubMed  Google Scholar 

  49. Schaefer, S. M. et al. Modulation of amygdalar activity by the conscious regulation of negative emotion. J. Cogn. Neurosci. 14, 913–921 (2002).

    Article  PubMed  Google Scholar 

  50. Anand, A., Li, Y., Wang, Y., Gardner, K. & Lowe, M. J. Reciprocal effects of antidepressant treatment on activity and connectivity of the mood regulating circuit: an FMRI study. J. Neuropsychiatry Clin. Neurosci. 19, 274–282 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Fu, C. H. et al. Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. Arch. Gen. Psychiatry 61, 877–889 (2004).

    Article  PubMed  Google Scholar 

  52. DeRubeis, R. J., Siegle, G. J. & Hollon, S. D. Cognitive therapy versus medication for depression: treatment outcomes and neural mechanisms. Nature Rev. Neurosci. 9, 788–796 (2008).

    Article  CAS  Google Scholar 

  53. Li, C. T. et al. Structural and cognitive deficits in remitting and non-remitting recurrent depression: a voxel-based morphometric study. Neuroimage 50, 347–356 (2010).

    Article  PubMed  Google Scholar 

  54. Siegle, G. J., Thompson, W., Carter, C. S., Steinhauer, S. R. & Thase, M. E. Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features. Biol. Psychiatry 61, 198–209 (2007).

    Article  PubMed  Google Scholar 

  55. Liotti, M., Mayberg, H. S., McGinnis, S., Brannan, S. L. & Jerabek, P. Unmasking disease-specific cerebral blood flow abnormalities: mood challenge in patients with remitted unipolar depression. Am. J. Psychiatry 159, 1830–1840 (2002).

    Article  PubMed  Google Scholar 

  56. Mottaghy, F. M. et al. Correlation of cerebral blood flow and treatment effects of repetitive transcranial magnetic stimulation in depressed patients. Psychiatry Res. 115, 1–14 (2002).

    Article  PubMed  Google Scholar 

  57. Ueda, K. et al. Brain activity during expectancy of emotional stimuli: an fMRI study. Neuroreport 14, 51–55 (2003).

    Article  PubMed  Google Scholar 

  58. Grimm, S. et al. Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment: an fMRI study in severe major depressive disorder. Biol. Psychiatry 63, 369–376 (2008).

    Article  PubMed  Google Scholar 

  59. Hooley, J. M., Gruber, S. A., Scott, L. A., Hiller, J. B. & Yurgelun-Todd, D. A. Activation in dorsolateral prefrontal cortex in response to maternal criticism and praise in recovered depressed and healthy control participants. Biol. Psychiatry 57, 809–812 (2005).

    Article  PubMed  Google Scholar 

  60. Schaefer, H. S., Putnam, K. M., Benca, R. M. & Davidson, R. J. Event-related functional magnetic resonance imaging measures of neural activity to positive social stimuli in pre- and post-treatment depression. Biol. Psychiatry 60, 974–986 (2006).

    Article  PubMed  Google Scholar 

  61. Greicius, M. D. et al. Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus. Biol. Psychiatry 62, 429–437 (2007). This is the first study to document alterations in default-mode (resting state) functional connectivity in the subgenual cingulate in adults with depression.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Guillery, R. W. Anatomical evidence concerning the role of the thalamus in corticocortical communication: a brief review. J. Anat. 187 (Pt 3), 583–592 (1995).

    PubMed  PubMed Central  Google Scholar 

  63. Sherman, S. M. & Guillery, R. W. The role of the thalamus in the flow of information to the cortex. Phil. Trans. R. Soc. Lond. B 357, 1695–1708 (2002).

    Article  Google Scholar 

  64. Ochsner, K. N. & Gross, J. J. The cognitive control of emotion. Trends Cogn. Sci. 9, 242–249 (2005).

    Article  PubMed  Google Scholar 

  65. Holthoff, V. A. et al. Changes in brain metabolism associated with remission in unipolar major depression. Acta Psychiatr. Scand. 110, 184–194 (2004).

    Article  CAS  PubMed  Google Scholar 

  66. Neumeister, A. et al. Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls. Arch. Gen. Psychiatry 61, 765–773 (2004).

    Article  CAS  PubMed  Google Scholar 

  67. Anand, A. et al. Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study. Biol. Psychiatry 57, 1079–1088 (2005).

    Article  PubMed  Google Scholar 

  68. Nutt, D. et al. The other face of depression, reduced positive affect: the role of catecholamines in causation and cure. J. Psychopharmacol. 21, 461–471 (2007).

    Article  CAS  PubMed  Google Scholar 

  69. Watson, D., Clark, L. A. & Carey, G. Positive and negative affectivity and their relation to anxiety and depressive disorders. J. Abnorm. Psychol. 97, 346–353 (1988).

    Article  CAS  PubMed  Google Scholar 

  70. Nestler, E. J. & Carlezon, W. A., Jr. The mesolimbic dopamine reward circuit in depression. Biol. Psychiatry 59, 1151–1159 (2006).

    Article  CAS  PubMed  Google Scholar 

  71. Tremblay, L. K. et al. Functional neuroanatomical substrates of altered reward processing in major depressive disorder revealed by a dopaminergic probe. Arch. Gen. Psychiatry 62, 1228–1236 (2005).

    Article  PubMed  Google Scholar 

  72. Del Arco, A. & Mora, F. Prefrontal cortex-nucleus accumbens interaction: in vivo modulation by dopamine and glutamate in the prefrontal cortex. Pharmacol. Biochem. Behav. 90, 226–235 (2008).

    Article  CAS  PubMed  Google Scholar 

  73. Wager, T. D., Davidson, M. L., Hughes, B. L., Lindquist, M. A. & Ochsner, K. N. Prefrontal-subcortical pathways mediating successful emotion regulation. Neuron 59, 1037–1050 (2008). This study demonstrates for the first time that activity in the ventral lateral PFC region predicts successful emotion regulation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kim, S. H. & Hamann, S. Neural correlates of positive and negative emotion regulation. J. Cogn. Neurosci. 19, 776–798 (2007).

    Article  PubMed  Google Scholar 

  75. Heller, A. S. et al. Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation. Proc. Natl Acad. Sci. USA 106, 22445–22450 (2009). This important study identifies the neurobiological underpinnings of a blunted response to positive stimuli, a key feature of depression.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Epstein, J. et al. Lack of ventral striatal response to positive stimuli in depressed versus normal subjects. Am. J. Psychiatry 163, 1784–1790 (2006).

    Article  PubMed  Google Scholar 

  77. Pizzagalli, D. A. et al. Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. Am. J. Psychiatry 166, 702–710 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  78. O'Doherty, J. et al. Dissociable roles of ventral and dorsal striatum in instrumental conditioning. Science 304, 452–454 (2004).

    Article  CAS  PubMed  Google Scholar 

  79. Tricomi, E. M., Delgado, M. R. & Fiez, J. A. Modulation of caudate activity by action contingency. Neuron 41, 281–292 (2004).

    Article  CAS  PubMed  Google Scholar 

  80. Spasojevic, J. & Alloy, L. B. Rumination as a common mechanism relating depressive risk factors to depression. Emotion 1, 25–37 (2001).

    Article  CAS  PubMed  Google Scholar 

  81. Denson, T. F., Pedersen, W. C., Ronquillo, J. & Nandy, A. S. The angry brain: neural correlates of anger, angry rumination, and aggressive personality. J. Cogn. Neurosci. 21, 734–744 (2009).

    Article  PubMed  Google Scholar 

  82. Siegle, G. J., Carter, C. S. & Thase, M. E. Use of FMRI to predict recovery from unipolar depression with cognitive behavior therapy. Am. J. Psychiatry 163, 735–738 (2006).

    Article  PubMed  Google Scholar 

  83. Cooney, R. E., Joormann, J., Eugene, F., Dennis, E. L. & Gotlib, I. H. Neural correlates of rumination in depression. Cogn. Affect Behav. Neurosci. 10, 470–478 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  84. McDonald, A. J., Mascagni, F. & Guo, L. Projections of the medial and lateral prefrontal cortices to the amygdala: a Phaseolus vulgaris leucoagglutinin study in the rat. Neuroscience 71, 55–75 (1996).

    Article  CAS  PubMed  Google Scholar 

  85. Gusnard, D. A., Akbudak, E., Shulman, G. L. & Raichle, M. E. Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function. Proc. Natl Acad. Sci. USA 98, 4259–4264 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Ray, R. D. et al. Individual differences in trait rumination and the neural systems supporting cognitive reappraisal. Cogn. Affect Behav. Neurosci. 5, 156–168 (2005).

    Article  PubMed  Google Scholar 

  87. 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. 27, 8877–8884 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Ochsner, K. N. et al. For. better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion. Neuroimage 23, 483–499 (2004).

    Article  PubMed  Google Scholar 

  89. Koster, E. H., De Raedt, R., Leyman, L. & De Lissnyder, E. Mood-congruent attention and memory bias in dysphoria: exploring the coherence among information-processing biases. Behav. Res. Ther. 48, 219–225 (2010).

    Article  PubMed  Google Scholar 

  90. Beevers, C. G., Ellis, A. J. & Reid, R. M. Heart rate variability predicts cognitive reactivity to a sad mood provocation. Cogn. Ther. Res. 16 Jun 2010 (doi:10.1007/s10608-010-9324-0).

    Article  Google Scholar 

  91. Hamilton, J. P. & Gotlib, I. H. Neural substrates of increased memory sensitivity for negative stimuli in major depression. Biol. Psychiatry 63, 1155–1162, (2008). Enhanced memory for negative information is a central feature of the cognitive model of depression. This study identifies the neural substrates of a negative memory bias in adults with depression.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Adolphs, R., Cahill, L., Schul, R. & Babinsky, R. Impaired declarative memory for emotional material following bilateral amygdala damage in humans. Learn. Mem. 4, 291–300 (1997).

    Article  CAS  PubMed  Google Scholar 

  93. Cahill, L., Babinsky, R., Markowitsch, H. J. & McGaugh, J. L. The amygdala and emotional memory. Nature 377, 295–296 (1995).

    Article  CAS  PubMed  Google Scholar 

  94. Packard, M. G., Cahill, L. & McGaugh, J. L. Amygdala modulation of hippocampal-dependent and caudate nucleus-dependent memory processes. Proc. Natl Acad. Sci. USA 91, 8477–8481 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Steinvorth, S., Levine, B. & Corkin, S. Medial temporal lobe structures are needed to re-experience remote autobiographical memories: evidence from H. M. and W. R. Neuropsychologia 43, 479–496 (2005).

    Article  PubMed  Google Scholar 

  96. Knutson, B., Fong, G. W., Adams, C. M., Varner, J. L. & Hommer, D. Dissociation of reward anticipation and outcome with event-related fMRI. Neuroreport 12, 3683–3687 (2001).

    Article  CAS  PubMed  Google Scholar 

  97. Elliott, R., Friston, K. J. & Dolan, R. J. Dissociable neural responses in human reward systems. J. Neurosci. 20, 6159–6165 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Keedwell, P. A., Andrew, C., Williams, S. C., Brammer, M. J. & Phillips, M. L. A double dissociation of ventromedial prefrontal cortical responses to sad and happy stimuli in depressed and healthy individuals. Biol. Psychiatry 58, 495–503 (2005).

    Article  PubMed  Google Scholar 

  99. Craik, F. I. M. et al. In search of the self: a positron emission tomography study. Psychol. Sci. 10, 26–34 (1999).

    Article  Google Scholar 

  100. Fossati, P. et al. In search of the emotional self: an fMRI study using positive and negative emotional words. Am. J. Psychiatry 160, 1938–1945 (2003).

    Article  PubMed  Google Scholar 

  101. Kelley, W. M. et al. Finding the self? An event-related fMRI study. J. Cogn. Neurosci. 14, 785–794 (2002).

    Article  CAS  PubMed  Google Scholar 

  102. Yoshimura, S. et al. Self-referential processing of negative stimuli within the ventral anterior cingulate gyrus and right amygdala. Brain Cogn. 69, 218–225 (2009).

    Article  PubMed  Google Scholar 

  103. Davidson, R. J. & Irwin, W. The functional neuroanatomy of emotion and affective style. Trends Cogn. Sci. 3, 11–21 (1999).

    Article  CAS  PubMed  Google Scholar 

  104. Sergerie, K., Chochol, C. & Armony, J. L. The role of the amygdala in emotional processing: a quantitative meta-analysis of functional neuroimaging studies. Neurosci. Biobehav. Rev. 32, 811–830 (2008).

    Article  PubMed  Google Scholar 

  105. Moran, J. M., Macrae, C. N., Heatherton, T. F., Wyland, C. L. & Kelley, W. M. Neuroanatomical evidence for distinct cognitive and affective components of self. J. Cogn. Neurosci. 18, 1586–1594 (2006).

    Article  CAS  PubMed  Google Scholar 

  106. Yoshimura, S. et al. Rostral anterior cingulate cortex activity mediates the relationship between the depressive symptoms and the medial prefrontal cortex activity. J. Affect Disord. 122, 76–85 (2010).

    Article  PubMed  Google Scholar 

  107. Meyer, J. H. Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J. Psychiatry Neurosci. 32, 86–102 (2007).

    PubMed  PubMed Central  Google Scholar 

  108. Meyer, J. H. et al. Dysfunctional attitudes and 5-HT2 receptors during depression and self-harm. Am. J. Psychiatry 160, 90–99 (2003). Increased dysfunctional attitudes represent a core feature of the cognitive model of depression. Across two studies, it was found that low levels of 5-hydroxytryptamine (5-HT) agonism in the brain cortex is associated with increased dysfunctional attitudes among adults with depression.

    Article  PubMed  Google Scholar 

  109. Owens, M. J. & Nemeroff, C. B. Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin. Chem. 40, 288–295 (1994).

    CAS  PubMed  Google Scholar 

  110. Bouvard, M., Charles, S., Guerin, J., Aimard, G. & Cottraux, J. [Study of Beck's hopelessness scale. Validation and factor analysis]. Encephale 18, 237–240 (1992).

    CAS  PubMed  Google Scholar 

  111. Bhagwagar, Z. et al. Increased 5-HT(2A) receptor binding in euthymic, medication-free patients recovered from depression: a positron emission study with [(11)C]MDL 100, 907. Am. J. Psychiatry 163, 1580–1587 (2006).

    Article  PubMed  Google Scholar 

  112. Werner, F. M. & Covenas, R. Classical neurotransmitters and neuropeptides involved in major depression: a review. Int. J. Neurosci. 120, 455–470 (2010).

    Article  CAS  PubMed  Google Scholar 

  113. Nutt, D. J. Relationship of neurotransmitters to the symptoms of major depressive disorder. J. Clin. Psychiatry 69 Suppl E1, 4–7 (2008).

    PubMed  Google Scholar 

  114. Drevets, W. C. & Raichle, M. E. Reciprocal suppression of regional cerebral blood flow during emotional versus higher cognitive processes: implications for interactions between emotion and cognition. Cogn. Emot. 12, 353–385 (1998).

    Article  Google Scholar 

  115. Hirschfeld, R. M. Efficacy of SSRIs and newer antidepressants in severe depression: comparison with TCAs. J. Clin. Psychiatry 60, 326–335 (1999).

    Article  CAS  PubMed  Google Scholar 

  116. Mayberg, H. S. et al. Deep brain stimulation for treatment-resistant depression. Neuron 45, 651–660 (2005).

    Article  CAS  PubMed  Google Scholar 

  117. Hakamata, Y. et al. Attention bias modification treatment: a meta-analysis toward the establishment of novel treatment for anxiety. Biol. Psychiatry 68, 982–990 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  118. Holmes, E. A., Lang, T. J. & Shah, D. M. Developing interpretation bias modification as a “cognitive vaccine” for depressed mood: imagining positive events makes you feel better than thinking about them verbally. J. Abnorm. Psychol. 118, 76–88 (2009).

    Article  PubMed  Google Scholar 

  119. Wells, T. T. & Beevers, C. G. Biased attention and dysphoria: manipulating selective attention reduces subsequent depressive symptoms. Cogn. Emot. 24, 719–728 (2010).

    Article  Google Scholar 

  120. Beck, A. T., Rush, A. J., Shaw, B. F. & Emery, G. Cognitive therapy of depression. (Guilford Press, New York, 1979).

    Google Scholar 

  121. Butler, A. C., Chapman, J. E., Forman, E. M. & Beck, A. T. The empirical status of cognitive-behavioral therapy: a review of meta-analyses. Clin. Psychol. Rev. 26, 17–31 (2006).

    Article  PubMed  Google Scholar 

  122. Goldapple, K. et al. Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch. Gen. Psychiatry 61, 34–41 (2004). This was the first study to examine the influence of cognitive behaviour therapy versus medication on cortico–limbic circuit functioning among adults with depression.

    Article  PubMed  Google Scholar 

  123. Suslow, T. et al. Automatic mood-congruent amygdala responses to masked facial expressions in major depression. Biol. Psychiatry 67, 155–160 (2010).

    Article  PubMed  Google Scholar 

  124. Chan, S. W., Harmer, C. J., Goodwin, G. M. & Norbury, R. Risk for depression is associated with neural biases in emotional categorisation. Neuropsychologia 46, 2896–2903 (2008).

    Article  PubMed  Google Scholar 

  125. Rude, S. S., Durham-Fowler, J. A., Baum, E. S., Rooney, S. B. & Maestas, K. L. Self-report and cognitive processing measures of depressive thinking predict subsequent major depressive disorder. Cogn. Ther. Res. 34, 107–115 (2010).

    Article  Google Scholar 

  126. Gibb, B. E., Schofield, C. A. & Coles, M. E. Reported history of childhood abuse and young adults' information-processing biases for facial displays of emotion. Child. Maltreat. 14, 148–156 (2009).

    Article  PubMed  Google Scholar 

  127. Greenberg, P. E., Stiglin, L. E., Finkelstein, S. N. & Berndt, E. R. The economic burden of depression in 1990. J. Clin. Psychiatry 54, 405–418 (1993).

    CAS  PubMed  Google Scholar 

  128. Philip, S. W., Gregory, S. & Ronald, C. K. The economic burden of depression and the cost-effectiveness of treatment. Int. J. Methods Psychiatr. Res. 12, 22–33 (2003).

    Article  Google Scholar 

  129. Kessler, R. C. et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R.). JAMA 289, 3095–3105 (2003).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Preparation of this article was supported by grant MH076897 and MH092430 from the US National Institute of Mental Health (NIMH) to C.B. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH or the National Institutes of Health. The authors wish to thank A. Butler, B. Gibb, and G. Siegle for discussions about ideas contained in this article, and three anonymous reviewers for their helpful feedback.

Author information

Authors and Affiliations

  1. Department of Psychology, The University of Texas at Austin, 1 University Station, A8000, Austin, 78712, Texas, USA

    Seth G. Disner & Christopher G. Beevers

  2. Department of Psychiatry, University of Pennsylvania, 3535 Market Street, Philadelphia, 19104-3309, Pennsylvania, USA

    Emily A. P. Haigh & Aaron T. Beck

Authors
  1. Seth G. Disner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher G. Beevers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emily A. P. Haigh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aaron T. Beck
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christopher G. Beevers.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Christopher G. Beevers' homepage

Aaron T. Beck's homepage

Glossary

Schemas

Internal beliefs or representations of stimuli, ideas or experiences that — if negative — can simultaneously contribute to and be exacerbated by depressive symptoms.

Cognitive hierarchy

An ordering of brain regions based on the relative complexity and abstraction of their cognitive functions.

Dysphoria

A negative mood state characterized by feelings of discontent, anguish, distress and depression.

Anterior cingulate cortex

(ACC). The frontal part of the cingulate cortex. As with many brain areas, subdivisions within the ACC, such as the dorsal, rostral and ventral ACC, are determined by functional differences rather than anatomical landmarks. As such, 'boundaries' for these regions may vary slightly across studies.

Thought record

A tool used in cognitive therapy to help to identify erroneous thought patterns and assist in the formulation of more balanced thoughts.

Guided discovery

The process of asking questions in order to uncover and evaluate the validity and functionality of beliefs about oneself, the world and other people.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Disner, S., Beevers, C., Haigh, E. et al. Neural mechanisms of the cognitive model of depression. Nat Rev Neurosci 12, 467–477 (2011). https://doi.org/10.1038/nrn3027

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn3027

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing