Skip to main content Accessibility help

Neural systems underlying affective disorders

  • Simon Surguladze, Paul Keedwell and Mary Phillips


Three main approaches are used to explore the neural correlates of mood disorder: neuropsychological studies, neuroimaging studies and post-mortem investigations. Lesion studies implicate disturbances in the frontal lobe, basal ganglia, striatum and anterior temporal cortex. Early neurocognitive and neuropathological investigations led to a ‘hypofrontality’ hypothesis of unipolar and bipolar depression, but functional neuroimaging has revealed a more complex picture. Thus, increased metabolism may occur in the subgenual anterior cingulate gyrus in resting-state studies of depression and sad-mood induction. Antidepressants may reduce this activity. Amygdala hyperactivation also is associated with affective disorders. Task-related studies reveal abnormal biases in memory, the experience of pleasure and the perception of emotional facial expressions. There is still little clarity whether the abnormalities in brain activation represent state or trait characteristics of affective disorders.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Neural systems underlying affective disorders
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Neural systems underlying affective disorders
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Neural systems underlying affective disorders
      Available formats



Hide All
Abercrombie, H. C., Schaefer, S. M., Larson, C. L. et al (1998) Metabolic rate in the right amygdala predicts negative affect in depressed patients. NeuroReport, 9, 33013307.
Attwell, D. & Iadecola, C. (2002) The neural basis of functional brain imaging signals. Trends in Neurosciences, 25, 621625.
Baumann, B., Danos, P., Krell, D. et al (1999) Reduced volume of limbic system-affiliated basal ganglia in mood disorders: preliminary data from a post mortem study. Journal of Neuropsychiatry and Clinical Neuroscience, 11, 7178.
Baxter, L. R., Phelps, M. E., Mazziotta, J. C. et al (1985) Cerebral metabolic rates for glucose in mood disorders. Studies with positron emission tomography and fluorodeoxyglucose F18. Archives of General Psychiatry, 42, 441447.
Baxter, L. R., Schwartz, J. M., Phelps, M. E. et al (1989) Reduction of prefrontal cortex glucose metabolism common to three types of depression. Archives of General Psychiatry, 46, 243250.
Bazin, N., Perruchet, P., DeBonis, M. et al (1994) The dissociation of explicit and implicit memory in depressed patients. Psychological Medicine, 24, 239245.
Beyer, J. L. & Krishnan, K. R. R. (2002) Volumetric brain imaging findings in mood disorders. Bipolar Disorders, 4, 89104.
Blumberg, H. P., Eldelberg, D., Koscis, J. H. et al (1999) Rostral and orbital prefrontal cortex dysfunction in the manic state of bipolar disorder. American Journal of Psychiatry, 156, 19861988.
Blumberg, H. P., Stern, E., Martinez, D. et al (2000) Increased anterior cingulate and caudate activity in bipolar mania. Biological Psychiatry, 48, 19451952.
Blumer, D. & Benson, D. F. (1975) Personality changes with frontal and temporal lesions. In Psychiatric Aspects of Neurologic Disease (eds Benson, D. F. & Blumer, D.) pp. 155157. New York: Grune & Stratton.
Bowley, M. P., Drevets, W. C., Ongur, D. et al (2002) Low glial numbers in the amygdala in major depressive disorder. Biological Psychiatry, 52, 404412.
Cavanagh, J. T. O., van Beck, M., Muir, W. et al (2002) Case–control study of neurocognitive function in euthymic patients with bipolar disorder: an association with mania. British Journal of Psychiatry, 180, 320326.
Clark, L., Iverson, S. D. & Goodwin, G. M. (2002) Sustained attention deficit in bipolar disorder. British Journal of Psychiatry, 180, 313319.
Cooley, E. L. & Nowicki, S. Jr (1989) Discrimination of facial expressions of emotion by depressed subjects. Genetic, Social, and General Psychology Monographs, 115, 449465.
Cotter, D., Mackay, D., Landau, S. et al (2001) Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Archives of General Psychiatry, 58, 545553.
Damasio, H., Grabowski, T., Frank, R. et al (1994) The return of Phineas Gage: the skull of famous patient yields clues about the brain. Science, 264, 11021105.
Danion, J. M., Willard-Schroeder, D., Zimmermann, M. A. et al (1991) Explicit memory and repetition priming in depression. Preliminary findings. Archives of General Psychiatry, 48, 707711.
Davidson, R. J., Pizzagalli, D., Nitschke, J. B. et al (2002) Depression: perspectives from affective neuroscience. Annual Review of Psychology, 53, 545574.
Drevets, W. C. (2000) Neuroimaging studies of mood disorders. Biological Psychiatry, 48, 813829.
Drevets, W. C. (2001) Neuroimaging and neuropathological studies of depression: implications for the cognitive–emotional features of mood disorders. Current Opinion in Neurobiology, 11, 240249.
Drevets, W. C., Videen, T. O., Price, J. L. et al (1992) A functional anatomical study of unipolar depression. Journal of Neuroscience, 12, 36283641.
Drevets, W. C., Price, J. L., Videen, T. O. et al (1995) Metabolic abnormalities in the subgenual prefrontal cortex and ventral striatum in mood disorders. Neuroscience Abstracts, 21, 260.
Drevets, W. C., Price, J. L., Simpson, J. R. et al (1997) Subgenual prefrontal cortex abnormalities in mood disorders. Nature, 386, 824827.
Drevets, W. C., Price, J. L., Bardgett, M. E. et al (2002) Glucose metabolism in the amygdala in depression. Relationship to diagnostic subtype and plasma cortisol levels. Pharmacology, Biochemistry and Behavior, 71, 431447.
Elliott, R., Sahakian, B. J., Michael, A. et al (1998) Abnormal neural response to feedback on planning and guessing tasks in patients with unipolar depression. Psychological Medicine, 28, 559571.
Ferrier, I. N., Stanton, B. R., Kelly, T. P. et al (1999) Neuropsychological function in euthymic patients with bipolar disorder. British Journal of Psychiatry, 175, 246251.
Gur, R. C., Erwin, R. J., Gur, R. E. et al (1992) Facial emotion discrimination. II: Behavioral findings in depression. Psychiatry Research, 42, 241251.
Hale III, W. W. (1998) Judgment of facial expressions and depression persistence. Psychiatry Research, 80, 265274.
Hariri, A. R., Mattay, V. S. & Tessitore III, A. (2002) Serotonin transporter genetic variation and the response of the human amygdala. Science, 297, 400403.
Keedwell, P. A., Andrew, C., Williams, S. C. R. et al (2003) The neural correlates of depression (abstract). Biological Psychiatry, 53, 171s.
Ketter, T. A., Kimbrell, T. A., George, M. S. et al (2001) Effects of mood and subtype on cerebral glucose metabolism in treatment-resistant bipolar disorder. Biological Psychiatry, 49, 97109.
Logothetis, N. K., Pauls, J., Augath, M. et al (2001) Neurophysiological investigation of the basis of the fMRI signal. Nature, 412, 150157.
Manji, H. K., Moore, G. J., Rajkowska, G. et al (2000) Neuroplasticity and cellular resilience in mood disorders. Molecular Psychiatry, 5, 578593.
Matthews, G. R. & Antes, J. R. (1992) Visual attention and depression: cognitive biases in the eye fixation of the dysphoric and non-depressed. Cognitive Therapy and Research, 16, 359371.
Mayberg, H. S. (2000) Depression. In Brain Mapping: The Disorders (eds Mazziotta, J. C., Toga, A. W. & Frackowiak, R. S. J.) London: Academic Press.
Mayberg, H. S., Liotti, M., Brannan, S. K. et al (1999) Reciprocal limbic–cortical function and negative mood. Converging PET findings in depression and normal sadness. American Journal of Psychiatry, 156, 675682.
Mayberg, H. S., Brannan, S. K., Tekell, J. L. et al (2000) Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biological Psychiatry, 48, 830843.
Mikhailova, E. S., Vladimirova, T. V., Iznak, A. F. et al (1996) Abnormal recognition of facial expression of emotions in depressed patients with major depression disorder and schizotypal personality disorder. Biological Psychiatry, 40, 697705.
Northoff, G., Richter, A., Gessner, M. et al (1999) Functional dissociation between medial and lateral prefrontal cortical spatiotemporal activation in negative and positive emotions. A combined fMRI/MEG study. Cerebral Cortex, 10, 93.
Ongur, D., Drevets, W. C. & Price, J. L. (1998) Glial reduction in the subgenual prefrontal cortex in mood disorders. Proceedings of the National Academy of Sciences of the USA, 95, 1329013295.
Pardo, J. V., Pardo, P. J. & Raichle, M. E. (1993) Neural correlates of self-induced dysphoria. American Journal of Psychiatry, 150, 713719.
Pariante, C. M. & Miller, A. H. (2001) Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Biological Psychiatry, 49, 391404.
Perrett, D. I., Rolls, E. T. & Caan, W. (1982) Visual neurones responsive to faces in the monkey temporal cortex. Experimental Brain Research, 47, 329342.
Rajkowska, G., Halaris, A. & Selemon, L. D. (2001) Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biological Psychiatry, 49, 741752.
Rolls, E. T. (1999) The functions of orbitofrontal cortex. Neurocase, 5, 301312.
Rubinow, D. R. & Post, R. M. (1992) Impaired recognition of affect in facial expression in depressed patients. Biological Psychiatry, 31, 947953.
Rubinsztein, J. S., Fletcher, P. C., Rogers, R. D. et al (2001) Decision-making in mania: a PET study. Brain, 124, 25502563.
Sheline, Y. I., Barch, D. M., Donnelly, J. M. et al (2001) Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biological Psychiatry, 50, 651658.
Siegle, G. J., Steinhauer, S. R., Thase, M. E. et al (2002) Can't shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals. Biological Psychiatry, 51, 693707.
Suslow, T., Junghanns, K. & Arolt, V. (2001) Detection of facial expressions of emotions in depression. Perceptual and Motor Skills, 92, 857868.
Talairach, J. & Tournoux, P. (1988) Co-planar Stereotactic Atlas of the Human Brain. Stuttgart: Thieme.
Veiel, H. O. F. (1997) A preliminary profile of neuropsychological deficits associated with major depression. Journal of Clinical and Experimental Neuropsychology, 19, 587603.
Watkins, P. C., Vache, K., Verney, S. P. et al (1996) Unconscious mood-congruent memory bias in depression. Journal of Abnormal Psychology, 105, 3441.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

BJPsych Advances
  • ISSN: 1355-5146
  • EISSN: 1472-1481
  • URL: /core/journals/bjpsych-advances
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Neural systems underlying affective disorders

  • Simon Surguladze, Paul Keedwell and Mary Phillips
Submit a response


No eLetters have been published for this article.


Reply to: Submit a response

Your details

Conflicting interests

Do you have any conflicting interests? *