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Handb Clin Neurol. 2019;166:371-379. doi: 10.1016/B978-0-444-64196-0.00021-2.

Cingulate-mediated depressive symptoms in neurologic disease and therapeutics.

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Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States.
Departments of Psychiatry and Surgery, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, Lebanon, NH, United States.
Departments of Neurology, Neurosurgery, Psychiatry, and Neuroscience, Center of Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address:


The depressive syndrome includes a number of symptoms that are clinically diverse. Research in the past decades has consistently demonstrated that the cingulate cortex plays an essential role in these manifestations. With anatomic studies initially showing volumetric changes, followed by the insights that functional imaging and physiology contributed to neuroscience and psychiatry, the distinct areas of the cingulate subdivisions were seen to have unique contributions. The subcallosal cingulate, with its functional responsivity to mood states and to antidepressant therapies, has been identified as a central node within the mood regulation network. In this chapter, detailed descriptions of the anatomic and functional changes that are seen in depression will be discussed. Finally, a focus on the development of deep brain stimulation in the subcallosal cingulate area will be used to emphasize the conceptualization of a network model with the cingulate as a hub, where engagement of remote areas of the depression network is needed to treat depression.


Cingulate cortex; Deep brain stimulation; Depression; Neuromodulation; Subcallosal cingulate; Treatment-resistant depression

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