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Review
. 2020 Oct 12;9(10):3260.
doi: 10.3390/jcm9103260.

A Decade of Progress in Deep Brain Stimulation of the Subcallosal Cingulate for the Treatment of Depression

Sharafuddin Khairuddin  1 , Fung Yin Ngo  1 , Wei Ling Lim  1   2 , Luca Aquili  3 , Naveed Ahmed Khan  4 , Man-Lung Fung  1 , Ying-Shing Chan  1 , Yasin Temel  5 , Lee Wei Lim  1   2
Affiliations
Review

A Decade of Progress in Deep Brain Stimulation of the Subcallosal Cingulate for the Treatment of Depression

Sharafuddin Khairuddin et al. J Clin Med. .

Abstract

Major depression contributes significantly to the global disability burden. Since the first clinical study of deep brain stimulation (DBS), over 406 patients with depression have now undergone this neuromodulation therapy, and 30 animal studies have investigated the efficacy of subgenual cingulate DBS for depression. In this review, we aim to provide a comprehensive overview of the progress of DBS of the subcallosal cingulate in humans and the medial prefrontal cortex, its rodent homolog. For preclinical animal studies, we discuss the various antidepressant-like behaviors induced by medial prefrontal cortex DBS and examine the possible mechanisms including neuroplasticity-dependent/independent cellular and molecular changes. Interestingly, the response rate of subcallosal cingulate Deep brain stimulation marks a milestone in the treatment of depression. DBS among patients with treatment-resistant depression was estimated to be approximately 54% across clinical studies. Although some studies showed its stimulation efficacy was limited, it still holds great promise as a therapy for patients with treatment-resistant depression. Overall, further research is still needed, including more credible clinical research, preclinical mechanistic studies, precise selection of patients, and customized electrical stimulation paradigms.

Keywords: deep brain stimulation; major depressive disorder; medial prefrontal cortex; subcallosal cingulate; treatment-resistant depression.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Changes in local and distal neuronal activity after electrical stimulation of the ventromedial prefrontal cortex. (B) Neuroplasticity-dependent and -independent changes in different structures following vmPFC-DBS. Abbreviations: AH, anterior hypothalamus; AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; BDNF, brain-derived neurotrophic factor; BLA, basolateral amygdaloid nucleus; Cg1,2, cingulate gyrus area 1, 2; CM, centromedial thalamic nucleus; DG, dentate gyrus; DMH, dorsomedial hypothalamus; DRD, dorsal raphe nucleus, dorsal part; DRVL, dorsal raphe nucleus, ventrolateral part; IntMC, interposed cerebellar nucleus, magnocelluar part; LA, lateral amygdaloid nucleus; LEnt, lateral entorhinal cortex; LHb, lateral habenula; MD, mediodorsal thalamic nucleus; mPFC, medial prefrontal cortex; OrbF, orbitofrontal cortex; PaMP, paraventricular hypothalamic nucleus, medial parvicellular; Pir, piriform cortex; PrL, prelimbic cortex; TeA, temporal association area; and 5-HT, serotonin.
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