Neuroanatomical predictors of response to subcallosal cingulate deep brain stimulation for treatment-resistant depression

Abstract

Background: Deep brain stimulation targeting the subcallosal cingulate gyrus (SCG DBS) improves the symptoms of treatment-resistant depression in some patients, but not in others. We hypothesized that there are pre-existing structural brain differences between responders and nonresponders to SCG DBS, detectable using structural MRI. Methods: We studied preoperative, T 1 -weighted MRI scans of 27 patients treated with SCG DBS from 2003 to 2011. Responders (n = 15) were patients with a > 50% improvement in Hamilton Rating Scale for Depression score following 12 months of SCG DBS. Preoperative subcallosal cingulate gyrus grey matter volume was obtained using manual segmentation by a trained observer blinded to patient identity. Volumes of hippocampus, thalamus, amygdala, whole-brain cortical grey matter and white matter volume were obtained using automated techniques. Results: Preoperative subcallosal cingulate gyrus, thalamic and amygdalar volumes were significantly larger in patients who went on to respond to SCG-DBS. Hippocampal volume did not differ between groups. Cortical grey matter volume was significantly smaller in responders, and cortical grey matter:white matter ratio distinguished between responders and nonresponders with high sensitivity and specificity. Limitations: Normalization by intracranial volume nullified some between-group differences in volumetric measures. Conclusion: There are structural brain differences between patients with treatment-resistant depression who respond to SCG DBS and those who do not. Specifically, the structural integrity of the subcallosal cingulate gyrus target region and its connected subcortical areas, and variations in cortical volume across the entire brain, appear to be important determinants of response. Structural MRI shows promise as a biomarker in deep brain stimulation for depression, and may play a role in refining patient selection for future trials.Predictors of response to deep brain stimulation for depression J Psychiatry Neurosci 2020;45(1) 53 Rizvi); and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States (Mayberg).

Deep Brain Stimulation Is Effective for Treatment-Resistant Depression: A Meta-Analysis and Meta-Regression

“…Twenty-six studies were candidates for inclusion at the abstract level. Thirteen studies were excluded because they did not compare active to sham stimulation [31][32][33][34][35][36][37][38][39][40][41][42][43], and one study was excluded as it included only three patients [44]. Therefore, 12 studies [15][16][17][18][19][20][21][22][23][24][25] (186 unique patients) were included in the meta-analysis and meta-regression ( Table 1).…”

“…The large-scale trials, however, did not reveal a significant difference between the control and treatment groups. A number of reasons have been posited to explain these negative results, including choice of stimulation target, electrode placement technique, patient selection, and short-term follow-up of patients [43,[46][47][48][49][50][51][52].…”

“…The available data have demonstrated that there is a subgroup of patients that respond to this therapy and a subgroup that does not. Determining patient-specific factors (e.g., anatomical or symptom-based) that predict response to DBS for TRD may enable targeted selection of patients for whom DBS would be therapeutic [43,[69][70][71][72][73][74][75]. These patient-specific factors could then be used as study inclusion criteria to enhance the probability of study success.…”

Sexually divergent cortical control of affective-autonomic integration

“…BA25 is also targeted for deep brain stimulation in patients with treatment-resistant depression, where larger volumes predict better treatment outcomes (Mayberg et al, 2005;Sankar et al, 2019). Subgenual regions of vmPFC have also been identified as components of a central autonomic network monitoring visceral functions (Beissner et al, 2013;Gianaros and Sheu, 2009;Gianaros and Wager, 2015;Myers, 2016;Shoemaker et al, 2016).…”

“…A subregion of the vmPFC, the subgenual cingulate cortex (BA25), is activated by sadness-provoking stimuli, responds to social isolation, and has reduced volume in MDD patients (Beckmann et al, 2009; Liotti et al, 2000; Vijayakumar et al, 2017). BA25 is also targeted for deep brain stimulation in patients with treatment-resistant depression, where larger volumes predict better treatment outcomes (Mayberg et al, 2005; Sankar et al, 2019). Subgenual regions of vmPFC have also been identified as components of a central autonomic network monitoring visceral functions (Beissner et al, 2013; Gianaros and Sheu, 2009; Gianaros and Wager, 2015; Myers, 2016; Shoemaker et al, 2016).…”