Deep Brain Stimulation for Treatment-Resistant Depression: Towards a More Personalized Treatment Approach
Abstract
:1. Introduction
2. Recent Insights on the Pathophysiology of Depression
Expanding the Cortico-Striatal-Thalamo-Cortical Mood Circuits
3. Deep Brain Stimulation for Treatment-Resistant Depression
3.1. Subgenual Cingulate Gyrus/Cortex
3.2. Nucleus Accumbens
3.3. Ventral Capsule/Ventral Striatum
3.4. The Ventral Part of the Anterior Limb of the Internal Capsule
3.5. Lateral Habenula
3.6. Thalamic Peduncles
3.7. Bed Nucleus of the Stria Terminalis
3.8. Medial Forebrain Bundle
4. Towards a More Personalized DBS Treatment Approach for Treatment-Resistant Depression
4.1. Clinical and Neurophysiological Subtypes of Depression
4.2. Individual Tractography
4.3. Combining Deep Brain Stimulation with Cognitive-Behavioral Therapy
4.4. Biomarkers
4.5. Insights into Symptomatic Improvement after Deep Brain Stimulation
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Region (DBS) | Study | Open-Labeled, RCT or Case-Report | N | Follow-Up | Age (Mean) | Length of Current Depressive Episode, Years (Mean) | Response Rate (%) in HDRS or MADRS Scores | Remission Rate (%) | Serious Adverse Events (N) |
---|---|---|---|---|---|---|---|---|---|
SCG | Mayberg et al., 2005 | Open-label | 6 | 6 months | 46 | 5.58 | 33.3 (1 month), # 83 (2 months), # 66.6 (6 months), # | 0 (1 month) 33.3 (3 months) 33.3 (6 months) | Suicidal ideation: 2 Syncope: 1 Lead problem: 1 |
Lozano et al., 2008 | Open-label | 20 | 12 months | 47.4 | 6.9 | 60 (6 months), # 55 (12 months), # | 35 (6 months) 35 (12 months) | Seizure: 1 Lead problem: 3 | |
Kennedy et al., 2011 | Open-label | 20 | 1, 2 and 3 years, last follow-up (3–6 years) | 47.4 | 6.9 | 62.5 (1 year), # 46.2 (2 years), # 75 (3 years), # 64.3 (last follow-up), # | 18.8 (1 year) 15.4 (2 years) 50 (3 years) | Worsening depression:3 Suicidal ideation:3 | |
Puigdemont et al., 2012 | Open-label | 8 | 12 months | 47.4 | 6.3 | 87.5 (1 week), # 37.5 (1 month), # 87.5 (6 months), # 62.5 (12 months), # | 50 (1 week) 37.5 (6 months) 50 (12 months) | Suicide attempt: 1 | |
Lozano et al., 2012 | Open-label | 21 | 12 months | 47.3 | 5.0 | 57 (1 month), # 48 (6 months), # 29 (12 months), # | - | Suicide: 1 Suicide attempt: 1 | |
Holtzheimer et al., 2012 | Open-label | 17 | 24 months | 42 | 5.34 | 41 (6 months), # 36 (12 months), # 92 (24 months), # | 18 (6 months) 36 (12 months) 58 (24 months) | Suicidal ideation: 1 Suicide attempt: 2 | |
Merkl et al., 2013 | Open-label | 6 | 24 h Last follow up (24–36 weeks) | 50.66 | 2.13 | 33.33 (36 weeks), # | 33.33 (36 weeks) | Headaches: 6 Tenseness in neck region: 1 | |
Holtzheimer et al., 2017 | RCT | 60 (52) | 6 months (24 months) | 50.53 | 12.62 | 22 (6 months), ‡ 54 (12 months), ‡ 48 (24 months), ‡ | 10 (6 months) 17 (12 months) 25 (24 months) | Suicide attempt: 2 Suicidal ideation: 2 Seizure: 2 | |
Eitan et al., 2018 | RCT HF vs. LF DBS | 9 | 13 months | 46 | - | 44.44 (13 months), ‡ | - | - | |
Merkl et al., 2018 | RCT | 8 | 28 months (n = 6) 4 years (n = 2) | 48.25 | 2 | 37.5 (6 months), # 43.0 (12 months), # 23.0 (28 months), # | 12.5 (6 months) 14.2 (12 months) 33.0 (24 months) 33.3 (28 months) | Manic episode: 1 | |
Crowell et al., 2019 | Open-label | 28 | 4 (n = 14) 8 (n = 11) years | 44.9 (45.9) | 45.1 (46.6) | 18 # | 21 | Suicide attempt: 6 Suicidal ideation: 8 Anxiety: 6 Worsening depression: 2 | |
PGR | Accolla et al., 2016 | Open-label | 5 (1) | 6 months (24 months) | 45.20 | - | - | - | - |
NAcc | Schlaepfer et al., 2008 | Open-label | 3 | 6–24 weeks | 46.7 | 7.2 | - | - | None |
Bewernick et al., 2010 | Open-label | 10 | 10 months | 48.6 | 10.8 | 50 (1 month), # 50 (6 months), # 50 (12 months), # | 30 (1 month) | Suicide: 1 Suicide attempt: 1 | |
Bewernick et al., 2012 | Open-label | 11 | 12 months 24 months Last follow up (max 4 years) | 48.36 | 9.26 | 45 (12 months), # | 9.1 (24 months) | Pain: 4 Seizure: 1 Agitation: 3 Suicide:1 Suicide attempt: 1 | |
VC/VS | Malone et al., 2009 | Open-label | 15 | 6 months (n = 15) 12 months (n = 11) | 46.3 | 21 | 20 (1 month), # 40 (6 months), # 53.3 (last follow-up) # | 20 (6 months) 40 (last follow-up) | Suicidal ideation: 2 Syncope: 1 Lead problem: 1 |
Dougherty et al., 2015 | RCT | 30 | 24 months | 47.7 | 11.4 | 20 (16 weeks), ¥ 20 (12 months), ¥ 23.3 (24 months), ¥ | 13 (12 months) 20 (24 months) | Suicide: 1 (stimulation off) Suicide attempt: 4 Suicidal ideation: 5 Lead revision: 3 | |
vALIC | Van der Wal et al., 2020 (follow-up of the RCT Bergfeld et al. 2016) | Open-label | 25 | 2 years | 52.5 | 7.42 | 32.0 (2 years, ITT) # | 20.0 (2 years, ITT) | Pain: 1 Agitation: 3 Suicidal ideation: 6 Fatigue: 4 |
Bergfeld et al., 2016 | RCT | 25 | 52 weeks | 53.2 | 6.98 | 40 (after optimization of DBS settings (T2)) # | 20 (T2) | Suicide attempt: 4 Suicidal ideation: 3 Automutilation: 1 | |
LHb | Sartorius et al., 2009 | Case-report | 1 | 60 weeks | 64.0 | 9.0 | - | - | - |
MFB | Schlaepfer et al., 2013 | Open-label | 7 | 12–33 weeks | 42.6 | 7.6 | 86, ¥ | 57 | Cranial bleeding: 1 |
Fenoy et al., 2016 (interim analysis) | Open-label | 4 | 52 weeks | - | - | 75 (7 days) ¥66 (26 weeks, OC) ¥ | - | - |
Brain Region | Function | Pathological Activity in MDD | HF-DBS Effect |
---|---|---|---|
SCG | Contains three white matter bundles; forceps minor + uncinate fasciculus connecting to the medial frontal cortex, cingulum connecting to the rostral and dorsal ACC and fronto-striatal fibers connecting to the NAcc, CN, Pt and anterior Th Connects higher ‘top-down’ cortical regions with subcortical modulatory regions Involvement in brain DMN [30] | Increased activity [31] Reduced volume in familial depression [32] Projections to: (1) NAcc may play a role in lack of interest, disruption in reward and underlie anhedonia (2) Hth and brainstem may play a role in circadian and sleep disturbances, problems with appetite and an abnormal stress responds and cortisol metabolism [31]. | Disruption of pathological activity Modulation of multiple regions connected to the SCG [31] |
NAcc | Receives projections from VTA, AG, OFC, mPFC, dCN, GP and Hip and projects to Cg25, mPFC, VP, Th, AG and Hth. Transmits information from emotion centers to motor control regions, causing motivational behavior to obtain rewards [33] Processes reward and pleasure information | In severe anhedonia; smaller size and less activation to reward [34] | Acute: Increase in exploratory motivation Chronic: reduction in anhedonia PET Imaging: ↑ activity in VS, bilateral dlPFC and dmPFC, cingulate cortex and bilateral AG. ↓ activity in vmPFC and vlPFC, dCN and Th [33] |
VC/VS | Contains fibers connecting the dPFC, dACC, OFC and vmPFC with THAL, AG, Hth and brainstem (SN, VTA, RN and PTN) [35] | Increased activity [36] Activation of the connection from left vs. to left caudate has been associated with anhedonia Increased connectivity of vs. to DMN is positively correlated to higher depression scores in the CES-D score [37] | - |
vALIC | Contains two fiber bundles: the anterior thalamic radiation and the supero-lateral branch of the MFB connecting the PFC to different subcortical structures such as the Th, NAcc, VTA and VS. Decreased integrity of the right vALIC in depressed patients [38] | - | Decreased metabolism in OFC, subgenual ACC and right DLPFC in patients with OCD [39] |
LHb | Activity corresponds negatively to anticipation and reception of a reward [40] | Increased activity [41] Possible down regulation of serotonergic, noradrenergic and dopaminergic systems [42], volume reduction [43] | Localized metabolic increase in one patient with FDG-PET, presumably due to functional inhibition [44] |
ITP | Interconnects the intralaminar nucleus and TRN with the OFC [30,45] | Hyperactivation in both TRN and OFC [46] | Cortical desynchronization Disruption of adrenergic and serotonergic malfunction [46] |
MFB | Interconnects the Nacc, VTA, vmHth, lHth and AG ventromedial and lateral nuclei of the Hth and AG with convergence onto the PFC [47,48] Plays a crucial role in the reward pathway; | Dysfunctional reward system. Responders showed a strong connectivity between the active electrode contact and the mPFC pre-operatively using individual DTI [49] | Insignificant changes in metabolism in 3 patients with PET measurements pre-operatively, 6 and 12 months post-operatively [49] |
BNST | Mayor output pathway of the AG Regulates stress response Integrates information from multiple brain areas to perform ‘valence surveillance’ [22,30] | Oscillatory activity with high a-power [50] | - |
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Roet, M.; Boonstra, J.; Sahin, E.; Mulders, A.E.P.; Leentjens, A.F.G.; Jahanshahi, A. Deep Brain Stimulation for Treatment-Resistant Depression: Towards a More Personalized Treatment Approach. J. Clin. Med. 2020, 9, 2729. https://doi.org/10.3390/jcm9092729
Roet M, Boonstra J, Sahin E, Mulders AEP, Leentjens AFG, Jahanshahi A. Deep Brain Stimulation for Treatment-Resistant Depression: Towards a More Personalized Treatment Approach. Journal of Clinical Medicine. 2020; 9(9):2729. https://doi.org/10.3390/jcm9092729
Chicago/Turabian StyleRoet, Milaine, Jackson Boonstra, Erdi Sahin, Anne E.P. Mulders, Albert F.G. Leentjens, and Ali Jahanshahi. 2020. "Deep Brain Stimulation for Treatment-Resistant Depression: Towards a More Personalized Treatment Approach" Journal of Clinical Medicine 9, no. 9: 2729. https://doi.org/10.3390/jcm9092729