Deep brain stimulation for treatment-resistant depression: an integrative review of preclinical and clinical findings and translational implications

Abstract

Although deep brain stimulation (DBS) is an established treatment choice for Parkinson's disease (PD), essential tremor and movement disorders, its effectiveness for the management of treatment-resistant depression (TRD) remains unclear. Herein, we conducted an integrative review on major neuroanatomical targets of DBS pursued for the treatment of intractable TRD. The aim of this review article is to provide a critical discussion of possible underlying mechanisms for DBS-generated antidepressant effects identified in preclinical studies and clinical trials, and to determine which brain target(s) elicited the most promising outcomes considering acute and maintenance treatment of TRD. Major electronic databases were searched to identify preclinical and clinical studies that have investigated the effects of DBS on depression-related outcomes. Overall, 92 references met inclusion criteria, and have evaluated six unique DBS targets namely the subcallosal cingulate gyrus (SCG), nucleus accumbens (NAc), ventral capsule/ventral striatum or anterior limb of internal capsule (ALIC), medial forebrain bundle (MFB), lateral habenula (LHb) and inferior thalamic peduncle for the treatment of unrelenting TRD. Electrical stimulation of these pertinent brain regions displayed differential effects on mood transition in patients with TRD. In addition, 47 unique references provided preclinical evidence for putative neurobiological mechanisms underlying antidepressant effects of DBS applied to the ventromedial prefrontal cortex, NAc, MFB, LHb and subthalamic nucleus. Preclinical studies suggest that stimulation parameters and neuroanatomical locations could influence DBS-related antidepressant effects, and also pointed that modulatory effects on monoamine neurotransmitters in target regions or interconnected brain networks following DBS could have a role in the antidepressant effects of DBS. Among several neuromodulatory targets that have been investigated, DBS in the neuroanatomical framework of the SCG, ALIC and MFB yielded more consistent antidepressant response rates in samples with TRD. Nevertheless, more well-designed randomized double-blind, controlled trials are warranted to further assess the efficacy, safety and tolerability of these more promising DBS targets for the management of TRD as therapeutic effects have been inconsistent across some controlled studies.

Neural Correlates of Positive and Negative Valence System Dysfunction in Adolescents Revealed by Data-Driven Parcellation and Resting-State Network Modeling

“…Specifically, overall depression severity was positively correlated with both CStr and ELoc in the right sgACC, an area that is heavily implicated in depression. Increased sgACC activity is frequently reported in neuroimaging studies of depressed adults (37) and adolescents (38), while sgACC activity decreases following many types of depression treatment, including traditional antidepressants, ketamine, and deep brain stimulation (39)(40)(41). Resting-state fMRI studies have indicated that depression severity is associated with sgACC connectivity changes in adults with clinical (42) and subclinical (43) depression as well as depressed adolescents (44,45), which may be related to early-life changes in white mater microstructure (46,47).…”

Medial Prefrontal Cortex Interacts with the Anteromedial Thalamus in Motivation and Dopaminergic Activity

“…1d). Responding on the left "active" lever was rewarded with a train of photostimulation in sessions 3-7 (the acquisition phase) and [11][12][13][14] (re-acquisition), while no photostimulation was delivered in sessions 1-2 (baseline) or 8-10 (extinction). Responding on the right "inactive" lever produced no consequence throughout sessions 1-14.…”

“…Consistently, dysregulation of the PFC is associated with disorders of goal-directed behavior, including drug addiction and depression 5,6,7,8 . Recently, these disorders have been treated with PFC stimulation procedures such as deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), with promising results 9,10,11,12,13 . Such treatment effects most likely depend on large-scale brain circuitry regulating the motivation that drives goal-directed behavior 14 , and the details of such circuitry are currently incomplete.…”

Short but Continuous Natural Pain for Depression Treatment and Beyond

“…Deep brain stimulation (DBS), which is an established treatment for movement disorders and Parkinson's disease, has also been actively explored for its effectiveness of the management of treatment-resistant depression (TRD) in preclinical studies and clinical trials. An integrated review by Dandekar et al provides useful insights that 1) stimulation of pertinent brain regions displayed differential effects on mood transition in TRD patients, 2) stimulation parameters and neuroanatomical locations affected DBS-associated antidepressant effects, and 3) modulatory influence on monoamine neurotransmitters in target regions or interconnected brain network could be the potential mechanism (76).…”