Bilateral Habenula deep brain stimulation for treatment-resistant depression: clinical findings and electrophysiological features

Abstract

Deep brain stimulation (DBS) of structures in the brain’s reward system is a promising therapeutic option for patients with treatment-resistant depression (TRD). Recently, DBS of the habenula (HB) in the brain’s anti-reward system has also been reported to alleviate depressive symptoms in patients with TRD or bipolar disorder (BD). In this pilot open-label prospective study, we explored the safety and clinical effectiveness of HB–DBS treatment in seven patients with TRD or BD. Also, local field potentials (LFPs) were recorded from the patients’ left and right HB to explore the power and asymmetry of oscillatory activities as putative biomarkers of the underlying disease state. At 1-month follow-up (FU), depression and anxiety symptoms were both reduced by 49% (n = 7) along with substantial improvements in patients’ health status, functional impairment, and quality of life. Although the dropout rate was high and large variability in clinical response existed, clinical improvements were generally maintained throughout the study [56%, 46%, and 64% reduction for depression and 61%, 48%, and 70% reduction for anxiety at 3-month FU (n = 5), 6-month FU (n = 5), and 12-month FU (n = 3), respectively]. After HB–DBS surgery, sustained improvements in mania symptoms were found in two patients who presented with mild hypomania at baseline. Another patient, however, experienced an acute manic episode 2 months after surgery that required hospitalization. Additionally, weaker and more symmetrical HB LFP oscillatory activities were associated with more severe depression and anxiety symptoms at baseline, in keeping with the hypothesis that HB dysfunction contributes to MDD pathophysiology. These preliminary findings indicate that HB–DBS may offer a valuable treatment option for depressive symptoms in patients who suffer from TRD or BD. Larger and well-controlled studies are warranted to examine the safety and efficacy of HB–DBS for treatment-refractory mood disorders in a more rigorous fashion.

Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signaling to the hypothalamus and habenula

“…This conclusion was based on the combined observations that: (i) virus tracing identified the LHb as a downstream target of LA-A2AR + neurons; (ii) c-Fos expression analysis confirmed the functional activation of LS-A2AR-LHb pathway upon LS-A2AR activation, in accordance with a recently identified stress-induced functional circuit from LS to LHb (46); (iii) optogenetic activation of LS-A2AR + →LHb projections induced depressant effects. The identification of the LS-A2AR + →LHb pathway as a downstream target for LS-A2AR control of depressivelike behavior is consistent with the role of the LHb in the development of depression, as heralded by the persistent and robust activity in the LHb of depressed animals (47,48) (reviewed in (49)), by the experimental ability of increased LHb activity to trigger depressive-like behaviors (50)(51)(52), by the ability of the fast-acting antidepressant drug ketamine to wane LHb neuronal activity (53) and by the impact of deep-brain stimulation in the LHb to alleviate depressive-like symptoms (54,55). While the specific types of neurons in the LHb controlled by the LS-A2AR + neurons still await to be identified, LS-A2AR signaling is concluded to be an upstream regulator of the LHb to implement stress-induced depressivelike maladaptive behavior.…”

Habenula bibliometrics: Thematic development and research fronts of a resurgent field

“…Deep brain stimulation (DBS) is a new therapeutic approach for treatment-resistant depression (TRD) ( Holtzheimer et al, 2017 ; Dandekar et al, 2018 ; Drobisz and Damborska, 2019 ) and other psychiatric disorders ( Harmsen et al, 2020 ). In the past decade, a series of preliminary clinical studies has explored the efficacy and safety of Hb-DBS for treatment-refractory psychiatric disorders ( Yadid et al, 2013 ; Zhang C. et al, 2019 , 2022 ; Wang Y. et al, 2020 ; Zhang C. et al, 2021 ). Despite the limited sample size in each of the study and the primary disadvantages of DBS such as poor spatial resolution and invasiveness, therapeutic benefits of Hb-DBS were generally consistent throughout the various studies and pointed out the encouraging and promising potential of Hb-DBS as a viable therapeutic target.…”

ROS-Targeted Depression Therapy via BSA-Incubated Ceria Nanoclusters

“…1,2 Current therapeutic strategies include psychotherapy, electroconvulsive therapy, and the use of antidepressants, but all with limited outcomes. 3,4 Among all these strategies, the use of antidepressants is the most straightforward and low-stimulative one; however, around 30% of patients with depression do not respond to antidepressant treatment strategies. 5 The limited therapeutic outcomes after using antidepressants revealed a complicated pathogenesis of depression and the importance of developing non-neurotransmitter pharmaceuticals for depression prevention and treatment.…”

“…Depression is one of the most common and worldwide mental illnesses with high morbidity and mortality, probably leading to disability or suicide. , Current therapeutic strategies include psychotherapy, electroconvulsive therapy, and the use of antidepressants, but all with limited outcomes. , Among all these strategies, the use of antidepressants is the most straightforward and low-stimulative one; however, around 30% of patients with depression do not respond to antidepressant treatment strategies …”