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.
Highlights
Major depressive disorder (MDD) is a common psychiatric disorder with an estimated lifetime prevalence of 14.6% in high-income countries [1]
Deep brain stimulation (DBS) of the habenula (HB) in the brain’s anti-reward system has been reported to alleviate depressive symptoms in patients with treatmentresistant depression (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
We hypothesized that symptom severity would be associated with family life), and quality of life (QoL) as assessed by the Medical the power of HB local field potentials (LFPs) oscillatory activity, assuming that this spectral Outcome Studies (MOS) 36-item Short Form Health Survey (SF-36), feature accurately reflects the role of HB in negative motivational the Sheehan Disability Scale (SDS), and the World Health states [17]
Summary
Major depressive disorder (MDD) is a common psychiatric disorder with an estimated lifetime prevalence of 14.6% in high-income countries [1]. The target site was located about 0–2 mm in front of the posterior commissure, 3–5 mm lateral, and 0–1 mm above the anterior commissure–posterior commissure Both quadripolar DBS electrodes (model 3389, Medtronic, in which we recorded local field potentials (LFPs) from HB–DBS Minneapolis, MN, USA; or 1210-40, SceneRay, Suzhou, China) and electrodes in patients with psychotic or mood disorders while they the pulse generator (37603 SC, Medtronic; or 1180, SceneRay) were were viewing pictures with positive, negative, and neutral implanted under general anesthesia. We hypothesized that symptom severity would be associated with family life), and quality of life (QoL) as assessed by the Medical the power of HB LFP oscillatory activity, assuming that this spectral Outcome Studies (MOS) 36-item Short Form Health Survey (SF-36), feature accurately reflects the role of HB in negative motivational the Sheehan Disability Scale (SDS), and the World Health states [17]. 5-minute resting unipolar LFPs were recorded from
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