Identification of a personalized intracranial biomarker of depression and response to DBS therapy

Abstract

Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) has shown promise as a therapy for refractory obsessive-compulsive disorder (OCD) [1,2] and major depressive disorder (MDD) [3]. DBS currently is ‘open-loop’ with stimulation parameters remaining fixed over time. In contrast, ‘closed-loop’ DBS delivers stimulation only when a biomarker of the target symptom state indicates it is needed, decreasing stimulation time-thereby potentially reducing the risk of side effects, prolonging battery life, and potentially improving efficacy by mitigating neural adaptation. This method has shown efficacy in treating epilepsy [4] and promise in treating Parkinson s disease [5]. One challenge to the development of closed-loop DBS for psychiatric indications is the dearth of biomarkers of symptom state [6]. Here, we report identification of an electrophysiological depression biomarker in a patient receiving DBS in the ALIC and nearby bed nucleus of the stria terminalis (BNST). This case represents a proof-of-concept that personalized biomarkers can be detected using existing commercially available DBS devices, marking a step towards the development of closed-loop systems. The patient is a 51-year-old man with a history of severe, treatment-refractory OCD (Yale-Brown Obsessive Compulsive Scale: Y-BOCS of 31) and co-morbid severe MDD. The patient s harm-based OCD began in his teenage years and was formally diagnosed at the age of 28 years. His OCD and depression did not adequately respond to trials of 5 SSRIs, 1 SNRI, augmentation strategies (2 antipsychotics, clomipramine, stimulant, IV ketamine), and transcranial magnetic stimulation. The patient had extensive trials of exposure-response prevention and psychodynamic therapy with limited benefit. Given this history of treatment refractoriness and significant functional impairment related to severe OCD and MDD, the patient was deemed an appropriate candidate for DBS targeting the ALIC, which has been shown to be helpful for both disorders [1e3].