Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has been reported to lead to rapid antidepressant effects. In this longitudinal study, we expand upon the initial results we reported at 26 weeks (Fenoy et al., 2016), showing sustained antidepressant effects of MFB DBS on six patients with treatment-resistant depression (TRD) over 1 year. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary assessment tool. Deterministic fiber tracking was used to individually map the target area; analysis was performed to compare modulated fiber tracts between patients. Intraoperatively, upon stimulation at target, responders reported immediate increases in energy and motivation. An insertional effect was seen during the 4-week sham stimulation phase from baseline (28% mean MADRS reduction, p = 0.02). However, after 1 week of initiating stimulation, three of six patients had a > 50% decrease in MADRS scores relative to baseline (43% mean MADRS reduction, p = 0.005). One patient withdrew from study participation. At 52 weeks, four of remaining five patients have > 70% decrease in MADRS scores relative to baseline (73% mean MADRS reduction, p = 0.007). Evaluation of modulated fiber tracts reveals significant common orbitofrontal connectivity to the target region in all responders. Neuropsychological testing and 18F-fluoro-deoxyglucose-positron emission tomography cerebral metabolism evaluations performed at baseline and at 52 weeks showed minimal changes and verified safety. This longitudinal evaluation of MFB DBS demonstrated rapid antidepressant effects, as initially reported by Schlaepfer et al. (2013), and supports the use of DBS for TRD.
The aims of this article are to discuss the rationale, design, and procedures of the Greater Houston Area Bipolar Registry (HBR), which aims at contributing to the effort involved in the investigation of neurobiological mechanisms underlying bipolar disorder (BD) as well as to identify clinical and neurobiological markers able to predict BD clinical course. The article will also briefly discuss examples of other initiatives that have made fundamental contributions to the field. This will be a longitudinal study with participants aged 6–17 at the time of enrollment. Participants will be required to meet diagnostic criteria for BD, or to be offspring of a parent with BD. We will also enroll healthy controls. Besides clinical information, which includes neurocognitive performance, participants will be asked to provide blood and saliva samples as well as to perform neuroimaging exams at baseline and follow-ups. Several studies point to the existence of genetic, inflammatory, and brain imaging alterations between individuals at higher genetic risk for BD compared with healthy controls. Longitudinal designs have shown high conversion rates to BD among high-risk offspring, with attempts to identify clinical predictors of disease onset, as well as clarifying the burden associated with environmental stressors. The HBR will help in the worldwide effort investigating the clinical course and neurobiological mechanisms of affected and high-risk children and adolescents with BD.
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