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Brain metabolic changes and clinical response to superolateral medial forebrain bundle deep brain stimulation for treatment-resistant depression

Abstract

Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle is an efficacious therapy for treatment-resistant depression, providing rapid antidepressant effects. In this study, we use 18F-fluorodeoxyglucose-positron emission tomography (PET) to identify brain metabolic changes over 12 months post-DBS implantation in ten of our patients, compared to baseline. The primary outcome measure was a 50% reduction in Montgomery–Åsberg Depression Rating Scale (MADRS) score, which was interpreted as a response. Deterministic fiber tracking was used to individually map the target area; probabilistic tractography was used to identify modulated fiber tracts modeled using the cathodal contacts. Eight of the ten patients included in this study were responders. PET imaging revealed significant decreases in bilateral caudate, mediodorsal thalamus, and dorsal anterior cingulate cortex metabolism that was evident at 6 months and continued to 12 months post surgery. At 12 months post-surgery, significant left ventral prefrontal cortical metabolic decreases were also observed. Right caudate metabolic decrease at 12 months was significantly correlated with mean MADRS reduction. Probabilistic tractography modeling revealed that such metabolic changes lay along cortico-limbic nodes structurally connected to the DBS target site. Such observed metabolic changes following DBS correlated with clinical response provide insights into how future studies can elaborate such data to create biomarkers to predict response, the development of which likely will require multimodal imaging analysis.

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Fig. 1: Group probabilistic DTI analysis.
Fig. 2: Group PET analysis at 6- and 12-month follow-up.
Fig. 3: Average PET changes in the caudate nuclei and MADRS scores for all subjects.

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Acknowledgements

The Center of Excellence on Mood Disorders is funded by the Pat Rutherford Jr. Chair in Psychiatry, John S. Dunn Foundation, and Anne and Don Fizer Foundation Endowment for Depression Research. We thank our patients for their participation.

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Contributions

AJF and CRC contributed to drafting the manuscript; all authors contributed to the final manuscript. CRC contributed to data collection, mathematical analysis, data processing, and figure development. AJF, JQ, and JCS contributed to clinical management and patient recruitment.

Corresponding authors

Correspondence to Christopher R. Conner or Albert J. Fenoy.

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Competing interests

AJF serves as a consultant for Medtronic, Inc and receives grant support from the NIH/NINDS (1R01NS113893-01A1). JQ receives research support from the NIH/NIMH (1R21MH117636-01A1), the Faillace Department of Psychiatry and Behavioral Sciences, and LivaNova; has speaker bureau membership with Myriad Neuroscience, Janssen Pharmaceuticals, and Abbvie; is a consultant for Eurofarma; is stockholder at Instituto de Neurociencias Dr. Joao Quevedo; and receives copyrights from Artmed Editora, Artmed Panamericana, and Elsevier/Academic Press. JCS receives grant/research support from Bristol-Meyers Squibb, Forest Laboratories, Merck, and Elan Pharmaceuticals, and serves as a consultant for Pfizer, Abbot, and Astellas Pharma, Inc. CRC reported no biomedical financial interests or potential conflicts of interest.

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Conner, C.R., Quevedo, J., Soares, J.C. et al. Brain metabolic changes and clinical response to superolateral medial forebrain bundle deep brain stimulation for treatment-resistant depression. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01726-0

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