Jason Yuen1,2, Aaron E Rusheen1,3, Joshua Blair Price1, Abhijeet S Barath1, Hojin Shin1,4, Abbas Z Kouzani5, Michael Berk2, Charles D Blaha1, Kendall H Lee1,4, Yoonbae Oh1,4. 1. Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA. 2. Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, VIC, Australia. 3. Medical Scientist Training Program, Mayo Clinic, Rochester, MN, USA. 4. Department of Biomedical Engineering, Mayo Clinic, Rochester, MN, USA. 5. School of Engineering, Deakin University, Geelong, VIC, Australia.
Abstract
OBJECTIVES: Despite recent advances in depression treatment, many patients still do not respond to serial conventional therapies and are considered "treatment resistant." Deep brain stimulation (DBS) has therapeutic potential in this context. This comprehensive review of recent studies of DBS for depression in animal models identifies potential biomarkers for improving therapeutic efficacy and predictability of conventional DBS to aid future development of closed-loop control of DBS system. MATERIALS AND METHODS: A systematic search was performed in Pubmed, EMBASE, and Cochrane Review using relevant keywords. In overall, 56 animal studies satisfied the inclusion criteria. RESULTS: Outcomes were divided into biochemical/physiological, electrophysiological, and behavioral categories. Promising biomarkers include biochemical assays (in particular, microdialysis and electrochemical measurements), which provide real-time results in awake animals. Electrophysiological tests, showing changes at both the target site and downstream structures also revealed characteristic changes at several anatomic targets (such as the medial prefrontal cortex and locus coeruleus). However, the substantial range of models and DBS targets limits the ability to draw generalizable conclusions in animal behavioral models. CONCLUSIONS: Overall, DBS is a promising therapeutic modality for treatment-resistant depression. Different outcomes have been used to assess its efficacy in animal studies. From the review, electrophysiological and biochemical markers appear to offer the greatest potential as biomarkers for depression. However, to develop closed-loop DBS for depression, additional preclinical and clinical studies with a focus on identifying reliable, safe, and effective biomarkers are warranted.
OBJECTIVES: Despite recent advances in depression treatment, many patients still do not respond to serial conventional therapies and are considered "treatment resistant." Deep brain stimulation (DBS) has therapeutic potential in this context. This comprehensive review of recent studies of DBS for depression in animal models identifies potential biomarkers for improving therapeutic efficacy and predictability of conventional DBS to aid future development of closed-loop control of DBS system. MATERIALS AND METHODS: A systematic search was performed in Pubmed, EMBASE, and Cochrane Review using relevant keywords. In overall, 56 animal studies satisfied the inclusion criteria. RESULTS: Outcomes were divided into biochemical/physiological, electrophysiological, and behavioral categories. Promising biomarkers include biochemical assays (in particular, microdialysis and electrochemical measurements), which provide real-time results in awake animals. Electrophysiological tests, showing changes at both the target site and downstream structures also revealed characteristic changes at several anatomic targets (such as the medial prefrontal cortex and locus coeruleus). However, the substantial range of models and DBS targets limits the ability to draw generalizable conclusions in animal behavioral models. CONCLUSIONS: Overall, DBS is a promising therapeutic modality for treatment-resistant depression. Different outcomes have been used to assess its efficacy in animal studies. From the review, electrophysiological and biochemical markers appear to offer the greatest potential as biomarkers for depression. However, to develop closed-loop DBS for depression, additional preclinical and clinical studies with a focus on identifying reliable, safe, and effective biomarkers are warranted.
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