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Biomarkers for Deep Brain Stimulation in Animal Models of Depression
journal contribution
posted on 2021-01-01, 00:00 authored by Jason Yuen, Aaron E Rusheen, Joshua Blair Price, Abhijeet S Barath, Hojin Shin, Abbas KouzaniAbbas Kouzani, Michael BerkMichael Berk, Charles D Blaha, Kendall H Lee, Yoonbae OhObjectives
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.
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.
History
Journal
Neuromodulation: Technology at the Neural InterfaceArticle number
ner.13483Pagination
1 - 10Publisher
WileyLocation
London, Eng.Publisher DOI
ISSN
1094-7159eISSN
1525-1403Language
engPublication classification
C1 Refereed article in a scholarly journalUsage metrics
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Categories
Keywords
Animal studiesbiomarkerclosed-loop systemdeep brain stimulationdepressionneurosciencepsychiatryScience & TechnologyLife Sciences & BiomedicineMedicine, Research & ExperimentalClinical NeurologyResearch & Experimental MedicineNeurosciences & NeurologyTREATMENT-RESISTANT DEPRESSIONMEDIAL FOREBRAIN-BUNDLESUBCALLOSAL CINGULATE GYRUSVENTRAL CAPSULE\/VENTRAL STRIATUMVENTROMEDIAL PREFRONTAL CORTEXPITUITARY-ADRENAL AXISBETA-BAND ACTIVITYELECTROCONVULSIVE-THERAPYNUCLEUS-ACCUMBENSMAJOR DEPRESSION