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Review
. 2022 Feb;25(2):161-170.
doi: 10.1111/ner.13483.

Biomarkers for Deep Brain Stimulation in Animal Models of Depression

Jason Yuen  1 , Aaron E Rusheen  2 , Joshua Blair Price  3 , Abhijeet S Barath  3 , Hojin Shin  4 , Abbas Z Kouzani  5 , Michael Berk  6 , Charles D Blaha  3 , Kendall H Lee  4 , Yoonbae Oh  7
Affiliations
Review

Biomarkers for Deep Brain Stimulation in Animal Models of Depression

Jason Yuen et al. Neuromodulation. 2022 Feb.

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 systems.

Materials and methods: A systematic search was performed in Pubmed, EMBASE, and Cochrane Review using relevant keywords. 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.

Keywords: Animal studies; biomarker; closed-loop system; deep brain stimulation; depression; neuroscience; psychiatry.

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Conflict of interest statement

Conflict of interest disclosure: None.

Figures

Figure 1.
Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart of literature search. Among the 2020 excluded, 893 are conference abstracts, 390 are editorials or review papers, 98 are not in English and the others are deemed non-relevant to the topic, e. g., focusing on other diseases such as Parkinson’s or obsessive-compulsive disorder.
Figure 2.
Figure 2.
A schematic view of the major outcomes measured in the literature. Created with aspects from BioRender.com [176]
See this image and copyright information in PMC

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