Biomarkers for Deep Brain Stimulation in Animal Models of Depression

Jason Yuen, Aaron E. Rusheen, Joshua Blair Price, Abhijeet S. Barath, Hojin Shin, Abbas Z. Kouzani, Michael Berk, Charles D. Blaha, Kendall H. Lee, Yoonbae Oh

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)161-170
Number of pages10
Issue number2
StatePublished - Feb 2022


  • Animal studies
  • biomarker
  • closed-loop system
  • deep brain stimulation
  • depression
  • neuroscience
  • psychiatry

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine


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