{"doi":"10.1016/j.brs.2021.06.009","title":"Identification of a personalized intracranial biomarker of depression and response to DBS therapy","abstract":"Deep brain stimulation (DBS) of the anterior limb of the internal capsule (ALIC) has shown promise as a therapy for refractory obsessive-compulsive disorder (OCD) [[1]Luyten L. Hendrickx S. Raymaekers S. Gabriëls L. Nuttin B. Electrical stimulation in the bed nucleus of the stria terminalis alleviates severe obsessive-compulsive disorder.Mol Psychiatr. 2016; 21: 1272-1280https://doi.org/10.1038/mp.2015.124Crossref PubMed Scopus (103) Google Scholar,[2]Mosley P.E. Windels F. Morris J. Coyne T. Marsh R. Giorni A. et al.A randomised, double-blind, sham-controlled trial of deep brain stimulation of the bed nucleus of the stria terminalis for treatment-resistant obsessive-compulsive disorder.Transl Psychiatry. 2021; : 11https://doi.org/10.1038/s41398-021-01307-9Crossref PubMed Scopus (8) Google Scholar] and major depressive disorder (MDD) [[3]Bergfeld I.O. Mantione M. Hoogendoorn M.L.C. Ruhé H.G. Notten P. Van Laarhoven J. et al.Deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression.JAMA Psychiatr. 2016; 73: 456-464https://doi.org/10.1001/jamapsychiatry.2016.0152Crossref PubMed Scopus (148) Google Scholar]. DBS currently is ‘open-loop’ with stimulation parameters remaining fixed over time. In contrast, ‘closed-loop’ DBS delivers stimulation only when a biomarker of the target symptom state indicates it is needed, decreasing stimulation time-thereby potentially reducing the risk of side effects, prolonging battery life, and potentially improving efficacy by mitigating neural adaptation. This method has shown efficacy in treating epilepsy [[4]Morrell M.J. RNS System in Epilepsy Study Group. Responsive cortical stimulation for the treatment of medically intractable partial epilepsy.Neurology. 2011; 77: 1295-1304https://doi.org/10.1212/WNL.0b013e3182302056Crossref PubMed Scopus (707) Google Scholar] and promise in treating Parkinson's disease [[5]Little S. Pogosyan A. Neal S. Zavala B. Zrinzo L. Hariz M. et al.Adaptive deep brain stimulation in advanced Parkinson disease.Ann Neurol. 2013; 74: 449-457https://doi.org/10.1002/ana.23951Crossref PubMed Scopus (652) Google Scholar]. One challenge to the development of closed-loop DBS for psychiatric indications is the dearth of biomarkers of symptom state [[6]Sani O.G. Yang Y. Lee M.B. Dawes H.E. Chang E.F. Shanechi M.M. Mood variations decoded from multi-site intracranial human brain activity.Nat Biotechnol. 2018; 36: 954https://doi.org/10.1038/nbt.4200Crossref PubMed Scopus (67) Google Scholar]. Here, we report identification of an electrophysiological depression biomarker in a patient receiving DBS in the ALIC and nearby bed nucleus of the stria terminalis (BNST). This case represents a proof-of-concept that personalized biomarkers can be detected using existing commercially available DBS devices, marking a step towards the development of closed-loop systems. The patient is a 51-year-old man with a history of severe, treatment-refractory OCD (Yale-Brown Obsessive Compulsive Scale: Y-BOCS of 31) and co-morbid severe MDD. The patient's harm-based OCD began in his teenage years and was formally diagnosed at the age of 28 years. His OCD and depression did not adequately respond to trials of 5 SSRIs, 1 SNRI, augmentation strategies (2 antipsychotics, clomipramine, stimulant, IV ketamine), and transcranial magnetic stimulation. The patient had extensive trials of exposure-response prevention and psychodynamic therapy with limited benefit. Given this history of treatment refractoriness and significant functional impairment related to severe OCD and MDD, the patient was deemed an appropriate candidate for DBS targeting the ALIC, which has been shown to be helpful for both disorders [1Luyten L. Hendrickx S. Raymaekers S. Gabriëls L. Nuttin B. Electrical stimulation in the bed nucleus of the stria terminalis alleviates severe obsessive-compulsive disorder.Mol Psychiatr. 2016; 21: 1272-1280https://doi.org/10.1038/mp.2015.124Crossref PubMed Scop","journal":"Brain stimulation","year":2021,"id":175543,"datarank":0.47670807455219194,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.0,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.96,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":345839,"name":"Katherine W. Scangos","orcid":"0000-0001-7983-7767","position":1,"is_corresponding":false},{"id":187652,"name":"Paul Larson","orcid":null,"position":2,"is_corresponding":false},{"id":716720,"name":"Tenzin Norbu","orcid":"0000-0001-7238-9463","position":3,"is_corresponding":false},{"id":471528,"name":"Anthony T. Lee","orcid":"0000-0003-2656-0519","position":4,"is_corresponding":false},{"id":716721,"name":"A Moses Lee","orcid":"0000-0003-0531-102X","position":5,"is_corresponding":false},{"id":704680,"name":"Adam C. Frank","orcid":"0000-0001-8203-8480","position":0,"is_corresponding":true}],"reference_count":12,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:47:15.431199Z","pmid":"34175247","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}