{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T07:05:43Z","timestamp":1776495943466,"version":"3.51.2"},"posted":{"date-parts":[[2025,1,24]]},"group-title":"Neurology","reference-count":90,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Major depressive disorder (MDD) is a debilitating condition that inflicts significant personal and economic burdens and affects around 8% of the US population. Approximately 30% of patients with MDD do not respond to conventional antidepressant and psychotherapeutic treatments. Current treatment options for refractory MDD include transcranial magnetic stimulation (TMS) and invasive surgical procedures such as surgical ablation, vagus nerve stimulation, and deep brain stimulation. In this context, therapeutic ultrasound emerges as a promising alternative for treating refractory MDD, which has the unique advantage of combining non-invasiveness with selective targeting. Over the past 10 years, there has been a growth in focused ultrasound research, leading to an exponential increase in interest in the technology. To support the future development of ultrasound for treating MDD, we conducted a systematic review following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>We identified 86 relevant studies from 1975 through June 2025. Our inclusion criteria were peer-reviewed prospective cohort studies, case-control studies, and randomized controlled trials that report ultrasound efficacy for treating depression in humans or depressive-like behaviors in animal models (PROSPERO registration number: CRD42024626093). 23 studies met all inclusion criteria. We summarized ultrasonic techniques for treating depression and their efficacy.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Two focused ultrasound (FUS) techniques used to treat depression include magnetic resonance-guided focused ultrasound (MRgFUS) for capsulotomy and low-intensity focused ultrasound (LIFUS) neuromodulation. MRgFUS capsulotomy results in permanent lesioning, whereas LIFUS is non-lesional and thought to have temporary effects. In human trials, the response rate (\u226550% improvement in depression score from baseline) for MRgFUS capsulotomy and LIFUS neuromodulation were 53.85% and 69.2%, respectively. The odds ratio for LIFUS was 2.8. In addition, LIFUS neuromodulation had a large effect (|Cohen\u2019s d| &gt; 0.8) on reducing standard depression scale scores in humans or resolving depressive-like behaviors in rodents. The certainty of evidence is moderate for human trials and low for rodent models. MRgFUS capsulotomy had inconsistent lesioning success and a limited response rate, while LIFUS neuromodulation lacked systematic exploration of the parameter space and clear delineation of the underlying mechanisms. Future work should refine patient selection for MRgFUS capsulotomy and optimize the parameters for individualized functional targeting.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>LIFUS neuromodulation achieved a large reduction in depressive behaviors in both rodent models and human trials. We conclude that LIFUS neuromodulation is a promising, noninvasive option for treating refractory MDD.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.01.23.25320960","type":"posted-content","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T14:00:15Z","timestamp":1737727215000},"source":"Crossref","is-referenced-by-count":3,"title":["Ultrasound applications in the treatment of major depressive disorder (MDD): A systematic review of techniques and therapeutic potentials in clinical trials and animal model studies"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8785-9499","authenticated-orcid":false,"given":"Gansheng","family":"Tan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric C.","family":"Leuthardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025072401151288000_2025.01.23.25320960v3.1","unstructured":"Major Depression - National Institute of Mental Health (NIMH). https:\/\/www.nimh.nih.gov\/health\/statistics\/major-depression."},{"key":"2025072401151288000_2025.01.23.25320960v3.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.09.006"},{"key":"2025072401151288000_2025.01.23.25320960v3.3","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.120"},{"key":"2025072401151288000_2025.01.23.25320960v3.4","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/s41593-021-00860-2","article-title":"Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions","volume":"24","year":"2021","journal-title":"Nat. Neurosci"},{"key":"2025072401151288000_2025.01.23.25320960v3.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02780-6"},{"key":"2025072401151288000_2025.01.23.25320960v3.6","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1001\/jamapsychiatry.2015.0071","article-title":"Large-Scale Network Dysfunction in Major Depressive Disorder: A Meta-analysis of Resting-State Functional Connectivity","volume":"72","year":"2015","journal-title":"JAMA Psychiatry"},{"key":"2025072401151288000_2025.01.23.25320960v3.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.03.052"},{"key":"2025072401151288000_2025.01.23.25320960v3.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.10.028"},{"key":"2025072401151288000_2025.01.23.25320960v3.9","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/40.2.288"},{"key":"2025072401151288000_2025.01.23.25320960v3.10","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.113.504.1237"},{"key":"2025072401151288000_2025.01.23.25320960v3.11","unstructured":"InformedHealth.Org. (Institute for Quality and Efficiency in Health Care (IQWiG), 2006)."},{"key":"2025072401151288000_2025.01.23.25320960v3.12","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.163.1.28"},{"key":"2025072401151288000_2025.01.23.25320960v3.13","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S198774"},{"key":"2025072401151288000_2025.01.23.25320960v3.14","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1038\/s41380-020-0737-1","article-title":"Magnetic resonance-guided focused ultrasound capsulotomy for refractory obsessive compulsive disorder and major depressive disorder: clinical and imaging results from two phase I trials","volume":"25","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"2025072401151288000_2025.01.23.25320960v3.15","doi-asserted-by":"crossref","unstructured":"S, H., A, F., T, N., T, K. & T, T. Radiofrequency Ablation for Movement Disorders: Risk Factors for Intracerebral Hemorrhage, a Retrospective Analysis. Oper. Neurosurg. Hagerstown Md 21, (2021).","DOI":"10.1093\/ons\/opab169"},{"key":"2025072401151288000_2025.01.23.25320960v3.16","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-023-05033-y"},{"key":"2025072401151288000_2025.01.23.25320960v3.17","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291713000512"},{"key":"2025072401151288000_2025.01.23.25320960v3.18","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.13r08815"},{"key":"2025072401151288000_2025.01.23.25320960v3.19","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1093\/gerona\/glab235","article-title":"Repetitive Transcranial Magnetic Stimulation for Major Depressive Disorder in Older Adults: Systematic Review and Meta-analysis","volume":"77","year":"2022","journal-title":"J. Gerontol. A. Biol. Sci. Med. Sci"},{"key":"2025072401151288000_2025.01.23.25320960v3.20","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l1079"},{"key":"2025072401151288000_2025.01.23.25320960v3.21","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.brs.2024.04.002","article-title":"Does vibrotactile stimulation of the auricular vagus nerve enhance working memory? A behavioral and physiological investigation","volume":"17","year":"2024","journal-title":"Brain Stimulat"},{"key":"2025072401151288000_2025.01.23.25320960v3.22","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jad.2023.05.048","article-title":"The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials","volume":"337","year":"2023","journal-title":"J. Affect. Disord"},{"key":"2025072401151288000_2025.01.23.25320960v3.23","doi-asserted-by":"publisher","DOI":"10.1002\/da.23004"},{"key":"2025072401151288000_2025.01.23.25320960v3.24","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000336766.18197.8E"},{"key":"2025072401151288000_2025.01.23.25320960v3.25","doi-asserted-by":"publisher","DOI":"10.1080\/02656736.2022.2112309"},{"key":"2025072401151288000_2025.01.23.25320960v3.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.02.058"},{"key":"2025072401151288000_2025.01.23.25320960v3.27","doi-asserted-by":"crossref","unstructured":"Yi, S. et al. Ultrasound Stimulation of Prefrontal Cortex Improves Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice. Front. Psychiatry 13, (2022).","DOI":"10.3389\/fpsyt.2022.864481"},{"key":"2025072401151288000_2025.01.23.25320960v3.28","doi-asserted-by":"crossref","first-page":"885","DOI":"10.30773\/pi.2024.0016","article-title":"Effect of Low-Intensity Transcranial Focused Ultrasound Stimulation in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Sham-Controlled Clinical Trial","volume":"21","year":"2024","journal-title":"Psychiatry Investig"},{"key":"2025072401151288000_2025.01.23.25320960v3.29","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/cns.13463","article-title":"Low-intensity pulsed ultrasound ameliorates depression-like behaviors in a rat model of chronic unpredictable stress","volume":"27","year":"2021","journal-title":"CNS Neurosci. Ther"},{"key":"2025072401151288000_2025.01.23.25320960v3.30","doi-asserted-by":"crossref","unstructured":"Zhu, Y. et al. Transcranial ultrasound stimulation relieves depression in mice with chronic restraint stress. J. Neural Eng. 20, (2023).","DOI":"10.1088\/1741-2552\/ac8bfd"},{"key":"2025072401151288000_2025.01.23.25320960v3.31","first-page":"1022","article-title":"Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy","volume":"14","year":"2021","journal-title":"Brain Stimul. Basic Transl. Clin. Res. Neuromodulation"},{"key":"2025072401151288000_2025.01.23.25320960v3.32","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1161\/STROKEAHA.124.046679","article-title":"Progress in Noninvasive Low-Intensity Focused Ultrasound Neuromodulation","volume":"55","year":"2024","journal-title":"Stroke"},{"key":"2025072401151288000_2025.01.23.25320960v3.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurom.2024.07.008"},{"key":"2025072401151288000_2025.01.23.25320960v3.34","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1166\/jmihi.2020.2917","article-title":"Preliminary Research on Depression Treatment: Combination of Transcranial Magnetic Stimulation and MRI-Guided Low-Intensity Focused Ultrasound Pulsation","volume":"10","year":"2020","journal-title":"J. Med. Imaging Health Inform"},{"key":"2025072401151288000_2025.01.23.25320960v3.35","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1016\/j.biopsych.2017.05.008","article-title":"Treatment of Major Depressive Disorder via Magnetic Resonance\u2013Guided Focused Ultrasound Surgery","volume":"83","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"2025072401151288000_2025.01.23.25320960v3.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2024.08.015"},{"key":"2025072401151288000_2025.01.23.25320960v3.37","unstructured":"Riis, T. S. et al. Noninvasive Modulation of the Subcallosal Cingulate and Depression With Focused Ultrasonic Waves. Biol. Psychiatry 0, (2024)."},{"key":"2025072401151288000_2025.01.23.25320960v3.38","first-page":"1004","article-title":"Deep transcranial ultrasound stimulation using personalized acoustic metamaterials improves treatment-resistant depression in humans","volume":"18","year":"2025","journal-title":"Brain Stimul. Basic Transl. Clin. Res. Neuromodulation"},{"key":"2025072401151288000_2025.01.23.25320960v3.39","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph20032333"},{"key":"2025072401151288000_2025.01.23.25320960v3.40","doi-asserted-by":"crossref","unstructured":"Schachtner, J. N. et al. Transcranial focused ultrasound targeting the default mode network for the treatment of depression. Front. Psychiatry 16, (2025).","DOI":"10.3389\/fpsyt.2025.1451828"},{"key":"2025072401151288000_2025.01.23.25320960v3.41","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1109\/TNSRE.2024.3378976","article-title":"Ultrasound Stimulation Attenuates CRS-Induced Depressive Behavior by Modulating Dopamine Release in the Prefrontal Cortex","volume":"32","year":"2024","journal-title":"IEEE Trans. Neural Syst. Rehabil. Eng"},{"key":"2025072401151288000_2025.01.23.25320960v3.42","doi-asserted-by":"crossref","first-page":"036037","DOI":"10.1088\/1741-2552\/acdea9","article-title":"Ultrasound neuromodulation ameliorates chronic corticosterone-induced depression-and anxiety-like behaviors in mice","volume":"20","year":"2023","journal-title":"J. Neural Eng"},{"key":"2025072401151288000_2025.01.23.25320960v3.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46461-y"},{"key":"2025072401151288000_2025.01.23.25320960v3.44","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1109\/TBME.2018.2845689","article-title":"Antidepressant-Like Effect of Low-Intensity Transcranial Ultrasound Stimulation","volume":"66","year":"2019","journal-title":"IEEE Trans. Biomed. Eng"},{"key":"2025072401151288000_2025.01.23.25320960v3.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2017.04.008"},{"key":"2025072401151288000_2025.01.23.25320960v3.46","first-page":"78","article-title":"The chronic mild stress (CMS) model of depression: History, evaluation and usage","volume":"6","year":"2016","journal-title":"Neurobiol. Stress"},{"key":"2025072401151288000_2025.01.23.25320960v3.47","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-019-02084-y"},{"key":"2025072401151288000_2025.01.23.25320960v3.48","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2010_108"},{"key":"2025072401151288000_2025.01.23.25320960v3.49","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"2025072401151288000_2025.01.23.25320960v3.50","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1017\/neu.2014.22","article-title":"Exploratory meta-analysis on deep brain stimulation in treatment-resistant depression: Smith DF. Exploratory meta-analysis on deep brain stimulation in treatment-resistant depression","volume":"26","year":"2014","journal-title":"Acta Neuropsychiatr"},{"key":"2025072401151288000_2025.01.23.25320960v3.51","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"2025072401151288000_2025.01.23.25320960v3.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2024.108602"},{"key":"2025072401151288000_2025.01.23.25320960v3.53","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-14-43"},{"key":"2025072401151288000_2025.01.23.25320960v3.54","doi-asserted-by":"publisher","DOI":"10.2307\/1164588"},{"key":"2025072401151288000_2025.01.23.25320960v3.55","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2013.00863"},{"key":"2025072401151288000_2025.01.23.25320960v3.56","unstructured":"9.5.2 Identifying and measuring heterogeneity. https:\/\/handbook-5-1.cochrane.org\/chapter_9\/9_5_2_identifying_and_measuring_heterogeneity.htm."},{"key":"2025072401151288000_2025.01.23.25320960v3.57","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1109\/TBME.2023.3313987","article-title":"Device for Multifocal Delivery of Ultrasound Into Deep Brain Regions in Humans","volume":"71","year":"2024","journal-title":"IEEE Trans. Biomed. Eng"},{"key":"2025072401151288000_2025.01.23.25320960v3.58","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s00221-023-06750-2","article-title":"Investigation of non-invasive focused ultrasound efficacy on depressive-like behavior in hemiparkinsonian rats","volume":"242","year":"2024","journal-title":"Exp. Brain Res"},{"key":"2025072401151288000_2025.01.23.25320960v3.59","doi-asserted-by":"crossref","first-page":"5917","DOI":"10.1007\/s12035-024-04656-w","article-title":"Transcriptomic Alterations in the Hippocampus and Prefrontal Cortex of Rats with Chronic Unpredictable Stress Induced by Low-Intensity Pulsed Ultrasound","volume":"62","year":"2025","journal-title":"Mol. Neurobiol"},{"key":"2025072401151288000_2025.01.23.25320960v3.60","first-page":"291","article-title":"Technical and radiographic considerations for magnetic resonance imaging-guided focused ultrasound capsulotomy","volume":"135","year":"2021","journal-title":"J. Neurosurg"},{"key":"2025072401151288000_2025.01.23.25320960v3.61","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1093\/ons\/opaa240","article-title":"Magnetic Resonance-Guided Focused Ultrasound Capsulotomy for Treatment-Resistant Psychiatric Disorders","volume":"19","year":"2020","journal-title":"Oper. Neurosurg"},{"key":"2025072401151288000_2025.01.23.25320960v3.62","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41398-020-01072-1","article-title":"Examining cognitive change in magnetic resonance-guided focused ultrasound capsulotomy for psychiatric illness","volume":"10","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"2025072401151288000_2025.01.23.25320960v3.63","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1186\/s13256-023-04194-4","article-title":"Durable effects of deep brain ultrasonic neuromodulation on major depression: a case report","volume":"17","year":"2023","journal-title":"J. Med. Case Reports"},{"key":"2025072401151288000_2025.01.23.25320960v3.64","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000254439.02736.D8"},{"key":"2025072401151288000_2025.01.23.25320960v3.65","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.40541"},{"key":"2025072401151288000_2025.01.23.25320960v3.66","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40998-0"},{"key":"2025072401151288000_2025.01.23.25320960v3.67","unstructured":"CDC. Chapter 7: GRADE Criteria Determining Certainty of Evidence. ACIP GRADE Handbook for Developing Evidence-based Recommendations https:\/\/www.cdc.gov\/acip-grade-handbook\/hcp\/chapter-7-grade-criteria-determining-certainty-of-evidence\/index.html (2024)."},{"key":"2025072401151288000_2025.01.23.25320960v3.68","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1001\/jamapsychiatry.2016.3644","article-title":"Repetitive Transcranial Magnetic Stimulation for the Acute Treatment of Major Depressive Episodes: A Systematic Review With Network Meta-analysis","volume":"74","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"2025072401151288000_2025.01.23.25320960v3.69","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2014.02.016"},{"key":"2025072401151288000_2025.01.23.25320960v3.70","first-page":"1239","article-title":"Efficacy of Deep Brain Stimulation for Treatment-Resistant Depression: Systematic Review and Meta-Analysis","volume":"9","year":"2024","journal-title":"Biol. Psychiatry Cogn. Neurosci. Neuroimaging"},{"key":"2025072401151288000_2025.01.23.25320960v3.71","doi-asserted-by":"publisher","DOI":"10.1002\/da.22746"},{"key":"2025072401151288000_2025.01.23.25320960v3.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2017.11.012"},{"key":"2025072401151288000_2025.01.23.25320960v3.73","doi-asserted-by":"publisher","DOI":"10.1016\/j.comppsych.2019.152156"},{"key":"2025072401151288000_2025.01.23.25320960v3.74","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2017.16010034"},{"key":"2025072401151288000_2025.01.23.25320960v3.75","first-page":"676","article-title":"Vagus nerve stimulation in treatment-resistant depression: A one-year, randomized, sham-controlled trial","volume":"18","year":"2025","journal-title":"Brain Stimul. Basic Transl. Clin. Res. Neuromodulation"},{"key":"2025072401151288000_2025.01.23.25320960v3.76","doi-asserted-by":"publisher","DOI":"10.1097\/00124509-200403000-00004"},{"key":"2025072401151288000_2025.01.23.25320960v3.77","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145714000418"},{"key":"2025072401151288000_2025.01.23.25320960v3.78","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-023-01599-z"},{"key":"2025072401151288000_2025.01.23.25320960v3.79","first-page":"300","article-title":"Ablation Surgeries for Treatment-Resistant Depression: A Meta-Analysis and Systematic Review of Reported Case Series","volume":"100","year":"2023","journal-title":"Stereotact. Funct. Neurosurg"},{"key":"2025072401151288000_2025.01.23.25320960v3.80","first-page":"280","article-title":"Suggested Biomarkers for Major Depressive Disorder","volume":"55","year":"2018","journal-title":"Arch. Neuropsychiatry"},{"key":"2025072401151288000_2025.01.23.25320960v3.81","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.25543"},{"key":"2025072401151288000_2025.01.23.25320960v3.82","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0585-z"},{"key":"2025072401151288000_2025.01.23.25320960v3.83","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1111\/cns.12998","article-title":"A brain network model for depression: From symptom understanding to disease intervention","volume":"24","year":"2018","journal-title":"CNS Neurosci. Ther"},{"key":"2025072401151288000_2025.01.23.25320960v3.84","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01456-8"},{"key":"2025072401151288000_2025.01.23.25320960v3.85","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.024"},{"key":"2025072401151288000_2025.01.23.25320960v3.86","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2025.01.007"},{"key":"2025072401151288000_2025.01.23.25320960v3.87","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2021.06.010"},{"key":"2025072401151288000_2025.01.23.25320960v3.88","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-021-01101-7"},{"key":"2025072401151288000_2025.01.23.25320960v3.89","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2012.04.028"},{"key":"2025072401151288000_2025.01.23.25320960v3.90","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.14.1840"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.01.23.25320960","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:26:14Z","timestamp":1768508774000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.01.23.25320960"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,24]]},"references-count":90,"URL":"https:\/\/doi.org\/10.1101\/2025.01.23.25320960","relation":{},"subject":[],"published":{"date-parts":[[2025,1,24]]},"subtype":"preprint"}}