{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T17:17:32Z","timestamp":1792343852386,"version":"4.4.0"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1038\/s41380-026-03493-8","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T12:00:13Z","timestamp":1771416013000},"page":"3674-3682","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sex differences in placebo and antidepressant response to intranasal esketamine for treatment-resistant depression"],"prefix":"10.1038","volume":"31","author":[{"given":"Marie","family":"Huc","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4818-2355","authenticated-orcid":false,"given":"Sara","family":"Siddiqi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mysa","family":"Myers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Colman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalina","family":"Salmaso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Jaworska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-1138","authenticated-orcid":false,"given":"Argel","family":"Aguilar-Valles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"3493_CR1","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1016\/S0140-6736(21)02143-7","volume":"398","author":"COVID-19 Mental Disorders Collaborators","year":"2021","unstructured":"COVID-19 Mental Disorders Collaborators. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet. 2021;398:1700\u201312.","journal-title":"Lancet"},{"key":"3493_CR2","doi-asserted-by":"publisher","first-page":"2133","DOI":"10.1016\/S0140-6736(24)00757-8","volume":"403","author":"GBD 2021 Diseases and Injuries Collaborators","year":"2024","unstructured":"GBD 2021 Diseases and Injuries Collaborators. Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403:2133\u201361.","journal-title":"Lancet"},{"key":"3493_CR3","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1111\/ejn.14547","volume":"53","author":"KA Dudek","year":"2021","unstructured":"Dudek KA, Dion-Albert L, Kaufmann FN, Tuck E, Lebel M, Menard C. Neurobiology of resilience in depression: immune and vascular insights from human and animal studies. Eur J Neurosci. 2021;53:183\u2013221.","journal-title":"Eur J Neurosci"},{"key":"3493_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpr.2021.102111","volume":"91","author":"J Ormel","year":"2022","unstructured":"Ormel J, Hollon SD, Kessler RC, Cuijpers P, Monroe SM. More treatment but no less depression: The treatment-prevalence paradox. Clin Psychol Rev. 2022;91:102111.","journal-title":"Clin Psychol Rev"},{"key":"3493_CR5","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1111\/bph.15753","volume":"179","author":"\u00c9 Borb\u00e9ly","year":"2022","unstructured":"Borb\u00e9ly \u00c9, Simon M, Fuchs E, Wiborg O, Cz\u00e9h B, Helyes Z. Novel drug developmental strategies for treatment\u2010resistant depression. Br J Pharmacol. 2022;179:1146\u201386.","journal-title":"Br J Pharmacol"},{"key":"3493_CR6","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1176\/appi.ajp.2020.20081251","volume":"178","author":"RS McIntyre","year":"2021","unstructured":"McIntyre RS, Rosenblat JD, Nemeroff CB, Sanacora G, Murrough JW, Berk M, et al. Synthesizing the evidence for ketamine and esketamine in treatment-resistant depression: An international expert opinion on the available evidence and implementation. Am J Psychiatry. 2021;178:383\u201399.","journal-title":"Am J Psychiatry"},{"key":"3493_CR7","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1080\/15622975.2019.1635270","volume":"20","author":"L Bartova","year":"2019","unstructured":"Bartova L, Dold M, Kautzky A, Fabbri C, Spies M, Serretti A, et al. Results of the European Group for the Study of Resistant Depression (GSRD) - basis for further research and clinical practice. World J Biol Psychiatry. 2019;20:427\u201348.","journal-title":"World J Biol Psychiatry"},{"key":"3493_CR8","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1038\/s41386-020-0644-9","volume":"45","author":"CG Abdallah","year":"2020","unstructured":"Abdallah CG, Averill LA, Gueorguieva R, Goktas S, Purohit P, Ranganathan M, et al. Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin. Neuropsychopharmacology. 2020;45:990\u20137.","journal-title":"Neuropsychopharmacology"},{"key":"3493_CR9","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1016\/j.jad.2020.09.071","volume":"278","author":"A Bahji","year":"2021","unstructured":"Bahji A, Vazquez GH, Zarate CA. Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis. J Affect Disord. 2021;278:542\u201355.","journal-title":"J Affect Disord"},{"key":"3493_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2022.114579","volume":"312","author":"K Benitah","year":"2022","unstructured":"Benitah K, Siegel AN, Lipsitz O, Rodrigues NB, Meshkat S, Lee Y, et al. Sex differences in ketamine\u2019s therapeutic effects for mood disorders: A systematic review. Psychiatry Res. 2022;312:114579.","journal-title":"Psychiatry Res"},{"key":"3493_CR11","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1093\/ijnp\/pyab082","volume":"25","author":"E Ponton","year":"2021","unstructured":"Ponton E, Turecki G, Nagy C. Sex differences in the behavioral, molecular, and structural effects of ketamine treatment in depression. Int J Neuropsychopharmacol. 2021;25:75\u201384.","journal-title":"Int J Neuropsychopharmacol"},{"key":"3493_CR12","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1146\/annurev-med-051322-120608","volume":"75","author":"J-W Kim","year":"2024","unstructured":"Kim J-W, Suzuki K, Kavalali ET, Monteggia LM. Ketamine: Mechanisms and relevance to treatment of depression. Annu Rev Med. 2024;75:129\u201343.","journal-title":"Annu Rev Med"},{"key":"3493_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2021.114892","volume":"197","author":"EM Hess","year":"2022","unstructured":"Hess EM, Riggs LM, Michaelides M, Gould TD. Mechanisms of ketamine and its metabolites as antidepressants. Biochem Pharmacol. 2022;197:114892.","journal-title":"Biochem Pharmacol"},{"key":"3493_CR14","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1176\/appi.ajp.2018.18070834","volume":"176","author":"JL Phillips","year":"2019","unstructured":"Phillips JL, Norris S, Talbot J, Birmingham M, Hatchard T, Ortiz A, et al. Single, repeated, and maintenance ketamine infusions for treatment-resistant depression: A randomized controlled trial. AJP. 2019;176:401\u20139.","journal-title":"AJP"},{"key":"3493_CR15","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/mp.2017.255","volume":"23","author":"P Zanos","year":"2018","unstructured":"Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018;23:801\u201311.","journal-title":"Mol Psychiatry"},{"key":"3493_CR16","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/s00737-021-01185-6","volume":"25","author":"RR Jones","year":"2022","unstructured":"Jones RR, Freeman MP, Kornstein SG, Cooper K, Daly EJ, Canuso CM, et al. Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: findings from short-term randomized, controlled trials. Arch Womens Ment Health. 2022;25:313\u201326.","journal-title":"Arch Womens Ment Health"},{"key":"3493_CR17","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2023.1283733","volume":"14","author":"C Chrenek","year":"2023","unstructured":"Chrenek C, Duong B, Khullar A, McRee C, Thomas R, Swainson J. Use of ketamine for treatment resistant depression: updated review of literature and practical applications to a community ketamine program in Edmonton, Alberta, Canada. Front Psychiatry. 2023;14:1283733.","journal-title":"Front Psychiatry"},{"key":"3493_CR18","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.tins.2023.12.004","volume":"47","author":"V Lewis","year":"2024","unstructured":"Lewis V, Rurak G, Salmaso N, Aguilar-Valles A. An integrative view on the cell-type-specific mechanisms of ketamine\u2019s antidepressant actions. Trends Neurosci. 2024;47:195\u2013208.","journal-title":"Trends Neurosci"},{"key":"3493_CR19","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/jnc.15652","volume":"166","author":"V Lewis","year":"2023","unstructured":"Lewis V, Rodrigue B, Arsenault E, Zhang M, Taghavi-Abkuh F-F, Silva WCC, et al. Translational control by ketamine and its implications for comorbid cognitive deficits in depressive disorders. J Neurochem. 2023;166:10\u201323.","journal-title":"J Neurochem"},{"key":"3493_CR20","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/s41586-020-03047-0","volume":"590","author":"A Aguilar-Valles","year":"2021","unstructured":"Aguilar-Valles A, De Gregorio D, Matta-Camacho E, Eslamizade MJ, Khlaifia A, Skaleka A, et al. Antidepressant actions of ketamine engage cell-specific translation via eIF4E. Nature. 2021;590:315\u20139.","journal-title":"Nature"},{"key":"3493_CR21","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1037\/bul0000102","volume":"143","author":"RH Salk","year":"2017","unstructured":"Salk RH, Hyde JS, Abramson LY. Gender differences in depression in representative national samples: Meta-analyses of diagnoses and symptoms. Psychol Bull. 2017;143:783\u2013822.","journal-title":"Psychol Bull"},{"key":"3493_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11920-019-1088-y","volume":"21","author":"JL Oliffe","year":"2019","unstructured":"Oliffe JL, Rossnagel E, Seidler ZE, Kealy D, Ogrodniczuk JS, Rice SM. Men\u2019s Depression and Suicide. Curr Psychiatry Rep. 2019;21:1\u20136.","journal-title":"Curr Psychiatry Rep"},{"key":"3493_CR23","doi-asserted-by":"publisher","first-page":"447","DOI":"10.31887\/DCNS.2016.18.4\/ncutler","volume":"18","author":"JJ Sramek","year":"2016","unstructured":"Sramek JJ, Murphy MF, Cutler NR. Sex differences in the psychopharmacological treatment of depression. Dialogues Clin Neurosci. 2016;18:447\u201357.","journal-title":"Dialogues Clin Neurosci"},{"key":"3493_CR24","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.jad.2014.06.018","volume":"167","author":"G Parker","year":"2014","unstructured":"Parker G, Fletcher K, Paterson A, Anderson J, Hong M. Gender differences in depression severity and symptoms across depressive sub-types. J Affect Disord. 2014;167:351\u20137.","journal-title":"J Affect Disord"},{"key":"3493_CR25","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.jpsychires.2019.01.010","volume":"110","author":"MP Freeman","year":"2019","unstructured":"Freeman MP, Papakostas GI, Hoeppner B, Mazzone E, Judge H, Cusin C, et al. Sex differences in response to ketamine as a rapidly acting intervention for treatment resistant depression. J Psychiatr Res. 2019;110:166\u201371.","journal-title":"J Psychiatr Res"},{"key":"3493_CR26","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/1747-597X-9-39","volume":"9","author":"W-Y Chen","year":"2014","unstructured":"Chen W-Y, Huang M-C, Lin S-K. Gender differences in subjective discontinuation symptoms associated with ketamine use. Subst Abuse Treat Prev Policy. 2014;9:39.","journal-title":"Subst Abuse Treat Prev Policy"},{"key":"3493_CR27","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1097\/ALN.0b013e3181b437b1","volume":"111","author":"M Sigtermans","year":"2009","unstructured":"Sigtermans M, Dahan A, Mooren R, Bauer M, Kest B, Sarton E, et al. S(+)-ketamine effect on experimental pain and cardiac output: A population pharmacokinetic-pharmacodynamic modeling study in healthy volunteers. Anesthesiology. 2009;111:892\u2013903.","journal-title":"Anesthesiology"},{"key":"3493_CR28","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.biopsych.2012.03.004","volume":"72","author":"CA Zarate","year":"2012","unstructured":"Zarate CA, Brutsche N, Laje G, Luckenbaugh DA, Venkata SLV, Ramamoorthy A, et al. Relationship of ketamine\u2019s plasma metabolites with response, diagnosis, and side effects in major depression. Biol Psychiatry. 2012;72:331\u20138.","journal-title":"Biol Psychiatry"},{"key":"3493_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45157-7","volume":"15","author":"T Di Ianni","year":"2024","unstructured":"Di Ianni T, Ewbank SN, Levinstein MR, Azadian MM, Budinich RC, Michaelides M, et al. Sex dependence of opioid-mediated responses to subanesthetic ketamine in rats. Nat Commun. 2024;15:893.","journal-title":"Nat Commun"},{"key":"3493_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2024.111095","volume":"135","author":"V Grasso","year":"2024","unstructured":"Grasso V, Gutierrez G, Alzbeidi N, Hernandorena C, V\u00e1zquez GH. Cognitive changes in patients with unipolar TRD treated with IV ketamine: A systematic review. Prog Neuro-Psychopharmacol Biol Psychiatry. 2024;135:111095.","journal-title":"Prog Neuro-Psychopharmacol Biol Psychiatry"},{"key":"3493_CR31","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.biopsych.2025.04.020","volume":"98","author":"MB Pomrenze","year":"2025","unstructured":"Pomrenze MB, Vaillancourt S, Llorach P, Rijsketic DR, Casey AB, Gregory N, et al. Ketamine evokes acute behavioral effects via \u03bc opioid receptor\u2013expressing neurons of the central amygdala. Biol Psychiatry. 2025;98:538\u201348.","journal-title":"Biol Psychiatry"},{"key":"3493_CR32","doi-asserted-by":"publisher","first-page":"2958","DOI":"10.1038\/s41591-025-03800-w","volume":"31","author":"LA Jelen","year":"2025","unstructured":"Jelen LA, Lythgoe DJ, Stone JM, Young AH, Mehta MA. Effect of naltrexone pretreatment on ketamine-induced glutamatergic activity and symptoms of depression: a randomized crossover study. Nat Med. 2025;31:2958\u201366.","journal-title":"Nat Med"},{"key":"3493_CR33","doi-asserted-by":"publisher","first-page":"5096","DOI":"10.1038\/s41380-022-01757-7","volume":"27","author":"RB Price","year":"2022","unstructured":"Price RB, Kissel N, Baumeister A, Rohac R, Woody ML, Ballard ED, et al. International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators. Mol Psychiatry. 2022;27:5096\u2013112.","journal-title":"Mol Psychiatry"},{"key":"3493_CR34","unstructured":"Janssen Research & Development, LLC. A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Adult Subjects Assessed to be at Imminent Risk for Suicide. clinicaltrials.gov; 2020."},{"key":"3493_CR35","unstructured":"Janssen Research & Development, LLC. An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression. clinicaltrials.gov; 2020."},{"key":"3493_CR36","unstructured":"Janssen Research & Development, LLC. A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Subjects With Treatment-resistant Depression. clinicaltrials.gov; 2020."},{"key":"3493_CR37","unstructured":"Janssen Research & Development, LLC. A Randomized, Double-blind, Multicenter Active-controlled Study to Evaluate the Efficacy, Pharmacokinetics, Safety and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Subjects With Treatment-resistant Depression. clinicaltrials.gov; 2024."},{"key":"3493_CR38","unstructured":"Janssen Pharmaceutical K.K. A Randomized, Double-blind, Multicenter, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Doses of Intranasal Esketamine in Japanese Subjects With Treatment Resistant Depression. clinicaltrials.gov; 2020."},{"key":"3493_CR39","unstructured":"Janssen Research & Development, LLC. A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Subjects With Treatment-resistant Depression. clinicaltrials.gov; 2020."},{"key":"3493_CR40","unstructured":"Janssen Research & Development, LLC. A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Intranasal Esketamine Plus an Oral Antidepressant in Elderly Subjects With Treatment-resistant Depression. clinicaltrials.gov; 2021."},{"key":"3493_CR41","unstructured":"Janssen Research & Development, LLC. A Double-Blind, Doubly-Randomized, Placebo-Controlled Study of Intranasal Esketamine in an Adaptive Treatment Protocol to Assess Safety and Efficacy in Treatment-Resistant Depression (SYNAPSE). clinicaltrials.gov; 2020."},{"key":"3493_CR42","unstructured":"Janssen Research & Development, LLC. A Randomized, Double-blind, Multicenter, Active-Controlled Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Treatment-resistant Depression. clinicaltrials.gov; 2020."},{"key":"3493_CR43","unstructured":"Janssen Research & Development, LLC. A Double-blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Subjects Who Are Assessed to be at Imminent Risk for Suicide. clinicaltrials.gov; 2024."},{"key":"3493_CR44","unstructured":"Janssen Research & Development, LLC. A Double-Blind, Double-Randomization, Placebo-Controlled Study of the Efficacy of Intravenous Esketamine in Adult Subjects With Treatment-Resistant Depression. clinicaltrials.gov; 2020."},{"key":"3493_CR45","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1176\/appi.ajp.2019.19020172","volume":"176","author":"V Popova","year":"2019","unstructured":"Popova V, Daly EJ, Trivedi M, Cooper K, Lane R, Lim P, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: A randomized double-blind active-controlled study. AJP. 2019;176:428\u201338.","journal-title":"AJP"},{"key":"3493_CR46","doi-asserted-by":"publisher","first-page":"693","DOI":"10.2147\/NDT.S391096","volume":"19","author":"X Chen","year":"2023","unstructured":"Chen X, Hou X, Bai D, Lane R, Zhang C, Canuso C, et al. Efficacy and safety of flexibly dosed esketamine nasal spray plus a newly initiated oral antidepressant in adult patients with treatment-resistant depression: A randomized, double-blind, multicenter, active-controlled study conducted in china and USA. Neuropsychiatr Dis Treat. 2023;19:693\u2013707.","journal-title":"Neuropsychiatr Dis Treat"},{"key":"3493_CR47","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-021-03538-y","volume":"21","author":"N Takahashi","year":"2021","unstructured":"Takahashi N, Yamada A, Shiraishi A, Shimizu H, Goto R, Tominaga Y. Efficacy and safety of fixed doses of intranasal Esketamine as an add-on therapy to Oral antidepressants in Japanese patients with treatment-resistant depression: a phase 2b randomized clinical study. BMC Psychiatry. 2021;21:526.","journal-title":"BMC Psychiatry"},{"key":"3493_CR48","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1093\/ijnp\/pyz039","volume":"22","author":"M Fedgchin","year":"2019","unstructured":"Fedgchin M, Trivedi M, Daly EJ, Melkote R, Lane R, Lim P, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: Results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22:616.","journal-title":"Int J Neuropsychopharmacol"},{"key":"3493_CR49","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.jagp.2019.10.008","volume":"28","author":"R Ochs-Ross","year":"2020","unstructured":"Ochs-Ross R, Daly EJ, Zhang Y, Lane R, Lim P, Morrison RL, et al. Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression\u2014TRANSFORM-3. Am J Geriatr Psychiatry. 2020;28:121\u201341.","journal-title":"Am J Geriatr Psychiatry"},{"key":"3493_CR50","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5\u00ae). American Psychiatric Pub; 2013.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"3493_CR51","first-page":"22","volume":"59","author":"DV Sheehan","year":"1998","unstructured":"Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59:22\u201333.","journal-title":"J Clin Psychiatry"},{"key":"3493_CR52","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1192\/bjp.134.4.382","volume":"134","author":"SA Montgomery","year":"1979","unstructured":"Montgomery SA, \u00c5sberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382\u20139.","journal-title":"Br J Psychiatry"},{"key":"3493_CR53","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1002\/mpr.1388","volume":"22","author":"LC Quilty","year":"2013","unstructured":"Quilty LC, Robinson JJ, Rolland J, Fruyt FD, Rouillon F, Bagby RM. The structure of the Montgomery\u2013\u00c5sberg depression rating scale over the course of treatment for depression. Int J Methods Psychiatr Res. 2013;22:175\u201384.","journal-title":"Int J Methods Psychiatr Res"},{"key":"3493_CR54","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S0165-0327(01)00451-7","volume":"72","author":"CJ Hawley","year":"2002","unstructured":"Hawley CJ, Gale TM, Sivakumaran T. Hertfordshire Neuroscience Research group. Defining remission by cut off score on the MADRS: Selecting the optimal value. J Affect Disord. 2002;72:177\u201384.","journal-title":"J Affect Disord"},{"key":"3493_CR55","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.bcp.2012.03.016","volume":"84","author":"KH Koh","year":"2012","unstructured":"Koh KH, Jurkovic S, Yang K, Choi S-Y, Jung JW, Kim KP, et al. Estradiol induces cytochrome P450 2B6 expression at high concentrations: implication in estrogen-mediated gene regulation in pregnancy. Biochem Pharmacol. 2012;84:93\u2013103.","journal-title":"Biochem Pharmacol"},{"key":"3493_CR56","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.3389\/fpsyg.2018.01072","volume":"9","author":"R Saylik","year":"2018","unstructured":"Saylik R, Raman E, Szameitat AJ. Sex differences in emotion recognition and working memory tasks. Front Psychol. 2018;9:1072.","journal-title":"Front Psychol"},{"key":"3493_CR57","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.jad.2017.08.027","volume":"225","author":"LM Jenkins","year":"2018","unstructured":"Jenkins LM, Kendall AD, Kassel MT, Patr\u00f3n VG, Gowins JR, Dion C, et al. Considering sex differences clarifies the effects of depression on facial emotion processing during fMRI. J Affect Disord. 2018;225:129\u201336.","journal-title":"J Affect Disord"},{"key":"3493_CR58","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1139\/jpn.0953","volume":"34","author":"P Fusar-Poli","year":"2009","unstructured":"Fusar-Poli P, Placentino A, Carletti F, Landi P, Allen P, Surguladze S, et al. Functional atlas of emotional faces processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. J Psychiatry Neurosci. 2009;34:418\u201332.","journal-title":"J Psychiatry Neurosci"},{"key":"3493_CR59","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1093\/scan\/nss137","volume":"9","author":"SL Weisenbach","year":"2014","unstructured":"Weisenbach SL, Rapport LJ, Briceno EM, Haase BD, Vederman AC, Bieliauskas LA, et al. Reduced emotion processing efficiency in healthy males relative to females. Soc Cogn Affect Neurosci. 2014;9:316\u201325.","journal-title":"Soc Cogn Affect Neurosci"},{"key":"3493_CR60","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.jad.2021.07.086","volume":"294","author":"S Daches","year":"2021","unstructured":"Daches S, Vine V, George CJ, Kovacs M. Age related sex differences in maladaptive regulatory responses to sadness: A study of youths at high and low familial risk for depression. J Affect Disord. 2021;294:574\u20139.","journal-title":"J Affect Disord"},{"key":"3493_CR61","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1080\/02699931.2015.1025707","volume":"30","author":"LM Bylsma","year":"2016","unstructured":"Bylsma LM, Yaroslavsky I, Rottenberg J, Kiss E, Kapornai K, Halas K, et al. Familiality of mood repair responses among youth with and without histories of depression. Cogn Emot. 2016;30:807\u201316.","journal-title":"Cogn Emot"},{"key":"3493_CR62","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1037\/0021-843X.100.4.569","volume":"100","author":"S Nolen-Hoeksema","year":"1991","unstructured":"Nolen-Hoeksema S. Responses to depression and their effects on the duration of depressive episodes. J Abnorm Psychol. 1991;100:569\u201382.","journal-title":"J Abnorm Psychol"},{"key":"3493_CR63","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1007\/s00038-018-1196-1","volume":"64","author":"A Miranda-Mendizabal","year":"2019","unstructured":"Miranda-Mendizabal A, Castellv\u00ed P, Par\u00e9s-Badell O, Alayo I, Almenara J, Alonso I, et al. Gender differences in suicidal behavior in adolescents and young adults: systematic review and meta-analysis of longitudinal studies. Int J Public Health. 2019;64:265\u201383.","journal-title":"Int J Public Health"},{"key":"3493_CR64","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1212\/WNL.0b013e31829a33bd","volume":"81","author":"WG Ondo","year":"2013","unstructured":"Ondo WG, Hossain MM, Gordon MF, Reess J. Predictors of placebo response in restless legs syndrome studies. Neurology. 2013;81:193\u20134.","journal-title":"Neurology"},{"key":"3493_CR65","first-page":"53","volume":"43","author":"CH Mallinckrodt","year":"2010","unstructured":"Mallinckrodt CH, Zhang L, Prucka WR, Millen BA. Signal detection and placebo response in schizophrenia: parallels with depression. Psychopharmacol Bull. 2010;43:53\u201372.","journal-title":"Psychopharmacol Bull"},{"key":"3493_CR66","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1017\/S1461145710001641","volume":"14","author":"A Yildiz","year":"2011","unstructured":"Yildiz A, Vieta E, Tohen M, Baldessarini RJ. Factors modifying drug and placebo responses in randomized trials for bipolar mania. Int J Neuropsychopharmacol. 2011;14:863\u201375.","journal-title":"Int J Neuropsychopharmacol"},{"key":"3493_CR67","doi-asserted-by":"publisher","DOI":"10.1111\/jne.12565","volume":"30","author":"R Moraga-Amaro","year":"2018","unstructured":"Moraga-Amaro R, van Waarde A, Doorduin J, de Vries EFJ. Sex steroid hormones and brain function: PET imaging as a tool for research. J Neuroendocrinol. 2018;30:e12565.","journal-title":"J Neuroendocrinol"},{"key":"3493_CR68","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1159\/000365248","volume":"61","author":"K Weimer","year":"2015","unstructured":"Weimer K, Colloca L, Enck P. Age and sex as moderators of the placebo response \u2013 an evaluation of systematic reviews and meta-analyses across medicine. Gerontology. 2015;61:97\u2013108.","journal-title":"Gerontology"},{"key":"3493_CR69","doi-asserted-by":"publisher","first-page":"4196","DOI":"10.3390\/ijms23084196","volume":"23","author":"\u00c1 Ortega","year":"2022","unstructured":"Ortega \u00c1, Salazar J, Galban N, Rojas M, Ariza D, Ch\u00e1vez-Castillo M, et al. Psycho-Neuro-Endocrine-Immunological basis of the placebo effect: Potential applications beyond pain therapy. Int J Mol Sci. 2022;23:4196.","journal-title":"Int J Mol Sci"},{"key":"3493_CR70","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.jagp.2014.05.007","volume":"23","author":"EM Brice\u00f1o","year":"2015","unstructured":"Brice\u00f1o EM, Rapport LJ, Kassel MT, Bieliauskas LA, Zubieta J-K, Weisenbach SL, et al. Age and gender modulate the neural circuitry supporting facial emotion processing in adults with major depressive disorder. Am J Geriatr Psychiatry. 2015;23:304\u201313.","journal-title":"Am J Geriatr Psychiatry"},{"key":"3493_CR71","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41531-025-00891-7","volume":"11","author":"S Siddiqi","year":"2025","unstructured":"Siddiqi S, Ortiz Z, Simard S, Li J, Lawrence K, Redmond M, et al. Race and ethnicity matter! Moving Parkinson\u2019s risk research towards diversity and inclusiveness. NPJ Parkinsons Dis. 2025;11:45.","journal-title":"NPJ Parkinsons Dis"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41380-026-03493-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-026-03493-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-026-03493-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:02:42Z","timestamp":1781510562000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41380-026-03493-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":71,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["3493"],"URL":"https:\/\/doi.org\/10.1038\/s41380-026-03493-8","relation":{},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"value":"1359-4184","type":"print"},{"value":"1476-5578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]},"assertion":[{"value":"30 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"AAV is a scientific advisor for BetterLife Pharma and previously held a research contract with Gilgamesh Pharma. None of these companies was involved in the current study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}