{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:07:06Z","timestamp":1789384026663,"version":"build-2803163510"},"reference-count":96,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Pers. Med.","JPM"],"abstract":"<jats:p>Background: Treatment-resistant depression (TRD) is an operational category based on inadequate outcome after adequate antidepressant treatment. The same label may encompass insufficient treatment exposure, an incorrect primary diagnosis, clinically important comorbidity, or depressive illnesses with different maintaining mechanisms. This heterogeneity limits the clinical meaning of treatment history alone and complicates individualized care. Objective: To integrate evidence on diagnostic reassessment, suicide risk, neurobiology, psychological and functional factors, and treatment, and to define a clinically testable personalized medicine framework for TRD. Methods: Targeted PubMed\/MEDLINE searches were conducted from database inception through 31 July 2026 and supplemented by reference-list searching. Two authors independently assessed publications for relevance, and disagreements were resolved by discussion and consensus. Ninety-six sources were included and synthesized narratively. Results: Inadequate exposure or adherence can produce pseudo-resistance, whereas bipolar spectrum illness, neurodevelopmental or trauma-related conditions, personality pathology, sleep or substance-related disorders, and medical disease may represent alternative diagnoses, comorbidities, or modifiers of treatment course. Glutamatergic signaling, impaired plasticity, stress-system dysregulation, inflammation, circadian disturbance, metabolism, and neural circuitry contribute to heterogeneity at the group level but do not define validated individual subtypes. Established pharmacological, psychological, and neuromodulatory interventions should be selected according to diagnosis, severity, urgency, previous response, comorbidity, functional impairment, safety, feasibility, and patient preference. Conclusions: TRD is an operational treatment-history category, not a unitary disease. A personalized medicine approach begins with confirmation of major depressive disorder, adequate treatment exposure and adherence, followed by parallel treatment of depression and clinically relevant comorbidity. Biomarkers should guide allocation only when they provide prospectively validated predictive value beyond high-quality clinical and functional assessment.<\/jats:p>","DOI":"10.3390\/jpm16090468","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:19:41Z","timestamp":1789381181000},"page":"468","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Treatment-Resistant Depression as a Heterogeneous Clinical Syndrome: A Personalized Medicine Framework for Diagnostic Reassessment, Suicide Risk, and Mechanism-Based Treatment"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7980-262X","authenticated-orcid":false,"given":"Davoud","family":"Amiri","sequence":"first","affiliation":[{"name":"Private Neuropsychiatric Practice, 753 10 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9116-6519","authenticated-orcid":false,"given":"Swetang J.","family":"Shah","sequence":"additional","affiliation":[{"name":"Bay Area Community Health, San Jose, CA 95127, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamberto","family":"Briziarelli","sequence":"additional","affiliation":[{"name":"Department of Public Health, University of Perugia, 06126 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9130-0384","authenticated-orcid":false,"given":"Sara","family":"Amiri","sequence":"additional","affiliation":[{"name":"Independent Researcher, 753 13 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/wps.21120","article-title":"Treatment-resistant depression: Definition, prevalence, detection, management, and investigational interventions","volume":"22","author":"McIntyre","year":"2023","journal-title":"World Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1038\/s41380-021-01381-x","article-title":"A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials","volume":"27","author":"Sforzini","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Gaynes, B.N., Asher, G., Gartlehner, G., Hoffman, V., Green, J., Boland, E., Lux, L., Weber, R.P., Randolph, C., and Bann, C. (2018). Definition of Treatment-Resistant Depression in the Medicare Population, AHRQ Technology Assessments.","DOI":"10.1002\/da.22968"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1177\/070674370705200108","article-title":"Definition, assessment, and staging of treatment-resistant refractory major depression: A review of current concepts and methods","volume":"52","author":"Berlim","year":"2007","journal-title":"Can. J. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jad.2011.02.020","article-title":"Staging methods for treatment-resistant depression: A systematic review","volume":"137","author":"Spijker","year":"2012","journal-title":"J. Affect. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1177\/07067437241245384","article-title":"Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults","volume":"69","author":"Lam","year":"2024","journal-title":"Can. J. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1399-5618.2007.00559.x","article-title":"Diagnostic guidelines for bipolar depression: A probabilistic approach","volume":"10","author":"Mitchell","year":"2008","journal-title":"Bipolar Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/j.1399-5618.2004.00137.x","article-title":"Bipolar depression: Phenomenological overview and clinical characteristics","volume":"6","author":"Mitchell","year":"2004","journal-title":"Bipolar Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.eurpsy.2018.11.001","article-title":"Updated European Consensus Statement on diagnosis and treatment of adult ADHD","volume":"56","author":"Kooij","year":"2019","journal-title":"Eur. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1017\/S0033291718002283","article-title":"Anxiety and depression in adults with autism spectrum disorder: A systematic review and meta-analysis","volume":"49","author":"Hollocks","year":"2019","journal-title":"Psychol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1037\/pst0000231","article-title":"A guide to guidelines for the treatment of posttraumatic stress disorder in adults: An update","volume":"56","author":"Hamblen","year":"2019","journal-title":"Psychotherapy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"334","DOI":"10.3109\/15622975.2013.804195","article-title":"World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders: Update 2013 on the acute and continuation treatment of unipolar depressive disorders","volume":"14","author":"Bauer","year":"2013","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S0006-3223(03)00231-2","article-title":"Diagnosis and definition of treatment-resistant depression","volume":"53","author":"Fava","year":"2003","journal-title":"Biol. Psychiatry"},{"key":"ref_14","first-page":"16","article-title":"Treatment-resistant depression","volume":"67","author":"Souery","year":"2006","journal-title":"J. Clin. Psychiatry"},{"key":"ref_15","unstructured":"National Institute for Health and Care Excellence (NICE) (2026, August 18). Depression in Adults: Treatment and Management (NG222), Available online: https:\/\/www.nice.org.uk\/guidance\/ng222."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1176\/ps.2009.60.11.1439","article-title":"What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression","volume":"60","author":"Gaynes","year":"2009","journal-title":"Psychiatr. Serv."},{"key":"ref_17","first-page":"369","article-title":"Treatment-resistant depression: Therapeutic trends, challenges, and future directions","volume":"6","year":"2012","journal-title":"Patient Prefer Adherence"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/bdi.12609","article-title":"Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder","volume":"20","author":"Yatham","year":"2018","journal-title":"Bipolar Disord."},{"key":"ref_19","unstructured":"Goodwin, F.K., and Jamison, K.R. (2007). Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression, Oxford University Press. [2nd ed.]."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"161","DOI":"10.4088\/JCP.v64n0209","article-title":"Perceptions and impact of bipolar disorder: How far have we really come? Results of the National Depressive and Manic-Depressive Association 2000 survey of individuals with bipolar disorder","volume":"64","author":"Hirschfeld","year":"2003","journal-title":"J. Clin. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s12402-016-0208-3","article-title":"The descriptive epidemiology of DSM-IV adult ADHD in the World Health Organization World Mental Health Surveys","volume":"9","author":"Fayyad","year":"2017","journal-title":"Atten. Defic. Hyperact Disord."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1176\/ajp.2006.163.4.716","article-title":"The prevalence and correlates of adult ADHD in the United States: Results from the National Comorbidity Survey Replication","volume":"163","author":"Kessler","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1016\/j.euroneuro.2016.09.369","article-title":"Attention-deficit hyperactivity disorder comorbidity and antidepressant resistance among patients with major depression: A nationwide longitudinal study","volume":"26","author":"Chen","year":"2016","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_24","first-page":"137","article-title":"Adult ADHD and comorbid depression: A consensus-derived diagnostic algorithm for ADHD","volume":"5","author":"McIntosh","year":"2009","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Katzman, M.A., Bilkey, T.S., Chokka, P.R., Fallu, A., and Klassen, L.J. (2017). Adult ADHD and comorbid disorders: Clinical implications of a dimensional approach. BMC Psychiatry, 17.","DOI":"10.1186\/s12888-017-1463-3"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10802-018-0402-1","article-title":"Prevalence of depressive disorders in individuals with autism spectrum disorder: A meta-analysis","volume":"47","author":"Hudson","year":"2019","journal-title":"J. Abnorm. Child Psychol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1007\/s10803-016-2722-8","article-title":"Psychiatric co-occurring symptoms and disorders in young, middle-aged, and older adults with autism spectrum disorder","volume":"46","author":"Lever","year":"2016","journal-title":"J. Autism Dev. Disord."},{"key":"ref_28","unstructured":"National Institute for Health and Care Excellence (NICE) (2026, August 18). Autism Spectrum Disorder in Adults: Diagnosis and Management (CG142), Available online: https:\/\/www.nice.org.uk\/guidance\/cg142."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S2215-0366(19)30289-5","article-title":"Prevalence of co-occurring mental health diagnoses in the autism population: A systematic review and meta-analysis","volume":"6","author":"Lai","year":"2019","journal-title":"Lancet Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1521\/pedi_2013_27_070","article-title":"Influence of personality on the outcome of treatment in depression: Systematic review and meta-analysis","volume":"28","author":"Tyrer","year":"2014","journal-title":"J. Pers. Disord."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jad.2013.08.023","article-title":"Comorbidity of personality disorders in mood disorders: A meta-analytic review of 122 studies from 1988 to 2010","volume":"152\u2013154","author":"Friborg","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.psc.2008.03.015","article-title":"The Frequency of Personality Disorders in Psychiatric Patients","volume":"31","author":"Zimmerman","year":"2008","journal-title":"Psychiatr. Clin. N. Am."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1176\/ajp.2006.163.7.1173","article-title":"Descriptive and longitudinal observations on the relationship of borderline personality disorder and bipolar disorder","volume":"163","author":"Gunderson","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"ref_34","unstructured":"National Institute for Health and Care Excellence (NICE) (2026, August 18). Borderline Personality Disorder: Recognition and Management (CG78), Available online: https:\/\/www.nice.org.uk\/guidance\/cg78."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"h6161","DOI":"10.1136\/bmj.h6161","article-title":"Post-traumatic stress disorder","volume":"351","author":"Bisson","year":"2015","journal-title":"BMJ"},{"key":"ref_36","unstructured":"National Institute for Health and Care Excellence (NICE) (2026, August 18). Post-Traumatic Stress Disorder. NICE Guideline NG116, Available online: https:\/\/www.nice.org.uk\/guidance\/ng116."},{"key":"ref_37","unstructured":"Department of Veterans Affairs, and Department of Defense (2023). VA\/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder, Version 4.0."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/jts.20697","article-title":"Treatment of complex PTSD: Results of the ISTSS expert clinician survey on best practices","volume":"24","author":"Cloitre","year":"2011","journal-title":"J. Trauma. Stress"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"171","DOI":"10.9758\/cpn.2014.12.3.171","article-title":"The many faces of dissociation: Opportunities for innovative research in psychiatry","volume":"12","year":"2014","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1176\/appi.ajp.2020.20081251","article-title":"Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation","volume":"178","author":"McIntyre","year":"2021","journal-title":"Am. J. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1111\/jsr.12594","article-title":"European guideline for the diagnosis and treatment of insomnia","volume":"26","author":"Riemann","year":"2017","journal-title":"J. Sleep Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1378\/chest.14-0970","article-title":"International classification of sleep disorders\u2014Third edition: Highlights and modifications","volume":"146","author":"Sateia","year":"2014","journal-title":"Chest"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nri.2015.5","article-title":"The role of inflammation in depression: From evolutionary imperative to modern treatment target","volume":"16","author":"Miller","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","article-title":"Depression","volume":"392","author":"Malhi","year":"2018","journal-title":"Lancet"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1192\/S0007125000298504","article-title":"Depression and endocrine disorders: Focus on the thyroid and adrenal system","volume":"168","author":"Musselman","year":"1996","journal-title":"Br. J. Psychiatry Suppl."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1001\/jamapsychiatry.2018.0190","article-title":"Association of Depression and Anxiety Disorders With Autoimmune Thyroiditis: A Systematic Review and Meta-analysis","volume":"75","author":"Siegmann","year":"2018","journal-title":"JAMA Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41398-022-02121-7","article-title":"Hyperthyroidism and clinical depression: A systematic review and meta-analysis","volume":"12","author":"Bode","year":"2022","journal-title":"Transl. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"480","DOI":"10.2337\/dc12-1442","article-title":"A systematic review and meta-analysis of the association between depression and insulin resistance","volume":"36","author":"Kan","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_49","first-page":"30","article-title":"Psychiatric Symptoms in Cushing\u2019s Syndrome: A Systematic Review","volume":"17","author":"Lin","year":"2020","journal-title":"Innov. Clin. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"S402","DOI":"10.4103\/indianjpsychiatry.indianjpsychiatry_30_22","article-title":"Management of Psychiatric Disorders in Patients with Endocrine Disorders","volume":"64","author":"Mishra","year":"2022","journal-title":"Indian J. Psychiatry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1007\/s43440-025-00782-x","article-title":"The cortisol axis and psychiatric disorders: An updated review","volume":"77","author":"George","year":"2025","journal-title":"Pharmacol. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jpsychires.2021.01.014","article-title":"Treatment-resistant depression and risk of all-cause mortality and suicidality in Danish patients with major depression","volume":"135","author":"Gronemann","year":"2021","journal-title":"J. Psychiatr. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e3171","DOI":"10.1002\/brb3.3171","article-title":"Suicide-specific mortality among patients with treatment-resistant major depressive disorder, major depressive disorder with prior suicidal ideation or suicide attempts, or major depressive disorder alone","volume":"13","author":"Kern","year":"2023","journal-title":"Brain Behav."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1136\/ebmental-2022-300549","article-title":"Risk factors for suicide in adults: Systematic review and meta-analysis of psychological autopsy studies","volume":"25","author":"Favril","year":"2022","journal-title":"Evid.-Based Ment. Health"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1080\/13811118.2019.1691692","article-title":"Risk Factors for Suicide and Suicide Attempts Among Patients With Treatment-Resistant Depression: Nested Case-Control Study","volume":"25","author":"Reutfors","year":"2021","journal-title":"Arch. Suicide Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1001\/jamapsychiatry.2023.2833","article-title":"Determinants and Outcomes of Suicidal Behavior Among Patients With Major Depressive Disorder","volume":"80","author":"Lundberg","year":"2023","journal-title":"JAMA Psychiatry"},{"key":"ref_57","unstructured":"National Institute for Health and Care Excellence (NICE) (2026, August 18). Self-harm: Assessment, Management and Preventing Recurrence (NG225), Available online: https:\/\/www.nice.org.uk\/guidance\/ng225."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"416","DOI":"10.7326\/ANNALS-24-01938","article-title":"Assessment and Management of Patients at Risk for Suicide: Synopsis of the 2024 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines","volume":"178","author":"Brenner","year":"2025","journal-title":"Ann. Intern. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"f3646","DOI":"10.1136\/bmj.f3646","article-title":"Lithium in the prevention of suicide in mood disorders: Updated systematic review and meta-analysis","volume":"346","author":"Cipriani","year":"2013","journal-title":"BMJ"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"20451253231151327","DOI":"10.1177\/20451253231151327","article-title":"Ketamine and esketamine in suicidal thoughts and behaviors: A systematic review","volume":"13","author":"Jollant","year":"2023","journal-title":"Ther. Adv. Psychopharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00228-023-03605-1","article-title":"A systematic review and meta-analysis of the efficacy of ketamine and esketamine on suicidal ideation in treatment-resistant depression","volume":"80","author":"Wang","year":"2024","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e328","DOI":"10.1017\/S0033291725102183","article-title":"Systematic review and meta-analysis of the effectiveness of ECT in reducing suicidal ideation, self-harm, suicide, and mortality","volume":"55","author":"Naismith","year":"2025","journal-title":"Psychol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1192\/bjp.2018.233","article-title":"Augmentation therapies for treatment-resistant depression: Systematic review and meta-analysis","volume":"214","author":"Strawbridge","year":"2019","journal-title":"Br. J. Psychiatry"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e487","DOI":"10.4088\/JCP.14r09204","article-title":"Comparative efficacy, acceptability, and tolerability of augmentation agents in treatment-resistant depression: Systematic review and network meta-analysis","volume":"76","author":"Zhou","year":"2015","journal-title":"J. Clin. Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1177\/02698811221104058","article-title":"Systematic review and meta-analysis of augmentation and combination treatments for early-stage treatment-resistant depression","volume":"37","author":"Scott","year":"2023","journal-title":"J. Psychopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1176\/appi.ajp.2009.09030312","article-title":"Atypical antipsychotic augmentation in major depressive disorder: A meta-analysis of placebo-controlled randomized trials","volume":"166","author":"Nelson","year":"2009","journal-title":"Am. J. Psychiatry"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jad.2021.12.134","article-title":"Augmentation strategies for treatment-resistant major depression: A systematic review and network meta-analysis","volume":"302","author":"Joseph","year":"2022","journal-title":"J. Affect. Disord."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.jad.2014.05.053","article-title":"A systematic review and meta-analysis of lithium augmentation of tricyclic and second-generation antidepressants in major depression","volume":"168","author":"Nelson","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3109\/15622970903170835","article-title":"WFSBP Task Force on Brain Stimulation. WFSBP Guidelines on Brain Stimulation Treatments in Psychiatry","volume":"11","author":"Schlaepfer","year":"2010","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1001\/jamapsychiatry.2024.1787","article-title":"Accelerated Intermittent Theta-Burst Stimulation and Treatment-Refractory Bipolar Depression: A Randomized Clinical Trial","volume":"81","author":"Sheline","year":"2024","journal-title":"JAMA Psychiatry"},{"key":"ref_71","first-page":"17","article-title":"A patient-level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression","volume":"6","author":"Berry","year":"2013","journal-title":"Med. Devices"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Sobstyl, M., Kupryjaniuk, A., Prokopienko, M., and Rylski, M. (2022). Subcallosal Cingulate Cortex Deep Brain Stimulation for Treatment-Resistant Depression: A Systematic Review. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.780481"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.bbi.2020.02.010","article-title":"Inflammatory markers in depression: A meta-analysis of mean differences and variability in 5,166 patients and 5,083 controls","volume":"87","author":"Osimo","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e165","DOI":"10.1192\/bjo.2024.787","article-title":"Inflammatory biomarkers in depression: Scoping review","volume":"10","author":"Paganin","year":"2024","journal-title":"BJPsych Open"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.2147\/NDT.S114542","article-title":"Biomarkers for depression: Recent insights, current challenges and future prospects","volume":"13","author":"Strawbridge","year":"2017","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Jha, M.K., and Trivedi, M.H. (2018). Personalized antidepressant selection and pathway to novel treatments: Clinical utility of targeting inflammation. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010233"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.biopsych.2015.03.004","article-title":"Voxel-based meta-analytical evidence of structural disconnectivity in major depression and bipolar disorder","volume":"79","author":"Wise","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/mp.2016.60","article-title":"Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group","volume":"22","author":"Schmaal","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jad.2017.10.049","article-title":"Neuroimaging biomarkers as predictors of treatment outcome in major depressive disorder","volume":"233","author":"Fonseka","year":"2018","journal-title":"J. Affect. Disord."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1001\/jamapsychiatry.2013.143","article-title":"Toward a neuroimaging treatment selection biomarker for major depressive disorder","volume":"70","author":"McGrath","year":"2013","journal-title":"JAMA Psychiatry"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2217\/pgs-2018-0142","article-title":"Pharmacogenetic tests and depressive symptom remission: A meta-analysis of randomized controlled trials","volume":"20","author":"Bousman","year":"2019","journal-title":"Pharmacogenomics"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/s41397-018-0027-3","article-title":"Genotype, phenotype, and medication recommendation agreement among commercial pharmacogenetic-based decision support tools","volume":"18","author":"Bousman","year":"2018","journal-title":"Pharmacogenom. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9758\/cpn.2020.18.1.1","article-title":"Genetics of treatment outcomes in major depressive disorder: Present and Future","volume":"18","author":"Fabbri","year":"2020","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S2215-0366(16)00017-1","article-title":"Commercial pharmacogenetic-based decision-support tools in psychiatry","volume":"3","author":"Bousman","year":"2016","journal-title":"Lancet Psychiatry"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.jad.2018.08.056","article-title":"The effect of pharmacogenomic testing on response and remission rates in the acute treatment of major depressive disorder: A meta-analysis","volume":"241","author":"Rosenblat","year":"2018","journal-title":"J. Affect. Disord."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e53","DOI":"10.1192\/j.eurpsy.2026.12210","article-title":"Precision medicine in mental health: Applications, challenges, and recommendations","volume":"69","author":"Arango","year":"2026","journal-title":"Eur. Psychiatry"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Lin, E., Lin, C.H., and Lane, H.Y. (2020). Precision Psychiatry Applications with Pharmacogenomics: Artificial Intelligence and Machine Learning Approaches. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030969"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Kam, H., and Jeong, H. (2020). Pharmacogenomic Biomarkers and Their Applications in Psychiatry. Genes, 11.","DOI":"10.3390\/genes11121445"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Pagonabarraga, J., \u00c1lamo, C., Castellanos, M., D\u00edaz, S., and Manzano, S. (2023). Depression in Major Neurodegenerative Diseases and Strokes: A Critical Review of Similarities and Differences among Neurological Disorders. Brain Sci., 13.","DOI":"10.3390\/brainsci13020318"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/01.yco.0000218601.17722.5b","article-title":"Depression in neurological disorders: An update","volume":"19","author":"Rickards","year":"2006","journal-title":"Curr. Opin. Psychiatry"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"15020","DOI":"10.1038\/nrdp.2015.20","article-title":"Attention-deficit\/hyperactivity disorder","volume":"1","author":"Faraone","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41572-019-0138-4","article-title":"Autism spectrum disorder","volume":"6","author":"Lord","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1192\/bjp.188.1.13","article-title":"Personality disorder and the outcome of depression: Meta-analysis of published studies","volume":"188","author":"Tyrer","year":"2006","journal-title":"Br. J. Psychiatry"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Fernandes, B.S., Williams, L.M., Steiner, J., Leboyer, M., Carvalho, A.F., and Berk, M. (2017). The new field of precision psychiatry. BMC Med., 15.","DOI":"10.1186\/s12916-017-0849-x"},{"key":"ref_95","first-page":"CD010558","article-title":"Psychological therapies for treatment-resistant depression in adults","volume":"5","author":"Ijaz","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/15622975.2026.2659772","article-title":"Inflammation and treatment strategies for suicidal behavior","volume":"27","author":"Behera","year":"2026","journal-title":"World J. Biol. Psychiatry"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/9\/468\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:42:22Z","timestamp":1789382542000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/16\/9\/468"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,13]]},"references-count":96,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["jpm16090468"],"URL":"https:\/\/doi.org\/10.3390\/jpm16090468","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,13]]}}}