{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T08:49:33Z","timestamp":1763369373020,"version":"3.45.0"},"reference-count":37,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u2018III Convocatoria Intramural de la Fundaci\u00f3n Vital Fundazioa\u2013IIS BIOARABA"},{"name":"Mental Health Network of \u00c1lava"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This pilot study analyzed the changes in body composition, cardiorespiratory fitness (CRF), biochemical profile, clinical symptoms, and quality of life (QoL) of adults with resistant major depression (RMD) following 12 weeks of combined exercise training.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eighteen adults diagnosed with RMD (42.5\u00a0\u00b1\u00a09.9 years, 66.7% women) participated in a supervised exercise group (2 days\/week). The combined exercise training consisted of low-to-moderate intensity aerobic interval exercise on a bicycle and strength-resistance exercises. All variables were assessed pre- and post-intervention, including clinical symptoms with the Montgomery-\u00c5sberg Depression Rating Scale (MADRS), the Clinical Global Impressions Scale (CGI-S), the Sheehan Disability Scale (SDS), and health-related QoL with the Short Form-36. A symptom-limited cardiopulmonary exercise peak test was performed to evaluate CRF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The baseline results classified the participants as metabolically unhealthy with overweight\/obesity, moderate depression, and low CRF and QoL. Following the intervention, there were no significant changes (\n                      <jats:italic>P<\/jats:italic>\n                      &gt;\u00a00.05) in body composition, the main CRF physiological variables, and the biochemical profile. However, regarding clinical symptoms, the MADRS (mean difference \u22128.31, 95% confidence interval (CI) [\u221215.1 to \u22121.5],\n                      <jats:italic>P<\/jats:italic>\n                      = 0.021), CGI-S (mean difference -1.17, 95% CI [\u22121.92 to \u22120.41],\n                      <jats:italic>P<\/jats:italic>\n                      = 0.006), and SDS (mean difference -5.46, 95% CI [\u221210.8 to \u22120.12],\n                      <jats:italic>P<\/jats:italic>\n                      = 0.046) scores decreased, and the domains of health-related QoL \u2013general health (mean difference 13.8, 95% CI [2.9\u201324.8],\n                      <jats:italic>P<\/jats:italic>\n                      = 0.017), vitality (mean difference 10.4, 95% CI [0.26\u201320.5],\n                      <jats:italic>P<\/jats:italic>\n                      = 0.045), social functioning (mean difference 25.9, 95% CI [8.1\u201343.7],\n                      <jats:italic>P<\/jats:italic>\n                      = 0.008), and the mental component summary (mean difference 6.9, 95% CI [1.1\u201312.8],\n                      <jats:italic>P<\/jats:italic>\n                      = 0.024) increased.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A supervised combined exercise program in people with RMD may induce positive and beneficial changes in functionality and clinical and QoL variables, and maintain body composition, CRF, and the biochemical profile. These preliminary results highlight the critical role of supervised exercise, regardless of intensity, in improving clinical symptoms in people with RMD. This study was registered with the International Standard Randomized Controlled Trial Code NCT 05136027.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.20356","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T08:43:56Z","timestamp":1763369036000},"page":"e20356","source":"Crossref","is-referenced-by-count":0,"title":["Effects of combined exercise training for adults with resistant major depression: a pilot study from the TRACE-RMD project"],"prefix":"10.7717","volume":"13","author":[{"given":"Mikel","family":"Tous-Espelosin","sequence":"first","affiliation":[{"name":"Bioaraba Health Research Institute, Physical Activity, Exercise, and Health Group, Vitoria-Gasteiz, Spain"},{"name":"Gizartea, Kirola eta Ariketa Fisikoa Ikerkuntza Taldea (GIKAFIT), Society, Sports, and Physical Exercise Research Group, Department of Physical Education and Sport, Faculty of Education and Sport, Physical Activity and Sport Sciences Section, University of the Basque Country (UPV\/EHU), Vitoria-Gasteiz,  Araba\/\u00c1lava, Basque Country, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crist\u00f3bal","family":"Pav\u00f3n-Navajas","sequence":"additional","affiliation":[{"name":"Bioaraba Health Research Institute, New Therapies in Mental Health Group, Vitoria-Gasteiz, Spain"},{"name":"Osakidetza Basque Health Service, Araba Mental Health Network, Psychiatric Hospital of Alava,  Vitoria-Gasteiz, Araba\/\u00c1lava. Basque Country, Spain"},{"name":"Department of Medicine, Faculty of Health Sciences, University of Deusto, Bilbao, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Etxaniz-Oses","sequence":"additional","affiliation":[{"name":"Bioaraba Health Research Institute, Physical Activity, Exercise, and Health Group, Vitoria-Gasteiz, Spain"},{"name":"Gizartea, Kirola eta Ariketa Fisikoa Ikerkuntza Taldea (GIKAFIT), Society, Sports, and Physical Exercise Research Group, Department of Physical Education and Sport, Faculty of Education and Sport, Physical Activity and Sport Sciences Section, University of the Basque Country (UPV\/EHU), Vitoria-Gasteiz,  Araba\/\u00c1lava, Basque Country, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Teresa","family":"Ca\u00f1as-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Bioaraba Health Research Institute, New Therapies in Mental Health Group, Vitoria-Gasteiz, Spain"},{"name":"Osakidetza Basque Health Service, Araba Mental Health Network, Psychiatric Hospital of Alava,  Vitoria-Gasteiz, Araba\/\u00c1lava. Basque Country, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Maldonado-Martin","sequence":"additional","affiliation":[{"name":"Bioaraba Health Research Institute, Physical Activity, Exercise, and Health Group, Vitoria-Gasteiz, Spain"},{"name":"Gizartea, Kirola eta Ariketa Fisikoa Ikerkuntza Taldea (GIKAFIT), Society, Sports, and Physical Exercise Research Group, Department of Physical Education and Sport, Faculty of Education and Sport, Physical Activity and Sport Sciences Section, University of the Basque Country (UPV\/EHU), Vitoria-Gasteiz,  Araba\/\u00c1lava, Basque Country, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julene","family":"Orru\u00f1o-Vivar","sequence":"additional","affiliation":[{"name":"Osakidetza Basque Health Service, Araba Mental Health Network, Psychiatric Hospital of Alava,  Vitoria-Gasteiz, Araba\/\u00c1lava. Basque Country, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Corres","sequence":"additional","affiliation":[{"name":"Bioaraba Health Research Institute, Physical Activity, Exercise, and Health Group, Vitoria-Gasteiz, Spain"},{"name":"Gizartea, Kirola eta Ariketa Fisikoa Ikerkuntza Taldea (GIKAFIT), Society, Sports, and Physical Exercise Research Group, Department of Physical Education and Sport, Faculty of Education and Sport, Physical Activity and Sport Sciences Section, University of the Basque Country (UPV\/EHU), Vitoria-Gasteiz,  Araba\/\u00c1lava, Basque Country, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagore","family":"Iriarte-Yoller","sequence":"additional","affiliation":[{"name":"Bioaraba Health Research Institute, New Therapies in Mental Health Group, Vitoria-Gasteiz, Spain"},{"name":"Osakidetza Basque Health Service, Araba Mental Health Network, Psychiatric Hospital of Alava,  Vitoria-Gasteiz, Araba\/\u00c1lava. Basque Country, Spain"},{"name":"Department of Medicine, Faculty of Health Sciences, University of Deusto, Bilbao, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"issue":"20","key":"10.7717\/peerj.20356\/ref-1","first-page":"771","article-title":"The Spanish version of the SF-36 health survey (the SF-36 health questionnaire): an instrument for measuring clinical results","volume":"104","author":"Alonso","year":"1995","journal-title":"Medicina Clinica"},{"issue":"14","key":"10.7717\/peerj.20356\/ref-2","first-page":"530","article-title":"Validation of the Spanish version of the Liebowitz social anxiety scale, social anxiety and distress scale and Sheehan disability inventory for the evaluation of social phobia","volume":"112","author":"Bobes","year":"1999","journal-title":"Medicina Clinica"},{"issue":"5","key":"10.7717\/peerj.20356\/ref-3","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1249\/00005768-198205000-00012","article-title":"Psychophysical bases of perceived exertion","volume":"14","author":"Borg","year":"1982","journal-title":"Medicine and Science in Sports and Exercise"},{"issue":"24","key":"10.7717\/peerj.20356\/ref-4","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1136\/bjsports-2020-102955","article-title":"World Health Organisation 2020 guidelines on physical activity and sedentary behaviour","volume":"54","author":"Bull","year":"2020","journal-title":"British Journal of Sports Medicine"},{"key":"10.7717\/peerj.20356\/ref-5","doi-asserted-by":"publisher","first-page":"1554062","DOI":"10.3389\/fpsyg.2025.1554062","article-title":"Inflammation and depression: an evolutionary framework for the role of physical activity and exercise","volume":"16","author":"Carrera-Bastos","year":"2025","journal-title":"Frontiers in Psychology"},{"issue":"5","key":"10.7717\/peerj.20356\/ref-6","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1176\/appi.ajp.2008.08091354","article-title":"Genomewide association studies: history, rationale, and prospects for psychiatric disorders.","volume":"166","author":"Cichon","year":"2009","journal-title":"The American Journal of Psychiatry"},{"issue":"9","key":"10.7717\/peerj.20356\/ref-7","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1111\/sms.12540","article-title":"Short-term low-intensity blood flow restricted interval training improves both aerobic fitness and muscle strength","volume":"26","author":"De\u00a0Oliveira","year":"2016","journal-title":"Scandinavian Journal of Medicine & Science in Sports"},{"key":"10.7717\/peerj.20356\/ref-8","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.apnu.2024.07.004","article-title":"Golden steps: A nursing approach for vitality, agility, and rumination in geriatric clients with depressive disorders through mindful walking","volume":"51","author":"El-Sayed","year":"2024","journal-title":"Archives of Psychiatric Nursing"},{"issue":"1517","key":"10.7717\/peerj.20356\/ref-9","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.140970.2","article-title":"Physical activity in the treatment-resistant depression and non-remitted depression: a systematic review of randomised controlled trials","volume":"12","author":"Etxaniz-Oses","year":"2024","journal-title":"F1000Research"},{"issue":"2","key":"10.7717\/peerj.20356\/ref-10","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.pbb.2003.10.020","article-title":"Exercise, antidepressant treatment, and BDNF mRNA expression in the aging brain","volume":"77","author":"Garza","year":"2004","journal-title":"Pharmacology, Biochemistry, and Behavior"},{"issue":"1","key":"10.7717\/peerj.20356\/ref-11","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1152\/japplphysiol.00565.2022","article-title":"The role of exerkines on brain mitochondria: a mini-review","volume":"134","author":"Heo","year":"2023","journal-title":"Journal of Applied Physiology"},{"issue":"1","key":"10.7717\/peerj.20356\/ref-12","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/s41398-024-02922-y","article-title":"From movement to motivation: a proposed framework to understand the antidepressant effect of exercise","volume":"14","author":"Hird","year":"2024","journal-title":"Translational Psychiatry"},{"issue":"42","key":"10.7717\/peerj.20356\/ref-13","doi-asserted-by":"publisher","first-page":"e31035","DOI":"10.1097\/MD.0000000000031035","article-title":"Effectiveness of hospital-based low intensity and inspected aerobic training on functionality and cardiorespiratory fitness in unconditioned stroke patients: importance of submaximal aerobic fitness markers","volume":"101","author":"Horv\u00e1th","year":"2022","journal-title":"Medicine"},{"issue":"4","key":"10.7717\/peerj.20356\/ref-14","doi-asserted-by":"publisher","first-page":"66","DOI":"10.3810\/pgm.2010.07.2176","article-title":"Therapeutic armamentarium for treating depression","volume":"122","author":"Howland","year":"2010","journal-title":"Postgraduate Medicine"},{"key":"10.7717\/peerj.20356\/ref-15","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1471-244X-7-7","article-title":"The improved Clinical Global Impression Scale (iCGI): Development and validation in depression","volume":"7","author":"Kadouri","year":"2007","journal-title":"BMC Psychiatry"},{"issue":"13","key":"10.7717\/peerj.20356\/ref-16","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/s0025-7753(02)72429-9","article-title":"Validation of the Spanish versions of the Montgomery-Asberg depression and Hamilton anxiety rating scales","volume":"118","author":"Lobo","year":"2002","journal-title":"Medicina Clinica"},{"issue":"9","key":"10.7717\/peerj.20356\/ref-17","doi-asserted-by":"publisher","first-page":"e106641","DOI":"10.1371\/journal.pone.0106641","article-title":"Profile of individuals who are metabolically healthy obese using different definition criteria. A population-based analysis in the Spanish population","volume":"9","author":"Mart\u00ednez-Larrad","year":"2014","journal-title":"PLOS ONE"},{"key":"10.7717\/peerj.20356\/ref-18","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1192\/bjp.180.5.411","article-title":"Effects of exercise on depressive symptoms in older adults with poorly responsive depressive disorder: randomised controlled trial","volume":"180","author":"Mather","year":"2002","journal-title":"The British Journal of Psychiatry"},{"key":"10.7717\/peerj.20356\/ref-19","doi-asserted-by":"publisher","first-page":"109502","DOI":"10.1155\/2008\/109502","article-title":"Exercise as a mean to control low-grade systemic inflammation","volume":"2008","author":"Mathur","year":"2008","journal-title":"Mediators of Inflammation"},{"issue":"12","key":"10.7717\/peerj.20356\/ref-20","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1111\/bph.16062","article-title":"Mitophagy: a promising therapeutic target for neuroprotection during ageing and age-related diseases","volume":"180","author":"Mishra","year":"2023","journal-title":"British Journal of Pharmacology"},{"issue":"2","key":"10.7717\/peerj.20356\/ref-21","doi-asserted-by":"publisher","first-page":"222","DOI":"10.52082\/jssm.2021.222","article-title":"Low-intensity exercise as a modifier of depressive symptoms and self-perceived stress level in women with metabolic syndrome","volume":"20","author":"Morga","year":"2021","journal-title":"Journal of Sports Science & Medicine"},{"issue":"8","key":"10.7717\/peerj.20356\/ref-22","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/j.jpsychires.2011.02.005","article-title":"Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder","volume":"45","author":"Mota-Pereira","year":"2011","journal-title":"Journal of Psychiatric Research"},{"issue":"6","key":"10.7717\/peerj.20356\/ref-23","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1017\/S1092852913000953","article-title":"Exercise as an add-on strategy for the treatment of major depressive disorder: a systematic review","volume":"19","author":"Mura","year":"2014","journal-title":"CNS Spectrums"},{"issue":"1","key":"10.7717\/peerj.20356\/ref-24","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.genhosppsych.2003.07.004","article-title":"Quality of life assessments in major depressive disorder: A review of the literature","volume":"26","author":"Papakostas","year":"2004","journal-title":"General Hospital Psychiatry"},{"issue":"7","key":"10.7717\/peerj.20356\/ref-25","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.3390\/life13071505","article-title":"Exercise for mental well-being: exploring neurobiological advances and intervention effects in depression","volume":"13","author":"Ren","year":"2023","journal-title":"Life"},{"issue":"6","key":"10.7717\/peerj.20356\/ref-26","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1176\/appi.ajp.20240142","article-title":"Systemic inflammation and anhedonic responses to an inflammatory challenge in adults with major depressive disorder: A randomised controlled trial","volume":"182","author":"Savitz","year":"2025","journal-title":"The American Journal of Psychiatry"},{"issue":"1","key":"10.7717\/peerj.20356\/ref-27","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s00421-012-2421-x","article-title":"Associations between borg\u2019s rating of perceived exertion and physiological measures of exercise intensity","volume":"113","author":"Scherr","year":"2013","journal-title":"European Journal of Applied Physiology"},{"key":"10.7717\/peerj.20356\/ref-28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neubiorev.2015.11.012","article-title":"Neurobiological effects of exercise on major depressive disorder: a systematic review","volume":"61","author":"Schuch","year":"2016","journal-title":"Neuroscience and Biobehavioral Reviews"},{"key":"10.7717\/peerj.20356\/ref-29","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.jpsychires.2016.02.023","article-title":"Exercise as a treatment for depression: a meta-analysis adjusting for publication bias","volume":"77","author":"Schuch","year":"2016","journal-title":"Journal of Psychiatric Research"},{"issue":"Suppl 3","key":"10.7717\/peerj.20356\/ref-30","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1097\/00004850-199606003-00015","article-title":"The measurement of disability","volume":"11","author":"Sheehan","year":"1996","journal-title":"International Clinical Psychopharmacology"},{"key":"10.7717\/peerj.20356\/ref-31","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.brat.2014.08.008","article-title":"The neuroscience of depression: implications for assessment and intervention","volume":"62","author":"Singh","year":"2014","journal-title":"Behaviour Research and Therapy"},{"key":"10.7717\/peerj.20356\/ref-32","doi-asserted-by":"publisher","first-page":"929781","DOI":"10.3389\/fneur.2022.929781","article-title":"Physical exercise and mitochondrial function: new therapeutic interventions for psychiatric and neurodegenerative disorders","volume":"13","author":"Sun","year":"2022","journal-title":"Frontiers in Neurology"},{"issue":"1\u20133","key":"10.7717\/peerj.20356\/ref-33","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.jad.2009.04.026","article-title":"Health related quality of life in recurrent depression: a comparison with a general population sample","volume":"120","author":"ten Doesschate\u00a0MC","year":"2010","journal-title":"Journal of Affective Disorders"},{"key":"10.7717\/peerj.20356\/ref-34","first-page":"23","article-title":"When at first you don\u2019t succeed: sequential strategies for antidepressant nonresponders","volume":"58","author":"Thase","year":"1997","journal-title":"The Journal of Clinical Psychiatry"},{"issue":"1","key":"10.7717\/peerj.20356\/ref-35","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1176\/appi.ajp.163.1.28","article-title":"Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice","volume":"163","author":"Trivedi","year":"2006","journal-title":"The American Journal of Psychiatry"},{"issue":"3","key":"10.7717\/peerj.20356\/ref-36","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1002\/wps.20458","article-title":"Sedentary behavior and physical activity levels in people with schizophrenia, bipolar disorder and major depressive disorder: a global systematic review and meta-analysis","volume":"16","author":"Vancampfort","year":"2017","journal-title":"World Psychiatry"},{"issue":"34","key":"10.7717\/peerj.20356\/ref-37","doi-asserted-by":"publisher","first-page":"3227","DOI":"10.1093\/eurheartj\/ehab484","article-title":"2021 ESC guidelines on cardiovascular disease prevention in clinical practice","volume":"42","author":"Visseren","year":"2021","journal-title":"European Heart Journal"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/20356.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/20356.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/20356.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/20356.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T08:43:58Z","timestamp":1763369038000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/20356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,17]]},"references-count":37,"alternative-id":["10.7717\/peerj.20356"],"URL":"https:\/\/doi.org\/10.7717\/peerj.20356","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"type":"electronic","value":"2167-8359"}],"subject":[],"published":{"date-parts":[[2025,11,17]]},"article-number":"e20356"}}