{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T09:21:37Z","timestamp":1774948897423,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development (CNPq)\n              https:\/\/ror.org\/03swz6y49","doi-asserted-by":"publisher","award":["303382\/2025-2"],"award-info":[{"award-number":["303382\/2025-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Fibromyalgia is increasingly viewed as a disorder of central sensitization, involving altered nociceptive processing and dysregulated stress and affective neural systems. Evidence supports shared neurobiological mechanisms linking chronic pain, emotional distress, and affect regulation, including corticolimbic and hypothalamic\u2013pituitary\u2013adrenal axis alterations. However, predictive models evaluating psychological distress as markers of these brain-based processes remain scarce. This study aimed to internally validate a preliminary model of fibromyalgia diagnosis using self-reported distress indicators as proxies of central dysregulation. Methods: A case-control design study with 180 participants was performed. Medically diagnosed fibromyalgia cases were recruited via a pain facility or referrals, alongside geographically matched controls from the general population. Psychological variables were conceptualized as neurobehavioral indicators reflecting central sensitization and stress-system dysregulation. Predictors were selected using LASSO penalized regression with 10-fold cross-validation. Retained variables were re-estimated using logistic regression. Model performance was evaluated through Nagelkerke\u2019s pseudo-R2, a likelihood ratio test, and area under the curve (AUC). Internal validation was conducted via 1000-bootstrap resampling with calibration-slope-based shrinkage. Results: The final model included global psychological distress, positive affect, sex, and age (R2=0.359, with good discrimination [AUC = 0.81; optimism-corrected AUC \u2248 0.79]). Higher distress and age were associated with increased odds of fibromyalgia. Conclusions: Self-reported psychological distress, particularly global distress and reduced positive affect, combined with sex and age, showed internal validity in predicting fibromyalgia diagnosis. These findings support the hypothesis that behavioral markers of emotional dysregulation may reflect underlying central sensitization and stress-system alterations implicated in chronic pain. Future research integrating psychological measures with neuroimaging and neuroendocrine markers may further clarify the neural mechanisms linking affective dysregulation and chronic pain vulnerability.<\/jats:p>","DOI":"10.3390\/brainsci16040381","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:09:18Z","timestamp":1774944558000},"page":"381","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neurobehavioral Predictors of Fibromyalgia: Internal Validation of a Model Based on Psychological Distress and Affective Regulation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1963-0788","authenticated-orcid":false,"given":"Marli Appel","family":"da Silva","sequence":"first","affiliation":[{"name":"Personality and Individual Differences Laboratory, Western Parana State University, Francisco Beltr\u00e3o 85601, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9014-6120","authenticated-orcid":false,"given":"Guilherme Welter","family":"Wendt","sequence":"additional","affiliation":[{"name":"Personality and Individual Differences Laboratory, Western Parana State University, Francisco Beltr\u00e3o 85601, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jurado-Priego, L.N., Cueto-Ure\u00f1a, C., Ram\u00edrez-Exp\u00f3sito, M.J., and Mart\u00ednez-Martos, J.M. (2024). Fibromyalgia: A Review of the Pathophysiological Mechanisms and Multidisciplinary Treatment Strategies. Biomedicines, 12.","DOI":"10.3390\/biomedicines12071543"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wolfe, F., Walitt, B., Perrot, S., Rasker, J.J., and H\u00e4user, W. (2018). Fibromyalgia Diagnosis and Biased Assessment: Sex, Prevalence and Bias. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0203755"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/art.40451","article-title":"Neurobiologic Features of Fibromyalgia Are Also Present Among Rheumatoid Arthritis Patients","volume":"70","author":"Basu","year":"2018","journal-title":"Arthritis Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1744806918819944","DOI":"10.1177\/1744806918819944","article-title":"Fibromyalgia: Genetics and Epigenetics Insights May Provide the Basis for the Development of Diagnostic Biomarkers","volume":"15","author":"Gerra","year":"2019","journal-title":"Mol. Pain"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ablin, J.N., and Shoenfeld, Y. (2021). Fibromyalgia Syndrome, Springer International Publishing.","DOI":"10.1007\/978-3-030-78638-0"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.jpain.2018.10.008","article-title":"AAPT Diagnostic Criteria for Fibromyalgia","volume":"20","author":"Arnold","year":"2019","journal-title":"J. Pain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105235","DOI":"10.1016\/j.neubiorev.2023.105235","article-title":"Neurophysiological and Psychosocial Mechanisms of Fibromyalgia: A Comprehensive Review and Call for an Integrative Model","volume":"151","author":"Pinto","year":"2023","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1097\/NMD.0000000000001836","article-title":"Psychiatric Comorbidities in Fibromyalgia: A Comparison with Chronic Conditions and Healthy Controls","volume":"213","author":"Avni","year":"2025","journal-title":"J. Nerv. Ment. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e44616","DOI":"10.1097\/MD.0000000000044616","article-title":"Negative Affect in Fibromyalgia in Comparison to Controls: A Cross-Sectional Investigation of Risk and Protective Factors","volume":"104","author":"Sygel","year":"2025","journal-title":"Medicine"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kadimpati, S., Zale, E.L., Hooten, M.W., Ditre, J.W., and Warner, D.O. (2015). Associations between Neuroticism and Depression in Relation to Catastrophizing and Pain-Related Anxiety in Chronic Pain Patients. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126351"},{"key":"ref_11","first-page":"228","article-title":"Pain Catastrophizing in Daughters of Women with Fibromyalgia: A Case-Control Study","volume":"71","author":"Muniz","year":"2021","journal-title":"Braz. J. Anesthesiol."},{"key":"ref_12","first-page":"1141","article-title":"Fibromyalgia: One Year in Review 2024","volume":"42","author":"Bianchi","year":"2024","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e20240002","DOI":"10.5935\/2595-0118.20240002-pt","article-title":"Envolvimento Do C\u00f3rtex Somest\u00e9sico Prim\u00e1rio Na Fibromialgia: Revis\u00e3o de Estudos de Neuroimagem","volume":"7","author":"Menezes","year":"2024","journal-title":"BRJP"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1097\/j.pain.0000000000002927","article-title":"Evidence of Neuroinflammation in Fibromyalgia Syndrome: A [18F]DPA-714 Positron Emission Tomography Study","volume":"164","author":"Mueller","year":"2023","journal-title":"Pain"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Demori, I., Losacco, S., Giordano, G., Mucci, V., Blanchini, F., and Burlando, B. (2024). Fibromyalgia Pathogenesis Explained by a Neuroendocrine Multistable Model. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0303573"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Findeisen, K., Guymer, E., and Littlejohn, G. (2025). Neuroinflammatory and Immunological Aspects of Fibromyalgia. Brain Sci., 15.","DOI":"10.3390\/brainsci15020206"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e250268","DOI":"10.1001\/jamanetworkopen.2025.0268","article-title":"Prevalence of Depression and Anxiety Among Adults with Chronic Pain: A Systematic Review and Meta-Analysis","volume":"8","author":"Aaron","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"69","DOI":"10.36922\/JCTR025290042","article-title":"The Impact of Fibromyalgia: A Cross-Sectional Examination across Different Life Domains","volume":"11","author":"Wendt","year":"2025","journal-title":"J. Clin. Transl. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1037\/0022-3514.54.6.1063","article-title":"Development and Validation of Brief Measures of Positive and Negative Affect: The PANAS Scales","volume":"54","author":"Watson","year":"1988","journal-title":"J. Personal. Soc. Psychol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/AJP.0000000000000092","article-title":"The Role of Positive Affect in Pain and Its Treatment","volume":"31","author":"Finan","year":"2015","journal-title":"Clin. J. Pain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"T70","DOI":"10.1016\/j.jpain.2016.01.001","article-title":"The Role of Psychosocial Processes in the Development and Maintenance of Chronic Pain","volume":"17","author":"Edwards","year":"2016","journal-title":"J. Pain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1007\/s10067-023-06778-3","article-title":"The Crosstalk of the Pathophysiologic Models in Fibromyalgia","volume":"42","author":"Ghavidel","year":"2023","journal-title":"Clin. Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Steyerberg, E.W. (2019). Clinical Prediction Models: A Practical Approach to Development, Validation, and Updating, Springer International Publishing. Statistics for Biology and Health.","DOI":"10.1007\/978-3-030-16399-0"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1002\/ejp.1937","article-title":"Development and External Validation of a Prediction Model for Patient-relevant Outcomes in Patients with Chronic Widespread Pain and Fibromyalgia","volume":"26","author":"Moen","year":"2022","journal-title":"Eur. J. Pain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.7326\/M14-0697","article-title":"Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD): The TRIPOD Statement","volume":"162","author":"Collins","year":"2015","journal-title":"Ann. Intern. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jad.2013.10.031","article-title":"Adaptation and Validation of the Depression, Anxiety and Stress Scale (DASS) to Brazilian Portuguese","volume":"155","author":"Vignola","year":"2014","journal-title":"J. Affect. Disord."},{"key":"ref_27","unstructured":"Zanon, C., and Hutz, C. (2014). Escala de Afetos Positivos e Negativos (PANAS). Avalia\u00e7\u00e3o em Psicologia Positiva, Artes M\u00e9dicas."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1001\/archpsyc.60.2.184","article-title":"Screening for Serious Mental Illness in the General Population","volume":"60","author":"Kessler","year":"2003","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_29","unstructured":"Hastie, T., Tibshirani, R., and Friedman, J.H. (2017). The Elements of Statistical Learning: Data Mining, Inference, and Prediction, Springer. [2nd ed.]."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jpain.2017.08.009","article-title":"Unravelling Fibromyalgia-Steps Toward Individualized Management","volume":"19","author":"Perrot","year":"2018","journal-title":"J. Pain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"784520","DOI":"10.1155\/2013\/784520","article-title":"A Review of Hypothalamic-Pituitary-Adrenal Axis Function in Chronic Fatigue Syndrome","volume":"2013","author":"Tomas","year":"2013","journal-title":"ISRN Neurosc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.psyneuen.2018.10.026","article-title":"Hypothalamic-Pituitary-Adrenal Axis Feedback Sensitivity in Different States of Back Pain","volume":"101","author":"Nees","year":"2019","journal-title":"Psychoneuroendocrinology"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Meester, I., Rivera-Silva, G.F., and Gonz\u00e1lez-Salazar, F. (2020). Immune System Sex Differences May Bridge the Gap Between Sex and Gender in Fibromyalgia. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01414"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/4\/381\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:25:21Z","timestamp":1774945521000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/4\/381"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":33,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["brainsci16040381"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16040381","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]}}}