{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:43:50Z","timestamp":1789062230333,"version":"build-2803163510"},"reference-count":102,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022774","name":"Nando and Elsa Peretti Foundation","doi-asserted-by":"publisher","award":["370"],"award-info":[{"award-number":["370"]}],"id":[{"id":"10.13039\/501100022774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003770","name":"Bank of Italy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003770","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001720","name":"Nutricia Research Foundation","doi-asserted-by":"publisher","award":["a2020-E3"],"award-info":[{"award-number":["a2020-E3"]}],"id":[{"id":"10.13039\/501100001720","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["7KTSAT"],"award-info":[{"award-number":["7KTSAT"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["P2022E4MLS"],"award-info":[{"award-number":["P2022E4MLS"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["101095426"],"award-info":[{"award-number":["101095426"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002803","name":"Cariplo Foundation","doi-asserted-by":"publisher","award":["2023\\u22121003"],"award-info":[{"award-number":["2023\\u22121003"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002803","name":"Cariplo Foundation","doi-asserted-by":"publisher","award":["2017-0865"],"award-info":[{"award-number":["2017-0865"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012352","name":"Universit\u00e0 degli Studi di Milano","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012352","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001675","name":"International Brain Research Organization","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001675","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2025,11]]},"DOI":"10.1016\/j.phrs.2025.107959","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T01:09:49Z","timestamp":1758589789000},"page":"107959","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Irisin\/BDNF pathway dysfunction subserves anorexia nervosa pathophysiology"],"prefix":"10.1016","volume":"221","author":[{"given":"Francesca","family":"Mottarlini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Parolaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Da Dalt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Taddini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Rizzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizia","family":"Bonacina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Chiara","family":"Cigognini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Vairano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"D\u2019Agostino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bertelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe Danilo","family":"Norata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Fumagalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Caffino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phrs.2025.107959_bib1","series-title":"Diagnostic and Statistical Manual of Mental Disorders","author":"DSM-V","year":"2013"},{"key":"10.1016\/j.phrs.2025.107959_bib2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/eip.12170","article-title":"Has the time come for a staging model to map the course of eating disorders from high risk to severe enduring illness? An examination of the evidence","volume":"9","author":"Treasure","year":"2015","journal-title":"Early Inter. Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib3","doi-asserted-by":"crossref","DOI":"10.1002\/erv.3039","article-title":"Novel treatments for anorexia nervosa: insights from neuroplasticity research","volume":"32","author":"Keeler","year":"2024","journal-title":"Eur. Eat. Disord. Rev."},{"key":"10.1016\/j.phrs.2025.107959_bib4","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1097\/YCO.0000000000000739","article-title":"Incidence, prevalence and mortality of anorexia nervosa and bulimia nervosa","volume":"34","author":"Van Eeden","year":"2021","journal-title":"Curr. Opin. Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib5","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/S2215-0366(15)00356-9","article-title":"Anorexia nervosa: aetiology, assessment, and treatment","volume":"2","author":"Zipfel","year":"2015","journal-title":"Lancet Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib6","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0031-9384(03)00102-1","article-title":"Hyperactivity in patients with anorexia nervosa and in semistarved rats: evidence for a pivotal role of hypoleptinemia","volume":"79","author":"Hebebrand","year":"2003","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.phrs.2025.107959_bib7","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/eat.22657","article-title":"The assessment and treatment of unhealthy exercise in adolescents with anorexia nervosa: a delphi study to synthesize clinical knowledge","volume":"50","author":"Noetel","year":"2017","journal-title":"Int J. Eat. Disord."},{"key":"10.1016\/j.phrs.2025.107959_bib8","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.comppsych.2007.12.007","article-title":"Compulsive exercise to control shape or weight in eating disorders: prevalence, associated features, and treatment outcome","volume":"49","author":"Dalle Grave","year":"2008","journal-title":"Compr. Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib9","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1093\/scan\/nst070","article-title":"Impaired inhibitory control in anorexia nervosa elicited by physical activity stimuli","volume":"9","author":"Kullmann","year":"2014","journal-title":"Soc. Cogn. Affect Neurosci."},{"key":"10.1016\/j.phrs.2025.107959_bib10","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.biopsycho.2013.10.004","article-title":"Understanding the reward system functioning in anorexia nervosa: crucial role of physical activity","volume":"94","author":"Giel","year":"2013","journal-title":"Biol. Psychol."},{"key":"10.1016\/j.phrs.2025.107959_bib11","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/eat.20753","article-title":"I\u2019m not physically active - I only go for walks\u201d: physical activity in patients with longstanding eating disorders","volume":"43","author":"Bratland-Sanda","year":"2010","journal-title":"Int J. Eat. Disord."},{"key":"10.1016\/j.phrs.2025.107959_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.psychres.2019.112703","article-title":"The relationship between moderate to vigorous physical activity and cognitive rigidity in anorexia nervosa","volume":"284","author":"Di Lodovico","year":"2020","journal-title":"Psychiatry Res"},{"key":"10.1016\/j.phrs.2025.107959_bib13","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1002\/eat.23503","article-title":"Physical exercise-related endophenotypes in anorexia nervosa","volume":"54","author":"Di Lodovico","year":"2021","journal-title":"Int J. Eat. Disord."},{"key":"10.1016\/j.phrs.2025.107959_bib14","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/eat.20758","article-title":"Behavioral assessment of the reinforcing effect of exercise in women with anorexia nervosa: further paradigm development and data","volume":"43","author":"Klein","year":"2010","journal-title":"Int J. Eat. Disord."},{"key":"10.1016\/j.phrs.2025.107959_bib15","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1038\/s41588-019-0439-2","article-title":"Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa","volume":"51","author":"Watson","year":"2019","journal-title":"Nat. Genet"},{"key":"10.1016\/j.phrs.2025.107959_bib16","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1176\/appi.ajp.2012.12081074","article-title":"The enigmatic persistence of anorexia nervosa","volume":"170","author":"Walsh","year":"2013","journal-title":"Am. J. Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib17","doi-asserted-by":"crossref","first-page":"6950","DOI":"10.1007\/s12035-023-03492-8","article-title":"Exercise reshapes the brain: molecular, cellular, and structural changes associated with cognitive improvements","volume":"60","author":"Augusto-Oliveira","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.phrs.2025.107959_bib18","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1038\/s42255-021-00438-z","article-title":"Exercise hormone irisin is a critical regulator of cognitive function","volume":"3","author":"Islam","year":"2021","journal-title":"Nat. Metab."},{"key":"10.1016\/j.phrs.2025.107959_bib19","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41591-018-0275-4","article-title":"Exercise-linked FNDC5\/irisin rescues synaptic plasticity and memory defects in Alzheimer\u2019s models","volume":"25","author":"Lourenco","year":"2019","journal-title":"Nat. Med"},{"key":"10.1016\/j.phrs.2025.107959_bib20","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/dmrr.2660","article-title":"Irisin, an exercise-induced myokine as a metabolic regulator: an updated narrative review","volume":"32","author":"Chen","year":"2016","journal-title":"Diabetes Metab. Res Rev."},{"key":"10.1016\/j.phrs.2025.107959_bib21","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.cell.2019.06.028","article-title":"Irisin mediates effects on bone and fat via \u03b1V integrin receptors","volume":"178","author":"Kim","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.phrs.2025.107959_bib22","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.cmet.2013.09.008","article-title":"Exercise induces hippocampal BDNF through a PGC-1\u03b1\/FNDC5 pathway","volume":"18","author":"Wrann","year":"2013","journal-title":"Cell Metab."},{"key":"10.1016\/j.phrs.2025.107959_bib23","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1080\/15622975.2021.2015432","article-title":"Growth factors in anorexia nervosa: a systematic review and meta-analysis of cross-sectional and longitudinal data","volume":"23","author":"Keeler","year":"2022","journal-title":"World J. Biol. Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib24","doi-asserted-by":"crossref","first-page":"444","DOI":"10.3109\/15622975.2011.562244","article-title":"A meta-analysis of circulating BDNF concentrations in anorexia nervosa","volume":"12","author":"Brandys","year":"2011","journal-title":"World J. Biol. Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib25","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.pscychresns.2018.10.007","article-title":"Hippocampal subfields in adolescent anorexia nervosa","volume":"282","author":"Myrvang","year":"2018","journal-title":"Psychiatry Res Neuroimaging"},{"key":"10.1016\/j.phrs.2025.107959_bib26","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/erv.2806","article-title":"Hippocampal volumes in anorexia nervosa at different stages of the disorder","volume":"29","author":"Collantoni","year":"2021","journal-title":"Eur. Eat. Disord. Rev."},{"key":"10.1016\/j.phrs.2025.107959_bib27","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1002\/eat.22397","article-title":"Structural hippocampal alterations, perceived stress, and coping deficiencies in patients with anorexia nervosa","volume":"48","author":"Burkert","year":"2015","journal-title":"Int J. Eat. Disord."},{"key":"10.1016\/j.phrs.2025.107959_bib28","article-title":"The utility of animal models for studying the metabo-psychiatric origins of anorexia nervosa","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib29","doi-asserted-by":"crossref","DOI":"10.3390\/nu16081171","article-title":"Anorexia-Induced hypoleptinemia drives adaptations in the JAK2\/STAT3 pathway in the ventral and dorsal hippocampus of female rats","volume":"16","author":"Targa","year":"2024","journal-title":"Nutrients"},{"key":"10.1016\/j.phrs.2025.107959_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.pnpbp.2024.111065","article-title":"Developmental activity-based anorexia alters hippocampal non-genomic stress response and induces structural instability and spatial memory impairment in female rats","volume":"134","author":"Mottarlini","year":"2024","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib31","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.physbeh.2017.06.013","article-title":"Impaired reversal learning in an animal model of anorexia nervosa","volume":"179","author":"Allen","year":"2017","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.phrs.2025.107959_bib32","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.biopsych.2020.06.022","article-title":"Suppression of corticostriatal circuit activity improves cognitive flexibility and prevents body weight loss in Activity-Based anorexia in rats","volume":"90","author":"Milton","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib33","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.84961","article-title":"Rapid, automated, and experimenter-free touchscreen testing reveals reciprocal interactions between cognitive flexibility and activity-based anorexia in female rats","volume":"12","author":"Huang","year":"2023","journal-title":"Elife"},{"key":"10.1016\/j.phrs.2025.107959_bib34","doi-asserted-by":"crossref","DOI":"10.1038\/s41380-024-02575-9","article-title":"Psilocybin restrains activity-based anorexia in female rats by enhancing cognitive flexibility: contributions from 5-HT1A and 5-HT2A receptor mechanisms","volume":"29","author":"Conn","year":"2024","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib35","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1080\/21622965.2013.775064","article-title":"Central coherence, organizational strategy, and visuospatial memory in children and adolescents with anorexia nervosa","volume":"3","author":"Rose","year":"2014","journal-title":"Appl. Neuropsychol. Child"},{"key":"10.1016\/j.phrs.2025.107959_bib36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/nu12123661","article-title":"Activity-based anorexia dynamically dysregulates the glutamatergic synapse in the nucleus accumbens of female adolescent rats","volume":"12","author":"Mottarlini","year":"2020","journal-title":"Nutrients"},{"key":"10.1016\/j.phrs.2025.107959_bib37","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/jnc.15605","article-title":"Cortical reorganization of the glutamate synapse in the activity-based anorexia rat model: impact on cognition","volume":"161","author":"Mottarlini","year":"2022","journal-title":"J. Neurochem."},{"key":"10.1016\/j.phrs.2025.107959_bib38","first-page":"1","article-title":"Rodent model of activity-based anorexia","author":"Carrera","year":"2014","journal-title":"Curr. Protoc. Neurosci."},{"key":"10.1016\/j.phrs.2025.107959_bib39","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/eat.22095","article-title":"A rat in the labyrinth of anorexia nervosa: contributions of the activity-based anorexia rodent model to the understanding of anorexia nervosa","volume":"46","author":"Gutierrez","year":"2013","journal-title":"Int J. Eat. Disord."},{"key":"10.1016\/j.phrs.2025.107959_bib40","unstructured":"D.M. Garner, The eating disorder inventory-3 professional manual., in: Psychological Assessment Resources, Psychological Assessment Resources, 2004."},{"key":"10.1016\/j.phrs.2025.107959_bib41","series-title":"and Matching Clinical Rating Scales","article-title":"The SCL-90-R, brief symptom inventory","author":"Derogatis","year":"1999"},{"key":"10.1016\/j.phrs.2025.107959_bib42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40337-018-0203-5","article-title":"How to integrate physical activity and exercise approaches into inpatient treatment for eating disorders: fifteen years of clinical experience and research","volume":"6","author":"Danielsen","year":"2018","journal-title":"J. Eat. Disord."},{"key":"10.1016\/j.phrs.2025.107959_bib43","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1037\/h0077509","article-title":"Maternal stress and pituitary\u2013adrenal manipulations during pregnancy in rats: effects on morphology and sexual behavior of Male offspring","volume":"92","author":"Chapman","year":"1978","journal-title":"J. Comp. Physiol. Psychol."},{"key":"10.1016\/j.phrs.2025.107959_bib44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12917-020-02451-y","article-title":"The ARRIVE guidelines 2.0: updated guidelines for reporting animal research","volume":"16","author":"Percie Du Sert","year":"2020","journal-title":"BMC Vet. Res"},{"key":"10.1016\/j.phrs.2025.107959_bib45","series-title":"The rat brain in stereotaxic coordinates","author":"George Paxinos","year":"2013"},{"key":"10.1016\/j.phrs.2025.107959_bib46","doi-asserted-by":"crossref","DOI":"10.1016\/j.dcn.2020.100789","article-title":"Repeated cocaine exposure during adolescence impairs recognition memory in early adulthood: a role for BDNF signaling in the perirhinal cortex","volume":"43","author":"Mottarlini","year":"2020","journal-title":"Dev. Cogn. Neurosci."},{"key":"10.1016\/j.phrs.2025.107959_bib47","doi-asserted-by":"crossref","DOI":"10.3390\/biomedicines10081853","article-title":"Single and repeated exposure to cannabidiol differently modulate BDNF expression and signaling in the Cortico-Striatal brain network","volume":"10","author":"Mottarlini","year":"2022","journal-title":"Biomedicines"},{"key":"10.1016\/j.phrs.2025.107959_bib48","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2020.108161","article-title":"Anhedonic-like behavior and BDNF dysregulation following a single injection of cocaine during adolescence","volume":"175","author":"Caffino","year":"2020","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.phrs.2025.107959_bib49","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/S0140-6736(20)30059-3","article-title":"Eating disorders","volume":"395","author":"Treasure","year":"2020","journal-title":"Lancet"},{"key":"10.1016\/j.phrs.2025.107959_bib50","doi-asserted-by":"crossref","DOI":"10.3390\/nu16162617","article-title":"The role of central and peripheral Brain-Derived neurotrophic factor (BDNF) as a biomarker of anorexia nervosa reconceptualized as a Metabo-Psychiatric disorder","volume":"16","author":"Cao","year":"2024","journal-title":"Nutrients"},{"key":"10.1016\/j.phrs.2025.107959_bib51","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.3233\/JAD-231347","article-title":"Plasma BDNF\/Irisin ratio associates with cognitive function in older people","volume":"99","author":"Huang","year":"2024","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.phrs.2025.107959_bib52","doi-asserted-by":"crossref","DOI":"10.1186\/s40337-022-00547-4","article-title":"Cognitive flexibility, central coherence, and quality of life in anorexia nervosa","volume":"10","author":"Brockmeyer","year":"2022","journal-title":"J. Eat. Disord."},{"key":"10.1016\/j.phrs.2025.107959_bib53","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1002\/eat.22929","article-title":"A systematic review of reviews of neurocognitive functioning in eating disorders: the state-of-the-literature and future directions","volume":"51","author":"Smith","year":"2018","journal-title":"Int J. Eat. Disord."},{"key":"10.1016\/j.phrs.2025.107959_bib54","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1152\/advan.00052.2006","article-title":"PGC-1alpha: a key regulator of energy metabolism","volume":"30","author":"Liang","year":"2006","journal-title":"Adv. Physiol. Educ."},{"key":"10.1016\/j.phrs.2025.107959_bib55","doi-asserted-by":"crossref","DOI":"10.1016\/j.diabres.2017.10.004","article-title":"Akt activation: a potential strategy to ameliorate insulin resistance","volume":"156","author":"Zhang","year":"2019","journal-title":"Diabetes Res Clin. Pr."},{"key":"10.1016\/j.phrs.2025.107959_bib56","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/jnr.21139","article-title":"Mouse and rat BDNF gene structure and expression revisited","volume":"85","author":"Aid","year":"2007","journal-title":"J. Neurosci. Res"},{"key":"10.1016\/j.phrs.2025.107959_bib57","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.mcn.2007.08.011","article-title":"BDNF mRNA splice variants display activity-dependent targeting to distinct hippocampal laminae","volume":"37","author":"Chiaruttini","year":"2008","journal-title":"Mol. Cell Neurosci."},{"key":"10.1016\/j.phrs.2025.107959_bib58","doi-asserted-by":"crossref","first-page":"16813","DOI":"10.1073\/pnas.1014168108","article-title":"Spatial segregation of BDNF transcripts enables BDNF to differentially shape distinct dendritic compartments","volume":"108","author":"Baj","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.phrs.2025.107959_bib59","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/eat.20769","article-title":"Physical activity and exercise dependence during inpatient treatment of longstanding eating disorders: an exploratory study of excessive and non-excessive exercisers","volume":"43","author":"Bratland-Sanda","year":"2010","journal-title":"Int J. Eat. Disord."},{"key":"10.1016\/j.phrs.2025.107959_bib60","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.comppsych.2007.12.007","article-title":"Compulsive exercise to control shape or weight in eating disorders: prevalence, associated features, and treatment outcome","volume":"49","author":"Dalle Grave","year":"2008","journal-title":"Compr. Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib61","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/7854_2024_499","article-title":"Adaptive and maladaptive exercise in eating disorders","volume":"67","author":"Schaumberg","year":"2024","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"10.1016\/j.phrs.2025.107959_bib62","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/eat.20753","article-title":"I\u2019m not physically active - I only go for walks\u201d: physical activity in patients with longstanding eating disorders","volume":"43","author":"Bratland-Sanda","year":"2010","journal-title":"Int J. Eat. Disord."},{"key":"10.1016\/j.phrs.2025.107959_bib63","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1002\/erv.1122","article-title":"Compulsive exercise and eating disorders","volume":"19","author":"Meyer","year":"2011","journal-title":"Eur. Eat. Disord. Rev."},{"key":"10.1016\/j.phrs.2025.107959_bib64","doi-asserted-by":"crossref","DOI":"10.1016\/j.physbeh.2023.114349","article-title":"Timing matters: the contribution of running during different periods of the light\/dark cycle to susceptibility to activity-based anorexia in rats","volume":"271","author":"Aston","year":"2023","journal-title":"Physiol. Behav."},{"key":"10.1016\/j.phrs.2025.107959_bib65","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0050453","article-title":"Identifying predictors of activity based anorexia susceptibility in diverse genetic rodent populations","volume":"7","author":"Pjetri","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.phrs.2025.107959_bib66","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/eat.23705","article-title":"In pursuit of biomarkers for predicting susceptibility to activity-based anorexia in adolescent female rats","volume":"55","author":"Milton","year":"2022","journal-title":"Int J. Eat. Disord."},{"key":"10.1016\/j.phrs.2025.107959_bib67","doi-asserted-by":"crossref","DOI":"10.3390\/molecules23123229","article-title":"Molecular and functional interaction of the myokine irisin with physical exercise and Alzheimer\u2019s disease","volume":"23","author":"Jin","year":"2018","journal-title":"Molecules"},{"key":"10.1016\/j.phrs.2025.107959_bib68","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.metabol.2013.10.005","article-title":"Regulation of cell proliferation and malignant potential by irisin in endometrial, colon, thyroid and esophageal cancer cell lines","volume":"63","author":"Moon","year":"2014","journal-title":"Metabolism"},{"key":"10.1016\/j.phrs.2025.107959_bib69","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1161\/CIRCHEARTFAILURE.112.969543","article-title":"Expression of the irisin precursor FNDC5 in skeletal muscle correlates with aerobic exercise performance in patients with heart failure","volume":"5","author":"Lecker","year":"2012","journal-title":"Circ. Heart Fail"},{"key":"10.1016\/j.phrs.2025.107959_bib70","doi-asserted-by":"crossref","DOI":"10.1111\/j.1753-0407.2012.00194.x","article-title":"Irisin: a new potential hormonal target for the treatment of obesity and type 2 diabetes","volume":"4","author":"Sanchis-Gomar","year":"2012","journal-title":"J. Diabetes"},{"key":"10.1016\/j.phrs.2025.107959_bib71","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2013.00202","article-title":"Irisin levels are not affected by physical activity in patients with anorexia nervosa","volume":"4","author":"Hofmann","year":"2014","journal-title":"Front Endocrinol."},{"key":"10.1016\/j.phrs.2025.107959_bib72","doi-asserted-by":"crossref","DOI":"10.1530\/EC-21-0488","article-title":"In patients with anorexia nervosa, myokine levels are altered but are not associated with bone mineral density loss and bone turnover alteration","volume":"11","author":"Ma\u00efmoun","year":"2022","journal-title":"Endocr. Connect"},{"key":"10.1016\/j.phrs.2025.107959_bib73","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.peptides.2012.11.014","article-title":"Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity--correlation with body mass index","volume":"39","author":"Stengel","year":"2013","journal-title":"Pept. (N. Y. )"},{"key":"10.1016\/j.phrs.2025.107959_bib74","doi-asserted-by":"crossref","DOI":"10.3390\/nu16162617","article-title":"The role of central and peripheral brain-derived neurotrophic factor (BDNF) as a biomarker of anorexia nervosa reconceptualized as a metabo-psychiatric disorder","volume":"16","author":"Cao","year":"2024","journal-title":"Nutrients"},{"key":"10.1016\/j.phrs.2025.107959_bib75","doi-asserted-by":"crossref","DOI":"10.1016\/j.psyneuen.2023.106069","article-title":"The role of the brain-derived neurotrophic factor (BDNF) in anorexia nervosa","volume":"151","author":"Trinh","year":"2023","journal-title":"Psychoneuroendocrinology"},{"key":"10.1016\/j.phrs.2025.107959_bib76","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1080\/15622975.2021.2015432","article-title":"Growth factors in anorexia nervosa: a systematic review and meta-analysis of cross-sectional and longitudinal data","volume":"23","author":"Keeler","year":"2022","journal-title":"World J. Biol. Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib77","doi-asserted-by":"crossref","first-page":"E568","DOI":"10.1503\/jpn.210049","article-title":"BDNF levels in adolescent patients with anorexia nervosa increase continuously to supranormal levels 2.5 years after first hospitalization","volume":"46","author":"Borsdorf","year":"2021","journal-title":"J. Psychiatry Neurosci."},{"key":"10.1016\/j.phrs.2025.107959_bib78","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.3233\/JAD-231347","article-title":"Plasma BDNF\/Irisin ratio associates with cognitive function in older people","volume":"99","author":"Huang","year":"2024","journal-title":"J. Alzheimer\u2019S. Dis."},{"key":"10.1016\/j.phrs.2025.107959_bib79","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/j.metabol.2012.09.002","article-title":"FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. Mrna expression and circulating concentrations in response to weight loss and exercise","volume":"61","author":"Huh","year":"2012","journal-title":"Metabolism"},{"key":"10.1016\/j.phrs.2025.107959_bib80","doi-asserted-by":"crossref","DOI":"10.1152\/ajpendo.00228.2003","article-title":"Akt signaling in skeletal muscle: regulation by exercise and passive stretch","volume":"285","author":"Sakamoto","year":"2003","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.phrs.2025.107959_bib81","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1042\/BJ20120772","article-title":"A novel PKB\/Akt inhibitor, MK-2206, effectively inhibits insulin-stimulated glucose metabolism and protein synthesis in isolated rat skeletal muscle","volume":"447","author":"Lai","year":"2012","journal-title":"Biochem J."},{"key":"10.1016\/j.phrs.2025.107959_bib82","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.112434","article-title":"Mitochondrial dynamics define muscle fiber type by modulating cellular metabolic pathways","volume":"42","author":"Yasuda","year":"2023","journal-title":"Cell Rep."},{"key":"10.1016\/j.phrs.2025.107959_bib83","doi-asserted-by":"crossref","DOI":"10.15252\/embr.201948791","article-title":"USP1 deubiquitinates akt to inhibit PI3K-Akt-FoxO signaling in muscle during prolonged starvation","volume":"21","author":"Goldbraikh","year":"2020","journal-title":"EMBO Rep."},{"key":"10.1016\/j.phrs.2025.107959_bib84","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3109\/10253890009001124","article-title":"Corticosterone effects on BDNF expression in the hippocampus. Implications for memory formation","volume":"3","author":"Schaaf","year":"2000","journal-title":"Stress"},{"key":"10.1016\/j.phrs.2025.107959_bib85","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.neuron.2006.11.025","article-title":"Persistence of long-term memory storage requires a late protein synthesis- and BDNF- dependent phase in the hippocampus","volume":"53","author":"Bekinschtein","year":"2007","journal-title":"Neuron"},{"key":"10.1016\/j.phrs.2025.107959_bib86","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.7150\/ijbs.20132","article-title":"Skeletal Muscle-Specific overexpression of PGC-1\u03b1 induces Fiber-Type conversion through enhanced mitochondrial respiration and fatty acid oxidation in mice and pigs","volume":"13","author":"Zhang","year":"2017","journal-title":"Int J. Biol. Sci."},{"key":"10.1016\/j.phrs.2025.107959_bib87","doi-asserted-by":"crossref","DOI":"10.3389\/fnbeh.2022.1087075","article-title":"Long-lasting BDNF signaling alterations in the amygdala of adolescent female rats exposed to the activity-based anorexia model","volume":"16","author":"Mottarlini","year":"2022","journal-title":"Front Behav. Neurosci."},{"key":"10.1016\/j.phrs.2025.107959_bib88","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.brainres.2014.10.058","article-title":"Brain-derived neurotrophic factor and addiction: pathological versus therapeutic effects on drug seeking","volume":"1628","author":"Barker","year":"2015","journal-title":"Brain Res"},{"key":"10.1016\/j.phrs.2025.107959_bib89","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.nbd.2016.02.021","article-title":"Prefrontal cortical BDNF: a regulatory key in cocaine- and food-reinforced behaviors","volume":"91","author":"Pitts","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.phrs.2025.107959_bib90","doi-asserted-by":"crossref","first-page":"4233","DOI":"10.1111\/bph.15523","article-title":"The effects of cocaine exposure in adolescence: behavioural effects and neuroplastic mechanisms in experimental models","volume":"179","author":"Caffino","year":"2022","journal-title":"Br. J. Pharm."},{"key":"10.1016\/j.phrs.2025.107959_bib91","doi-asserted-by":"crossref","first-page":"8149","DOI":"10.1523\/JNEUROSCI.2711-14.2016","article-title":"Systemic delivery of a Brain-Penetrant TrkB antagonist reduces cocaine Self-Administration and normalizes TrkB signaling in the nucleus accumbens and prefrontal cortex","volume":"36","author":"Verheij","year":"2016","journal-title":"J. Neurosci."},{"key":"10.1016\/j.phrs.2025.107959_bib92","doi-asserted-by":"crossref","DOI":"10.3389\/fncel.2022.953991","article-title":"Irisin stimulates protective signaling pathways in rat hippocampal neurons","volume":"16","author":"Lourenco","year":"2022","journal-title":"Front Cell Neurosci."},{"key":"10.1016\/j.phrs.2025.107959_bib93","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1124\/pr.111.005108","article-title":"Brain-derived neurotrophic factor and neuropsychiatric disorders","volume":"64","author":"Autry","year":"2012","journal-title":"Pharm. Rev."},{"key":"10.1016\/j.phrs.2025.107959_bib94","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/YCT.0000000000000922","article-title":"Anorexia nervosa with comorbid severe depression: a systematic scoping review of brain stimulation treatments","volume":"39","author":"Andersson","year":"2023","journal-title":"J. ECT"},{"key":"10.1016\/j.phrs.2025.107959_bib95","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.jad.2010.09.014","article-title":"Relationship between malnutrition and depression or anxiety in anorexia nervosa: a critical review of the literature","volume":"132","author":"Mattar","year":"2011","journal-title":"J. Affect Disord."},{"key":"10.1016\/j.phrs.2025.107959_bib96","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.pnpbp.2018.03.004","article-title":"Central irisin administration affords antidepressant-like effect and modulates neuroplasticity-related genes in the hippocampus and prefrontal cortex of mice","volume":"84","author":"Siteneski","year":"2018","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"10.1016\/j.phrs.2025.107959_bib97","doi-asserted-by":"crossref","DOI":"10.1016\/j.neulet.2023.137245","article-title":"Effects of chronic irisin treatment on brain monoamine levels in the hypothalamic and subcortical nuclei of adult Male and female rats: an HPLC-ECD study","volume":"806","author":"Yardimci","year":"2023","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.phrs.2025.107959_bib98","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1002\/erv.2806","article-title":"Hippocampal volumes in anorexia nervosa at different stages of the disorder","volume":"29","author":"Collantoni","year":"2021","journal-title":"Eur. Eat. Disord. Rev."},{"key":"10.1016\/j.phrs.2025.107959_bib99","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1080\/17512433.2020.1850256","article-title":"Hippocampal volume, function, and related molecular activity in anorexia nervosa: a scoping review","volume":"13","author":"Keeler","year":"2020","journal-title":"Expert Rev. Clin. Pharm."},{"key":"10.1016\/j.phrs.2025.107959_bib100","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/pcn.13626","article-title":"Differential longitudinal changes of hippocampal subfields in patients with anorexia nervosa","volume":"78","author":"Bahnsen","year":"2024","journal-title":"Psychiatry Clin. Neurosci."},{"key":"10.1016\/j.phrs.2025.107959_bib101","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1097\/PSY.0b013e31824ef10e","article-title":"Structural brain abnormalities in adolescent anorexia nervosa before and after weight recovery and associated hormonal changes","volume":"74","author":"Mainz","year":"2012","journal-title":"Psychosom. Med"},{"key":"10.1016\/j.phrs.2025.107959_bib102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.physbeh.2019.01.016","article-title":"Behavioral assessment of activity-based-anorexia: how cognition can become the drive wheel","volume":"202","author":"Lamanna","year":"2019","journal-title":"Physiol. Behav."}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661825003846?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661825003846?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T21:44:44Z","timestamp":1778795084000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661825003846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":102,"alternative-id":["S1043661825003846"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2025.107959","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Irisin\/BDNF pathway dysfunction subserves anorexia nervosa pathophysiology","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2025.107959","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"107959"}}