{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T13:16:09Z","timestamp":1774876569610,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Attention-deficit\/hyperactivity disorder (ADHD), brain\u2013derived neurotrophic factor (BDNF), and enuresis are interconnected in several ways, primarily through their potential links to neurodevelopmental factors and brain function. ADHD is considered a neurobehavioral and neuropsychiatric condition characterized by numerous comorbidities, and it represents one of the most frequently encountered neuropsychiatric disorders in clinical practice. Enuresis constitutes a subgroup of intermittent incontinence occurring during sleep that can be further subdivided into monosymptomatic (MNE) and non-monosymptomatic enuresis (NMNE). BDNF plays a crucial role in neurodevelopment, including neuronal growth, proliferation, survival, differentiation, and synaptic plasticity. This narrative review synthesized available literature identified through a systematic search of PubMed\/MEDLINE, Science Direct, and Scopus databases (January 2000\u2013December 2025). However, the evidence base is heterogeneous, and findings regarding BDNF in ADHD are inconsistent. Studies examining BDNF in enuresis often involve urinary BDNF, which reflects local bladder production rather than central BDNF activity. Further research is needed to clarify the specific roles of BDNF in the development and manifestation of these conditions and to fully elucidate the complex relationship between BDNF, ADHD, and enuresis.<\/jats:p>","DOI":"10.3390\/brainsci16040372","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T12:11:44Z","timestamp":1774872704000},"page":"372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enuresis, ADHD and BDNF: A Narrative Review of the Hypothesized Interconnections and Potential Triplet Relationship"],"prefix":"10.3390","volume":"16","author":[{"given":"Maria","family":"Milioudi","sequence":"first","affiliation":[{"name":"1st Pediatric Department, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9843-8198","authenticated-orcid":false,"given":"Stella","family":"Stabouli","sequence":"additional","affiliation":[{"name":"1st Pediatric Department, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2187-9299","authenticated-orcid":false,"given":"Dimitrios","family":"Zafeiriou","sequence":"additional","affiliation":[{"name":"1st Pediatric Department, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Efthymia","family":"Vargiami","sequence":"additional","affiliation":[{"name":"1st Pediatric Department, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1097\/CHI.0b013e318190045c","article-title":"Prevalence of enuresis and its association with attention-deficit\/hyperactivity disorder among U.S. children: Results from a nationally representative study","volume":"48","author":"Shreeram","year":"2009","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00787-014-0577-0","article-title":"Comorbidity of ADHD and incontinence in children","volume":"24","author":"Equit","year":"2015","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Colucci-D\u2019Amato, L., Speranza, L., and Volpicelli, F. (2020). Neurotrophic factor BDNF, physiological functions and therapeutic potential in depression, neurodegeneration and brain cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207777"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1126\/science.270.5236.593","article-title":"Neurotrophins and neuronal plasticity","volume":"270","author":"Thoenen","year":"1995","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1016\/j.pnpbp.2008.08.005","article-title":"Increased levels of plasma brain-derived neurotrophic factor (BDNF) in children with attention deficit-hyperactivity disorder (ADHD)","volume":"32","author":"Shim","year":"2008","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.mehy.2006.06.025","article-title":"Attention-deficit hyperactivity disorder may be associated with decreased central brain-derived neurotrophic factor activity: Clinical and therapeutic implications","volume":"68","author":"Tsai","year":"2007","journal-title":"Med. Hypotheses"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"255.e1","DOI":"10.1016\/j.jpurol.2019.03.010","article-title":"BDNF and NGF gene polymorphisms and urine BDNF-NGF levels in children with primary monosymptomatic nocturnal enuresis","volume":"15","author":"Ece","year":"2019","journal-title":"J. Pediatr. Urol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s004670050186","article-title":"Cure of nocturnal enuresis: Why isn\u2019t desmopressin very effective?","volume":"10","author":"Koff","year":"1996","journal-title":"Pediatr. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1124\/mol.106.022715","article-title":"The phenotypic differentiation of locus ceruleus noradrenergic neurons mediated by brain-derived neurotrophic factor is enhanced by corticotropin releasing factor through the activation of a cAMP-dependent signaling pathway","volume":"70","author":"Traver","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/350230a0","article-title":"BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra","volume":"350","author":"Hyman","year":"1991","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/S0002-9440(10)65221-2","article-title":"Abundant production of brain-derived neurotrophic factor by adult visceral epithelia: Implications for paracrine and target-derived neurotrophic functions","volume":"155","author":"Lommatzsch","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nrurol.2012.178","article-title":"Neurotrophins as regulators of urinary bladder function","volume":"9","author":"Ochodnicky","year":"2012","journal-title":"Nat. Rev. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s13052-023-01456-1","article-title":"The global prevalence of ADHD in children and adolescents: A systematic review and meta-analysis","volume":"49","author":"Salari","year":"2023","journal-title":"Ital. J. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.yebeh.2014.04.021","article-title":"Key issues in addressing the comorbidity of attention deficit hyperactivity disorder and pediatric epilepsy","volume":"37","author":"Salpekar","year":"2014","journal-title":"Epilepsy Behav."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/epi.13652","article-title":"WO-NOEP appraisal: Biomarkers of epilepsy-associated comorbidities","volume":"58","author":"Ravizza","year":"2017","journal-title":"Epilepsia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41380-025-03178-8","article-title":"Prevalence of attention deficit hyperactivity disorder\/hyperkinetic disorder of pediatric and adult populations in clinical settings: A systematic review, meta-analysis and meta-regression","volume":"31","author":"Johnson","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2333794X221076607","DOI":"10.1177\/2333794X221076607","article-title":"Comorbidities associated with attention-deficit\/hyperactivity disorder in children and adolescents at a tertiary care setting","volume":"9","author":"Jogia","year":"2022","journal-title":"Glob. Pediatr. Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/S2215-0366(20)30312-6","article-title":"Environmental risk factors, protective factors, and peripheral biomarkers for ADHD: An umbrella review","volume":"7","author":"Kim","year":"2020","journal-title":"Lancet Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1177\/1087054712438766","article-title":"Strategy selection in ADHD characteristics children: A study in arithmetic","volume":"23","author":"Sella","year":"2019","journal-title":"J. Atten. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"949","DOI":"10.2147\/NDT.S2234","article-title":"Effects of psycho-educational training and stimulant medication on visual perceptual skills in children with attention deficit hyperactivity disorder","volume":"3","author":"Papavasiliou","year":"2007","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1016\/j.juro.2014.01.110","article-title":"The standardization of terminology of lower urinary tract function in children and adolescents: Update report from the Standardization Committee of the International Children\u2019s Continence Society","volume":"191","author":"Austin","year":"2014","journal-title":"J. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"159.e1","DOI":"10.1016\/j.jpurol.2015.11.011","article-title":"Prevalence of nocturnal enuresis and its influence on quality of life in school-aged children","volume":"12","author":"Sarici","year":"2016","journal-title":"J. Pediatr. Urol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1007\/s00431-016-2729-3","article-title":"The pathophysiology of monosymptomatic nocturnal enuresis with special emphasis on the circadian rhythm of renal physiology","volume":"175","author":"Dossche","year":"2016","journal-title":"Eur. J. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1016\/S0022-5347(05)65611-X","article-title":"The genetics of enuresis: A review","volume":"166","author":"Schaumburg","year":"2001","journal-title":"J. Urol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S2352-4642(20)30350-3","article-title":"Identification of genetic loci associated with nocturnal enuresis: A genome-wide association study","volume":"5","author":"Horsdal","year":"2021","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/jnc.13658","article-title":"BDNF isoforms: A round trip ticket between neurogenesis and serotonin?","volume":"138","author":"Foltran","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s11055-017-0391-5","article-title":"Differences in the biological functions of BDNF and proBDNF in the central nervous system","volume":"47","author":"Borodinova","year":"2017","journal-title":"Neurosci. Behav. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s11255-013-0540-x","article-title":"Urinary brain-derived neurotrophic factor: A potential biomarker for objective diagnosis of overactive bladder","volume":"46","author":"Wang","year":"2014","journal-title":"Int. Urol. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1002\/nau.24142","article-title":"Urinary nerve growth factor can predict therapeutic efficacy in children with monosymptomatic nocturnal enuresis","volume":"38","author":"Morizawa","year":"2019","journal-title":"Neurourol. Urodyn."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/j.1460-2075.1982.tb01207.x","article-title":"Purification of a new neurotrophic factor from mammalian brain","volume":"1","author":"Barde","year":"1982","journal-title":"EMBO J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10099","DOI":"10.1523\/JNEUROSCI.2680-04.2004","article-title":"The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology","volume":"24","author":"Pezawas","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/S0028-3908(98)00141-5","article-title":"Transport of brain-derived neurotrophic factor across the blood-brain barrier","volume":"37","author":"Pan","year":"1998","journal-title":"Neuropharmacology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/0006-8993(95)01321-0","article-title":"Presence of brain-derived neurotrophic factor in brain and human and rat but not mouse serum detected by a sensitive and specific immunoassay","volume":"709","author":"Radka","year":"1996","journal-title":"Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.neurobiolaging.2004.03.002","article-title":"The impact of age, weight and gender on BDNF levels in human platelets and plasma","volume":"26","author":"Lommatzsch","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S0165-1781(02)00005-7","article-title":"Decreased serum brain-derived neurotrophic factor levels in major depressed patients","volume":"109","author":"Karege","year":"2002","journal-title":"Psychiatry Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/jdn.10332","article-title":"BDNF, proBDNF and proBDNF\/BDNF ratio with electroencephalographic abnormalities in children with attention deficit hyperactivity disorder: Possible relations to cognition and severity","volume":"84","author":"Afify","year":"2024","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/j.juro.2010.11.051","article-title":"Psychological and psychiatric issues in urinary and fecal incontinence","volume":"185","author":"Baeyens","year":"2011","journal-title":"J. Urol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s00787-010-0090-z","article-title":"Molecular genetics of attention-deficit\/hyperactivity disorder: An overview","volume":"19","author":"Banaschewski","year":"2010","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"285","DOI":"10.4306\/pi.2010.7.4.285","article-title":"Gender-specific association of the brain-derived neurotrophic factor gene with attention-deficit\/hyperactivity disorder","volume":"7","author":"Cho","year":"2010","journal-title":"Psychiatry Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s43045-021-00099-4","article-title":"Plasma brain-derived neurotrophic factor (BDNF) in Egyptian children with attention deficit hyperactivity disorder","volume":"28","author":"Nagib","year":"2021","journal-title":"Middle East Curr. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00787-013-0447-1","article-title":"Serum brain-derived neurotrophic factor (BDNF) levels in attention deficit-hyperactivity disorder (ADHD)","volume":"23","author":"Scassellati","year":"2014","journal-title":"Eur. Child Adolesc. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00213-016-4460-1","article-title":"BDNF concentrations and daily fluctuations differ among ADHD children and respond differently to methylphenidate with no relationship with depressive symptomatology","volume":"234","author":"Uberos","year":"2017","journal-title":"Psychopharmacology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1017\/S1461145712001629","article-title":"Decreased serum levels of brain-derived neurotrophic factor in adults with attention-deficit hyperactivity disorder","volume":"16","author":"Ribases","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1249\/mss.0b013e31802f04c7","article-title":"The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function","volume":"39","author":"Ferris","year":"2007","journal-title":"Med. Sci. Sports Exerc."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/4\/372\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T12:15:28Z","timestamp":1774872928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/4\/372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,29]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["brainsci16040372"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16040372","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,29]]}}}