Methylphenidate Ameliorates Depressive Comorbidity in ADHD Children without any Modification on Differences in Serum Melatonin Concentration between ADHD Subtypes
Open accessAbstract
The vast majority of Attention-deficit/hyperactivity disorder (ADHD) patients have other associated pathologies, with depressive symptoms as one of the most prevalent. Among the mediators that may participate in ADHD, melatonin is thought to regulate circadian rhythms, neurological function and stress response. To determine (1) the serum baseline daily variations and nocturnal excretion of melatonin in ADHD subtypes and (2) the effect of chronic administration of methylphenidate, as well as the effects on symptomatology, 136 children with ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision: DSM-IV-TR criteria) were divided into subgroups using the “Children’s Depression Inventory” (CDI). Blood samples were drawn at 20:00 and 09:00 h, and urine was collected between 21:00 and 09:00 h, at inclusion and after 4.61 ± 2.29 months of treatment. Melatonin and its urine metabolite were measured by radioimmunoassay RIA. Factorial analysis was performed using STATA 12.0. Melatonin was higher predominantly in hyperactive-impulsive/conduct disordered children (PHI/CD) of the ADHD subtype, without the influence of comorbid depressive symptoms. Methylphenidate ameliorated this comorbidity without induction of any changes in the serum melatonin profile, but treatment with it was associated with a decrease in 6-s-melatonin excretion in both ADHD subtypes. Conclusions: In untreated children, partial homeostatic restoration of disrupted neuroendocrine equilibrium most likely led to an increased serum melatonin in PHI/CD children. A differential cerebral melatonin metabolization after methylphenidate may underlie some of the clinical benefit.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In children with hyperactive-impulsive ADHD and comorbid conduct disorder, serum melatonin levels are higher than in inattentive ADHD.
“A higher level of serum melatonin in children with hyperactive-impulsive ADHD with comorbid conduct disorder compared to inattentive ADHD was noted by (Cubero-Milla ´n et al. 2014) in a study of 148 children.”
From A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder (2017) · cites this paper as Cubero-Millán et al. 2014
Methylphenidate treatment is associated with a lower level of the melatonin metabolite 6-sulfatoxymelatonin.
“These authors also report that methylphenidate treatment was associated with a lower level of the melatonin metabolite 6-sulfatoxymelatonin.”
From A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder (2017) · cites this paper as Cubero-Millán et al. 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A Review of the Multiple Actions of Melatonin on the Immune System
Carrillo‐Vico, A., Guerrero, J. M., Lardone, P. J., & Reiter, R. J. (2005) · Endocrine · doi:10.1385/endo:27:2:189 · Cited by 664 · see citing works
NIGG, J. T., & CASEY, B. J. (2005) · Development and Psychopathology · doi:10.1017/s0954579405050376 · Cited by 593 · see citing works
Barkley, R. A. (1997) · Psychological Bulletin · doi:10.1037//0033-2909.121.1.65 · Cited by 580 · see citing works
Preedy, V. R., & WATSON, R. R. (2009) · Springer eBooks · doi:10.1007/978-0-387-78665-0_5543 · Cited by 554 · see citing works
Nigg, J. T. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.11.011 · Cited by 513 · see citing works
Hardeland, R., Tan, D., & Reiter, R. J. (2009) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2009.00701.x · Cited by 474 · see citing works
Hardeland, R., Madrid, J. A., Tan, D. X., & Reiter, R. J. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00934.x · Cited by 449 · see citing works
Antiinflammatory Activity of Melatonin in Central Nervous System
Esposito, E., & Cuzzocrea, S. (2010) · Current Neuropharmacology · doi:10.2174/157015910792246155 · Cited by 408 · see citing works
Sleep Problems in Children With Attention-Deficit/Hyperactivity Disorder
Sung, V., Hiscock, H., Sciberras, E., & Efron, D. (2008) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.162.4.336 · Cited by 407 · see citing works
Stehle, J. H., Saade, A., Rawashdeh, O., Ackermann, K., Jilg, A., Sebesteny, T., & Maronde, E. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00856.x · Cited by 401 · see citing works
van Ewijk, H., Heslenfeld, D. J., Zwiers, M. P., Buitelaar, J. K., & Oosterlaan, J. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.01.003 · Cited by 377 · see citing works
Melatonin and its analogs in insomnia and depression
Cardinali, D. P., Srinivasan, V., Brzezinski, A., & Brown, G. M. (2011) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00962.x · Cited by 354 · see citing works
The ADHD and Sleep Conundrum: A Review
OWENS, J. A. (2005) · Journal of Developmental & Behavioral Pediatrics · doi:10.1097/00004703-200508000-00011 · Cited by 349 · see citing works
Brickenkamp, R., & Zilmer, E. (1998) · PsycTESTS Dataset · doi:10.1037/t03299-000 · Cited by 268 · see citing works
Melatonin-mitochondria Interplay in Health and Disease
Acuña-Castroviejo, D., López, L. C., Escames, G., López, A., García, J. A., & Reiter, R. J. (2011) · Current Topics in Medicinal Chemistry · doi:10.2174/156802611794863517 · Cited by 245 · see citing works
Assessment and Management of Sleep Problems in Youths With Attention-Deficit/Hyperactivity Disorder
Cortese, S., Brown, T. E., Corkum, P. V., Gruber, R., O'Brien, L. M., Stein, M. A., Weiss, M. D., & Owens, J. A. (2013) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2013.06.001 · Cited by 241 · see citing works
The Antiapoptotic Activity of Melatonin in Neurodegenerative Diseases
Wang, X. (2009) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2009.00105.x · Cited by 232 · see citing works
Mayes, S. D., Calhoun, S. L., Bixler, E. O., Vgontzas, A. N., Mahr, F., Garcia, J. H., Elamir, B., Edhere-Ekezie, L., & Parvin, M. (2008) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/jsn083 · Cited by 232 · see citing works
Neurosteroids as modulators of neurogenesis and neuronal survival
Charalampopoulos, I., Remboutsika, E., Margioris, A. N., & Gravanis, A. (2008) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2008.07.004 · Cited by 201 · see citing works
Environmental risk factors by gender associated with attention-deficit/hyperactivity disorder
Silva, D., Colvin, L., Hagemann, E., & Bower, C. (2014) · PEDIATRICS · doi:10.1542/peds.2013-1434 · Cited by 201 · see citing works
Neurotoxins: Free radical mechanisms and melatonin protection
J. Reiter, R., C. Manchester, L., & Tan, D.-X. (2010) · Current Neuropharmacology · doi:10.2174/157015910792246236 · Cited by 179 · see citing works
Imam, S. Z., EL‐YAZAL, J., Newport, G. D., Itzhak, Y., Cadet, J. L., Slikker, W., & Ali, S. F. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb03646.x · Cited by 173 · see citing works
Melatonin improves glucose homeostasis in young Zucker diabetic fatty rats
Agil, A., Rosado, I., Ruiz, R., Figueroa, A., Zen, N., & Fernández‐Vázquez, G. (2012) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00928.x · Cited by 169 · see citing works
Walters, A. S., Silvestri, R., Zucconi, M., Chandrashekariah, R., & Konofal, É. (2008) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.27356 · Cited by 167 · see citing works
The role of dopamine receptors in the neurotoxicity of methamphetamine
Ares‐Santos, S., Granado, N., & Moratalla, R. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12049 · Cited by 138 · see citing works
Plasma cortisol-dehydroepiandrosterone (DHEA) ratios in schizophrenia and bipolar disorder
GALLAGHER, P., WATSON, S., SMITH, M., YOUNG, A., & FERRIER, I. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2006.11.020 · Cited by 129 · see citing works
Attention Deficit Hyperactivity Disorder
Matthews, M., Nigg, J. T., & Fair, D. A. (2013) · Current topics in behavioral neurosciences · doi:10.1007/978-3-662-45758-0_249 · Cited by 121 · see citing works
McLoughlin, G., Palmer, J. A., Rijsdijk, F., & Makeig, S. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.07.020 · Cited by 100 · see citing works
Biological rhythms and melatonin in mood disorders and their treatments
Lanfumey, L., Mongeau, R., & Hamon, M. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.01.005 · Cited by 96 · see citing works
Effects of Melatonin on Nervous System Aging: Neurogenesis and Neurodegeneration
Sarlak, G., Jenwitheesuk, A., Chetsawang, B., & Govitrapong, P. (2013) · Journal of Pharmacological Sciences · doi:10.1254/jphs.13r01sr · Cited by 87 · see citing works
Berardis, D. D., Marini, S., Fornaro, M., Srinivasan, V., Iasevoli, F., Tomasetti, C., Valchera, A., Perna, G., Quera-Salva, M.-A., Martinotti, G., et al. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140612458 · Cited by 85 · see citing works
Latent class subtyping of attention-deficit/hyperactivity disorder and comorbid conditions
Acosta, M. T., Castellanos, F. X., Bolton, K. L., Balog, J. Z., Eagen, P., Nee, L., Jones, J., Palacio, L., Sarampote, C., Russell, H. F., et al. (2008) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/chi.0b013e318173f70b · Cited by 82 · see citing works
Molina‐Carballo, A., Muñoz‐Hoyos, A., Sánchez-Forte, M., Uberos-Fernández, J., Moreno-Madrid, F., & Acuña-Castroviejo, D. (2007) · Neuropediatrics · doi:10.1055/s-2007-985138 · Cited by 79 · see citing works
Self-citationDopamine-Induced Behavioral Changes and Oxidative Stress in Methamphetamine-Induced Neurotoxicity
Kita, T., Miyazaki, I., Asanuma, M., Takeshima, M., & Wagner, G. C. (2009) · International review of neurobiology · doi:10.1016/s0074-7742(09)88003-3 · Cited by 77 · see citing works
Analysis of neurosteroid levels in attention deficit hyperactivity disorder
Strous, R. D., Spivak, B., Yoran-Hegesh, R., Maayan, R., Averbuch, E., Kotler, M., Mester, R., & Weizman, A. (2001) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145701002462 · Cited by 75 · see citing works
Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons
Wiltschko, A. B., Pettibone, J. R., & Berke, J. D. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.226 · Cited by 71 · see citing works
Development of attentional processes in ADHD and normal children
Gupta, R., & Kar, B. R. (2009) · Progress in brain research · doi:10.1016/s0079-6123(09)17614-8 · Cited by 69 · see citing works
McNelis, J., Manolopoulos, K. N., Gathercole, L., Bujalska, I. J., Stewart, P. M., Tomlinson, J., & Arlt, W. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00314.2012 · Cited by 66 · see citing works
Moreno, M., Economidou, D., Mar, A. C., López-Granero, C., Caprioli, D., Theobald, D. E. H., Fernando, A. B. P., Newman, A. H., Robbins, T. W., & Dalley, J. W. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3010-3 · Cited by 63 · see citing works
Attention Deficit Hyperactivity Disorder
Matthews, M., Nigg, J. T., & Fair, D. A. (2013) · Current topics in behavioral neurosciences · doi:10.1007/7854_2013_249 · Cited by 63 · see citing works
Association of the steroid sulfatase (STS) gene with attention deficit hyperactivity disorder
Brookes, K. J., Hawi, Z., Kirley, A., Barry, E., Gill, M., & Kent, L. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30873 · Cited by 62 · see citing works
Farré-Riba, A., & Narbona, J. (1997) · Cited by 62 · see citing works
Use of sleep medication in children with ADHD
Efron, D., Lycett, K., & Sciberras, E. (2014) · Sleep Medicine · doi:10.1016/j.sleep.2013.10.018 · Cited by 56 · see citing works
Uberos, J., Augustin-Morales, M.-D.-C., Molina‐Carballo, A., et al. (2010) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2010.00828.x · Cited by 56 · see citing works
Self-citationMelatonin as a potential therapeutic agent in psychiatric illness
y Aibar, M. D. M., Reiter, R. J., & Pérez-San-Gregorio, M. Á. (2009) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.1032 · Cited by 54 · see citing works
Wang, L.-J., Huang, Y.-S., Hsiao, C.-C., Chiang, Y.-L., Wu, C.-C., Shang, Z.-Y., & Chen, C.-K. (2011) · World Journal of Biological Psychiatry · doi:10.3109/15622975.2010.512090 · Cited by 53 · see citing works
Muñoz‐Hoyos, A., Bonillo-Perales, A., Ávila-Villegas, R., et al. (2007) · Neonatology · doi:10.1159/000102957 · Cited by 50 · see citing works
Self-citationStrickland, A. (2014) · Medical Hypotheses · doi:10.1016/j.mehy.2014.02.003 · Cited by 45 · see citing works
Comorbid Symptom Severity in Attention-Deficit/Hyperactivity Disorder
Connor, D. F., & Ford, J. D. (2012) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.11m07099 · Cited by 44 · see citing works
Biochemical and genetic analyses of childhood attention deficit/hyperactivity disorder
Çaylak, E. (2012) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32077 · Cited by 44 · see citing works
Molina-Carballo, A., Naranjo-Gómez, A., Uberos, J., Justicia-Martínez, F., Ruiz-Ramos, M.-J., Cubero-Millán, I., Contreras-Chova, F., Augustin-Morales, M.-D.-C., Khaldy-Belkadi, H., & Muñoz-Hoyos, A. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.09.020 · Cited by 43 · see citing works
Self-citationTrent, S., Dean, R., Veit, B., Cassano, T., Bedse, G., Ojarikre, O. A., Humby, T., & Davies, W. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.12.002 · Cited by 39 · see citing works
Farré-Riba, A., & Narbona, J. (1997) · PubMed · Cited by 36 · see citing works
Psychosocial dwarfism: Psychopathological aspects and putative neuroendocrine markers
Muñoz‐Hoyos, A., Molina‐Carballo, A., Augustin-Morales, M.-D.-C., Contreras‐Chova, F., Naranjo-Gómez, A., Justicia-Martínez, F., & Uberos, J. (2010) · Psychiatry Research · doi:10.1016/j.psychres.2010.10.004 · Cited by 30 · see citing works
Self-citationProtective Effect of Melatonin on Methamphetamine-Induced Apoptosis in Glioma Cell Line
Jumnongprakhon, P., Govitrapong, P., Tocharus, C., Tungkum, W., & Tocharus, J. (2013) · Neurotoxicity Research · doi:10.1007/s12640-013-9419-y · Cited by 25 · see citing works
Alexiuk, N. A. M., & Vriend, J. P. (2006) · Journal of Neural Transmission · doi:10.1007/s00702-006-0582-7 · Cited by 23 · see citing works
Wang, L., Hsiao, C., Huang, Y., Chiang, Y.-L., Ree, S., Chen, Y., Wu, Y., Wu, C., Shang, Z.-Y., & Chen, C. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.02.014 · Cited by 19 · see citing works
Dosing Time-Dependent Actions of Psychostimulants
Manev, H., & Uz, T. (2009) · International review of neurobiology · doi:10.1016/s0074-7742(09)88002-1 · Cited by 16 · see citing works
[The effect of melatonin as anti-convulsant and neuron protector].
Sánchez-Forte, M., Moreno-Madrid, F., Muñoz‐Hoyos, A., et al. (1997) · PubMed · Cited by 15 · see citing works
Self-citationMolina‐Carballo, A., Justicia-Martínez, F., Moreno‐Madrid, F., Cubero-Millán, I., Machado-Casas, I., Moreno-García, L., León, J., Luna, J. D. D., Uberos, J., & Muñoz‐Hoyos, A. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3514-5 · Cited by 14 · see citing works
Self-citationZambrano-Sánchez, E., Martínez-Cortés, J. A., del Río-Carlos, Y., Martínez-Wbaldo, M. D. C., & Poblano, A. (2010) · Psychiatry Research · doi:10.1016/j.psychres.2010.09.004 · Cited by 10 · see citing works
Circadian rhythms of saliva melatonin in ADHD, anxious and normal children.
Paclt, I., Ptáček, R., Kuželová, H., et al. (2011) · PubMed · Cited by 9 · see citing works
Presman, D. M., Levi, V., Pignataro, O. P., & Pecci, A. (2011) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.10.026 · Cited by 7 · see citing works
López, C. R. S., Cruz, F. D., & Pérez, C. R. (2010) · Revista de Neurología · doi:10.33588/rn.5106.2010373 · Cited by 5 · see citing works
Muñoz‐Hoyos, A., Molina‐Carballo, A., Uberos, J., et al. (2009) · PubMed · Cited by 5 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Coogan, A. N., & McGowan, N. M. (2017) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-016-0214-5 · Cited by 208 · see citing works
- Authors
- Cubero-Millán, I., Molina-Carballo, A., Machado-Casas, I., Fernández-López, L., Martínez-Serrano, S., Tortosa-Pinto, P., Ruiz-López, A., Luna-del-Castillo, J.-D.-D., Uberos, J., & Muñoz-Hoyos, A.
- Affiliations
- Neuropediatric, Neuropsicology and Early intervention Unit Pediatric Service, Clinico San Cecilio Hospital, 18012 Granada, Spain
- Biostatistical Department, School of Medicine, Granada University, 18140 Granada, Spain
- ORCID
- Uberos, José
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2014-09-25
- Volume
- 15
- Issue
- 9
- Pages
- 17115-17129
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC4200748
- OpenAlex
- W2064903653
- Cited by
- 19
- References
- 65
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 3 · 2017: 2 · 2016: 2
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repository of the University of Granada (University of Granada) (submittedVersion, cc-by-nc-nd)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Health Research Fund (FIS; Spanish Ministry of Science and Innovation) (FIS-PI07-0603)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- methylphenidate, attention deficit hyperactivity disorder, depressive symptoms, comorbidities, melatonin, serum melatonin, ADHD subtypes, children, circadian rhythm, neuroendocrine regulation
- MeSH terms
- Adolescent, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Circadian Rhythm, Depression, Female, Homeostasis, Humans, Impulsive Behavior, Male, Melatonin, Methylphenidate, Personality Inventory, Conduct Disorder, Sleep Disorders, Intrinsic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
