DNA methylation epi-signature and biological age in attention deficit hyperactivity disorder patients
Attention Deficit/Hyperactivity Disorder (ADHD) is a common behavioral syndrome that begins in childhood and affects 3.4% of children worldwide. Due to its etiological complexity, there are no consistent biomarkers for ADHD, however the high heritability presented by the disorder indicates a genetic...
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| Veröffentlicht in: | Clinical neurology and neurosurgery 2023-05, Vol.228, p.107714-107714, Article 107714 |
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| container_title | Clinical neurology and neurosurgery |
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| creator | Carvalho, Gleyson Francisco da Silva Costa, Thais Virginia Moura Machado Nascimento, Amom Mendes Wolff, Beatriz Martins Damasceno, Julian Gabriel Vieira, Lucas Liro Almeida, Vanessa Tavares Oliveira, Yanca Gasparini de Mello, Claudia Berlim de Muszkat, Mauro Kulikowski, Leslie Domenici |
| description | Attention Deficit/Hyperactivity Disorder (ADHD) is a common behavioral syndrome that begins in childhood and affects 3.4% of children worldwide. Due to its etiological complexity, there are no consistent biomarkers for ADHD, however the high heritability presented by the disorder indicates a genetic/epigenetic influence. The main epigenetic mechanism is DNA methylation, a process with an important role in gene expression and in many psychiatric disorders. Thus, our study sought to identify epi-signatures biomarkers in 29 children clinically diagnosed with ADHD.
After DNA extraction and bisulfite conversion, we performed methylation array experiment for differential methylation, ontological and biological age analysis.
The biological response in ADHD patients was not sufficient to determine a conclusive epi-signature in our study. However, our results highlighted the interaction of energy metabolism and oxidative stress pathways in ADHD patients detected by differential methylation patterns. Furthermore, we were able to identify a marginal association between the DNAmAge and ADHD.
Our study present new methylation biomarkers findings associated with energy metabolism and oxidative stress pathways, in addition to DNAmAge in ADHD patients. However, we propose that further multiethnic studies, with larger cohorts and including maternal conditions, are necessary to demonstrate a definitive association between ADHD and these methylation biomarkers.
•There is still no conclusive episignature for ADHD.•Oxidative stress and energy metabolism play a crucial role in the pathophysiology of ADHD.•Biological methylation age (DNAmAge) acceleration has a marginal association with clinical status of ADHD. |
| doi_str_mv | 10.1016/j.clineuro.2023.107714 |
| format | Article |
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After DNA extraction and bisulfite conversion, we performed methylation array experiment for differential methylation, ontological and biological age analysis.
The biological response in ADHD patients was not sufficient to determine a conclusive epi-signature in our study. However, our results highlighted the interaction of energy metabolism and oxidative stress pathways in ADHD patients detected by differential methylation patterns. Furthermore, we were able to identify a marginal association between the DNAmAge and ADHD.
Our study present new methylation biomarkers findings associated with energy metabolism and oxidative stress pathways, in addition to DNAmAge in ADHD patients. However, we propose that further multiethnic studies, with larger cohorts and including maternal conditions, are necessary to demonstrate a definitive association between ADHD and these methylation biomarkers.
•There is still no conclusive episignature for ADHD.•Oxidative stress and energy metabolism play a crucial role in the pathophysiology of ADHD.•Biological methylation age (DNAmAge) acceleration has a marginal association with clinical status of ADHD.</description><identifier>ISSN: 0303-8467</identifier><identifier>EISSN: 1872-6968</identifier><identifier>DOI: 10.1016/j.clineuro.2023.107714</identifier><identifier>PMID: 37054476</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>ADHD ; Age ; Aging ; Attention Deficit Disorder with Hyperactivity - genetics ; Attention Deficit Disorder with Hyperactivity - metabolism ; Attention deficit hyperactivity disorder ; Biomarkers ; Biomarkers - metabolism ; Bisulfite ; Blood ; Cancer ; Child ; Children ; DNA methylation ; DNA Methylation - genetics ; DNAmAge ; Energy metabolism ; Epi-signature ; Epigenesis, Genetic ; Epigenetic ; Epigenetics ; Etiology ; Gene expression ; Genes ; Genetic testing ; Heritability ; Humans ; Hyperactivity ; Kruskal-Wallis test ; Mental disorders ; Metabolism ; Methylation ; Nervous system ; Neurology ; Ontology ; Oxidative metabolism ; Oxidative stress</subject><ispartof>Clinical neurology and neurosurgery, 2023-05, Vol.228, p.107714-107714, Article 107714</ispartof><rights>2023 Elsevier B.V.</rights><rights>Copyright © 2023 Elsevier B.V. All rights reserved.</rights><rights>2023. Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-401e184aa266785f050391d69f7d45b822817c6254ce059127cbb0febd8c01313</citedby><cites>FETCH-LOGICAL-c396t-401e184aa266785f050391d69f7d45b822817c6254ce059127cbb0febd8c01313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0303846723001300$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37054476$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carvalho, Gleyson Francisco da Silva</creatorcontrib><creatorcontrib>Costa, Thais Virginia Moura Machado</creatorcontrib><creatorcontrib>Nascimento, Amom Mendes</creatorcontrib><creatorcontrib>Wolff, Beatriz Martins</creatorcontrib><creatorcontrib>Damasceno, Julian Gabriel</creatorcontrib><creatorcontrib>Vieira, Lucas Liro</creatorcontrib><creatorcontrib>Almeida, Vanessa Tavares</creatorcontrib><creatorcontrib>Oliveira, Yanca Gasparini de</creatorcontrib><creatorcontrib>Mello, Claudia Berlim de</creatorcontrib><creatorcontrib>Muszkat, Mauro</creatorcontrib><creatorcontrib>Kulikowski, Leslie Domenici</creatorcontrib><title>DNA methylation epi-signature and biological age in attention deficit hyperactivity disorder patients</title><title>Clinical neurology and neurosurgery</title><addtitle>Clin Neurol Neurosurg</addtitle><description>Attention Deficit/Hyperactivity Disorder (ADHD) is a common behavioral syndrome that begins in childhood and affects 3.4% of children worldwide. Due to its etiological complexity, there are no consistent biomarkers for ADHD, however the high heritability presented by the disorder indicates a genetic/epigenetic influence. The main epigenetic mechanism is DNA methylation, a process with an important role in gene expression and in many psychiatric disorders. Thus, our study sought to identify epi-signatures biomarkers in 29 children clinically diagnosed with ADHD.
After DNA extraction and bisulfite conversion, we performed methylation array experiment for differential methylation, ontological and biological age analysis.
The biological response in ADHD patients was not sufficient to determine a conclusive epi-signature in our study. However, our results highlighted the interaction of energy metabolism and oxidative stress pathways in ADHD patients detected by differential methylation patterns. Furthermore, we were able to identify a marginal association between the DNAmAge and ADHD.
Our study present new methylation biomarkers findings associated with energy metabolism and oxidative stress pathways, in addition to DNAmAge in ADHD patients. However, we propose that further multiethnic studies, with larger cohorts and including maternal conditions, are necessary to demonstrate a definitive association between ADHD and these methylation biomarkers.
•There is still no conclusive episignature for ADHD.•Oxidative stress and energy metabolism play a crucial role in the pathophysiology of ADHD.•Biological methylation age (DNAmAge) acceleration has a marginal association with clinical status of ADHD.</description><subject>ADHD</subject><subject>Age</subject><subject>Aging</subject><subject>Attention Deficit Disorder with Hyperactivity - genetics</subject><subject>Attention Deficit Disorder with Hyperactivity - metabolism</subject><subject>Attention deficit hyperactivity disorder</subject><subject>Biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Bisulfite</subject><subject>Blood</subject><subject>Cancer</subject><subject>Child</subject><subject>Children</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>DNAmAge</subject><subject>Energy metabolism</subject><subject>Epi-signature</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetic</subject><subject>Epigenetics</subject><subject>Etiology</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic testing</subject><subject>Heritability</subject><subject>Humans</subject><subject>Hyperactivity</subject><subject>Kruskal-Wallis test</subject><subject>Mental disorders</subject><subject>Metabolism</subject><subject>Methylation</subject><subject>Nervous system</subject><subject>Neurology</subject><subject>Ontology</subject><subject>Oxidative metabolism</subject><subject>Oxidative stress</subject><issn>0303-8467</issn><issn>1872-6968</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkU9P3DAQxa2qVVlovwKy1EsvWfwvtnMDQVuQUHspZ8uxJ4tX2TjYDtJ--3pZ6KGXnkYa_d6b0XsInVOypoTKi-3ajWGCJcU1I4zXpVJUvEMrqhVrZCf1e7QinPBGC6lO0GnOW0II51J_RCdckVYIJVcIbn5e4R2Ux_1oS4gThjk0OWwmW5YE2E4e9yGOcROcHbHdAA4TtqXA9EJ7GIILBT_uZ0jWlfAcyh77kGPykPBcPSuZP6EPgx0zfH6dZ-jh-7ff17fN_a8fd9dX943jnSyNIBSoFtYyKZVuB9IS3lEvu0F50faaMU2Vk6wVDkjbUaZc35MBeq8doZzyM_T16Dun-LRALmYXsoNxtBPEJRumCe1qIJxX9Ms_6DYuaarfHShxuNS1lZJHyqWYc4LBzCnsbNobSsyhCLM1b0WYQxHmWEQVnr_aL_0O_F_ZW_IVuDwCUPN4DpBMdjUrBz4kcMX4GP534w_ZQ5z7</recordid><startdate>202305</startdate><enddate>202305</enddate><creator>Carvalho, Gleyson Francisco da Silva</creator><creator>Costa, Thais Virginia Moura Machado</creator><creator>Nascimento, Amom Mendes</creator><creator>Wolff, Beatriz Martins</creator><creator>Damasceno, Julian Gabriel</creator><creator>Vieira, Lucas Liro</creator><creator>Almeida, Vanessa Tavares</creator><creator>Oliveira, Yanca Gasparini de</creator><creator>Mello, Claudia Berlim de</creator><creator>Muszkat, Mauro</creator><creator>Kulikowski, Leslie Domenici</creator><general>Elsevier B.V</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>202305</creationdate><title>DNA methylation epi-signature and biological age in attention deficit hyperactivity disorder patients</title><author>Carvalho, Gleyson Francisco da Silva ; Costa, Thais Virginia Moura Machado ; Nascimento, Amom Mendes ; Wolff, Beatriz Martins ; Damasceno, Julian Gabriel ; Vieira, Lucas Liro ; Almeida, Vanessa Tavares ; Oliveira, Yanca Gasparini de ; Mello, Claudia Berlim de ; Muszkat, Mauro ; Kulikowski, Leslie Domenici</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-401e184aa266785f050391d69f7d45b822817c6254ce059127cbb0febd8c01313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>ADHD</topic><topic>Age</topic><topic>Aging</topic><topic>Attention Deficit Disorder with Hyperactivity - genetics</topic><topic>Attention Deficit Disorder with Hyperactivity - metabolism</topic><topic>Attention deficit hyperactivity disorder</topic><topic>Biomarkers</topic><topic>Biomarkers - metabolism</topic><topic>Bisulfite</topic><topic>Blood</topic><topic>Cancer</topic><topic>Child</topic><topic>Children</topic><topic>DNA methylation</topic><topic>DNA Methylation - genetics</topic><topic>DNAmAge</topic><topic>Energy metabolism</topic><topic>Epi-signature</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetic</topic><topic>Epigenetics</topic><topic>Etiology</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic testing</topic><topic>Heritability</topic><topic>Humans</topic><topic>Hyperactivity</topic><topic>Kruskal-Wallis test</topic><topic>Mental disorders</topic><topic>Metabolism</topic><topic>Methylation</topic><topic>Nervous system</topic><topic>Neurology</topic><topic>Ontology</topic><topic>Oxidative metabolism</topic><topic>Oxidative stress</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carvalho, Gleyson Francisco da Silva</creatorcontrib><creatorcontrib>Costa, Thais Virginia Moura Machado</creatorcontrib><creatorcontrib>Nascimento, Amom Mendes</creatorcontrib><creatorcontrib>Wolff, Beatriz Martins</creatorcontrib><creatorcontrib>Damasceno, Julian Gabriel</creatorcontrib><creatorcontrib>Vieira, Lucas Liro</creatorcontrib><creatorcontrib>Almeida, Vanessa Tavares</creatorcontrib><creatorcontrib>Oliveira, Yanca Gasparini de</creatorcontrib><creatorcontrib>Mello, Claudia Berlim de</creatorcontrib><creatorcontrib>Muszkat, Mauro</creatorcontrib><creatorcontrib>Kulikowski, Leslie Domenici</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical neurology and neurosurgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carvalho, Gleyson Francisco da Silva</au><au>Costa, Thais Virginia Moura Machado</au><au>Nascimento, Amom Mendes</au><au>Wolff, Beatriz Martins</au><au>Damasceno, Julian Gabriel</au><au>Vieira, Lucas Liro</au><au>Almeida, Vanessa Tavares</au><au>Oliveira, Yanca Gasparini de</au><au>Mello, Claudia Berlim de</au><au>Muszkat, Mauro</au><au>Kulikowski, Leslie Domenici</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA methylation epi-signature and biological age in attention deficit hyperactivity disorder patients</atitle><jtitle>Clinical neurology and neurosurgery</jtitle><addtitle>Clin Neurol Neurosurg</addtitle><date>2023-05</date><risdate>2023</risdate><volume>228</volume><spage>107714</spage><epage>107714</epage><pages>107714-107714</pages><artnum>107714</artnum><issn>0303-8467</issn><eissn>1872-6968</eissn><abstract>Attention Deficit/Hyperactivity Disorder (ADHD) is a common behavioral syndrome that begins in childhood and affects 3.4% of children worldwide. Due to its etiological complexity, there are no consistent biomarkers for ADHD, however the high heritability presented by the disorder indicates a genetic/epigenetic influence. The main epigenetic mechanism is DNA methylation, a process with an important role in gene expression and in many psychiatric disorders. Thus, our study sought to identify epi-signatures biomarkers in 29 children clinically diagnosed with ADHD.
After DNA extraction and bisulfite conversion, we performed methylation array experiment for differential methylation, ontological and biological age analysis.
The biological response in ADHD patients was not sufficient to determine a conclusive epi-signature in our study. However, our results highlighted the interaction of energy metabolism and oxidative stress pathways in ADHD patients detected by differential methylation patterns. Furthermore, we were able to identify a marginal association between the DNAmAge and ADHD.
Our study present new methylation biomarkers findings associated with energy metabolism and oxidative stress pathways, in addition to DNAmAge in ADHD patients. However, we propose that further multiethnic studies, with larger cohorts and including maternal conditions, are necessary to demonstrate a definitive association between ADHD and these methylation biomarkers.
•There is still no conclusive episignature for ADHD.•Oxidative stress and energy metabolism play a crucial role in the pathophysiology of ADHD.•Biological methylation age (DNAmAge) acceleration has a marginal association with clinical status of ADHD.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>37054476</pmid><doi>10.1016/j.clineuro.2023.107714</doi><tpages>1</tpages></addata></record> |
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| ispartof | Clinical neurology and neurosurgery, 2023-05, Vol.228, p.107714-107714, Article 107714 |
| issn | 0303-8467 1872-6968 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | ADHD Age Aging Attention Deficit Disorder with Hyperactivity - genetics Attention Deficit Disorder with Hyperactivity - metabolism Attention deficit hyperactivity disorder Biomarkers Biomarkers - metabolism Bisulfite Blood Cancer Child Children DNA methylation DNA Methylation - genetics DNAmAge Energy metabolism Epi-signature Epigenesis, Genetic Epigenetic Epigenetics Etiology Gene expression Genes Genetic testing Heritability Humans Hyperactivity Kruskal-Wallis test Mental disorders Metabolism Methylation Nervous system Neurology Ontology Oxidative metabolism Oxidative stress |
| title | DNA methylation epi-signature and biological age in attention deficit hyperactivity disorder patients |
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