A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia
Abstract Compelling evidence supports the involvement of the endocannabinoid system (ECS) in psychosis vulnerability. We here evaluated the transcriptional regulation of ECS components in human peripheral blood mononuclear cells (PBMCs) obtained from subjects suffering from bipolar disorder, major d...
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| Veröffentlicht in: | Schizophrenia research 2017-10, Vol.188, p.132-140 |
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| creator | D'Addario, Claudio Micale, Vincenzo Di Bartolomeo, Martina Stark, Tibor Pucci, Mariangela Sulcova, Alexandra Palazzo, Mariacarlotta Babinska, Zuzana Cremaschi, Laura Drago, Filippo Carlo Altamura, A Maccarrone, Mauro Dell'Osso, Bernardo |
| description | Abstract Compelling evidence supports the involvement of the endocannabinoid system (ECS) in psychosis vulnerability. We here evaluated the transcriptional regulation of ECS components in human peripheral blood mononuclear cells (PBMCs) obtained from subjects suffering from bipolar disorder, major depressive disorder and schizophrenia, focusing in particular on the effects of DNA methylation. We observed selective alterations of DNA methylation at the promoter of CNR1 , the gene coding for the type-1 cannabinoid receptor, in schizophrenic patients ( N = 25) with no changes in any other disorder. We confirmed the regulation of CNR1 in a well-validated animal model of schizophrenia, induced by prenatal methylazoxymethanol (MAM) acetate exposure ( N = 7 per group) where we found, in the prefrontal cortex, a significant increase in CNR1 expression and a consistent reduction in DNA methylation at specific CpG sites of gene promoter. Overall, our findings suggest a selective dysregulation of ECS in psychosis, and highlight the evaluation of CNR1 DNA methylation levels in PBMCs as a potential biomarker for schizophrenia. |
| doi_str_mv | 10.1016/j.schres.2017.01.022 |
| format | Article |
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We here evaluated the transcriptional regulation of ECS components in human peripheral blood mononuclear cells (PBMCs) obtained from subjects suffering from bipolar disorder, major depressive disorder and schizophrenia, focusing in particular on the effects of DNA methylation. We observed selective alterations of DNA methylation at the promoter of CNR1 , the gene coding for the type-1 cannabinoid receptor, in schizophrenic patients ( N = 25) with no changes in any other disorder. We confirmed the regulation of CNR1 in a well-validated animal model of schizophrenia, induced by prenatal methylazoxymethanol (MAM) acetate exposure ( N = 7 per group) where we found, in the prefrontal cortex, a significant increase in CNR1 expression and a consistent reduction in DNA methylation at specific CpG sites of gene promoter. Overall, our findings suggest a selective dysregulation of ECS in psychosis, and highlight the evaluation of CNR1 DNA methylation levels in PBMCs as a potential biomarker for schizophrenia.</description><identifier>ISSN: 0920-9964</identifier><identifier>EISSN: 1573-2509</identifier><identifier>DOI: 10.1016/j.schres.2017.01.022</identifier><identifier>PMID: 28108228</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Bipolar Disorder - genetics ; Bipolar Disorder - metabolism ; Cannabinoid receptor type-1 ; Cohort Studies ; CpG Islands ; Depressive Disorder, Major - genetics ; Depressive Disorder, Major - metabolism ; Disease Models, Animal ; DNA Methylation ; Endocannabinoid system (ECS) ; Endocannabinoids - metabolism ; Female ; Gene Expression Regulation ; Humans ; Leukocytes, Mononuclear - metabolism ; Male ; Methylazoxymethanol (MAM) rat model ; Methylazoxymethanol Acetate ; Middle Aged ; Prefrontal Cortex - metabolism ; Promoter Regions, Genetic ; Psychiatry ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1 - genetics ; Receptor, Cannabinoid, CB1 - metabolism ; Schizophrenia ; Schizophrenia - genetics ; Schizophrenia - metabolism</subject><ispartof>Schizophrenia research, 2017-10, Vol.188, p.132-140</ispartof><rights>Elsevier B.V.</rights><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-2a3f1502a294283f8120c55b6b3d87b19976237b3a3c2f8d5d4657a43be509df3</citedby><cites>FETCH-LOGICAL-c455t-2a3f1502a294283f8120c55b6b3d87b19976237b3a3c2f8d5d4657a43be509df3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0920996417300312$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28108228$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:137085699$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>D'Addario, Claudio</creatorcontrib><creatorcontrib>Micale, Vincenzo</creatorcontrib><creatorcontrib>Di Bartolomeo, Martina</creatorcontrib><creatorcontrib>Stark, Tibor</creatorcontrib><creatorcontrib>Pucci, Mariangela</creatorcontrib><creatorcontrib>Sulcova, Alexandra</creatorcontrib><creatorcontrib>Palazzo, Mariacarlotta</creatorcontrib><creatorcontrib>Babinska, Zuzana</creatorcontrib><creatorcontrib>Cremaschi, Laura</creatorcontrib><creatorcontrib>Drago, Filippo</creatorcontrib><creatorcontrib>Carlo Altamura, A</creatorcontrib><creatorcontrib>Maccarrone, Mauro</creatorcontrib><creatorcontrib>Dell'Osso, Bernardo</creatorcontrib><title>A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia</title><title>Schizophrenia research</title><addtitle>Schizophr Res</addtitle><description>Abstract Compelling evidence supports the involvement of the endocannabinoid system (ECS) in psychosis vulnerability. We here evaluated the transcriptional regulation of ECS components in human peripheral blood mononuclear cells (PBMCs) obtained from subjects suffering from bipolar disorder, major depressive disorder and schizophrenia, focusing in particular on the effects of DNA methylation. We observed selective alterations of DNA methylation at the promoter of CNR1 , the gene coding for the type-1 cannabinoid receptor, in schizophrenic patients ( N = 25) with no changes in any other disorder. We confirmed the regulation of CNR1 in a well-validated animal model of schizophrenia, induced by prenatal methylazoxymethanol (MAM) acetate exposure ( N = 7 per group) where we found, in the prefrontal cortex, a significant increase in CNR1 expression and a consistent reduction in DNA methylation at specific CpG sites of gene promoter. Overall, our findings suggest a selective dysregulation of ECS in psychosis, and highlight the evaluation of CNR1 DNA methylation levels in PBMCs as a potential biomarker for schizophrenia.</description><subject>Animals</subject><subject>Bipolar Disorder - genetics</subject><subject>Bipolar Disorder - metabolism</subject><subject>Cannabinoid receptor type-1</subject><subject>Cohort Studies</subject><subject>CpG Islands</subject><subject>Depressive Disorder, Major - genetics</subject><subject>Depressive Disorder, Major - metabolism</subject><subject>Disease Models, Animal</subject><subject>DNA Methylation</subject><subject>Endocannabinoid system (ECS)</subject><subject>Endocannabinoids - metabolism</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Male</subject><subject>Methylazoxymethanol (MAM) rat model</subject><subject>Methylazoxymethanol Acetate</subject><subject>Middle Aged</subject><subject>Prefrontal Cortex - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Psychiatry</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, Cannabinoid, CB1 - genetics</subject><subject>Receptor, Cannabinoid, CB1 - metabolism</subject><subject>Schizophrenia</subject><subject>Schizophrenia - genetics</subject><subject>Schizophrenia - metabolism</subject><issn>0920-9964</issn><issn>1573-2509</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUsuO1DAQjBCInV34A4R85JLBjzgPDkijWViQVovE42w5TofxbGIPbodV-BV-FocZVogLp261qqtVVZ1lzxhdM8rKl_s1ml0AXHPKqjVla8r5g2zFZCVyLmnzMFvRhtO8acriLDtH3FNKmaTV4-yM14zWnNer7OeGHAIMdrROh5lgnLqZ-J6A67zRzunWOm87gjNGGEmAr9Ogo_WOWEcOOJudR4uvyKXFaJ2JRA8Rwm8ELjzbm48sXfCjT2NyebMhI8Td_BdH6sBFJHc27kiSZH_4Q9LlrH6SPer1gPD0VC-yL2_ffN6-y68_XL3fbq5zU0gZc65Fn3RxzZuC16KvGadGyrZsRVdXLWuaquSiaoUWhvd1J7uilJUuRAvJpq4XF1l-5MU7OEytOgQ7JjOU11adRrepA1UkL1md8C-O-KTr2wQY1WjRwDBoB35CxeqSybricoEWR6gJHjFAf0_OqFpiVHt1jFEtMSrKVIoxrT0_XZjaEbr7pT-5JcDrIwCSL98thMSSbDTQ2QAmqs7b_134l8AM1lmjh1uYAfd-Ci55rphCrqj6tLzS8kmsEpQKxsUv_B_IoA</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>D'Addario, Claudio</creator><creator>Micale, Vincenzo</creator><creator>Di Bartolomeo, Martina</creator><creator>Stark, Tibor</creator><creator>Pucci, Mariangela</creator><creator>Sulcova, Alexandra</creator><creator>Palazzo, Mariacarlotta</creator><creator>Babinska, Zuzana</creator><creator>Cremaschi, Laura</creator><creator>Drago, Filippo</creator><creator>Carlo Altamura, A</creator><creator>Maccarrone, Mauro</creator><creator>Dell'Osso, Bernardo</creator><general>Elsevier B.V</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>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>20171001</creationdate><title>A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia</title><author>D'Addario, Claudio ; Micale, Vincenzo ; Di Bartolomeo, Martina ; Stark, Tibor ; Pucci, Mariangela ; Sulcova, Alexandra ; Palazzo, Mariacarlotta ; Babinska, Zuzana ; Cremaschi, Laura ; Drago, Filippo ; Carlo Altamura, A ; Maccarrone, Mauro ; Dell'Osso, Bernardo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-2a3f1502a294283f8120c55b6b3d87b19976237b3a3c2f8d5d4657a43be509df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Bipolar Disorder - genetics</topic><topic>Bipolar Disorder - metabolism</topic><topic>Cannabinoid receptor type-1</topic><topic>Cohort Studies</topic><topic>CpG Islands</topic><topic>Depressive Disorder, Major - genetics</topic><topic>Depressive Disorder, Major - metabolism</topic><topic>Disease Models, Animal</topic><topic>DNA Methylation</topic><topic>Endocannabinoid system (ECS)</topic><topic>Endocannabinoids - metabolism</topic><topic>Female</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Male</topic><topic>Methylazoxymethanol (MAM) rat model</topic><topic>Methylazoxymethanol Acetate</topic><topic>Middle Aged</topic><topic>Prefrontal Cortex - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Psychiatry</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, Cannabinoid, CB1 - genetics</topic><topic>Receptor, Cannabinoid, CB1 - metabolism</topic><topic>Schizophrenia</topic><topic>Schizophrenia - genetics</topic><topic>Schizophrenia - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>D'Addario, Claudio</creatorcontrib><creatorcontrib>Micale, Vincenzo</creatorcontrib><creatorcontrib>Di Bartolomeo, Martina</creatorcontrib><creatorcontrib>Stark, Tibor</creatorcontrib><creatorcontrib>Pucci, Mariangela</creatorcontrib><creatorcontrib>Sulcova, Alexandra</creatorcontrib><creatorcontrib>Palazzo, Mariacarlotta</creatorcontrib><creatorcontrib>Babinska, Zuzana</creatorcontrib><creatorcontrib>Cremaschi, Laura</creatorcontrib><creatorcontrib>Drago, Filippo</creatorcontrib><creatorcontrib>Carlo Altamura, A</creatorcontrib><creatorcontrib>Maccarrone, Mauro</creatorcontrib><creatorcontrib>Dell'Osso, Bernardo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Schizophrenia research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>D'Addario, Claudio</au><au>Micale, Vincenzo</au><au>Di Bartolomeo, Martina</au><au>Stark, Tibor</au><au>Pucci, Mariangela</au><au>Sulcova, Alexandra</au><au>Palazzo, Mariacarlotta</au><au>Babinska, Zuzana</au><au>Cremaschi, Laura</au><au>Drago, Filippo</au><au>Carlo Altamura, A</au><au>Maccarrone, Mauro</au><au>Dell'Osso, Bernardo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia</atitle><jtitle>Schizophrenia research</jtitle><addtitle>Schizophr Res</addtitle><date>2017-10-01</date><risdate>2017</risdate><volume>188</volume><spage>132</spage><epage>140</epage><pages>132-140</pages><issn>0920-9964</issn><eissn>1573-2509</eissn><abstract>Abstract Compelling evidence supports the involvement of the endocannabinoid system (ECS) in psychosis vulnerability. We here evaluated the transcriptional regulation of ECS components in human peripheral blood mononuclear cells (PBMCs) obtained from subjects suffering from bipolar disorder, major depressive disorder and schizophrenia, focusing in particular on the effects of DNA methylation. We observed selective alterations of DNA methylation at the promoter of CNR1 , the gene coding for the type-1 cannabinoid receptor, in schizophrenic patients ( N = 25) with no changes in any other disorder. We confirmed the regulation of CNR1 in a well-validated animal model of schizophrenia, induced by prenatal methylazoxymethanol (MAM) acetate exposure ( N = 7 per group) where we found, in the prefrontal cortex, a significant increase in CNR1 expression and a consistent reduction in DNA methylation at specific CpG sites of gene promoter. Overall, our findings suggest a selective dysregulation of ECS in psychosis, and highlight the evaluation of CNR1 DNA methylation levels in PBMCs as a potential biomarker for schizophrenia.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28108228</pmid><doi>10.1016/j.schres.2017.01.022</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Bipolar Disorder - genetics Bipolar Disorder - metabolism Cannabinoid receptor type-1 Cohort Studies CpG Islands Depressive Disorder, Major - genetics Depressive Disorder, Major - metabolism Disease Models, Animal DNA Methylation Endocannabinoid system (ECS) Endocannabinoids - metabolism Female Gene Expression Regulation Humans Leukocytes, Mononuclear - metabolism Male Methylazoxymethanol (MAM) rat model Methylazoxymethanol Acetate Middle Aged Prefrontal Cortex - metabolism Promoter Regions, Genetic Psychiatry Rats, Sprague-Dawley Receptor, Cannabinoid, CB1 - genetics Receptor, Cannabinoid, CB1 - metabolism Schizophrenia Schizophrenia - genetics Schizophrenia - metabolism |
| title | A preliminary study of endocannabinoid system regulation in psychosis: Distinct alterations of CNR1 promoter DNA methylation in patients with schizophrenia |
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