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Influence of BDNF and MTHFR polymorphisms on hippocampal volume in first-episode psychosis
The BDNF and MTHFR genes are independently linked to the pathogenesis of schizophrenia and its neuroimaging correlates. The aim of this study was to explore, for the first time, the individual and interactional effects of the Val66Met and C677T polymorphisms on hippocampal atrophy in first-episode p...
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| Published in: | Schizophrenia research 2020-09, Vol.223, p.345-352 |
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| creator | Pujol, Nuria Mané, Anna Bergé, Daniel Mezquida, Gisela Amoretti, Silvia Pérez, Lucía González-Pinto, Ana Barcones, Fe Cuesta, Manuel J. Sánchez-Tomico, Georgina Vieta, Eduard Castro-Fornieles, Josefina Bernardo, Miquel Parellada, Mara |
| description | The BDNF and MTHFR genes are independently linked to the pathogenesis of schizophrenia and its neuroimaging correlates. The aim of this study was to explore, for the first time, the individual and interactional effects of the Val66Met and C677T polymorphisms on hippocampal atrophy in first-episode psychosis (FEP).
Multi-site case-control study based on clinical, genetic (rs 6265, rs 1801133) and structural magnetic resonance imaging data from 98 non-affective FEP patients and 117 matched healthy controls (HC). Hippocampal volume was estimated using FreeSurfer software and this volume was compared between diagnostic (FEP vs HC) and genotype (Val66Met, C677T) groups. The BDNF Val66Met x MTHFR C677T effect on hippocampal volume was further evaluated through stratified analyses.
After applying Bonferroni correction, diagnosis showed a significant effect for adjusted left and right hippocampal volume (FEP |
| doi_str_mv | 10.1016/j.schres.2020.08.002 |
| format | article |
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Multi-site case-control study based on clinical, genetic (rs 6265, rs 1801133) and structural magnetic resonance imaging data from 98 non-affective FEP patients and 117 matched healthy controls (HC). Hippocampal volume was estimated using FreeSurfer software and this volume was compared between diagnostic (FEP vs HC) and genotype (Val66Met, C677T) groups. The BDNF Val66Met x MTHFR C677T effect on hippocampal volume was further evaluated through stratified analyses.
After applying Bonferroni correction, diagnosis showed a significant effect for adjusted left and right hippocampal volume (FEP < HC). Stratified analyses showed that the interactive effect contributed to adjusted hippocampal size in both the HC (left and right hippocampus) and FEP groups (right hippocampus); among BDNF Met carriers, those with the CT-TT genotype exhibited decreased hippocampal volume compared to individuals with the homozygous normal CC genotype.
Our results provide preliminary evidence indicating that the Val66Met x C677T interaction may be a potential genetic risk factor for reduced hippocampal size in both healthy controls and in patients with FEP. Further research in independent samples including different ethnic groups is warranted to confirm this new finding.</description><identifier>ISSN: 0920-9964</identifier><identifier>EISSN: 1573-2509</identifier><identifier>DOI: 10.1016/j.schres.2020.08.002</identifier><identifier>PMID: 32988741</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>BDNF Val66Met polymorphism ; Brain-Derived Neurotrophic Factor - genetics ; Case-Control Studies ; First-episode psychosis ; Genotype ; Hippocampus ; Hippocampus - diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Methylenetetrahydrofolate Reductase (NADPH2) - genetics ; MTHFR C677T polymorphism ; Polymorphism, Single Nucleotide - genetics ; Psychotic Disorders - diagnostic imaging ; Psychotic Disorders - genetics ; Schizophrenia - diagnostic imaging ; Schizophrenia - genetics</subject><ispartof>Schizophrenia research, 2020-09, Vol.223, p.345-352</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-329886e8a5d0ccf408d6a2c7a33c9fe97f9fe2cd81f84135a8eee52abf08629d3</citedby><cites>FETCH-LOGICAL-c362t-329886e8a5d0ccf408d6a2c7a33c9fe97f9fe2cd81f84135a8eee52abf08629d3</cites><orcidid>0000-0003-0632-2687 ; 0000-0001-6017-2734 ; 0000-0001-8748-6717 ; 0000-0002-0548-0053</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32988741$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pujol, Nuria</creatorcontrib><creatorcontrib>Mané, Anna</creatorcontrib><creatorcontrib>Bergé, Daniel</creatorcontrib><creatorcontrib>Mezquida, Gisela</creatorcontrib><creatorcontrib>Amoretti, Silvia</creatorcontrib><creatorcontrib>Pérez, Lucía</creatorcontrib><creatorcontrib>González-Pinto, Ana</creatorcontrib><creatorcontrib>Barcones, Fe</creatorcontrib><creatorcontrib>Cuesta, Manuel J.</creatorcontrib><creatorcontrib>Sánchez-Tomico, Georgina</creatorcontrib><creatorcontrib>Vieta, Eduard</creatorcontrib><creatorcontrib>Castro-Fornieles, Josefina</creatorcontrib><creatorcontrib>Bernardo, Miquel</creatorcontrib><creatorcontrib>Parellada, Mara</creatorcontrib><creatorcontrib>PEPs GROUP</creatorcontrib><title>Influence of BDNF and MTHFR polymorphisms on hippocampal volume in first-episode psychosis</title><title>Schizophrenia research</title><addtitle>Schizophr Res</addtitle><description>The BDNF and MTHFR genes are independently linked to the pathogenesis of schizophrenia and its neuroimaging correlates. The aim of this study was to explore, for the first time, the individual and interactional effects of the Val66Met and C677T polymorphisms on hippocampal atrophy in first-episode psychosis (FEP).
Multi-site case-control study based on clinical, genetic (rs 6265, rs 1801133) and structural magnetic resonance imaging data from 98 non-affective FEP patients and 117 matched healthy controls (HC). Hippocampal volume was estimated using FreeSurfer software and this volume was compared between diagnostic (FEP vs HC) and genotype (Val66Met, C677T) groups. The BDNF Val66Met x MTHFR C677T effect on hippocampal volume was further evaluated through stratified analyses.
After applying Bonferroni correction, diagnosis showed a significant effect for adjusted left and right hippocampal volume (FEP < HC). Stratified analyses showed that the interactive effect contributed to adjusted hippocampal size in both the HC (left and right hippocampus) and FEP groups (right hippocampus); among BDNF Met carriers, those with the CT-TT genotype exhibited decreased hippocampal volume compared to individuals with the homozygous normal CC genotype.
Our results provide preliminary evidence indicating that the Val66Met x C677T interaction may be a potential genetic risk factor for reduced hippocampal size in both healthy controls and in patients with FEP. Further research in independent samples including different ethnic groups is warranted to confirm this new finding.</description><subject>BDNF Val66Met polymorphism</subject><subject>Brain-Derived Neurotrophic Factor - genetics</subject><subject>Case-Control Studies</subject><subject>First-episode psychosis</subject><subject>Genotype</subject><subject>Hippocampus</subject><subject>Hippocampus - diagnostic imaging</subject><subject>Humans</subject><subject>Magnetic Resonance Imaging</subject><subject>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</subject><subject>MTHFR C677T polymorphism</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Psychotic Disorders - diagnostic imaging</subject><subject>Psychotic Disorders - genetics</subject><subject>Schizophrenia - diagnostic imaging</subject><subject>Schizophrenia - genetics</subject><issn>0920-9964</issn><issn>1573-2509</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kD1vFDEQhi0EIpfAP0DIJc0uY3s_7AYJEi6JFBIJhYbGcuyxzqfdtbFvI92_Z48LKdPMNO_HzEPIBwY1A9Z93tbFbjKWmgOHGmQNwF-RFWt7UfEW1GuyAsWhUqprTshpKVsAYC30b8mJ4ErKvmEr8vt68sOMk0UaPf12cbumZnL0x_3V-idNcdiPMadNKGOhcaKbkFK0ZkxmoI9xmEekYaI-5LKrMIUSHdJU9nYTSyjvyBtvhoLvn_YZ-bX-fn9-Vd3cXV6ff72prOj4rvp3S4fStA6s9Q1I1xlueyOEVR5V75fJrZPMy4aJ1khEbLl58CA7rpw4I5-OuSnHPzOWnR5DsTgMZsI4F82bphdMKMEXaXOU2hxLyeh1ymE0ea8Z6ANVvdVHqvpAVYPUC9XF9vGpYX4Y0T2b_mNcBF-OAlz-fAyYl5RwgOpCRrvTLoaXG_4CX6WLSA</recordid><startdate>202009</startdate><enddate>202009</enddate><creator>Pujol, Nuria</creator><creator>Mané, Anna</creator><creator>Bergé, Daniel</creator><creator>Mezquida, Gisela</creator><creator>Amoretti, Silvia</creator><creator>Pérez, Lucía</creator><creator>González-Pinto, Ana</creator><creator>Barcones, Fe</creator><creator>Cuesta, Manuel J.</creator><creator>Sánchez-Tomico, Georgina</creator><creator>Vieta, Eduard</creator><creator>Castro-Fornieles, Josefina</creator><creator>Bernardo, Miquel</creator><creator>Parellada, Mara</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><orcidid>https://orcid.org/0000-0003-0632-2687</orcidid><orcidid>https://orcid.org/0000-0001-6017-2734</orcidid><orcidid>https://orcid.org/0000-0001-8748-6717</orcidid><orcidid>https://orcid.org/0000-0002-0548-0053</orcidid></search><sort><creationdate>202009</creationdate><title>Influence of BDNF and MTHFR polymorphisms on hippocampal volume in first-episode psychosis</title><author>Pujol, Nuria ; Mané, Anna ; Bergé, Daniel ; Mezquida, Gisela ; Amoretti, Silvia ; Pérez, Lucía ; González-Pinto, Ana ; Barcones, Fe ; Cuesta, Manuel J. ; Sánchez-Tomico, Georgina ; Vieta, Eduard ; Castro-Fornieles, Josefina ; Bernardo, Miquel ; Parellada, Mara</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-329886e8a5d0ccf408d6a2c7a33c9fe97f9fe2cd81f84135a8eee52abf08629d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>BDNF Val66Met polymorphism</topic><topic>Brain-Derived Neurotrophic Factor - genetics</topic><topic>Case-Control Studies</topic><topic>First-episode psychosis</topic><topic>Genotype</topic><topic>Hippocampus</topic><topic>Hippocampus - diagnostic imaging</topic><topic>Humans</topic><topic>Magnetic Resonance Imaging</topic><topic>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</topic><topic>MTHFR C677T polymorphism</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Psychotic Disorders - diagnostic imaging</topic><topic>Psychotic Disorders - genetics</topic><topic>Schizophrenia - diagnostic imaging</topic><topic>Schizophrenia - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pujol, Nuria</creatorcontrib><creatorcontrib>Mané, Anna</creatorcontrib><creatorcontrib>Bergé, Daniel</creatorcontrib><creatorcontrib>Mezquida, Gisela</creatorcontrib><creatorcontrib>Amoretti, Silvia</creatorcontrib><creatorcontrib>Pérez, Lucía</creatorcontrib><creatorcontrib>González-Pinto, Ana</creatorcontrib><creatorcontrib>Barcones, Fe</creatorcontrib><creatorcontrib>Cuesta, Manuel J.</creatorcontrib><creatorcontrib>Sánchez-Tomico, Georgina</creatorcontrib><creatorcontrib>Vieta, Eduard</creatorcontrib><creatorcontrib>Castro-Fornieles, Josefina</creatorcontrib><creatorcontrib>Bernardo, Miquel</creatorcontrib><creatorcontrib>Parellada, Mara</creatorcontrib><creatorcontrib>PEPs GROUP</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><jtitle>Schizophrenia research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pujol, Nuria</au><au>Mané, Anna</au><au>Bergé, Daniel</au><au>Mezquida, Gisela</au><au>Amoretti, Silvia</au><au>Pérez, Lucía</au><au>González-Pinto, Ana</au><au>Barcones, Fe</au><au>Cuesta, Manuel J.</au><au>Sánchez-Tomico, Georgina</au><au>Vieta, Eduard</au><au>Castro-Fornieles, Josefina</au><au>Bernardo, Miquel</au><au>Parellada, Mara</au><aucorp>PEPs GROUP</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of BDNF and MTHFR polymorphisms on hippocampal volume in first-episode psychosis</atitle><jtitle>Schizophrenia research</jtitle><addtitle>Schizophr Res</addtitle><date>2020-09</date><risdate>2020</risdate><volume>223</volume><spage>345</spage><epage>352</epage><pages>345-352</pages><issn>0920-9964</issn><eissn>1573-2509</eissn><abstract>The BDNF and MTHFR genes are independently linked to the pathogenesis of schizophrenia and its neuroimaging correlates. The aim of this study was to explore, for the first time, the individual and interactional effects of the Val66Met and C677T polymorphisms on hippocampal atrophy in first-episode psychosis (FEP).
Multi-site case-control study based on clinical, genetic (rs 6265, rs 1801133) and structural magnetic resonance imaging data from 98 non-affective FEP patients and 117 matched healthy controls (HC). Hippocampal volume was estimated using FreeSurfer software and this volume was compared between diagnostic (FEP vs HC) and genotype (Val66Met, C677T) groups. The BDNF Val66Met x MTHFR C677T effect on hippocampal volume was further evaluated through stratified analyses.
After applying Bonferroni correction, diagnosis showed a significant effect for adjusted left and right hippocampal volume (FEP < HC). Stratified analyses showed that the interactive effect contributed to adjusted hippocampal size in both the HC (left and right hippocampus) and FEP groups (right hippocampus); among BDNF Met carriers, those with the CT-TT genotype exhibited decreased hippocampal volume compared to individuals with the homozygous normal CC genotype.
Our results provide preliminary evidence indicating that the Val66Met x C677T interaction may be a potential genetic risk factor for reduced hippocampal size in both healthy controls and in patients with FEP. Further research in independent samples including different ethnic groups is warranted to confirm this new finding.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>32988741</pmid><doi>10.1016/j.schres.2020.08.002</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-0632-2687</orcidid><orcidid>https://orcid.org/0000-0001-6017-2734</orcidid><orcidid>https://orcid.org/0000-0001-8748-6717</orcidid><orcidid>https://orcid.org/0000-0002-0548-0053</orcidid></addata></record> |
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| subjects | BDNF Val66Met polymorphism Brain-Derived Neurotrophic Factor - genetics Case-Control Studies First-episode psychosis Genotype Hippocampus Hippocampus - diagnostic imaging Humans Magnetic Resonance Imaging Methylenetetrahydrofolate Reductase (NADPH2) - genetics MTHFR C677T polymorphism Polymorphism, Single Nucleotide - genetics Psychotic Disorders - diagnostic imaging Psychotic Disorders - genetics Schizophrenia - diagnostic imaging Schizophrenia - genetics |
| title | Influence of BDNF and MTHFR polymorphisms on hippocampal volume in first-episode psychosis |
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