Association of GSK3β Polymorphisms With Brain Structural Changes in Major Depressive Disorder
CONTEXT Indirect evidence suggests that the glycogen synthase kinase-3β (GSK3β) gene might be implicated in major depressive disorder (MDD). BACKGROUND We evaluated 15 GSK3β single-nucleotide polymorphisms (SNPs) to test for associations with regional gray matter (GM) volume differences in patients...
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| Veröffentlicht in: | Archives of general psychiatry 2009-07, Vol.66 (7), p.721-728 |
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| creator | Inkster, Becky Nichols, Thomas E Saemann, Philipp G Auer, Dorothee P Holsboer, Florian Muglia, Pierandrea Matthews, Paul M |
| description | CONTEXT Indirect evidence suggests that the glycogen synthase kinase-3β (GSK3β) gene might be implicated in major depressive disorder (MDD). BACKGROUND We evaluated 15 GSK3β single-nucleotide polymorphisms (SNPs) to test for associations with regional gray matter (GM) volume differences in patients with recurrent MDD. We then used the defined regions of interest based on significant associations to test for MDD × genotype interactions by including a matched control group without any psychiatric disorder, including MDD. DESIGN General linear model with nonstationary cluster-based inference. SETTING Munich, Germany. PARTICIPANTS Patients with recurrent MDD (n = 134) and age-, sex-, and ethnicity-matched healthy controls (n = 143). MAIN OUTCOME MEASURES Associations between GSK3β polymorphisms and regional GM volume differences. RESULTS Variation in GM volume was associated with GSK3β polymorphisms; the most significant associations were found for rs6438552, a putative functional intronic SNP that showed 3 significant GM clusters in the right and left superior temporal gyri and the right hippocampus (P |
| doi_str_mv | 10.1001/archgenpsychiatry.2009.70 |
| format | Article |
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BACKGROUND We evaluated 15 GSK3β single-nucleotide polymorphisms (SNPs) to test for associations with regional gray matter (GM) volume differences in patients with recurrent MDD. We then used the defined regions of interest based on significant associations to test for MDD × genotype interactions by including a matched control group without any psychiatric disorder, including MDD. DESIGN General linear model with nonstationary cluster-based inference. SETTING Munich, Germany. PARTICIPANTS Patients with recurrent MDD (n = 134) and age-, sex-, and ethnicity-matched healthy controls (n = 143). MAIN OUTCOME MEASURES Associations between GSK3β polymorphisms and regional GM volume differences. RESULTS Variation in GM volume was associated with GSK3β polymorphisms; the most significant associations were found for rs6438552, a putative functional intronic SNP that showed 3 significant GM clusters in the right and left superior temporal gyri and the right hippocampus (P < .001, P = .02, and P = .02, respectively, corrected for multiple comparisons across the whole brain). Similar results were obtained with rs12630592, an SNP in high linkage disequilibrium. A significant SNP × MDD status interaction was observed for the effect on GM volumes in the right hippocampus and superior temporal gyri (P < .001 and P = .01, corrected, respectively). CONCLUSIONS The GSK3β gene may have a role in determining regional GM volume differences of the right hippocampus and bilateral superior temporal gyri. The association between genotype and brain structure was specific to the patients with MDD, suggesting that GSK3β genotypes might interact with MDD status. We speculate that this is a consequence of regional neocortical, glial, or neuronal growth or survival. In considering core cognitive features of MDD, the association of GSK3β polymorphisms with structural variation in the temporal lobe and hippocampus is of particular interest in the context of other evidence for structural and functional abnormalities in the hippocampi of patients with MDD.Arch Gen Psychiatry. 2009;66(7):721-728--></description><identifier>ISSN: 0003-990X</identifier><identifier>EISSN: 1538-3636</identifier><identifier>DOI: 10.1001/archgenpsychiatry.2009.70</identifier><identifier>CODEN: ARGPAQ</identifier><language>eng</language><publisher>Chicago, IL: American Medical Association</publisher><subject>Adult and adolescent clinical studies ; Biological and medical sciences ; Depression ; Medical sciences ; Mood disorders ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry</subject><ispartof>Archives of general psychiatry, 2009-07, Vol.66 (7), p.721-728</ispartof><rights>2009 INIST-CNRS</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a309t-2b922ba0a70d4672753beafb14db9a1eeccac58ea27fa9112505e6030df8997e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jamapsychiatry/articlepdf/10.1001/archgenpsychiatry.2009.70$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jamapsychiatry/fullarticle/10.1001/archgenpsychiatry.2009.70$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,314,776,780,3327,27901,27902,76458,76461</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21753256$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Inkster, Becky</creatorcontrib><creatorcontrib>Nichols, Thomas E</creatorcontrib><creatorcontrib>Saemann, Philipp G</creatorcontrib><creatorcontrib>Auer, Dorothee P</creatorcontrib><creatorcontrib>Holsboer, Florian</creatorcontrib><creatorcontrib>Muglia, Pierandrea</creatorcontrib><creatorcontrib>Matthews, Paul M</creatorcontrib><title>Association of GSK3β Polymorphisms With Brain Structural Changes in Major Depressive Disorder</title><title>Archives of general psychiatry</title><description>CONTEXT Indirect evidence suggests that the glycogen synthase kinase-3β (GSK3β) gene might be implicated in major depressive disorder (MDD). BACKGROUND We evaluated 15 GSK3β single-nucleotide polymorphisms (SNPs) to test for associations with regional gray matter (GM) volume differences in patients with recurrent MDD. We then used the defined regions of interest based on significant associations to test for MDD × genotype interactions by including a matched control group without any psychiatric disorder, including MDD. DESIGN General linear model with nonstationary cluster-based inference. SETTING Munich, Germany. PARTICIPANTS Patients with recurrent MDD (n = 134) and age-, sex-, and ethnicity-matched healthy controls (n = 143). MAIN OUTCOME MEASURES Associations between GSK3β polymorphisms and regional GM volume differences. RESULTS Variation in GM volume was associated with GSK3β polymorphisms; the most significant associations were found for rs6438552, a putative functional intronic SNP that showed 3 significant GM clusters in the right and left superior temporal gyri and the right hippocampus (P < .001, P = .02, and P = .02, respectively, corrected for multiple comparisons across the whole brain). Similar results were obtained with rs12630592, an SNP in high linkage disequilibrium. A significant SNP × MDD status interaction was observed for the effect on GM volumes in the right hippocampus and superior temporal gyri (P < .001 and P = .01, corrected, respectively). CONCLUSIONS The GSK3β gene may have a role in determining regional GM volume differences of the right hippocampus and bilateral superior temporal gyri. The association between genotype and brain structure was specific to the patients with MDD, suggesting that GSK3β genotypes might interact with MDD status. We speculate that this is a consequence of regional neocortical, glial, or neuronal growth or survival. In considering core cognitive features of MDD, the association of GSK3β polymorphisms with structural variation in the temporal lobe and hippocampus is of particular interest in the context of other evidence for structural and functional abnormalities in the hippocampi of patients with MDD.Arch Gen Psychiatry. 2009;66(7):721-728--></description><subject>Adult and adolescent clinical studies</subject><subject>Biological and medical sciences</subject><subject>Depression</subject><subject>Medical sciences</subject><subject>Mood disorders</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. 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Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><toplevel>online_resources</toplevel><creatorcontrib>Inkster, Becky</creatorcontrib><creatorcontrib>Nichols, Thomas E</creatorcontrib><creatorcontrib>Saemann, Philipp G</creatorcontrib><creatorcontrib>Auer, Dorothee P</creatorcontrib><creatorcontrib>Holsboer, Florian</creatorcontrib><creatorcontrib>Muglia, Pierandrea</creatorcontrib><creatorcontrib>Matthews, Paul M</creatorcontrib><collection>Pascal-Francis</collection><collection>CrossRef</collection><jtitle>Archives of general psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Inkster, Becky</au><au>Nichols, Thomas E</au><au>Saemann, Philipp G</au><au>Auer, Dorothee P</au><au>Holsboer, Florian</au><au>Muglia, Pierandrea</au><au>Matthews, Paul M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of GSK3β Polymorphisms With Brain Structural Changes in Major Depressive Disorder</atitle><jtitle>Archives of general psychiatry</jtitle><date>2009-07-01</date><risdate>2009</risdate><volume>66</volume><issue>7</issue><spage>721</spage><epage>728</epage><pages>721-728</pages><issn>0003-990X</issn><eissn>1538-3636</eissn><coden>ARGPAQ</coden><abstract>CONTEXT Indirect evidence suggests that the glycogen synthase kinase-3β (GSK3β) gene might be implicated in major depressive disorder (MDD). BACKGROUND We evaluated 15 GSK3β single-nucleotide polymorphisms (SNPs) to test for associations with regional gray matter (GM) volume differences in patients with recurrent MDD. We then used the defined regions of interest based on significant associations to test for MDD × genotype interactions by including a matched control group without any psychiatric disorder, including MDD. DESIGN General linear model with nonstationary cluster-based inference. SETTING Munich, Germany. PARTICIPANTS Patients with recurrent MDD (n = 134) and age-, sex-, and ethnicity-matched healthy controls (n = 143). MAIN OUTCOME MEASURES Associations between GSK3β polymorphisms and regional GM volume differences. RESULTS Variation in GM volume was associated with GSK3β polymorphisms; the most significant associations were found for rs6438552, a putative functional intronic SNP that showed 3 significant GM clusters in the right and left superior temporal gyri and the right hippocampus (P < .001, P = .02, and P = .02, respectively, corrected for multiple comparisons across the whole brain). Similar results were obtained with rs12630592, an SNP in high linkage disequilibrium. A significant SNP × MDD status interaction was observed for the effect on GM volumes in the right hippocampus and superior temporal gyri (P < .001 and P = .01, corrected, respectively). CONCLUSIONS The GSK3β gene may have a role in determining regional GM volume differences of the right hippocampus and bilateral superior temporal gyri. The association between genotype and brain structure was specific to the patients with MDD, suggesting that GSK3β genotypes might interact with MDD status. We speculate that this is a consequence of regional neocortical, glial, or neuronal growth or survival. In considering core cognitive features of MDD, the association of GSK3β polymorphisms with structural variation in the temporal lobe and hippocampus is of particular interest in the context of other evidence for structural and functional abnormalities in the hippocampi of patients with MDD.Arch Gen Psychiatry. 2009;66(7):721-728--></abstract><cop>Chicago, IL</cop><pub>American Medical Association</pub><doi>10.1001/archgenpsychiatry.2009.70</doi><tpages>8</tpages></addata></record> |
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| subjects | Adult and adolescent clinical studies Biological and medical sciences Depression Medical sciences Mood disorders Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry |
| title | Association of GSK3β Polymorphisms With Brain Structural Changes in Major Depressive Disorder |
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