Abnormal Temporal Lobe White Matter as a Biomarker for Genetic Risk of Bipolar Disorder
Background Brain white matter (WM) abnormalities have been hypothesized to play an important role in the neurobiology of bipolar disorder (BD). The nature of these abnormalities is not well-characterized, however, and it is unknown whether they occur after disease onset or represent potential marker...
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| Veröffentlicht in: | Biological psychiatry (1969) 2013-01, Vol.73 (2), p.177-182 |
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| container_title | Biological psychiatry (1969) |
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| creator | Mahon, Katie Burdick, Katherine E Ikuta, Toshikazu Braga, Raphael J Gruner, Patricia Malhotra, Anil K Szeszko, Philip R |
| description | Background Brain white matter (WM) abnormalities have been hypothesized to play an important role in the neurobiology of bipolar disorder (BD). The nature of these abnormalities is not well-characterized, however, and it is unknown whether they occur after disease onset or represent potential markers of genetic risk. Methods We examined WM integrity (assessed via fractional anisotropy [FA]) with diffusion tensor imaging in patients with BD ( n =26), unaffected siblings of patients with BD ( n =15), and healthy volunteers ( n =27) to identify WM biomarkers of genetic risk. Results The FA differed significantly ( p unaffected siblings>BD). Moreover, FA values in this region correlated negatively and significantly with trait impulsivity in unaffected siblings. Probabilistic tractography indicated that the regional abnormality lies along the inferior fronto-occipital fasciculus, a large intrahemispheric association pathway. Conclusions Our results suggest that lower WM integrity in the right temporal lobe might be a biomarker for genetic risk of BD. It is conceivable that the attenuated nature of these WM abnormalities present in unaffected siblings allows for some preservation of adaptive emotional regulation, whereas more pronounced alterations observed in patients is related to the marked emotional dysregulation characteristic of BD. |
| doi_str_mv | 10.1016/j.biopsych.2012.07.033 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3760506</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006322312006920</els_id><sourcerecordid>1283734158</sourcerecordid><originalsourceid>FETCH-LOGICAL-c622t-d05490d0db19ad93c974e38fe279b07380e822557d0932d10bbe1984b404c9ba3</originalsourceid><addsrcrecordid>eNqFkk1v1DAQhiMEotvCX6hyQeKSMLaTOL5UlAIFaRESFPVo-WPCejeJg52ttP--Xu22fFw4eax55p2x38mycwIlAdK8WZfa-SnuzKqkQGgJvATGnmQL0nJW0Aro02wBAE3BKGUn2WmM63TllJLn2QllwBpRt4vs9lKPPgyqz29wmHxIwdJrzG9Xbsb8i5pnDLmKucrfOT-osEnXzof8Gkecncm_ubjJfZeyk-9VyN-76IPF8CJ71qk-4svjeZb9-Pjh5upTsfx6_fnqclmYhtK5sFBXAixYTYSyghnBK2Rth5QLDZy1gC2ldc0tCEYtAa2RiLbSFVRGaMXOsouD7rTVA1qD45zeIKfg0rA76ZWTf2dGt5I__Z1kvIEamiTw-igQ_K8txlkOLhrsezWi30ZJaMs4q0jdJrQ5oCb4GAN2j20IyL0rci0fXJF7VyRwmVxJhed_DvlY9mBDAl4dARWN6rugRuPib44TDhxI4t4eOExfeucwyGgcjgatC2hmab37_ywX_0iY3o0udd3gDuPab8OYDJNExlQjv-93aL9ChKZAUGD3kj3DGg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1283734158</pqid></control><display><type>article</type><title>Abnormal Temporal Lobe White Matter as a Biomarker for Genetic Risk of Bipolar Disorder</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Mahon, Katie ; Burdick, Katherine E ; Ikuta, Toshikazu ; Braga, Raphael J ; Gruner, Patricia ; Malhotra, Anil K ; Szeszko, Philip R</creator><creatorcontrib>Mahon, Katie ; Burdick, Katherine E ; Ikuta, Toshikazu ; Braga, Raphael J ; Gruner, Patricia ; Malhotra, Anil K ; Szeszko, Philip R</creatorcontrib><description>Background Brain white matter (WM) abnormalities have been hypothesized to play an important role in the neurobiology of bipolar disorder (BD). The nature of these abnormalities is not well-characterized, however, and it is unknown whether they occur after disease onset or represent potential markers of genetic risk. Methods We examined WM integrity (assessed via fractional anisotropy [FA]) with diffusion tensor imaging in patients with BD ( n =26), unaffected siblings of patients with BD ( n =15), and healthy volunteers ( n =27) to identify WM biomarkers of genetic risk. Results The FA differed significantly ( p <.05; corrected) among the three groups within the right temporal WM. Unaffected siblings had FA values that were intermediate to and significantly different from those of healthy volunteers and patients with BD (healthy control subjects>unaffected siblings>BD). Moreover, FA values in this region correlated negatively and significantly with trait impulsivity in unaffected siblings. Probabilistic tractography indicated that the regional abnormality lies along the inferior fronto-occipital fasciculus, a large intrahemispheric association pathway. Conclusions Our results suggest that lower WM integrity in the right temporal lobe might be a biomarker for genetic risk of BD. It is conceivable that the attenuated nature of these WM abnormalities present in unaffected siblings allows for some preservation of adaptive emotional regulation, whereas more pronounced alterations observed in patients is related to the marked emotional dysregulation characteristic of BD.</description><identifier>ISSN: 0006-3223</identifier><identifier>EISSN: 1873-2402</identifier><identifier>DOI: 10.1016/j.biopsych.2012.07.033</identifier><identifier>PMID: 23036958</identifier><identifier>CODEN: BIPCBF</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Adult and adolescent clinical studies ; Anisotropy ; Biological and medical sciences ; Bipolar ; Bipolar Disorder - complications ; Bipolar Disorder - genetics ; Bipolar Disorder - pathology ; Bipolar Disorder - psychology ; Bipolar disorders ; Case-Control Studies ; Diffusion Tensor Imaging - methods ; Diffusion Tensor Imaging - psychology ; DTI ; endophenotype ; Endophenotypes ; Female ; fractional anisotropy ; Genetic Predisposition to Disease - psychology ; Humans ; Image Processing, Computer-Assisted ; Impulsive Behavior - complications ; Impulsive Behavior - pathology ; Impulsive Behavior - psychology ; Male ; Medical sciences ; Mood disorders ; Nerve Fibers, Myelinated - pathology ; Neural Pathways - pathology ; Neuroimaging - methods ; Neuroimaging - psychology ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; siblings ; Siblings - psychology ; Temporal Lobe - pathology ; tractography</subject><ispartof>Biological psychiatry (1969), 2013-01, Vol.73 (2), p.177-182</ispartof><rights>Society of Biological Psychiatry</rights><rights>2013 Society of Biological Psychiatry</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c622t-d05490d0db19ad93c974e38fe279b07380e822557d0932d10bbe1984b404c9ba3</citedby><cites>FETCH-LOGICAL-c622t-d05490d0db19ad93c974e38fe279b07380e822557d0932d10bbe1984b404c9ba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biopsych.2012.07.033$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,781,785,886,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27170701$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23036958$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mahon, Katie</creatorcontrib><creatorcontrib>Burdick, Katherine E</creatorcontrib><creatorcontrib>Ikuta, Toshikazu</creatorcontrib><creatorcontrib>Braga, Raphael J</creatorcontrib><creatorcontrib>Gruner, Patricia</creatorcontrib><creatorcontrib>Malhotra, Anil K</creatorcontrib><creatorcontrib>Szeszko, Philip R</creatorcontrib><title>Abnormal Temporal Lobe White Matter as a Biomarker for Genetic Risk of Bipolar Disorder</title><title>Biological psychiatry (1969)</title><addtitle>Biol Psychiatry</addtitle><description>Background Brain white matter (WM) abnormalities have been hypothesized to play an important role in the neurobiology of bipolar disorder (BD). The nature of these abnormalities is not well-characterized, however, and it is unknown whether they occur after disease onset or represent potential markers of genetic risk. Methods We examined WM integrity (assessed via fractional anisotropy [FA]) with diffusion tensor imaging in patients with BD ( n =26), unaffected siblings of patients with BD ( n =15), and healthy volunteers ( n =27) to identify WM biomarkers of genetic risk. Results The FA differed significantly ( p <.05; corrected) among the three groups within the right temporal WM. Unaffected siblings had FA values that were intermediate to and significantly different from those of healthy volunteers and patients with BD (healthy control subjects>unaffected siblings>BD). Moreover, FA values in this region correlated negatively and significantly with trait impulsivity in unaffected siblings. Probabilistic tractography indicated that the regional abnormality lies along the inferior fronto-occipital fasciculus, a large intrahemispheric association pathway. Conclusions Our results suggest that lower WM integrity in the right temporal lobe might be a biomarker for genetic risk of BD. It is conceivable that the attenuated nature of these WM abnormalities present in unaffected siblings allows for some preservation of adaptive emotional regulation, whereas more pronounced alterations observed in patients is related to the marked emotional dysregulation characteristic of BD.</description><subject>Adult</subject><subject>Adult and adolescent clinical studies</subject><subject>Anisotropy</subject><subject>Biological and medical sciences</subject><subject>Bipolar</subject><subject>Bipolar Disorder - complications</subject><subject>Bipolar Disorder - genetics</subject><subject>Bipolar Disorder - pathology</subject><subject>Bipolar Disorder - psychology</subject><subject>Bipolar disorders</subject><subject>Case-Control Studies</subject><subject>Diffusion Tensor Imaging - methods</subject><subject>Diffusion Tensor Imaging - psychology</subject><subject>DTI</subject><subject>endophenotype</subject><subject>Endophenotypes</subject><subject>Female</subject><subject>fractional anisotropy</subject><subject>Genetic Predisposition to Disease - psychology</subject><subject>Humans</subject><subject>Image Processing, Computer-Assisted</subject><subject>Impulsive Behavior - complications</subject><subject>Impulsive Behavior - pathology</subject><subject>Impulsive Behavior - psychology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mood disorders</subject><subject>Nerve Fibers, Myelinated - pathology</subject><subject>Neural Pathways - pathology</subject><subject>Neuroimaging - methods</subject><subject>Neuroimaging - psychology</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>siblings</subject><subject>Siblings - psychology</subject><subject>Temporal Lobe - pathology</subject><subject>tractography</subject><issn>0006-3223</issn><issn>1873-2402</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1v1DAQhiMEotvCX6hyQeKSMLaTOL5UlAIFaRESFPVo-WPCejeJg52ttP--Xu22fFw4eax55p2x38mycwIlAdK8WZfa-SnuzKqkQGgJvATGnmQL0nJW0Aro02wBAE3BKGUn2WmM63TllJLn2QllwBpRt4vs9lKPPgyqz29wmHxIwdJrzG9Xbsb8i5pnDLmKucrfOT-osEnXzof8Gkecncm_ubjJfZeyk-9VyN-76IPF8CJ71qk-4svjeZb9-Pjh5upTsfx6_fnqclmYhtK5sFBXAixYTYSyghnBK2Rth5QLDZy1gC2ldc0tCEYtAa2RiLbSFVRGaMXOsouD7rTVA1qD45zeIKfg0rA76ZWTf2dGt5I__Z1kvIEamiTw-igQ_K8txlkOLhrsezWi30ZJaMs4q0jdJrQ5oCb4GAN2j20IyL0rci0fXJF7VyRwmVxJhed_DvlY9mBDAl4dARWN6rugRuPib44TDhxI4t4eOExfeucwyGgcjgatC2hmab37_ywX_0iY3o0udd3gDuPab8OYDJNExlQjv-93aL9ChKZAUGD3kj3DGg</recordid><startdate>20130115</startdate><enddate>20130115</enddate><creator>Mahon, Katie</creator><creator>Burdick, Katherine E</creator><creator>Ikuta, Toshikazu</creator><creator>Braga, Raphael J</creator><creator>Gruner, Patricia</creator><creator>Malhotra, Anil K</creator><creator>Szeszko, Philip R</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><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>5PM</scope></search><sort><creationdate>20130115</creationdate><title>Abnormal Temporal Lobe White Matter as a Biomarker for Genetic Risk of Bipolar Disorder</title><author>Mahon, Katie ; Burdick, Katherine E ; Ikuta, Toshikazu ; Braga, Raphael J ; Gruner, Patricia ; Malhotra, Anil K ; Szeszko, Philip R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c622t-d05490d0db19ad93c974e38fe279b07380e822557d0932d10bbe1984b404c9ba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Adult and adolescent clinical studies</topic><topic>Anisotropy</topic><topic>Biological and medical sciences</topic><topic>Bipolar</topic><topic>Bipolar Disorder - complications</topic><topic>Bipolar Disorder - genetics</topic><topic>Bipolar Disorder - pathology</topic><topic>Bipolar Disorder - psychology</topic><topic>Bipolar disorders</topic><topic>Case-Control Studies</topic><topic>Diffusion Tensor Imaging - methods</topic><topic>Diffusion Tensor Imaging - psychology</topic><topic>DTI</topic><topic>endophenotype</topic><topic>Endophenotypes</topic><topic>Female</topic><topic>fractional anisotropy</topic><topic>Genetic Predisposition to Disease - psychology</topic><topic>Humans</topic><topic>Image Processing, Computer-Assisted</topic><topic>Impulsive Behavior - complications</topic><topic>Impulsive Behavior - pathology</topic><topic>Impulsive Behavior - psychology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mood disorders</topic><topic>Nerve Fibers, Myelinated - pathology</topic><topic>Neural Pathways - pathology</topic><topic>Neuroimaging - methods</topic><topic>Neuroimaging - psychology</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>siblings</topic><topic>Siblings - psychology</topic><topic>Temporal Lobe - pathology</topic><topic>tractography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mahon, Katie</creatorcontrib><creatorcontrib>Burdick, Katherine E</creatorcontrib><creatorcontrib>Ikuta, Toshikazu</creatorcontrib><creatorcontrib>Braga, Raphael J</creatorcontrib><creatorcontrib>Gruner, Patricia</creatorcontrib><creatorcontrib>Malhotra, Anil K</creatorcontrib><creatorcontrib>Szeszko, Philip R</creatorcontrib><collection>Pascal-Francis</collection><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>PubMed Central (Full Participant titles)</collection><jtitle>Biological psychiatry (1969)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mahon, Katie</au><au>Burdick, Katherine E</au><au>Ikuta, Toshikazu</au><au>Braga, Raphael J</au><au>Gruner, Patricia</au><au>Malhotra, Anil K</au><au>Szeszko, Philip R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Abnormal Temporal Lobe White Matter as a Biomarker for Genetic Risk of Bipolar Disorder</atitle><jtitle>Biological psychiatry (1969)</jtitle><addtitle>Biol Psychiatry</addtitle><date>2013-01-15</date><risdate>2013</risdate><volume>73</volume><issue>2</issue><spage>177</spage><epage>182</epage><pages>177-182</pages><issn>0006-3223</issn><eissn>1873-2402</eissn><coden>BIPCBF</coden><abstract>Background Brain white matter (WM) abnormalities have been hypothesized to play an important role in the neurobiology of bipolar disorder (BD). The nature of these abnormalities is not well-characterized, however, and it is unknown whether they occur after disease onset or represent potential markers of genetic risk. Methods We examined WM integrity (assessed via fractional anisotropy [FA]) with diffusion tensor imaging in patients with BD ( n =26), unaffected siblings of patients with BD ( n =15), and healthy volunteers ( n =27) to identify WM biomarkers of genetic risk. Results The FA differed significantly ( p <.05; corrected) among the three groups within the right temporal WM. Unaffected siblings had FA values that were intermediate to and significantly different from those of healthy volunteers and patients with BD (healthy control subjects>unaffected siblings>BD). Moreover, FA values in this region correlated negatively and significantly with trait impulsivity in unaffected siblings. Probabilistic tractography indicated that the regional abnormality lies along the inferior fronto-occipital fasciculus, a large intrahemispheric association pathway. Conclusions Our results suggest that lower WM integrity in the right temporal lobe might be a biomarker for genetic risk of BD. It is conceivable that the attenuated nature of these WM abnormalities present in unaffected siblings allows for some preservation of adaptive emotional regulation, whereas more pronounced alterations observed in patients is related to the marked emotional dysregulation characteristic of BD.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>23036958</pmid><doi>10.1016/j.biopsych.2012.07.033</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Adult and adolescent clinical studies Anisotropy Biological and medical sciences Bipolar Bipolar Disorder - complications Bipolar Disorder - genetics Bipolar Disorder - pathology Bipolar Disorder - psychology Bipolar disorders Case-Control Studies Diffusion Tensor Imaging - methods Diffusion Tensor Imaging - psychology DTI endophenotype Endophenotypes Female fractional anisotropy Genetic Predisposition to Disease - psychology Humans Image Processing, Computer-Assisted Impulsive Behavior - complications Impulsive Behavior - pathology Impulsive Behavior - psychology Male Medical sciences Mood disorders Nerve Fibers, Myelinated - pathology Neural Pathways - pathology Neuroimaging - methods Neuroimaging - psychology Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry siblings Siblings - psychology Temporal Lobe - pathology tractography |
| title | Abnormal Temporal Lobe White Matter as a Biomarker for Genetic Risk of Bipolar Disorder |
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