Functional and effective frontotemporal connectivity and genetic risk for schizophrenia
Functional neuroimaging and electrophysiologic studies have found disturbed frontotemporal interaction in schizophrenia. We sought to determine whether abnormalities of frontotemporal connectivity are trait markers of genetic risk for schizophrenia. We investigated 64 schizophrenia patients, 79 of t...
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Veröffentlicht in: | Biological psychiatry (1969) 2003-12, Vol.54 (11), p.1181-1192 |
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creator | Winterer, Georg Coppola, Richard Egan, Michael F Goldberg, Terry E Weinberger, Daniel R |
description | Functional neuroimaging and electrophysiologic studies have found disturbed frontotemporal interaction in schizophrenia. We sought to determine whether abnormalities of frontotemporal connectivity are trait markers of genetic risk for schizophrenia.
We investigated 64 schizophrenia patients, 79 of their clinically unaffected siblings, and 88 unrelated normal controls with an auditory oddball electroencephalogram (EEG) evoked potential paradigm. We measured: 1) frontotemporal event-related EEG-coherence (i.e. a measure of functional connectivity); and 2) we performed structural equation modeling of the effective connectivity between the frontal P300 and temporoparietal P300-amplitude.
Schizophrenic patients and their siblings showed a reduction of frontotemporal coherence. At peak activation during the P300 time-window, a negative (“inhibitory”) frontotemporal path coefficient was found in normal controls, whereas a positive coefficient was seen in schizophrenic patients with siblings being intermediate. Intra-class correlations between sib-pairs and relative risk estimates of the applied connectivity measures were non-significant. Topographic correlation matrix analyses suggested that the altered functional and effective frontotemporal connectivity indirectly reflect regional abnormalities of increased activation variance.
Impaired interaction of the frontotemporal macro-circuit indirectly reflects genetically determined abnormalities of frontal and temporoparietal microcircuits. The reasons why frontotemporal connectivity appears to be a poor predictor of genetic risk for schizophrenia are discussed. |
doi_str_mv | 10.1016/S0006-3223(03)00532-8 |
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We investigated 64 schizophrenia patients, 79 of their clinically unaffected siblings, and 88 unrelated normal controls with an auditory oddball electroencephalogram (EEG) evoked potential paradigm. We measured: 1) frontotemporal event-related EEG-coherence (i.e. a measure of functional connectivity); and 2) we performed structural equation modeling of the effective connectivity between the frontal P300 and temporoparietal P300-amplitude.
Schizophrenic patients and their siblings showed a reduction of frontotemporal coherence. At peak activation during the P300 time-window, a negative (“inhibitory”) frontotemporal path coefficient was found in normal controls, whereas a positive coefficient was seen in schizophrenic patients with siblings being intermediate. Intra-class correlations between sib-pairs and relative risk estimates of the applied connectivity measures were non-significant. Topographic correlation matrix analyses suggested that the altered functional and effective frontotemporal connectivity indirectly reflect regional abnormalities of increased activation variance.
Impaired interaction of the frontotemporal macro-circuit indirectly reflects genetically determined abnormalities of frontal and temporoparietal microcircuits. The reasons why frontotemporal connectivity appears to be a poor predictor of genetic risk for schizophrenia are discussed.</description><identifier>ISSN: 0006-3223</identifier><identifier>EISSN: 1873-2402</identifier><identifier>DOI: 10.1016/S0006-3223(03)00532-8</identifier><identifier>PMID: 14643085</identifier><identifier>CODEN: BIPCBF</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Adult and adolescent clinical studies ; Biological and medical sciences ; Electrodiagnosis. Electric activity recording ; Electroencephalography ; Event-Related Potentials, P300 - physiology ; Female ; Frontal Lobe - physiopathology ; frontotemporal connectivity ; Genetic Predisposition to Disease ; genetics ; Humans ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical sciences ; Nervous system ; Neural Pathways - physiopathology ; P300 ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychoses ; Risk Factors ; Schizophrenia ; Schizophrenia - genetics ; Schizophrenia - physiopathology ; Siblings ; Temporal Lobe - physiopathology</subject><ispartof>Biological psychiatry (1969), 2003-12, Vol.54 (11), p.1181-1192</ispartof><rights>2003 Society of Biological Psychiatry</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-3fb86e585b9c576f14006af2958edf129bc9a1e13aa1ecde86846cefc018056c3</citedby><cites>FETCH-LOGICAL-c391t-3fb86e585b9c576f14006af2958edf129bc9a1e13aa1ecde86846cefc018056c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006322303005328$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15334620$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14643085$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Winterer, Georg</creatorcontrib><creatorcontrib>Coppola, Richard</creatorcontrib><creatorcontrib>Egan, Michael F</creatorcontrib><creatorcontrib>Goldberg, Terry E</creatorcontrib><creatorcontrib>Weinberger, Daniel R</creatorcontrib><title>Functional and effective frontotemporal connectivity and genetic risk for schizophrenia</title><title>Biological psychiatry (1969)</title><addtitle>Biol Psychiatry</addtitle><description>Functional neuroimaging and electrophysiologic studies have found disturbed frontotemporal interaction in schizophrenia. We sought to determine whether abnormalities of frontotemporal connectivity are trait markers of genetic risk for schizophrenia.
We investigated 64 schizophrenia patients, 79 of their clinically unaffected siblings, and 88 unrelated normal controls with an auditory oddball electroencephalogram (EEG) evoked potential paradigm. We measured: 1) frontotemporal event-related EEG-coherence (i.e. a measure of functional connectivity); and 2) we performed structural equation modeling of the effective connectivity between the frontal P300 and temporoparietal P300-amplitude.
Schizophrenic patients and their siblings showed a reduction of frontotemporal coherence. At peak activation during the P300 time-window, a negative (“inhibitory”) frontotemporal path coefficient was found in normal controls, whereas a positive coefficient was seen in schizophrenic patients with siblings being intermediate. Intra-class correlations between sib-pairs and relative risk estimates of the applied connectivity measures were non-significant. Topographic correlation matrix analyses suggested that the altered functional and effective frontotemporal connectivity indirectly reflect regional abnormalities of increased activation variance.
Impaired interaction of the frontotemporal macro-circuit indirectly reflects genetically determined abnormalities of frontal and temporoparietal microcircuits. The reasons why frontotemporal connectivity appears to be a poor predictor of genetic risk for schizophrenia are discussed.</description><subject>Adult</subject><subject>Adult and adolescent clinical studies</subject><subject>Biological and medical sciences</subject><subject>Electrodiagnosis. Electric activity recording</subject><subject>Electroencephalography</subject><subject>Event-Related Potentials, P300 - physiology</subject><subject>Female</subject><subject>Frontal Lobe - physiopathology</subject><subject>frontotemporal connectivity</subject><subject>Genetic Predisposition to Disease</subject><subject>genetics</subject><subject>Humans</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nervous system</subject><subject>Neural Pathways - physiopathology</subject><subject>P300</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychoses</subject><subject>Risk Factors</subject><subject>Schizophrenia</subject><subject>Schizophrenia - genetics</subject><subject>Schizophrenia - physiopathology</subject><subject>Siblings</subject><subject>Temporal Lobe - physiopathology</subject><issn>0006-3223</issn><issn>1873-2402</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLJDEQgIO46Kz6E5S-uOwees2jk06fRIZ1d0HYg4rHkKmuaLQnGZMeQX-9mQd6XChSFPVVpfgIOWb0J6NMnV1TSlUtOBffqfhBqRS81jtkwnQrat5QvksmH8g--ZrzYylbztke2WeNagTVckLuLpcBRh-DHSob-gqdw1K_YOVSDGMccb6IqTQhhrDu-PF1Td5jwNFDlXx-qlxMVYYH_xYXDwmDt4fki7NDxqNtPiC3l79upn_qq3-__04vrmoQHRtr4WZaodRy1oFslWNNOdk63kmNvWO8m0FnGTJhyws9aqUbBeiAMk2lAnFAvm32LlJ8XmIezdxnwGGwAeMym5Y1rBOyLaDcgJBizgmdWSQ_t-nVMGpWRs3aqFnpMrTEyqjRZe5k-8FyNsf-c2qrsACnW8BmsINLNoDPn5wUolGcFu58w2HR8eIxmQweA2DvUxFr-uj_c8o7t7OT5Q</recordid><startdate>20031201</startdate><enddate>20031201</enddate><creator>Winterer, Georg</creator><creator>Coppola, Richard</creator><creator>Egan, Michael F</creator><creator>Goldberg, Terry E</creator><creator>Weinberger, Daniel R</creator><general>Elsevier Inc</general><general>Elsevier Science</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></search><sort><creationdate>20031201</creationdate><title>Functional and effective frontotemporal connectivity and genetic risk for schizophrenia</title><author>Winterer, Georg ; Coppola, Richard ; Egan, Michael F ; Goldberg, Terry E ; Weinberger, Daniel R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-3fb86e585b9c576f14006af2958edf129bc9a1e13aa1ecde86846cefc018056c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adult</topic><topic>Adult and adolescent clinical studies</topic><topic>Biological and medical sciences</topic><topic>Electrodiagnosis. Electric activity recording</topic><topic>Electroencephalography</topic><topic>Event-Related Potentials, P300 - physiology</topic><topic>Female</topic><topic>Frontal Lobe - physiopathology</topic><topic>frontotemporal connectivity</topic><topic>Genetic Predisposition to Disease</topic><topic>genetics</topic><topic>Humans</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nervous system</topic><topic>Neural Pathways - physiopathology</topic><topic>P300</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychoses</topic><topic>Risk Factors</topic><topic>Schizophrenia</topic><topic>Schizophrenia - genetics</topic><topic>Schizophrenia - physiopathology</topic><topic>Siblings</topic><topic>Temporal Lobe - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Winterer, Georg</creatorcontrib><creatorcontrib>Coppola, Richard</creatorcontrib><creatorcontrib>Egan, Michael F</creatorcontrib><creatorcontrib>Goldberg, Terry E</creatorcontrib><creatorcontrib>Weinberger, Daniel 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><jtitle>Biological psychiatry (1969)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Winterer, Georg</au><au>Coppola, Richard</au><au>Egan, Michael F</au><au>Goldberg, Terry E</au><au>Weinberger, Daniel R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Functional and effective frontotemporal connectivity and genetic risk for schizophrenia</atitle><jtitle>Biological psychiatry (1969)</jtitle><addtitle>Biol Psychiatry</addtitle><date>2003-12-01</date><risdate>2003</risdate><volume>54</volume><issue>11</issue><spage>1181</spage><epage>1192</epage><pages>1181-1192</pages><issn>0006-3223</issn><eissn>1873-2402</eissn><coden>BIPCBF</coden><abstract>Functional neuroimaging and electrophysiologic studies have found disturbed frontotemporal interaction in schizophrenia. We sought to determine whether abnormalities of frontotemporal connectivity are trait markers of genetic risk for schizophrenia.
We investigated 64 schizophrenia patients, 79 of their clinically unaffected siblings, and 88 unrelated normal controls with an auditory oddball electroencephalogram (EEG) evoked potential paradigm. We measured: 1) frontotemporal event-related EEG-coherence (i.e. a measure of functional connectivity); and 2) we performed structural equation modeling of the effective connectivity between the frontal P300 and temporoparietal P300-amplitude.
Schizophrenic patients and their siblings showed a reduction of frontotemporal coherence. At peak activation during the P300 time-window, a negative (“inhibitory”) frontotemporal path coefficient was found in normal controls, whereas a positive coefficient was seen in schizophrenic patients with siblings being intermediate. Intra-class correlations between sib-pairs and relative risk estimates of the applied connectivity measures were non-significant. Topographic correlation matrix analyses suggested that the altered functional and effective frontotemporal connectivity indirectly reflect regional abnormalities of increased activation variance.
Impaired interaction of the frontotemporal macro-circuit indirectly reflects genetically determined abnormalities of frontal and temporoparietal microcircuits. The reasons why frontotemporal connectivity appears to be a poor predictor of genetic risk for schizophrenia are discussed.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>14643085</pmid><doi>10.1016/S0006-3223(03)00532-8</doi><tpages>12</tpages></addata></record> |
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subjects | Adult Adult and adolescent clinical studies Biological and medical sciences Electrodiagnosis. Electric activity recording Electroencephalography Event-Related Potentials, P300 - physiology Female Frontal Lobe - physiopathology frontotemporal connectivity Genetic Predisposition to Disease genetics Humans Investigative techniques, diagnostic techniques (general aspects) Male Medical sciences Nervous system Neural Pathways - physiopathology P300 Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychoses Risk Factors Schizophrenia Schizophrenia - genetics Schizophrenia - physiopathology Siblings Temporal Lobe - physiopathology |
title | Functional and effective frontotemporal connectivity and genetic risk for schizophrenia |
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