Improvement of prepulse inhibition and executive function by the COMT inhibitor tolcapone depends on COMT Val158Met polymorphism
Recent evidence suggests that prepulse inhibition (PPI) levels relate to executive function possibly by a prefrontal cortex (PFC) dopamine (DA) link. We explored the effects of enhanced PFC DA signaling by the nonstimulant catechol-O-methyltransferase (COMT) inhibitor tolcapone, on PPI and working m...
Gespeichert in:
| Veröffentlicht in: | Neuropsychopharmacology (New York, N.Y.) N.Y.), 2008-12, Vol.33 (13), p.3058-3068 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3068 |
|---|---|
| container_issue | 13 |
| container_start_page | 3058 |
| container_title | Neuropsychopharmacology (New York, N.Y.) |
| container_volume | 33 |
| creator | Giakoumaki, Stella G Roussos, Panos Bitsios, Panos |
| description | Recent evidence suggests that prepulse inhibition (PPI) levels relate to executive function possibly by a prefrontal cortex (PFC) dopamine (DA) link. We explored the effects of enhanced PFC DA signaling by the nonstimulant catechol-O-methyltransferase (COMT) inhibitor tolcapone, on PPI and working memory of subjects homozygous for the Val (low PFC DA) and the Met (high PFC DA) alleles of the COMT Val158Met polymorphism. Twelve Val/Val and eleven Met/Met healthy male subjects entered the study. Tolcapone 200 mg was administered in two weekly sessions, according to a balanced, crossover, double-blind, placebo-controlled design. PPI was assessed with 5 dB and 15 dB above background prepulses, at 30-, 60-, and 120 ms prepulse-pulse intervals. Subjects also underwent the n-back and the letter-number sequencing (LNS) tasks. PPI was lower in the Val/Val compared to the Met/Met group in the placebo condition. Tolcapone increased PPI significantly in the Val/Val group and tended to have the opposite effect in the Met/Met group. Baseline startle was not affected by tolcapone in the Val/Val group but it was slightly increased in the Met/Met group. Tolcapone improved performance in the n-back and LNS tasks only in the Val/Val group. Enhancement of PFC DA signaling with tolcapone improves both PPI and working memory in a COMT Val158Met genotype-specific manner. These results suggest that early information processing and working memory may both depend on PFC DA signaling, and that they may both relate to PFC DA levels according to an inverted U-shaped curve function. |
| doi_str_mv | 10.1038/npp.2008.82 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69769278</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>69769278</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3322-fd31f6fae549eb64e94d8ec8ca055ca6c51cdd77eade1e16757fafb9c5b43c773</originalsourceid><addsrcrecordid>eNpd0ctrFTEUB-Agir1WV-4luHBT5prH5DFLuWgttHRTpbuQSU64U2aSmMyU3p1_utP2iuDqwOHjPPgh9J6SLSVcf445bxkheqvZC7ShqiWN5O3tS7QhuuMN5fz2BL2p9Y4QKpTUr9EJ1YJL2ekN-n0x5ZLuYYI44xRwLpCXsQIe4n7oh3lIEdvoMTyAW-bhHnBYontq9wc87wHvrq9u_upU8JxGZ3OKgD1kiL7ilT6Zn3akQl_BjHMaD1MqeT_U6S16Fey68N2xnqIf377e7L43l9fnF7svl43jnLEmeE6DDBZE20EvW-har8FpZ4kQzkonqPNeKbAeKFCphAo29J0TfcudUvwUfXqeu777a4E6m2moDsbRRkhLNbJTsmNKr_Djf_AuLSWutxnGBGOaULmis2fkSqq1QDC5DJMtB0OJeUzFrKmYx1SMZqv-cBy59BP4f_YYA_8DyLiK7A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>225228016</pqid></control><display><type>article</type><title>Improvement of prepulse inhibition and executive function by the COMT inhibitor tolcapone depends on COMT Val158Met polymorphism</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Giakoumaki, Stella G ; Roussos, Panos ; Bitsios, Panos</creator><creatorcontrib>Giakoumaki, Stella G ; Roussos, Panos ; Bitsios, Panos</creatorcontrib><description>Recent evidence suggests that prepulse inhibition (PPI) levels relate to executive function possibly by a prefrontal cortex (PFC) dopamine (DA) link. We explored the effects of enhanced PFC DA signaling by the nonstimulant catechol-O-methyltransferase (COMT) inhibitor tolcapone, on PPI and working memory of subjects homozygous for the Val (low PFC DA) and the Met (high PFC DA) alleles of the COMT Val158Met polymorphism. Twelve Val/Val and eleven Met/Met healthy male subjects entered the study. Tolcapone 200 mg was administered in two weekly sessions, according to a balanced, crossover, double-blind, placebo-controlled design. PPI was assessed with 5 dB and 15 dB above background prepulses, at 30-, 60-, and 120 ms prepulse-pulse intervals. Subjects also underwent the n-back and the letter-number sequencing (LNS) tasks. PPI was lower in the Val/Val compared to the Met/Met group in the placebo condition. Tolcapone increased PPI significantly in the Val/Val group and tended to have the opposite effect in the Met/Met group. Baseline startle was not affected by tolcapone in the Val/Val group but it was slightly increased in the Met/Met group. Tolcapone improved performance in the n-back and LNS tasks only in the Val/Val group. Enhancement of PFC DA signaling with tolcapone improves both PPI and working memory in a COMT Val158Met genotype-specific manner. These results suggest that early information processing and working memory may both depend on PFC DA signaling, and that they may both relate to PFC DA levels according to an inverted U-shaped curve function.</description><identifier>ISSN: 0893-133X</identifier><identifier>EISSN: 1740-634X</identifier><identifier>DOI: 10.1038/npp.2008.82</identifier><identifier>PMID: 18536698</identifier><identifier>CODEN: NEROEW</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Acoustic Stimulation ; Adult ; Amino Acid Substitution - genetics ; Behavioral sciences ; Benzophenones - pharmacology ; Catechol O-Methyltransferase - genetics ; Catechol O-Methyltransferase Inhibitors ; Cognition & reasoning ; Cognition - drug effects ; Cognition - physiology ; Cohort Studies ; Cross-Over Studies ; DNA Mutational Analysis ; Dopamine ; Dopamine - metabolism ; Double-Blind Method ; Enzyme Inhibitors - pharmacology ; Executive function ; Genetic Testing ; Genotype ; Humans ; Information processing ; Male ; Medical imaging ; Memory ; Memory, Short-Term - drug effects ; Memory, Short-Term - physiology ; Methionine - genetics ; Neural Inhibition - drug effects ; Neural Inhibition - genetics ; Neuroimaging ; Nitrophenols - pharmacology ; Polymorphism ; Polymorphism, Genetic - genetics ; Prefrontal Cortex - drug effects ; Prefrontal Cortex - metabolism ; Schizophrenia ; Sensory Gating - drug effects ; Sensory Gating - physiology ; Valine - genetics ; Young Adult</subject><ispartof>Neuropsychopharmacology (New York, N.Y.), 2008-12, Vol.33 (13), p.3058-3068</ispartof><rights>Copyright Nature Publishing Group Dec 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3322-fd31f6fae549eb64e94d8ec8ca055ca6c51cdd77eade1e16757fafb9c5b43c773</citedby><cites>FETCH-LOGICAL-c3322-fd31f6fae549eb64e94d8ec8ca055ca6c51cdd77eade1e16757fafb9c5b43c773</cites></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/18536698$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Giakoumaki, Stella G</creatorcontrib><creatorcontrib>Roussos, Panos</creatorcontrib><creatorcontrib>Bitsios, Panos</creatorcontrib><title>Improvement of prepulse inhibition and executive function by the COMT inhibitor tolcapone depends on COMT Val158Met polymorphism</title><title>Neuropsychopharmacology (New York, N.Y.)</title><addtitle>Neuropsychopharmacology</addtitle><description>Recent evidence suggests that prepulse inhibition (PPI) levels relate to executive function possibly by a prefrontal cortex (PFC) dopamine (DA) link. We explored the effects of enhanced PFC DA signaling by the nonstimulant catechol-O-methyltransferase (COMT) inhibitor tolcapone, on PPI and working memory of subjects homozygous for the Val (low PFC DA) and the Met (high PFC DA) alleles of the COMT Val158Met polymorphism. Twelve Val/Val and eleven Met/Met healthy male subjects entered the study. Tolcapone 200 mg was administered in two weekly sessions, according to a balanced, crossover, double-blind, placebo-controlled design. PPI was assessed with 5 dB and 15 dB above background prepulses, at 30-, 60-, and 120 ms prepulse-pulse intervals. Subjects also underwent the n-back and the letter-number sequencing (LNS) tasks. PPI was lower in the Val/Val compared to the Met/Met group in the placebo condition. Tolcapone increased PPI significantly in the Val/Val group and tended to have the opposite effect in the Met/Met group. Baseline startle was not affected by tolcapone in the Val/Val group but it was slightly increased in the Met/Met group. Tolcapone improved performance in the n-back and LNS tasks only in the Val/Val group. Enhancement of PFC DA signaling with tolcapone improves both PPI and working memory in a COMT Val158Met genotype-specific manner. These results suggest that early information processing and working memory may both depend on PFC DA signaling, and that they may both relate to PFC DA levels according to an inverted U-shaped curve function.</description><subject>Acoustic Stimulation</subject><subject>Adult</subject><subject>Amino Acid Substitution - genetics</subject><subject>Behavioral sciences</subject><subject>Benzophenones - pharmacology</subject><subject>Catechol O-Methyltransferase - genetics</subject><subject>Catechol O-Methyltransferase Inhibitors</subject><subject>Cognition & reasoning</subject><subject>Cognition - drug effects</subject><subject>Cognition - physiology</subject><subject>Cohort Studies</subject><subject>Cross-Over Studies</subject><subject>DNA Mutational Analysis</subject><subject>Dopamine</subject><subject>Dopamine - metabolism</subject><subject>Double-Blind Method</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Executive function</subject><subject>Genetic Testing</subject><subject>Genotype</subject><subject>Humans</subject><subject>Information processing</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Memory</subject><subject>Memory, Short-Term - drug effects</subject><subject>Memory, Short-Term - physiology</subject><subject>Methionine - genetics</subject><subject>Neural Inhibition - drug effects</subject><subject>Neural Inhibition - genetics</subject><subject>Neuroimaging</subject><subject>Nitrophenols - pharmacology</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Prefrontal Cortex - drug effects</subject><subject>Prefrontal Cortex - metabolism</subject><subject>Schizophrenia</subject><subject>Sensory Gating - drug effects</subject><subject>Sensory Gating - physiology</subject><subject>Valine - genetics</subject><subject>Young Adult</subject><issn>0893-133X</issn><issn>1740-634X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpd0ctrFTEUB-Agir1WV-4luHBT5prH5DFLuWgttHRTpbuQSU64U2aSmMyU3p1_utP2iuDqwOHjPPgh9J6SLSVcf445bxkheqvZC7ShqiWN5O3tS7QhuuMN5fz2BL2p9Y4QKpTUr9EJ1YJL2ekN-n0x5ZLuYYI44xRwLpCXsQIe4n7oh3lIEdvoMTyAW-bhHnBYontq9wc87wHvrq9u_upU8JxGZ3OKgD1kiL7ilT6Zn3akQl_BjHMaD1MqeT_U6S16Fey68N2xnqIf377e7L43l9fnF7svl43jnLEmeE6DDBZE20EvW-har8FpZ4kQzkonqPNeKbAeKFCphAo29J0TfcudUvwUfXqeu777a4E6m2moDsbRRkhLNbJTsmNKr_Djf_AuLSWutxnGBGOaULmis2fkSqq1QDC5DJMtB0OJeUzFrKmYx1SMZqv-cBy59BP4f_YYA_8DyLiK7A</recordid><startdate>200812</startdate><enddate>200812</enddate><creator>Giakoumaki, Stella G</creator><creator>Roussos, Panos</creator><creator>Bitsios, Panos</creator><general>Nature Publishing Group</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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>200812</creationdate><title>Improvement of prepulse inhibition and executive function by the COMT inhibitor tolcapone depends on COMT Val158Met polymorphism</title><author>Giakoumaki, Stella G ; Roussos, Panos ; Bitsios, Panos</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3322-fd31f6fae549eb64e94d8ec8ca055ca6c51cdd77eade1e16757fafb9c5b43c773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Acoustic Stimulation</topic><topic>Adult</topic><topic>Amino Acid Substitution - genetics</topic><topic>Behavioral sciences</topic><topic>Benzophenones - pharmacology</topic><topic>Catechol O-Methyltransferase - genetics</topic><topic>Catechol O-Methyltransferase Inhibitors</topic><topic>Cognition & reasoning</topic><topic>Cognition - drug effects</topic><topic>Cognition - physiology</topic><topic>Cohort Studies</topic><topic>Cross-Over Studies</topic><topic>DNA Mutational Analysis</topic><topic>Dopamine</topic><topic>Dopamine - metabolism</topic><topic>Double-Blind Method</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Executive function</topic><topic>Genetic Testing</topic><topic>Genotype</topic><topic>Humans</topic><topic>Information processing</topic><topic>Male</topic><topic>Medical imaging</topic><topic>Memory</topic><topic>Memory, Short-Term - drug effects</topic><topic>Memory, Short-Term - physiology</topic><topic>Methionine - genetics</topic><topic>Neural Inhibition - drug effects</topic><topic>Neural Inhibition - genetics</topic><topic>Neuroimaging</topic><topic>Nitrophenols - pharmacology</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Prefrontal Cortex - drug effects</topic><topic>Prefrontal Cortex - metabolism</topic><topic>Schizophrenia</topic><topic>Sensory Gating - drug effects</topic><topic>Sensory Gating - physiology</topic><topic>Valine - genetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Giakoumaki, Stella G</creatorcontrib><creatorcontrib>Roussos, Panos</creatorcontrib><creatorcontrib>Bitsios, Panos</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Neuropsychopharmacology (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Giakoumaki, Stella G</au><au>Roussos, Panos</au><au>Bitsios, Panos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improvement of prepulse inhibition and executive function by the COMT inhibitor tolcapone depends on COMT Val158Met polymorphism</atitle><jtitle>Neuropsychopharmacology (New York, N.Y.)</jtitle><addtitle>Neuropsychopharmacology</addtitle><date>2008-12</date><risdate>2008</risdate><volume>33</volume><issue>13</issue><spage>3058</spage><epage>3068</epage><pages>3058-3068</pages><issn>0893-133X</issn><eissn>1740-634X</eissn><coden>NEROEW</coden><abstract>Recent evidence suggests that prepulse inhibition (PPI) levels relate to executive function possibly by a prefrontal cortex (PFC) dopamine (DA) link. We explored the effects of enhanced PFC DA signaling by the nonstimulant catechol-O-methyltransferase (COMT) inhibitor tolcapone, on PPI and working memory of subjects homozygous for the Val (low PFC DA) and the Met (high PFC DA) alleles of the COMT Val158Met polymorphism. Twelve Val/Val and eleven Met/Met healthy male subjects entered the study. Tolcapone 200 mg was administered in two weekly sessions, according to a balanced, crossover, double-blind, placebo-controlled design. PPI was assessed with 5 dB and 15 dB above background prepulses, at 30-, 60-, and 120 ms prepulse-pulse intervals. Subjects also underwent the n-back and the letter-number sequencing (LNS) tasks. PPI was lower in the Val/Val compared to the Met/Met group in the placebo condition. Tolcapone increased PPI significantly in the Val/Val group and tended to have the opposite effect in the Met/Met group. Baseline startle was not affected by tolcapone in the Val/Val group but it was slightly increased in the Met/Met group. Tolcapone improved performance in the n-back and LNS tasks only in the Val/Val group. Enhancement of PFC DA signaling with tolcapone improves both PPI and working memory in a COMT Val158Met genotype-specific manner. These results suggest that early information processing and working memory may both depend on PFC DA signaling, and that they may both relate to PFC DA levels according to an inverted U-shaped curve function.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>18536698</pmid><doi>10.1038/npp.2008.82</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0893-133X |
| ispartof | Neuropsychopharmacology (New York, N.Y.), 2008-12, Vol.33 (13), p.3058-3068 |
| issn | 0893-133X 1740-634X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69769278 |
| source | MEDLINE; SpringerLink Journals; EZB-FREE-00999 freely available EZB journals |
| subjects | Acoustic Stimulation Adult Amino Acid Substitution - genetics Behavioral sciences Benzophenones - pharmacology Catechol O-Methyltransferase - genetics Catechol O-Methyltransferase Inhibitors Cognition & reasoning Cognition - drug effects Cognition - physiology Cohort Studies Cross-Over Studies DNA Mutational Analysis Dopamine Dopamine - metabolism Double-Blind Method Enzyme Inhibitors - pharmacology Executive function Genetic Testing Genotype Humans Information processing Male Medical imaging Memory Memory, Short-Term - drug effects Memory, Short-Term - physiology Methionine - genetics Neural Inhibition - drug effects Neural Inhibition - genetics Neuroimaging Nitrophenols - pharmacology Polymorphism Polymorphism, Genetic - genetics Prefrontal Cortex - drug effects Prefrontal Cortex - metabolism Schizophrenia Sensory Gating - drug effects Sensory Gating - physiology Valine - genetics Young Adult |
| title | Improvement of prepulse inhibition and executive function by the COMT inhibitor tolcapone depends on COMT Val158Met polymorphism |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T09%3A36%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Improvement%20of%20prepulse%20inhibition%20and%20executive%20function%20by%20the%20COMT%20inhibitor%20tolcapone%20depends%20on%20COMT%20Val158Met%20polymorphism&rft.jtitle=Neuropsychopharmacology%20(New%20York,%20N.Y.)&rft.au=Giakoumaki,%20Stella%20G&rft.date=2008-12&rft.volume=33&rft.issue=13&rft.spage=3058&rft.epage=3068&rft.pages=3058-3068&rft.issn=0893-133X&rft.eissn=1740-634X&rft.coden=NEROEW&rft_id=info:doi/10.1038/npp.2008.82&rft_dat=%3Cproquest_cross%3E69769278%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=225228016&rft_id=info:pmid/18536698&rfr_iscdi=true |