Pharmacogenetic Analysis of Genes Implicated in Rodent Models of Antidepressant Response: Association of TREK1 and Treatment Resistance in the STARD Study
Recent rodent models of antidepressant response implicate a novel set of genes in mechanisms of antidepressant action. The authors examined variants in four such genes ( KCNK2 ( TREK1 ), SLC18A2 ( VMAT2 ), S100A10 , and HDAC5 ) for association with remission in a large effectiveness trial of antidep...
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| Veröffentlicht in: | Neuropsychopharmacology (New York, N.Y.) N.Y.), 2008-11, Vol.33 (12), p.2810-2819 |
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| creator | Perlis, Roy H Moorjani, Priya Fagerness, Jesen Purcell, Shaun Trivedi, Madhukar H Fava, Maurizio Rush, A John Smoller, Jordan W |
| description | Recent rodent models of antidepressant response implicate a novel set of genes in mechanisms of antidepressant action. The authors examined variants in four such genes (
KCNK2
(
TREK1
),
SLC18A2
(
VMAT2
),
S100A10
, and
HDAC5
) for association with remission in a large effectiveness trial of antidepressant treatments. Subjects were drawn from the Sequenced Treatment Alternatives to Relieve Depression (STAR
*
D) study, a multicenter, prospective, effectiveness trial in major depressive disorder (MDD). Outpatients with nonpsychotic MDD were initially treated with citalopram for up to 14 weeks; those who did not remit with citalopram were sequentially randomized to a series of next-step treatments, each for up to 12 weeks. Single-nucleotide polymorphisms in four genes were examined for association with remission, defined as a clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-C
16
) score ⩽5. Of 1554 participants for whom DNA was available, 565 (36%) reached remission with citalopram treatment. No association with any of the four genes was identified. However, among the 751 who entered next-step treatment, variants in
KCNK2
were associated with treatment response (Bonferroni-corrected, gene-based empirical
p |
| doi_str_mv | 10.1038/npp.2008.6 |
| format | Article |
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KCNK2
(
TREK1
),
SLC18A2
(
VMAT2
),
S100A10
, and
HDAC5
) for association with remission in a large effectiveness trial of antidepressant treatments. Subjects were drawn from the Sequenced Treatment Alternatives to Relieve Depression (STAR
*
D) study, a multicenter, prospective, effectiveness trial in major depressive disorder (MDD). Outpatients with nonpsychotic MDD were initially treated with citalopram for up to 14 weeks; those who did not remit with citalopram were sequentially randomized to a series of next-step treatments, each for up to 12 weeks. Single-nucleotide polymorphisms in four genes were examined for association with remission, defined as a clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-C
16
) score ⩽5. Of 1554 participants for whom DNA was available, 565 (36%) reached remission with citalopram treatment. No association with any of the four genes was identified. However, among the 751 who entered next-step treatment, variants in
KCNK2
were associated with treatment response (Bonferroni-corrected, gene-based empirical
p
<0.001). In follow-up analyses,
KCNK2
was also associated with effects of similar magnitude for third-step treatment among those with unsatisfactory benefit to both citalopram and one next-step pharmacotherapy (
n
=225). These findings indicate that genetic variation in
KCNK2
may identify individuals at risk for treatment resistance. More broadly, they indicate the utility of animal models in identifying genes for pharmacogenetic studies of antidepressant response.</description><identifier>ISSN: 0893-133X</identifier><identifier>EISSN: 1740-634X</identifier><identifier>DOI: 10.1038/npp.2008.6</identifier><identifier>PMID: 18288090</identifier><identifier>CODEN: NEROEW</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Antidepressants ; Behavioral Sciences ; Biological Psychology ; Brain research ; Genes ; Medicine ; Medicine & Public Health ; Mental depression ; Neurosciences ; original-article ; Pharmacotherapy ; Psychiatry</subject><ispartof>Neuropsychopharmacology (New York, N.Y.), 2008-11, Vol.33 (12), p.2810-2819</ispartof><rights>American College of Neuropsychopharmacology 2008</rights><rights>Copyright Nature Publishing Group Nov 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-5d396af8bad05fc5b412e94a306d2e0df9fd23db8662806acb0c34149cf78b603</citedby><cites>FETCH-LOGICAL-c386t-5d396af8bad05fc5b412e94a306d2e0df9fd23db8662806acb0c34149cf78b603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/npp.2008.6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/npp.2008.6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids></links><search><creatorcontrib>Perlis, Roy H</creatorcontrib><creatorcontrib>Moorjani, Priya</creatorcontrib><creatorcontrib>Fagerness, Jesen</creatorcontrib><creatorcontrib>Purcell, Shaun</creatorcontrib><creatorcontrib>Trivedi, Madhukar H</creatorcontrib><creatorcontrib>Fava, Maurizio</creatorcontrib><creatorcontrib>Rush, A John</creatorcontrib><creatorcontrib>Smoller, Jordan W</creatorcontrib><title>Pharmacogenetic Analysis of Genes Implicated in Rodent Models of Antidepressant Response: Association of TREK1 and Treatment Resistance in the STARD Study</title><title>Neuropsychopharmacology (New York, N.Y.)</title><addtitle>Neuropsychopharmacol</addtitle><description>Recent rodent models of antidepressant response implicate a novel set of genes in mechanisms of antidepressant action. The authors examined variants in four such genes (
KCNK2
(
TREK1
),
SLC18A2
(
VMAT2
),
S100A10
, and
HDAC5
) for association with remission in a large effectiveness trial of antidepressant treatments. Subjects were drawn from the Sequenced Treatment Alternatives to Relieve Depression (STAR
*
D) study, a multicenter, prospective, effectiveness trial in major depressive disorder (MDD). Outpatients with nonpsychotic MDD were initially treated with citalopram for up to 14 weeks; those who did not remit with citalopram were sequentially randomized to a series of next-step treatments, each for up to 12 weeks. Single-nucleotide polymorphisms in four genes were examined for association with remission, defined as a clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-C
16
) score ⩽5. Of 1554 participants for whom DNA was available, 565 (36%) reached remission with citalopram treatment. No association with any of the four genes was identified. However, among the 751 who entered next-step treatment, variants in
KCNK2
were associated with treatment response (Bonferroni-corrected, gene-based empirical
p
<0.001). In follow-up analyses,
KCNK2
was also associated with effects of similar magnitude for third-step treatment among those with unsatisfactory benefit to both citalopram and one next-step pharmacotherapy (
n
=225). These findings indicate that genetic variation in
KCNK2
may identify individuals at risk for treatment resistance. More broadly, they indicate the utility of animal models in identifying genes for pharmacogenetic studies of antidepressant response.</description><subject>Antidepressants</subject><subject>Behavioral Sciences</subject><subject>Biological Psychology</subject><subject>Brain research</subject><subject>Genes</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mental depression</subject><subject>Neurosciences</subject><subject>original-article</subject><subject>Pharmacotherapy</subject><subject>Psychiatry</subject><issn>0893-133X</issn><issn>1740-634X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNptkVFrFDEQx4Mo9mx98RMEH5U9J5vdXNYXWWpbixXL9YS-hWySvUvZTbZJTriv0k9rzitKoU8DMz9-M8wfoXcE5gQo_-SmaV4C8Dl7gWZkUUHBaHX7Es2AN7QglN4eoTcx3gGQesH4a3REeMk5NDBDD9cbGUap_No4k6zCrZPDLtqIfY8vci_iy3EarJLJaGwdXnptXMI_chn-Qq1LVpspmBhlHixNnLyL5jNuY_TKymS923Or5dl3gqXTeBWMTKM5wDYm6ZTZq9PG4JtVu_yKb9JW707Qq14O0bx9rMfo1_nZ6vRbcfXz4vK0vSoU5SwVtaYNkz3vpIa6V3VXkdI0laTAdGlA902vS6o7zljJgUnVgaIVqRrVL3jHgB6jLwfvtO1Go1U-LMhBTMGOMuyEl1Y8nTi7EWv_WxAAWvGKZ8P7R0Pw91sTk7jz25AfGUVZ1iUleUuGPhwgFXyMwfT_NhAQ-xxFzlHscxQswx8PcMyQW5vw3_gM_QdYaaDB</recordid><startdate>20081101</startdate><enddate>20081101</enddate><creator>Perlis, Roy H</creator><creator>Moorjani, Priya</creator><creator>Fagerness, Jesen</creator><creator>Purcell, Shaun</creator><creator>Trivedi, Madhukar H</creator><creator>Fava, Maurizio</creator><creator>Rush, A John</creator><creator>Smoller, Jordan W</creator><general>Springer International Publishing</general><general>Nature Publishing Group</general><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>5PM</scope></search><sort><creationdate>20081101</creationdate><title>Pharmacogenetic Analysis of Genes Implicated in Rodent Models of Antidepressant Response: Association of TREK1 and Treatment Resistance in the STARD Study</title><author>Perlis, Roy H ; Moorjani, Priya ; Fagerness, Jesen ; Purcell, Shaun ; Trivedi, Madhukar H ; Fava, Maurizio ; Rush, A John ; Smoller, Jordan W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-5d396af8bad05fc5b412e94a306d2e0df9fd23db8662806acb0c34149cf78b603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Antidepressants</topic><topic>Behavioral Sciences</topic><topic>Biological Psychology</topic><topic>Brain research</topic><topic>Genes</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mental depression</topic><topic>Neurosciences</topic><topic>original-article</topic><topic>Pharmacotherapy</topic><topic>Psychiatry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Perlis, Roy H</creatorcontrib><creatorcontrib>Moorjani, Priya</creatorcontrib><creatorcontrib>Fagerness, Jesen</creatorcontrib><creatorcontrib>Purcell, Shaun</creatorcontrib><creatorcontrib>Trivedi, Madhukar H</creatorcontrib><creatorcontrib>Fava, Maurizio</creatorcontrib><creatorcontrib>Rush, A John</creatorcontrib><creatorcontrib>Smoller, Jordan W</creatorcontrib><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>ProQuest Psychology</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>PubMed Central (Full Participant titles)</collection><jtitle>Neuropsychopharmacology (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Perlis, Roy H</au><au>Moorjani, Priya</au><au>Fagerness, Jesen</au><au>Purcell, Shaun</au><au>Trivedi, Madhukar H</au><au>Fava, Maurizio</au><au>Rush, A John</au><au>Smoller, Jordan W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacogenetic Analysis of Genes Implicated in Rodent Models of Antidepressant Response: Association of TREK1 and Treatment Resistance in the STARD Study</atitle><jtitle>Neuropsychopharmacology (New York, N.Y.)</jtitle><stitle>Neuropsychopharmacol</stitle><date>2008-11-01</date><risdate>2008</risdate><volume>33</volume><issue>12</issue><spage>2810</spage><epage>2819</epage><pages>2810-2819</pages><issn>0893-133X</issn><eissn>1740-634X</eissn><coden>NEROEW</coden><abstract>Recent rodent models of antidepressant response implicate a novel set of genes in mechanisms of antidepressant action. The authors examined variants in four such genes (
KCNK2
(
TREK1
),
SLC18A2
(
VMAT2
),
S100A10
, and
HDAC5
) for association with remission in a large effectiveness trial of antidepressant treatments. Subjects were drawn from the Sequenced Treatment Alternatives to Relieve Depression (STAR
*
D) study, a multicenter, prospective, effectiveness trial in major depressive disorder (MDD). Outpatients with nonpsychotic MDD were initially treated with citalopram for up to 14 weeks; those who did not remit with citalopram were sequentially randomized to a series of next-step treatments, each for up to 12 weeks. Single-nucleotide polymorphisms in four genes were examined for association with remission, defined as a clinician-rated Quick Inventory of Depressive Symptomatology (QIDS-C
16
) score ⩽5. Of 1554 participants for whom DNA was available, 565 (36%) reached remission with citalopram treatment. No association with any of the four genes was identified. However, among the 751 who entered next-step treatment, variants in
KCNK2
were associated with treatment response (Bonferroni-corrected, gene-based empirical
p
<0.001). In follow-up analyses,
KCNK2
was also associated with effects of similar magnitude for third-step treatment among those with unsatisfactory benefit to both citalopram and one next-step pharmacotherapy (
n
=225). These findings indicate that genetic variation in
KCNK2
may identify individuals at risk for treatment resistance. More broadly, they indicate the utility of animal models in identifying genes for pharmacogenetic studies of antidepressant response.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>18288090</pmid><doi>10.1038/npp.2008.6</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | Springer Nature - Complete Springer Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Antidepressants Behavioral Sciences Biological Psychology Brain research Genes Medicine Medicine & Public Health Mental depression Neurosciences original-article Pharmacotherapy Psychiatry |
| title | Pharmacogenetic Analysis of Genes Implicated in Rodent Models of Antidepressant Response: Association of TREK1 and Treatment Resistance in the STARD Study |
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