Antipanic efficacy of paroxetine and polymorphism within the promoter of the serotonin transporter gene
Serotonin selective reuptake inhibitors (SSRIs) are the drugs of choice in the treatment of panic disorder (PD). The serotonin transporter (5-HTT) is a prime target for SSRIs. A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was...
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| Veröffentlicht in: | Neuropsychopharmacology (New York, N.Y.) N.Y.), 2005-12, Vol.30 (12), p.2230-2235 |
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| creator | PERNA, Giampaolo FAVARON, Elisa DI BELLA, Daniela BUSSI, Riccardo BELLODI, Laura |
| description | Serotonin selective reuptake inhibitors (SSRIs) are the drugs of choice in the treatment of panic disorder (PD). The serotonin transporter (5-HTT) is a prime target for SSRIs. A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was repeatedly reported to influence the response to SSRIs in mood disorders while the response of patients with OCD seems unrelated. We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antipanic response to paroxetine. In total, 92 patients with PD completed a treatment with a variable dose of paroxetine for 12 weeks. The severity of panic-phobic symptomatology was measured before the beginning of the treatment and after 12 weeks. Allelic variation in each subject was determined using a PCR-based method. Both homozygotes for the long variant (l/l) of the 5-HTT promoter and heterozygotes (l/s) showed a better response to paroxetine than homozygotes for the short variant (s/s) (chi(2)=6.9, p |
| doi_str_mv | 10.1038/sj.npp.1300822 |
| format | Article |
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The serotonin transporter (5-HTT) is a prime target for SSRIs. A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was repeatedly reported to influence the response to SSRIs in mood disorders while the response of patients with OCD seems unrelated. We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antipanic response to paroxetine. In total, 92 patients with PD completed a treatment with a variable dose of paroxetine for 12 weeks. The severity of panic-phobic symptomatology was measured before the beginning of the treatment and after 12 weeks. Allelic variation in each subject was determined using a PCR-based method. Both homozygotes for the long variant (l/l) of the 5-HTT promoter and heterozygotes (l/s) showed a better response to paroxetine than homozygotes for the short variant (s/s) (chi(2)=6.9, p<0.03). This result emerged in the whole sample, but was related only to female patients (chi(2)=7.6, p<0.02). The presence of the long allelic variant was associated with a better response of panic attacks while was not significantly associated with the response of anticipatory anxiety or phobic avoidance. In conclusion, paroxetine efficacy in PD seems to be related to allelic variation within the promoter of the 5-HTT gene in female subjects. This gender effect might be related to the genomic effects of sex hormones. Understanding the interaction between gender and genes coding for structures target of psychotropic drugs could help to individualize the pharmacological treatment of PD.</description><identifier>ISSN: 0893-133X</identifier><identifier>EISSN: 1740-634X</identifier><identifier>DOI: 10.1038/sj.npp.1300822</identifier><identifier>PMID: 16034444</identifier><identifier>CODEN: NEROEW</identifier><language>eng</language><publisher>New York, NY: Nature Publishing</publisher><subject>Adult ; Alleles ; Antidepressive Agents, Second-Generation - therapeutic use ; Biological and medical sciences ; Drugs ; Fear - psychology ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Medical sciences ; Panic attacks ; Panic Disorder - drug therapy ; Panic Disorder - genetics ; Panic Disorder - psychology ; Paroxetine - therapeutic use ; Polymorphism ; Promoter Regions, Genetic - genetics ; Psychiatric Status Rating Scales ; Reverse Transcriptase Polymerase Chain Reaction ; Serotonin ; Serotonin Plasma Membrane Transport Proteins - genetics ; Surveys and Questionnaires</subject><ispartof>Neuropsychopharmacology (New York, N.Y.), 2005-12, Vol.30 (12), p.2230-2235</ispartof><rights>2006 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Dec 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-823493f434c3330adb90ae38307153f800182fc0dbafd178c2f49dba8b1b52493</citedby><cites>FETCH-LOGICAL-c456t-823493f434c3330adb90ae38307153f800182fc0dbafd178c2f49dba8b1b52493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17283957$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16034444$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PERNA, Giampaolo</creatorcontrib><creatorcontrib>FAVARON, Elisa</creatorcontrib><creatorcontrib>DI BELLA, Daniela</creatorcontrib><creatorcontrib>BUSSI, Riccardo</creatorcontrib><creatorcontrib>BELLODI, Laura</creatorcontrib><title>Antipanic efficacy of paroxetine and polymorphism within the promoter of the serotonin transporter gene</title><title>Neuropsychopharmacology (New York, N.Y.)</title><addtitle>Neuropsychopharmacology</addtitle><description>Serotonin selective reuptake inhibitors (SSRIs) are the drugs of choice in the treatment of panic disorder (PD). The serotonin transporter (5-HTT) is a prime target for SSRIs. A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was repeatedly reported to influence the response to SSRIs in mood disorders while the response of patients with OCD seems unrelated. We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antipanic response to paroxetine. In total, 92 patients with PD completed a treatment with a variable dose of paroxetine for 12 weeks. The severity of panic-phobic symptomatology was measured before the beginning of the treatment and after 12 weeks. Allelic variation in each subject was determined using a PCR-based method. Both homozygotes for the long variant (l/l) of the 5-HTT promoter and heterozygotes (l/s) showed a better response to paroxetine than homozygotes for the short variant (s/s) (chi(2)=6.9, p<0.03). This result emerged in the whole sample, but was related only to female patients (chi(2)=7.6, p<0.02). The presence of the long allelic variant was associated with a better response of panic attacks while was not significantly associated with the response of anticipatory anxiety or phobic avoidance. In conclusion, paroxetine efficacy in PD seems to be related to allelic variation within the promoter of the 5-HTT gene in female subjects. This gender effect might be related to the genomic effects of sex hormones. Understanding the interaction between gender and genes coding for structures target of psychotropic drugs could help to individualize the pharmacological treatment of PD.</description><subject>Adult</subject><subject>Alleles</subject><subject>Antidepressive Agents, Second-Generation - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Drugs</subject><subject>Fear - psychology</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genotype</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Panic attacks</subject><subject>Panic Disorder - drug therapy</subject><subject>Panic Disorder - genetics</subject><subject>Panic Disorder - psychology</subject><subject>Paroxetine - therapeutic use</subject><subject>Polymorphism</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Psychiatric Status Rating Scales</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Serotonin</subject><subject>Serotonin Plasma Membrane Transport Proteins - 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Academic</collection><jtitle>Neuropsychopharmacology (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PERNA, Giampaolo</au><au>FAVARON, Elisa</au><au>DI BELLA, Daniela</au><au>BUSSI, Riccardo</au><au>BELLODI, Laura</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antipanic efficacy of paroxetine and polymorphism within the promoter of the serotonin transporter gene</atitle><jtitle>Neuropsychopharmacology (New York, N.Y.)</jtitle><addtitle>Neuropsychopharmacology</addtitle><date>2005-12-01</date><risdate>2005</risdate><volume>30</volume><issue>12</issue><spage>2230</spage><epage>2235</epage><pages>2230-2235</pages><issn>0893-133X</issn><eissn>1740-634X</eissn><coden>NEROEW</coden><abstract>Serotonin selective reuptake inhibitors (SSRIs) are the drugs of choice in the treatment of panic disorder (PD). The serotonin transporter (5-HTT) is a prime target for SSRIs. A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was repeatedly reported to influence the response to SSRIs in mood disorders while the response of patients with OCD seems unrelated. We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antipanic response to paroxetine. In total, 92 patients with PD completed a treatment with a variable dose of paroxetine for 12 weeks. The severity of panic-phobic symptomatology was measured before the beginning of the treatment and after 12 weeks. Allelic variation in each subject was determined using a PCR-based method. Both homozygotes for the long variant (l/l) of the 5-HTT promoter and heterozygotes (l/s) showed a better response to paroxetine than homozygotes for the short variant (s/s) (chi(2)=6.9, p<0.03). This result emerged in the whole sample, but was related only to female patients (chi(2)=7.6, p<0.02). The presence of the long allelic variant was associated with a better response of panic attacks while was not significantly associated with the response of anticipatory anxiety or phobic avoidance. In conclusion, paroxetine efficacy in PD seems to be related to allelic variation within the promoter of the 5-HTT gene in female subjects. This gender effect might be related to the genomic effects of sex hormones. Understanding the interaction between gender and genes coding for structures target of psychotropic drugs could help to individualize the pharmacological treatment of PD.</abstract><cop>New York, NY</cop><pub>Nature Publishing</pub><pmid>16034444</pmid><doi>10.1038/sj.npp.1300822</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Alleles Antidepressive Agents, Second-Generation - therapeutic use Biological and medical sciences Drugs Fear - psychology Female Gene Frequency Genotype Humans Male Medical sciences Panic attacks Panic Disorder - drug therapy Panic Disorder - genetics Panic Disorder - psychology Paroxetine - therapeutic use Polymorphism Promoter Regions, Genetic - genetics Psychiatric Status Rating Scales Reverse Transcriptase Polymerase Chain Reaction Serotonin Serotonin Plasma Membrane Transport Proteins - genetics Surveys and Questionnaires |
| title | Antipanic efficacy of paroxetine and polymorphism within the promoter of the serotonin transporter gene |
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