Serotonin system gene variants and regional brain volume differences in pediatric OCD
Obsessive-compulsive disorder (OCD) is phenotypically heterogeneous and genetically complex. This study aimed to reduce heterogeneity using structural brain imaging to study putative intermediate phenotypes for OCD. We hypothesized that select serotonin gene variants would differ in their relationsh...
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| creator | Sinopoli, Vanessa M. Erdman, Lauren Burton, Christie L. Easter, Phillip Rajendram, Rageen Baldwin, Gregory Peterman, Kelli Coste, Julie Shaheen, S-M Hanna, Gregory L. Rosenberg, David R. Arnold, Paul D. |
| description | Obsessive-compulsive disorder (OCD) is phenotypically heterogeneous and genetically complex. This study aimed to reduce heterogeneity using structural brain imaging to study putative intermediate phenotypes for OCD. We hypothesized that select serotonin gene variants would differ in their relationship with brain volume in specific regions of the cortico-striato-thalamo-cortical (CSTC) circuits between OCD patients and controls. In a total of 200 pediatric subjects, we genotyped candidate serotonin genes (
SLC6A4
,
HTR2A
,
HTR1B
, and
HTR2C
) and conducted structural magnetic resonance imaging (sMRI) to measure regional brain volumes within CSTC circuits. In males and females separately, we first tested the association between serotonin gene variants and OCD and the effect of serotonin gene variants on brain volume irrespective of diagnosis. We then carried out a series of analyses to assess the effect of genotype-diagnosis interaction on brain volume. In females, but not in males, we identified a statistically significant genotype-diagnosis interaction for two single nucleotide polymorphisms (SNPs) in
HTR2C
, rs12860460 (interaction term estimate of 5.45 cc and interaction
P
value of 9.70e-8) and rs12854485 (interaction term estimate of 4.28 cc and interaction
P
value of 2.07e-6). The tested allele in each SNP was associated with decreased anterior cingulate cortex (ACC) volume in controls and with increased ACC volume in OCD patients. Our findings suggest that, in females, sequence variation in
HTR2C
influences ACC volume in pediatric OCD. The variants may contribute to differences in ACC volume and to OCD in a sex-specific manner when acting together with other genetic, biological, and/or environmental factors. |
| doi_str_mv | 10.1007/s11682-019-00092-w |
| format | Article |
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SLC6A4
,
HTR2A
,
HTR1B
, and
HTR2C
) and conducted structural magnetic resonance imaging (sMRI) to measure regional brain volumes within CSTC circuits. In males and females separately, we first tested the association between serotonin gene variants and OCD and the effect of serotonin gene variants on brain volume irrespective of diagnosis. We then carried out a series of analyses to assess the effect of genotype-diagnosis interaction on brain volume. In females, but not in males, we identified a statistically significant genotype-diagnosis interaction for two single nucleotide polymorphisms (SNPs) in
HTR2C
, rs12860460 (interaction term estimate of 5.45 cc and interaction
P
value of 9.70e-8) and rs12854485 (interaction term estimate of 4.28 cc and interaction
P
value of 2.07e-6). The tested allele in each SNP was associated with decreased anterior cingulate cortex (ACC) volume in controls and with increased ACC volume in OCD patients. Our findings suggest that, in females, sequence variation in
HTR2C
influences ACC volume in pediatric OCD. The variants may contribute to differences in ACC volume and to OCD in a sex-specific manner when acting together with other genetic, biological, and/or environmental factors.</description><identifier>ISSN: 1931-7557</identifier><identifier>EISSN: 1931-7565</identifier><identifier>DOI: 10.1007/s11682-019-00092-w</identifier><identifier>PMID: 31187473</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Biomedical and Life Sciences ; Biomedicine ; Brain ; Brain - diagnostic imaging ; Child ; Circuits ; Cortex (cingulate) ; Diagnosis ; Environmental factors ; Female ; Females ; Heterogeneity ; Humans ; Magnetic Resonance Imaging ; Male ; Males ; Medical imaging ; Neuroimaging ; Neuropsychology ; Neuroradiology ; Neurosciences ; Obsessive compulsive disorder ; Obsessive-Compulsive Disorder - diagnostic imaging ; Obsessive-Compulsive Disorder - genetics ; Original Research ; Pediatrics ; Phenotypes ; Polymorphism, Single Nucleotide - genetics ; Psychiatry ; Receptor, Serotonin, 5-HT2C - genetics ; Serotonin ; Serotonin Plasma Membrane Transport Proteins ; Single-nucleotide polymorphism ; Statistical analysis</subject><ispartof>Brain imaging and behavior, 2020-10, Vol.14 (5), p.1612-1625</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>Brain Imaging and Behavior is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-f4c1b048f0a8a2608db3d3c7078ed031b119da601807e48c037915225c194cfe3</citedby><cites>FETCH-LOGICAL-c475t-f4c1b048f0a8a2608db3d3c7078ed031b119da601807e48c037915225c194cfe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11682-019-00092-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11682-019-00092-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,777,781,882,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31187473$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sinopoli, Vanessa M.</creatorcontrib><creatorcontrib>Erdman, Lauren</creatorcontrib><creatorcontrib>Burton, Christie L.</creatorcontrib><creatorcontrib>Easter, Phillip</creatorcontrib><creatorcontrib>Rajendram, Rageen</creatorcontrib><creatorcontrib>Baldwin, Gregory</creatorcontrib><creatorcontrib>Peterman, Kelli</creatorcontrib><creatorcontrib>Coste, Julie</creatorcontrib><creatorcontrib>Shaheen, S-M</creatorcontrib><creatorcontrib>Hanna, Gregory L.</creatorcontrib><creatorcontrib>Rosenberg, David R.</creatorcontrib><creatorcontrib>Arnold, Paul D.</creatorcontrib><title>Serotonin system gene variants and regional brain volume differences in pediatric OCD</title><title>Brain imaging and behavior</title><addtitle>Brain Imaging and Behavior</addtitle><addtitle>Brain Imaging Behav</addtitle><description>Obsessive-compulsive disorder (OCD) is phenotypically heterogeneous and genetically complex. This study aimed to reduce heterogeneity using structural brain imaging to study putative intermediate phenotypes for OCD. We hypothesized that select serotonin gene variants would differ in their relationship with brain volume in specific regions of the cortico-striato-thalamo-cortical (CSTC) circuits between OCD patients and controls. In a total of 200 pediatric subjects, we genotyped candidate serotonin genes (
SLC6A4
,
HTR2A
,
HTR1B
, and
HTR2C
) and conducted structural magnetic resonance imaging (sMRI) to measure regional brain volumes within CSTC circuits. In males and females separately, we first tested the association between serotonin gene variants and OCD and the effect of serotonin gene variants on brain volume irrespective of diagnosis. We then carried out a series of analyses to assess the effect of genotype-diagnosis interaction on brain volume. In females, but not in males, we identified a statistically significant genotype-diagnosis interaction for two single nucleotide polymorphisms (SNPs) in
HTR2C
, rs12860460 (interaction term estimate of 5.45 cc and interaction
P
value of 9.70e-8) and rs12854485 (interaction term estimate of 4.28 cc and interaction
P
value of 2.07e-6). The tested allele in each SNP was associated with decreased anterior cingulate cortex (ACC) volume in controls and with increased ACC volume in OCD patients. Our findings suggest that, in females, sequence variation in
HTR2C
influences ACC volume in pediatric OCD. The variants may contribute to differences in ACC volume and to OCD in a sex-specific manner when acting together with other genetic, biological, and/or environmental factors.</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain</subject><subject>Brain - diagnostic imaging</subject><subject>Child</subject><subject>Circuits</subject><subject>Cortex (cingulate)</subject><subject>Diagnosis</subject><subject>Environmental factors</subject><subject>Female</subject><subject>Females</subject><subject>Heterogeneity</subject><subject>Humans</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Males</subject><subject>Medical imaging</subject><subject>Neuroimaging</subject><subject>Neuropsychology</subject><subject>Neuroradiology</subject><subject>Neurosciences</subject><subject>Obsessive compulsive disorder</subject><subject>Obsessive-Compulsive Disorder - diagnostic imaging</subject><subject>Obsessive-Compulsive Disorder - genetics</subject><subject>Original Research</subject><subject>Pediatrics</subject><subject>Phenotypes</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Psychiatry</subject><subject>Receptor, Serotonin, 5-HT2C - genetics</subject><subject>Serotonin</subject><subject>Serotonin Plasma Membrane Transport Proteins</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistical analysis</subject><issn>1931-7557</issn><issn>1931-7565</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</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>eNp9kUFvEzEQhS1ERUvhD3BAljgvzNjrtX1CKKUFqVIPbc-W1zsbXCV2sDep-u_ZNiXAhZMtzzfvzfgx9g7hIwLoTxWxM6IBtA0AWNHcv2AnaCU2WnXq5eGu9DF7XesdgGqNxVfsWCIa3Wp5wm6vqeQpp5h4fagTrfmSEvGdL9GnqXKfBl5oGXPyK94XP3O7vNquiQ9xHKlQClT5_LqhIfqpxMCvFmdv2NHoV5XePp-n7Pb8683iW3N5dfF98eWyCa1WUzO2AXtozQjeeNGBGXo5yKBBGxpAYo9oB98BGtDUmgBSW1RCqIC2DSPJU_Z5r7vZ9msaAqWp-JXblLj25cFlH92_lRR_uGXeOQQl0HZqVvjwrFDyzy3Vyd3lbZmXrU4IaYSynXikxJ4KJddaaDxYILjHLNw-Czdn4Z6ycPdz0_u_hzu0_P78GZB7oM6ltKTyx_s_sr8AuEmWAw</recordid><startdate>20201001</startdate><enddate>20201001</enddate><creator>Sinopoli, Vanessa M.</creator><creator>Erdman, Lauren</creator><creator>Burton, Christie L.</creator><creator>Easter, Phillip</creator><creator>Rajendram, Rageen</creator><creator>Baldwin, Gregory</creator><creator>Peterman, Kelli</creator><creator>Coste, Julie</creator><creator>Shaheen, S-M</creator><creator>Hanna, Gregory L.</creator><creator>Rosenberg, David R.</creator><creator>Arnold, Paul D.</creator><general>Springer US</general><general>Springer Nature B.V</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>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</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>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</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>20201001</creationdate><title>Serotonin system gene variants and regional brain volume differences in pediatric OCD</title><author>Sinopoli, Vanessa M. ; Erdman, Lauren ; Burton, Christie L. ; Easter, Phillip ; Rajendram, Rageen ; Baldwin, Gregory ; Peterman, Kelli ; Coste, Julie ; Shaheen, S-M ; Hanna, Gregory L. ; Rosenberg, David R. ; Arnold, Paul D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-f4c1b048f0a8a2608db3d3c7078ed031b119da601807e48c037915225c194cfe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain</topic><topic>Brain - diagnostic imaging</topic><topic>Child</topic><topic>Circuits</topic><topic>Cortex (cingulate)</topic><topic>Diagnosis</topic><topic>Environmental factors</topic><topic>Female</topic><topic>Females</topic><topic>Heterogeneity</topic><topic>Humans</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Males</topic><topic>Medical imaging</topic><topic>Neuroimaging</topic><topic>Neuropsychology</topic><topic>Neuroradiology</topic><topic>Neurosciences</topic><topic>Obsessive compulsive disorder</topic><topic>Obsessive-Compulsive Disorder - diagnostic imaging</topic><topic>Obsessive-Compulsive Disorder - genetics</topic><topic>Original Research</topic><topic>Pediatrics</topic><topic>Phenotypes</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Psychiatry</topic><topic>Receptor, Serotonin, 5-HT2C - genetics</topic><topic>Serotonin</topic><topic>Serotonin Plasma Membrane Transport Proteins</topic><topic>Single-nucleotide polymorphism</topic><topic>Statistical analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sinopoli, Vanessa M.</creatorcontrib><creatorcontrib>Erdman, Lauren</creatorcontrib><creatorcontrib>Burton, Christie L.</creatorcontrib><creatorcontrib>Easter, Phillip</creatorcontrib><creatorcontrib>Rajendram, Rageen</creatorcontrib><creatorcontrib>Baldwin, Gregory</creatorcontrib><creatorcontrib>Peterman, Kelli</creatorcontrib><creatorcontrib>Coste, Julie</creatorcontrib><creatorcontrib>Shaheen, S-M</creatorcontrib><creatorcontrib>Hanna, Gregory L.</creatorcontrib><creatorcontrib>Rosenberg, David R.</creatorcontrib><creatorcontrib>Arnold, Paul D.</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>Proquest Nursing & Allied Health Source</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest 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 SciTech Collection</collection><collection>ProQuest Technology 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)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Database (1962 - 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This study aimed to reduce heterogeneity using structural brain imaging to study putative intermediate phenotypes for OCD. We hypothesized that select serotonin gene variants would differ in their relationship with brain volume in specific regions of the cortico-striato-thalamo-cortical (CSTC) circuits between OCD patients and controls. In a total of 200 pediatric subjects, we genotyped candidate serotonin genes (
SLC6A4
,
HTR2A
,
HTR1B
, and
HTR2C
) and conducted structural magnetic resonance imaging (sMRI) to measure regional brain volumes within CSTC circuits. In males and females separately, we first tested the association between serotonin gene variants and OCD and the effect of serotonin gene variants on brain volume irrespective of diagnosis. We then carried out a series of analyses to assess the effect of genotype-diagnosis interaction on brain volume. In females, but not in males, we identified a statistically significant genotype-diagnosis interaction for two single nucleotide polymorphisms (SNPs) in
HTR2C
, rs12860460 (interaction term estimate of 5.45 cc and interaction
P
value of 9.70e-8) and rs12854485 (interaction term estimate of 4.28 cc and interaction
P
value of 2.07e-6). The tested allele in each SNP was associated with decreased anterior cingulate cortex (ACC) volume in controls and with increased ACC volume in OCD patients. Our findings suggest that, in females, sequence variation in
HTR2C
influences ACC volume in pediatric OCD. The variants may contribute to differences in ACC volume and to OCD in a sex-specific manner when acting together with other genetic, biological, and/or environmental factors.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>31187473</pmid><doi>10.1007/s11682-019-00092-w</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Brain imaging and behavior, 2020-10, Vol.14 (5), p.1612-1625 |
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| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Biomedical and Life Sciences Biomedicine Brain Brain - diagnostic imaging Child Circuits Cortex (cingulate) Diagnosis Environmental factors Female Females Heterogeneity Humans Magnetic Resonance Imaging Male Males Medical imaging Neuroimaging Neuropsychology Neuroradiology Neurosciences Obsessive compulsive disorder Obsessive-Compulsive Disorder - diagnostic imaging Obsessive-Compulsive Disorder - genetics Original Research Pediatrics Phenotypes Polymorphism, Single Nucleotide - genetics Psychiatry Receptor, Serotonin, 5-HT2C - genetics Serotonin Serotonin Plasma Membrane Transport Proteins Single-nucleotide polymorphism Statistical analysis |
| title | Serotonin system gene variants and regional brain volume differences in pediatric OCD |
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