Adenylate Cyclase 7 Is Implicated in the Biology of Depression and Modulation of Affective Neural Circuitry
Identifieur interne : 00A122 ( Main/Merge ); précédent : 00A121; suivant : 00A123Adenylate Cyclase 7 Is Implicated in the Biology of Depression and Modulation of Affective Neural Circuitry
Auteurs : Jennifer Joeyen-Waldorf [États-Unis] ; Yuliya S. Nikolova [États-Unis] ; Nicole Edgar [États-Unis] ; Chris Walsh [États-Unis] ; Rama Kota [États-Unis] ; David A. Lewis [États-Unis] ; Robert Ferrell [États-Unis] ; Stephen B. Manuck [États-Unis] ; Ahmad R. Hariri [États-Unis] ; Etienne Sibille [États-Unis]Source :
- Biological psychiatry : (1969) [ 0006-3223 ] ; 2012.
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English descriptors
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Abstract
Background: Evolutionarily conserved genes and their associated molecular pathways can serve as a translational bridge between human and mouse research, extending our understanding of biological pathways mediating individual differences in behavior and risk for psychopathology. Methods: Comparative gene array analysis in the amygdala and cingulate cortex between the serotonin transporter knockout mouse, a genetic animal model replicating features of human depression, and existing brain transcriptome data from postmortem tissue derived from clinically depressed humans was conducted to identify genes with similar changes across species (i.e., conserved) that may help explain risk of depressive-like phenotypes. Human neuroimaging analysis was then used to investigate the impact of a common single-nucleotide polymorphism (rs1064448) in a gene with identified conserved human-mouse changes, adenylate cyclase 7 (ADCY7), on threat-associated amygdala reactivity in two large independent samples. Results: Comparative analysis identified genes with conserved transcript changes in amygdala (n = 29) and cingulate cortex (n = 19), both critically involved in the generation and regulation of emotion. Selected results were confirmed by real-time quantitative polymerase chain reaction, including upregulation in the amygdala of transcripts forADCY7, a gene previously implicated in human depression and associated with altered emotional responsiveness in mouse models. Translating these results back to living healthy human subjects, we show that genetic variation (rs1064448) in ADCY7 biases threat-related amygdala reactivity. Conclusions: This converging cross-species evidence implicates ADCY7 in the modulation of mood regulatory neural mechanisms and, possibly, risk for and pathophysiology of depression, together supporting a continuous dimensional approach to major depressive disorder and other affective disorders.
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Nikolova</name><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Psychology and Neuroscience and Institute for Genome Sciences and Policy Duke University</s1><s2>Durham, North Carolina</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Edgar, Nicole" sort="Edgar, Nicole" uniqKey="Edgar N" first="Nicole" last="Edgar">Nicole Edgar</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Pittsburgh</s1><s2>Pittsburgh, Pennsylvania</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Neuroscience, University of Pittsburgh</s1><s2>Pittsburgh, Pennsylvania</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Walsh, Chris" sort="Walsh, Chris" uniqKey="Walsh C" first="Chris" last="Walsh">Chris Walsh</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Pittsburgh</s1><s2>Pittsburgh, Pennsylvania</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Kota, Rama" sort="Kota, Rama" uniqKey="Kota R" first="Rama" last="Kota">Rama Kota</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Pittsburgh</s1><s2>Pittsburgh, Pennsylvania</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Lewis, David A" sort="Lewis, David A" uniqKey="Lewis D" first="David A." last="Lewis">David A. Lewis</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Pittsburgh</s1><s2>Pittsburgh, Pennsylvania</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Neuroscience, University of Pittsburgh</s1><s2>Pittsburgh, Pennsylvania</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Ferrell, Robert" sort="Ferrell, Robert" uniqKey="Ferrell R" first="Robert" last="Ferrell">Robert Ferrell</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Departments of Human Genetics, University of Pittsburgh</s1><s2>Pittsburgh, Pennsylvania</s2><s3>USA</s3><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Manuck, Stephen B" sort="Manuck, Stephen B" uniqKey="Manuck S" first="Stephen B." last="Manuck">Stephen B. Manuck</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Department of Psychology, University of Pittsburgh</s1><s2>Pittsburgh, Pennsylvania</s2><s3>USA</s3><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Hariri, Ahmad R" sort="Hariri, Ahmad R" uniqKey="Hariri A" first="Ahmad R." last="Hariri">Ahmad R. Hariri</name><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Psychology and Neuroscience and Institute for Genome Sciences and Policy Duke University</s1><s2>Durham, North Carolina</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName></affiliation></author><author><name sortKey="Sibille, Etienne" sort="Sibille, Etienne" uniqKey="Sibille E" first="Etienne" last="Sibille">Etienne Sibille</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Department of Psychiatry, University of Pittsburgh</s1><s2>Pittsburgh, Pennsylvania</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Neuroscience, University of Pittsburgh</s1><s2>Pittsburgh, Pennsylvania</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>6 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author></analytic><series><title level="j" type="main">Biological psychiatry : (1969)</title><title level="j" type="abbreviated">Biol. psychiatry : (1969)</title><idno type="ISSN">0006-3223</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Biological psychiatry : (1969)</title><title level="j" type="abbreviated">Biol. psychiatry : (1969)</title><idno type="ISSN">0006-3223</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenylate cyclase</term><term>Affect affectivity</term><term>Amygdala</term><term>Amygdaloid nucleus</term><term>Animal</term><term>Biology</term><term>Depression</term><term>Human</term><term>Mouse</term><term>Serotonin transporter</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Adenylate cyclase</term><term>Biologie</term><term>Etat dépressif</term><term>Affect affectivité</term><term>Noyau amygdalien</term><term>Amygdale</term><term>Transporteur de la sérotonine</term><term>Homme</term><term>Souris</term><term>Animal</term><term>Transporteur sérotonine</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Biologie</term><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: Evolutionarily conserved genes and their associated molecular pathways can serve as a translational bridge between human and mouse research, extending our understanding of biological pathways mediating individual differences in behavior and risk for psychopathology. Methods: Comparative gene array analysis in the amygdala and cingulate cortex between the serotonin transporter knockout mouse, a genetic animal model replicating features of human depression, and existing brain transcriptome data from postmortem tissue derived from clinically depressed humans was conducted to identify genes with similar changes across species (i.e., conserved) that may help explain risk of depressive-like phenotypes. Human neuroimaging analysis was then used to investigate the impact of a common single-nucleotide polymorphism (rs1064448) in a gene with identified conserved human-mouse changes, adenylate cyclase 7 (ADCY7), on threat-associated amygdala reactivity in two large independent samples. Results: Comparative analysis identified genes with conserved transcript changes in amygdala (n = 29) and cingulate cortex (n = 19), both critically involved in the generation and regulation of emotion. Selected results were confirmed by real-time quantitative polymerase chain reaction, including upregulation in the amygdala of transcripts forADCY7, a gene previously implicated in human depression and associated with altered emotional responsiveness in mouse models. Translating these results back to living healthy human subjects, we show that genetic variation (rs1064448) in ADCY7 biases threat-related amygdala reactivity. Conclusions: This converging cross-species evidence implicates ADCY7 in the modulation of mood regulatory neural mechanisms and, possibly, risk for and pathophysiology of depression, together supporting a continuous dimensional approach to major depressive disorder and other affective disorders.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li><li>Pennsylvanie</li></region><settlement><li>Pittsburgh</li></settlement><orgName><li>Université de Pittsburgh</li></orgName></list><tree><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Joeyen Waldorf, Jennifer" sort="Joeyen Waldorf, Jennifer" uniqKey="Joeyen Waldorf J" first="Jennifer" last="Joeyen-Waldorf">Jennifer Joeyen-Waldorf</name></region><name sortKey="Edgar, Nicole" sort="Edgar, Nicole" uniqKey="Edgar N" first="Nicole" last="Edgar">Nicole Edgar</name><name sortKey="Edgar, Nicole" sort="Edgar, Nicole" uniqKey="Edgar N" first="Nicole" last="Edgar">Nicole Edgar</name><name sortKey="Ferrell, Robert" sort="Ferrell, Robert" uniqKey="Ferrell R" first="Robert" last="Ferrell">Robert Ferrell</name><name sortKey="Hariri, Ahmad R" sort="Hariri, Ahmad R" uniqKey="Hariri A" first="Ahmad R." last="Hariri">Ahmad R. Hariri</name><name sortKey="Kota, Rama" sort="Kota, Rama" uniqKey="Kota R" first="Rama" last="Kota">Rama Kota</name><name sortKey="Lewis, David A" sort="Lewis, David A" uniqKey="Lewis D" first="David A." last="Lewis">David A. Lewis</name><name sortKey="Lewis, David A" sort="Lewis, David A" uniqKey="Lewis D" first="David A." last="Lewis">David A. Lewis</name><name sortKey="Manuck, Stephen B" sort="Manuck, Stephen B" uniqKey="Manuck S" first="Stephen B." last="Manuck">Stephen B. Manuck</name><name sortKey="Nikolova, Yuliya S" sort="Nikolova, Yuliya S" uniqKey="Nikolova Y" first="Yuliya S." last="Nikolova">Yuliya S. Nikolova</name><name sortKey="Sibille, Etienne" sort="Sibille, Etienne" uniqKey="Sibille E" first="Etienne" last="Sibille">Etienne Sibille</name><name sortKey="Sibille, Etienne" sort="Sibille, Etienne" uniqKey="Sibille E" first="Etienne" last="Sibille">Etienne Sibille</name><name sortKey="Walsh, Chris" sort="Walsh, Chris" uniqKey="Walsh C" first="Chris" last="Walsh">Chris Walsh</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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