Testing the Predictive Value of Peripheral Gene Expression for Nonremission Following Citalopram Treatment for Major Depression
Identifieur interne : 000212 ( France/Analysis ); précédent : 000211; suivant : 000213Testing the Predictive Value of Peripheral Gene Expression for Nonremission Following Citalopram Treatment for Major Depression
Auteurs : Jean-Philippe Guilloux [France, États-Unis] ; Sabrina Bassi [États-Unis, Argentine] ; Ying Ding [États-Unis] ; Chris Walsh [États-Unis] ; Gustavo Turecki [Canada] ; George Tseng [États-Unis] ; Jill M. Cyranowski [États-Unis] ; Etienne Sibille [États-Unis]Source :
- Neuropsychopharmacology [ 0893-133X ] ; 2014.
Descripteurs français
- KwdFr :
- Adulte, Analyse de profil d'expression de gènes, Anxiété (), Anxiété (sang), Anxiété (traitement médicamenteux), Apprentissage machine, Association thérapeutique, Citalopram (usage thérapeutique), Femelle, Humains, Induction de rémission, Inhibiteurs de la capture de la sérotonine (usage thérapeutique), Jeune adulte, Marqueurs biologiques (sang), Modèles génétiques, Mâle, Psychothérapie, Résultat thérapeutique, Trouble dépressif majeur (), Trouble dépressif majeur (génétique), Trouble dépressif majeur (sang), Trouble dépressif majeur (traitement médicamenteux), Valeur prédictive des tests, Échelles d'évaluation en psychiatrie, Études cas-témoins.
- MESH :
- génétique : Trouble dépressif majeur.
- sang : Anxiété, Marqueurs biologiques, Trouble dépressif majeur.
- traitement médicamenteux : Anxiété, Trouble dépressif majeur.
- usage thérapeutique : Citalopram, Inhibiteurs de la capture de la sérotonine.
- Adulte, Analyse de profil d'expression de gènes, Anxiété, Apprentissage machine, Association thérapeutique, Femelle, Humains, Induction de rémission, Jeune adulte, Modèles génétiques, Mâle, Psychothérapie, Résultat thérapeutique, Trouble dépressif majeur, Valeur prédictive des tests, Échelles d'évaluation en psychiatrie, Études cas-témoins.
English descriptors
- KwdEn :
- Adult, Anxiety (blood), Anxiety (complications), Anxiety (drug therapy), Biomarkers (blood), Case-Control Studies, Citalopram (therapeutic use), Combined Modality Therapy, Depressive Disorder, Major (blood), Depressive Disorder, Major (complications), Depressive Disorder, Major (drug therapy), Depressive Disorder, Major (genetics), Female, Gene Expression Profiling, Humans, Machine Learning, Male, Models, Genetic, Predictive Value of Tests, Psychiatric Status Rating Scales, Psychotherapy, Remission Induction, Serotonin Uptake Inhibitors (therapeutic use), Treatment Outcome, Young Adult.
- MESH :
- chemical , blood : Biomarkers.
- blood : Anxiety, Depressive Disorder, Major.
- complications : Anxiety, Depressive Disorder, Major.
- drug therapy : Anxiety, Depressive Disorder, Major.
- genetics : Depressive Disorder, Major.
- chemical , therapeutic use : Citalopram, Serotonin Uptake Inhibitors.
- Adult, Case-Control Studies, Combined Modality Therapy, Female, Gene Expression Profiling, Humans, Machine Learning, Male, Models, Genetic, Predictive Value of Tests, Psychiatric Status Rating Scales, Psychotherapy, Remission Induction, Treatment Outcome, Young Adult.
Abstract
Major depressive disorder (MDD) in general, and anxious-depression in particular, are characterized by poor rates of remission with first-line treatments, contributing to the chronic illness burden suffered by many patients. Prospective research is needed to identify the biomarkers predicting nonremission prior to treatment initiation. We collected blood samples from a discovery cohort of 34 adult MDD patients with co-occurring anxiety and 33 matched, nondepressed controls at baseline and after 12 weeks (of citalopram plus psychotherapy treatment for the depressed cohort). Samples were processed on gene arrays and group differences in gene expression were investigated. Exploratory analyses suggest that at pretreatment baseline, nonremitting patients differ from controls with gene function and transcription factor analyses potentially related to elevated inflammation and immune activation. In a second phase, we applied an unbiased machine learning prediction model and corrected for model-selection bias. Results show that baseline gene expression predicted nonremission with 79.4% corrected accuracy with a 13-gene model. The same gene-only model predicted nonremission after 8 weeks of citalopram treatment with 76% corrected accuracy in an independent validation cohort of 63 MDD patients treated with citalopram at another institution. Together, these results demonstrate the potential, but also the limitations, of baseline peripheral blood-based gene expression to predict nonremission after citalopram treatment. These results not only support their use in future prediction tools but also suggest that increased accuracy may be obtained with the inclusion of additional predictors (eg, genetics and clinical scales).
Url:
DOI: 10.1038/npp.2014.226
PubMed: 25176167
PubMed Central: 4289958
Affiliations:
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PMC:4289958Le document en format XML
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sort="Guilloux, Jean Philippe" uniqKey="Guilloux J" first="Jean-Philippe" last="Guilloux">Jean-Philippe Guilloux</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Université Paris-Sud EA 3544, Faculté de Pharmacie</institution>, Châtenay-Malabry,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Psychiatry, University of Pittsburgh</institution>, Pittsburgh, PA,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bassi, Sabrina" sort="Bassi, Sabrina" uniqKey="Bassi S" first="Sabrina" last="Bassi">Sabrina Bassi</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Psychiatry, University of Pittsburgh</institution>, Pittsburgh, PA,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Instituto de Ciencias Básicas y Medicina Experimental, Hospital Italiano de Buenos Aires</institution>, Buenos Aires,<country>Argentina</country></nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ding, Ying" sort="Ding, Ying" uniqKey="Ding Y" first="Ying" last="Ding">Ying Ding</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Joint CMU-Pitt PhD Program in Computational Biology, University of Pittsburgh</institution>, Pittsburgh, PA,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Walsh, Chris" sort="Walsh, Chris" uniqKey="Walsh C" first="Chris" last="Walsh">Chris Walsh</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Psychiatry, University of Pittsburgh</institution>, Pittsburgh, PA,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Turecki, Gustavo" sort="Turecki, Gustavo" uniqKey="Turecki G" first="Gustavo" last="Turecki">Gustavo Turecki</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>McGill Group for Suicide Studies and Depressive Program, Douglas Mental Health Institute</institution>, Montréal, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Tseng, George" sort="Tseng, George" uniqKey="Tseng G" first="George" last="Tseng">George Tseng</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Joint CMU-Pitt PhD Program in Computational Biology, University of Pittsburgh</institution>, Pittsburgh, PA,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Department of Biostatistics, University of Pittsburgh</institution>, Pittsburgh, PA,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Cyranowski, Jill M" sort="Cyranowski, Jill M" uniqKey="Cyranowski J" first="Jill M" last="Cyranowski">Jill M. Cyranowski</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Psychiatry, University of Pittsburgh</institution>, Pittsburgh, PA,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sibille, Etienne" sort="Sibille, Etienne" uniqKey="Sibille E" first="Etienne" last="Sibille">Etienne Sibille</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Psychiatry, University of Pittsburgh</institution>, Pittsburgh, PA,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Center for Neuroscience, University of Pittsburgh</institution>, Pittsburgh, PA,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Neuropsychopharmacology</title><idno type="ISSN">0893-133X</idno><idno type="eISSN">1740-634X</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Anxiety (blood)</term><term>Anxiety (complications)</term><term>Anxiety (drug therapy)</term><term>Biomarkers (blood)</term><term>Case-Control Studies</term><term>Citalopram (therapeutic use)</term><term>Combined Modality Therapy</term><term>Depressive Disorder, Major (blood)</term><term>Depressive Disorder, Major (complications)</term><term>Depressive Disorder, Major (drug therapy)</term><term>Depressive Disorder, Major (genetics)</term><term>Female</term><term>Gene Expression Profiling</term><term>Humans</term><term>Machine Learning</term><term>Male</term><term>Models, Genetic</term><term>Predictive Value of Tests</term><term>Psychiatric Status Rating Scales</term><term>Psychotherapy</term><term>Remission Induction</term><term>Serotonin Uptake Inhibitors (therapeutic use)</term><term>Treatment Outcome</term><term>Young Adult</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term><term>Analyse de profil d'expression de gènes</term><term>Anxiété ()</term><term>Anxiété (sang)</term><term>Anxiété (traitement médicamenteux)</term><term>Apprentissage machine</term><term>Association thérapeutique</term><term>Citalopram (usage thérapeutique)</term><term>Femelle</term><term>Humains</term><term>Induction de rémission</term><term>Inhibiteurs de la capture de la sérotonine (usage thérapeutique)</term><term>Jeune adulte</term><term>Marqueurs biologiques (sang)</term><term>Modèles génétiques</term><term>Mâle</term><term>Psychothérapie</term><term>Résultat thérapeutique</term><term>Trouble dépressif majeur ()</term><term>Trouble dépressif majeur (génétique)</term><term>Trouble dépressif majeur (sang)</term><term>Trouble dépressif majeur (traitement médicamenteux)</term><term>Valeur prédictive des tests</term><term>Échelles d'évaluation en psychiatrie</term><term>Études cas-témoins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Biomarkers</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Anxiety</term><term>Depressive Disorder, Major</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Anxiety</term><term>Depressive Disorder, Major</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Anxiety</term><term>Depressive Disorder, Major</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Depressive Disorder, Major</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Trouble dépressif majeur</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Anxiété</term><term>Marqueurs biologiques</term><term>Trouble dépressif majeur</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Citalopram</term><term>Serotonin Uptake Inhibitors</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Anxiété</term><term>Trouble dépressif majeur</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Citalopram</term><term>Inhibiteurs de la capture de la sérotonine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Case-Control Studies</term><term>Combined Modality Therapy</term><term>Female</term><term>Gene Expression Profiling</term><term>Humans</term><term>Machine Learning</term><term>Male</term><term>Models, Genetic</term><term>Predictive Value of Tests</term><term>Psychiatric Status Rating Scales</term><term>Psychotherapy</term><term>Remission Induction</term><term>Treatment Outcome</term><term>Young Adult</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte</term><term>Analyse de profil d'expression de gènes</term><term>Anxiété</term><term>Apprentissage machine</term><term>Association thérapeutique</term><term>Femelle</term><term>Humains</term><term>Induction de rémission</term><term>Jeune adulte</term><term>Modèles génétiques</term><term>Mâle</term><term>Psychothérapie</term><term>Résultat thérapeutique</term><term>Trouble dépressif majeur</term><term>Valeur prédictive des tests</term><term>Échelles d'évaluation en psychiatrie</term><term>Études cas-témoins</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Major depressive disorder (MDD) in general, and anxious-depression in particular, are characterized by poor rates of remission with first-line treatments, contributing to the chronic illness burden suffered by many patients. Prospective research is needed to identify the biomarkers predicting nonremission prior to treatment initiation. We collected blood samples from a discovery cohort of 34 adult MDD patients with co-occurring anxiety and 33 matched, nondepressed controls at baseline and after 12 weeks (of citalopram plus psychotherapy treatment for the depressed cohort). Samples were processed on gene arrays and group differences in gene expression were investigated. Exploratory analyses suggest that at pretreatment baseline, nonremitting patients differ from controls with gene function and transcription factor analyses potentially related to elevated inflammation and immune activation. In a second phase, we applied an unbiased machine learning prediction model and corrected for model-selection bias. Results show that baseline gene expression predicted nonremission with 79.4% corrected accuracy with a 13-gene model. The same gene-only model predicted nonremission after 8 weeks of citalopram treatment with 76% corrected accuracy in an independent validation cohort of 63 MDD patients treated with citalopram at another institution. Together, these results demonstrate the potential, but also the limitations, of baseline peripheral blood-based gene expression to predict nonremission after citalopram treatment. These results not only support their use in future prediction tools but also suggest that increased accuracy may be obtained with the inclusion of additional predictors (eg, genetics and clinical scales).</p></div></front></TEI><affiliations><list><country><li>Argentine</li><li>Canada</li><li>France</li><li>États-Unis</li></country></list><tree><country name="France"><noRegion><name sortKey="Guilloux, Jean Philippe" sort="Guilloux, Jean Philippe" uniqKey="Guilloux J" first="Jean-Philippe" last="Guilloux">Jean-Philippe Guilloux</name></noRegion></country><country name="États-Unis"><noRegion><name sortKey="Guilloux, Jean Philippe" sort="Guilloux, Jean Philippe" uniqKey="Guilloux J" first="Jean-Philippe" last="Guilloux">Jean-Philippe Guilloux</name></noRegion><name sortKey="Bassi, Sabrina" sort="Bassi, Sabrina" uniqKey="Bassi S" first="Sabrina" last="Bassi">Sabrina Bassi</name><name sortKey="Cyranowski, Jill M" sort="Cyranowski, Jill M" uniqKey="Cyranowski J" first="Jill M" last="Cyranowski">Jill M. Cyranowski</name><name sortKey="Ding, Ying" sort="Ding, Ying" uniqKey="Ding Y" first="Ying" last="Ding">Ying Ding</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="Tseng, George" sort="Tseng, George" uniqKey="Tseng G" first="George" last="Tseng">George Tseng</name><name sortKey="Tseng, George" sort="Tseng, George" uniqKey="Tseng G" first="George" last="Tseng">George Tseng</name><name sortKey="Walsh, Chris" sort="Walsh, Chris" uniqKey="Walsh C" first="Chris" last="Walsh">Chris Walsh</name></country><country name="Argentine"><noRegion><name sortKey="Bassi, Sabrina" sort="Bassi, Sabrina" uniqKey="Bassi S" first="Sabrina" last="Bassi">Sabrina Bassi</name></noRegion></country><country name="Canada"><noRegion><name sortKey="Turecki, Gustavo" sort="Turecki, Gustavo" uniqKey="Turecki G" first="Gustavo" last="Turecki">Gustavo Turecki</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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