A molecular pathway analysis of the glutamatergic-monoaminergic interplay serves to investigate the number of depressive records during citalopram treatment

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A molecular pathway analysis of the glutamatergic-monoaminergic interplay serves to investigate the number of depressive records during citalopram treatment. / Drago, Antonio; Cocchi, Enrico; Crisafulli, Concetta; Serretti, Alessandro.

I: Journal of neural transmission (Vienna, Austria : 1996), Bind 122, Nr. 3, 03.2015, s. 465-75.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Drago, A, Cocchi, E, Crisafulli, C & Serretti, A 2015, 'A molecular pathway analysis of the glutamatergic-monoaminergic interplay serves to investigate the number of depressive records during citalopram treatment', Journal of neural transmission (Vienna, Austria : 1996), bind 122, nr. 3, s. 465-75. https://doi.org/10.1007/s00702-014-1267-2

APA

Drago, A., Cocchi, E., Crisafulli, C., & Serretti, A. (2015). A molecular pathway analysis of the glutamatergic-monoaminergic interplay serves to investigate the number of depressive records during citalopram treatment. Journal of neural transmission (Vienna, Austria : 1996), 122(3), 465-75. https://doi.org/10.1007/s00702-014-1267-2

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MLA

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Author

Drago, Antonio ; Cocchi, Enrico ; Crisafulli, Concetta ; Serretti, Alessandro. / A molecular pathway analysis of the glutamatergic-monoaminergic interplay serves to investigate the number of depressive records during citalopram treatment. I: Journal of neural transmission (Vienna, Austria : 1996). 2015 ; Bind 122, Nr. 3. s. 465-75.

Bibtex

@article{99e7e24036b94fed9a02a880b0155fd6,
title = "A molecular pathway analysis of the glutamatergic-monoaminergic interplay serves to investigate the number of depressive records during citalopram treatment",
abstract = "The efficacy of current antidepressant (AD) drugs for the treatment of major depressive disorder (MDD) lays behind expectations. The correct genetic differentiation between severe and less severe cases before treatment may pave the way to the most correct clinical choices in clinical practice. Genetics may pave the way such identification, which in turns may provide perspectives for the synthesis of new ADs by correcting the molecular unbalances that differentiate severe and less severe depressive patients. We investigated 1,903 MDD patients from the STAR*D study. Outcome was the number of severe depressive records, defined as a Quick Inventory of Depressive Symptomatology (QIDS)-Clinician rated (C) total score >15, corrected for the number of observations for each patient during the first 14 weeks of citalopram treatment. Predictors were the genetic variations harbored by genes involved in the glutamatergic-monoaminergic interplay as defined in a previous work published by our group. Clinical and socio-demographic stratification factor analyses were taken in cases and controls. Covariated linear regression was the statistical model for the analysis. SNPs were analyzed in groups (molecular pathway analysis) testing the hypothesis that the distribution of significant (p < 0.05) associations between SNPs and the outcome segregates within each pathway/gene subset. The best associated results are relative to two signle SNPs, (rs7744492 in AKAP12 p = 0.0004 and rs17046113 in CAMK2D p = 0.0006) and a molecular pathway (cAMP biosynthetic process p = 0.005). After correction for multitesting, none of them resulted to be significantly associated. These results are consistent with previous findings in literature and further stress that the molecular mechanisms targeted by current ADs may not be the key biological variables that differentiate severe from mild depression.",
keywords = "A Kinase Anchor Proteins, Adolescent, Adult, Aged, Antidepressive Agents, Second-Generation, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Cell Cycle Proteins, Citalopram, Cyclic AMP, Depressive Disorder, Major, Female, Genetic Association Studies, Humans, Linear Models, Male, Middle Aged, Pharmacogenetics, Polymorphism, Single Nucleotide, Psychiatric Status Rating Scales, Young Adult",
author = "Antonio Drago and Enrico Cocchi and Concetta Crisafulli and Alessandro Serretti",
year = "2015",
month = mar,
doi = "10.1007/s00702-014-1267-2",
language = "English",
volume = "122",
pages = "465--75",
journal = "Journal of Neural Transmission",
issn = "0300-9564",
publisher = "Springer Wien",
number = "3",

}

RIS

TY - JOUR

T1 - A molecular pathway analysis of the glutamatergic-monoaminergic interplay serves to investigate the number of depressive records during citalopram treatment

AU - Drago, Antonio

AU - Cocchi, Enrico

AU - Crisafulli, Concetta

AU - Serretti, Alessandro

PY - 2015/3

Y1 - 2015/3

N2 - The efficacy of current antidepressant (AD) drugs for the treatment of major depressive disorder (MDD) lays behind expectations. The correct genetic differentiation between severe and less severe cases before treatment may pave the way to the most correct clinical choices in clinical practice. Genetics may pave the way such identification, which in turns may provide perspectives for the synthesis of new ADs by correcting the molecular unbalances that differentiate severe and less severe depressive patients. We investigated 1,903 MDD patients from the STAR*D study. Outcome was the number of severe depressive records, defined as a Quick Inventory of Depressive Symptomatology (QIDS)-Clinician rated (C) total score >15, corrected for the number of observations for each patient during the first 14 weeks of citalopram treatment. Predictors were the genetic variations harbored by genes involved in the glutamatergic-monoaminergic interplay as defined in a previous work published by our group. Clinical and socio-demographic stratification factor analyses were taken in cases and controls. Covariated linear regression was the statistical model for the analysis. SNPs were analyzed in groups (molecular pathway analysis) testing the hypothesis that the distribution of significant (p < 0.05) associations between SNPs and the outcome segregates within each pathway/gene subset. The best associated results are relative to two signle SNPs, (rs7744492 in AKAP12 p = 0.0004 and rs17046113 in CAMK2D p = 0.0006) and a molecular pathway (cAMP biosynthetic process p = 0.005). After correction for multitesting, none of them resulted to be significantly associated. These results are consistent with previous findings in literature and further stress that the molecular mechanisms targeted by current ADs may not be the key biological variables that differentiate severe from mild depression.

AB - The efficacy of current antidepressant (AD) drugs for the treatment of major depressive disorder (MDD) lays behind expectations. The correct genetic differentiation between severe and less severe cases before treatment may pave the way to the most correct clinical choices in clinical practice. Genetics may pave the way such identification, which in turns may provide perspectives for the synthesis of new ADs by correcting the molecular unbalances that differentiate severe and less severe depressive patients. We investigated 1,903 MDD patients from the STAR*D study. Outcome was the number of severe depressive records, defined as a Quick Inventory of Depressive Symptomatology (QIDS)-Clinician rated (C) total score >15, corrected for the number of observations for each patient during the first 14 weeks of citalopram treatment. Predictors were the genetic variations harbored by genes involved in the glutamatergic-monoaminergic interplay as defined in a previous work published by our group. Clinical and socio-demographic stratification factor analyses were taken in cases and controls. Covariated linear regression was the statistical model for the analysis. SNPs were analyzed in groups (molecular pathway analysis) testing the hypothesis that the distribution of significant (p < 0.05) associations between SNPs and the outcome segregates within each pathway/gene subset. The best associated results are relative to two signle SNPs, (rs7744492 in AKAP12 p = 0.0004 and rs17046113 in CAMK2D p = 0.0006) and a molecular pathway (cAMP biosynthetic process p = 0.005). After correction for multitesting, none of them resulted to be significantly associated. These results are consistent with previous findings in literature and further stress that the molecular mechanisms targeted by current ADs may not be the key biological variables that differentiate severe from mild depression.

KW - A Kinase Anchor Proteins

KW - Adolescent

KW - Adult

KW - Aged

KW - Antidepressive Agents, Second-Generation

KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2

KW - Cell Cycle Proteins

KW - Citalopram

KW - Cyclic AMP

KW - Depressive Disorder, Major

KW - Female

KW - Genetic Association Studies

KW - Humans

KW - Linear Models

KW - Male

KW - Middle Aged

KW - Pharmacogenetics

KW - Polymorphism, Single Nucleotide

KW - Psychiatric Status Rating Scales

KW - Young Adult

U2 - 10.1007/s00702-014-1267-2

DO - 10.1007/s00702-014-1267-2

M3 - Journal article

C2 - 24986638

VL - 122

SP - 465

EP - 475

JO - Journal of Neural Transmission

JF - Journal of Neural Transmission

SN - 0300-9564

IS - 3

ER -