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Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans.

ABSTRACT: Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively. Proteomics and metabolomics profiles of PLF and PSF groups were acquired for the hippocampus and plasma to identify molecular pathways and biosignatures that stratify paroxetine-treated mouse sub-groups. The critical role of purine and pyrimidine metabolisms for chronic paroxetine treatment response in the mouse was further corroborated by pathway protein expression differences in both mice and patients that underwent chronic antidepressant treatment. The integrated -omics data indicate purine and pyrimidine metabolism pathway activity differences between PLF and PSF mice. Furthermore, the pathway protein levels in peripheral specimens strongly correlated with the antidepressant treatment response in patients. Our results suggest that chronic SSRI treatment differentially affects purine and pyrimidine metabolisms, which may explain the heterogeneous antidepressant treatment response and represents a potential biosignature.

SUBMITTER: Park DI

PROVIDER: S-EPMC5059694 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans.

Park Dong Ik DI Dournes Carine C Sillaber Inge I Uhr Manfred M Asara John M JM Gassen Nils C NC Rein Theo T Ising Marcus M Webhofer Christian C Filiou Michaela D MD Müller Marianne B MB Turck Christoph W CW

Scientific reports 20161012

Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were st ...[more]

PMID: 27731396

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Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans.

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Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans.

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