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An Exploratory Pilot Study with Plasma Protein Signatures Associated with Response of Patients with Depression to Antidepressant Treatment for 10 Weeks.

ABSTRACT: Major depressive disorder (MDD) is a leading cause of global disability with a chronic and recurrent course. Recognition of biological markers that could predict and monitor response to drug treatment could personalize clinical decision-making, minimize unnecessary drug exposure, and achieve better outcomes. Four longitudinal plasma samples were collected from each of ten patients with MDD treated with antidepressants for 10 weeks. Plasma proteins were analyzed qualitatively and quantitatively with a nanoflow LC-MS/MS technique. Of 1153 proteins identified in the 40 longitudinal plasma samples, 37 proteins were significantly associated with response/time and clustered into six according to time and response by the linear mixed model. Among them, three early-drug response markers (PHOX2B, SH3BGRL3, and YWHAE) detectable within one week were verified by liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS) in the well-controlled 24 patients. In addition, 11 proteins correlated significantly with two or more psychiatric measurement indices. This pilot study might be useful in finding protein marker candidates that can monitor response to antidepressant treatment during follow-up visits within 10 weeks after the baseline visit.

SUBMITTER: Kim EY

PROVIDER: S-EPMC7692261 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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An Exploratory Pilot Study with Plasma Protein Signatures Associated with Response of Patients with Depression to Antidepressant Treatment for 10 Weeks.

Kim Eun Young EY Ahn Hee-Sung HS Lee Min Young MY Yu Jiyoung J Yeom Jeonghun J Jeong Hwangkyo H Min Hophil H Lee Hyun Jeong HJ Kim Kyunggon K Ahn Yong Min YM

Biomedicines 20201028 11

Major depressive disorder (MDD) is a leading cause of global disability with a chronic and recurrent course. Recognition of biological markers that could predict and monitor response to drug treatment could personalize clinical decision-making, minimize unnecessary drug exposure, and achieve better outcomes. Four longitudinal plasma samples were collected from each of ten patients with MDD treated with antidepressants for 10 weeks. Plasma proteins were analyzed qualitatively and quantitatively w ...[more]

PMID: 33126421

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Project description:The "antidepressant efficacy" survey (AES) was deployed to > 50,000 23andMe, Inc. research participants to investigate the genetic basis of treatment-resistant depression (TRD) and non-treatment-resistant depression (NTRD). Genome-wide association studies (GWAS) were performed, including TRD vs. NTRD, selective serotonin reuptake inhibitor (SSRI) responders vs. non-responders, serotonin-norepinephrine reuptake inhibitor (SNRI) responders vs. non-responders, and norepinephrine-dopamine reuptake inhibitor responders vs. non-responders. Only the SSRI association reached the genome-wide significance threshold (p < 5 × 10-8): one genomic region in RNF219-AS1 (SNP rs4884091, p = 2.42 × 10-8, OR = 1.21); this association was also observed in the meta-analysis (13,130 responders vs. 6,610 non-responders) of AES and an earlier "antidepressant efficacy and side effects" survey (AESES) cohort. Meta-analysis for SNRI response phenotype derived from AES and AESES (4030 responders vs. 3049 non-responders) identified another genomic region (lead SNP rs4955665, p = 1.62 × 10-9, OR = 1.25) in an intronic region of MECOM passing the genome-wide significance threshold. Meta-analysis for the TRD phenotype (31,068 NTRD vs 5,714 TRD) identified one additional genomic region (lead SNP rs150245813, p = 8.07 × 10-9, OR = 0.80) in 10p11.1 passing the genome-wide significance threshold. A stronger association for rs150245813 was observed in current study (p = 7.35 × 10-7, OR = 0.79) than the previous study (p = 1.40 × 10-3, OR = 0.81), and for rs4955665, a stronger association in previous study (p = 1.21 × 10-6, OR = 1.27) than the current study (p = 2.64 × 10-4, OR = 1.21). In total, three novel loci associated with SSRI or SNRI (responders vs. non-responders), and NTRD vs TRD were identified; gene level association and gene set enrichment analyses implicate enrichment of genes involved in immune process.

Dataset Information

An Exploratory Pilot Study with Plasma Protein Signatures Associated with Response of Patients with Depression to Antidepressant Treatment for 10 Weeks.

Publications

An Exploratory Pilot Study with Plasma Protein Signatures Associated with Response of Patients with Depression to Antidepressant Treatment for 10 Weeks.

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