Population pharmacokinetic analysis of lanicemine (AZD6765), an NMDA channel blocker, in healthy subjects and patients with major depressive disorder

IntroductionAccelerated aging is associated with major depressive disorder (MDD) and studies of yoga and meditation based lifestyle intervention (YMLI) on biomarkers of cellular aging are lacking.Aim and objectivesTo investigate the peripheral blood biomarkers of cellular aging in MDD patients after short term YMLI. Biomarkers include DNA damage, oxidative stress (OS), telomere attrition, and nutrition sensing assessed respectively by 8-hydroxy 2’- deoxyguanosine (8-OHdG); reactive oxygen species (ROS) and total antioxidant capacity (TAC); telomere length and telomerase activity; and sirtuin-1.MethodsWe consecutively enrolled 33 MDD patients and 40 healthy subjects; 30 MDD patients were followed up with 12- week YMLI. Biomarkers of cellular aging in peripheral blood were measured with assay kits. All patients were evaluated by examining the correlation between cellular aging markers and Montgomery–Asberg Depression Rating Scale (MADRS) scores.ResultsThe levels of DNA damage, OS, and telomere attrition in MDD patients were significantly higher than healthy subjects (all P = 0.005). The MADRS scores had a significantly positive association with 8-OHdG and ROS levels and negative association with TAC, telomerase and sirtuin-1 levels (all P < 0.01).ConclusionsPeripheral blood biomarker levels in our results suggest significant cellular aging in MDD patients compared to healthy subjects. There was strong correlation between the changes in biomarkers of cellular aging and clinical improvement in MDD. Our study is the first to show significant increase in sirtuin-1 levels in MDD patients after yoga and meditation. Therefore, biomarkers of cellular aging might be indicators of MDD severity and clinical remission after YMLI.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Significantly lower nerve growth factor levels in patients with major depressive disorder than in healthy subjects: a meta-analysis and systematic review

Neuropsychiatric Disease and Treatment ◽

10.2147/ndt.s81432 ◽

2015 ◽

pp. 925 ◽

Cited By ~ 4

Author(s):

Ping-Tao Tseng ◽

Pao-Yen Lin ◽

Kun-Yu Tu ◽

Yu-Shian Cheng ◽

Ching-Kuan Wu ◽

...

Keyword(s):

Systematic Review ◽

Major Depressive Disorder ◽

Nerve Growth Factor ◽

Growth Factor ◽

Depressive Disorder ◽

Healthy Subjects ◽

Meta Analysis ◽

Major Depressive ◽

Nerve Growth

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Population Pharmacokinetic Analysis of Apomorphine Sublingual Film and Subcutaneous Apomorphine in Healthy Subjects and Patients With Parkinson’s Disease

Clinical and Translational Science ◽

10.1111/cts.13008 ◽

2021 ◽

Author(s):

Felix Agbo ◽

Ryan L. Crass ◽

Yu‐Yuan Chiu ◽

Sunny Chapel ◽

Gerald Galluppi ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Healthy Subjects ◽

Population Pharmacokinetic Analysis ◽

Pharmacokinetic Analysis ◽

Population Pharmacokinetic ◽

Subcutaneous Apomorphine

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Voxel-based morphometric brain comparison between healthy subjects and major depressive disorder patients in Japanese with the s/s genotype of 5-HTTLPR

Scientific Reports ◽

10.1038/s41598-017-04347-8 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 8

Author(s):

Natsuki Igata ◽

Shingo Kakeda ◽

Keita Watanabe ◽

Satoru Ide ◽

Taro Kishi ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Healthy Subjects ◽

Major Depressive

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Identification of major depressive disorder disease-related genes and functional pathways based on system dynamic changes of network connectivity

10.21203/rs.2.16893/v2 ◽

2020 ◽

Author(s):

Ruijie Geng ◽

Xiao Huang

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Pathway Analysis ◽

Healthy Subjects ◽

Kegg Pathway ◽

Network Connectivity ◽

Differentially Expressed ◽

Therapeutic Drug ◽

Major Depressive ◽

Kegg Pathway Analysis

Abstract Objective: Major depressive disorder (MDD) is a leading psychiatric disorder that involves complex abnormal biological functions and neural networks. This study aimed to compare the changes in the network connectivity of different brain tissues under different pathological conditions, analyzed the biological pathways and genes that are significantly related to disease progression, and further predicted the potential therapeutic drug targets.Methods: Expression of differentially expressed genes (DEGs) were analyzed with postmortem cingulate cortex (ACC) and prefrontal cortex (PFC) mRNA expression profile datasets downloaded from the Gene Expression Omnibus (GEO) database, including 76 MDD patients and 76 healthy subjects in ACC and 63 MDD patients and 63 healthy subjects in PFC. The co-expression network construction was based on system network analysis. The function of the genes was annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Human Protein Reference Database (HPRD, http://www.hprd.org/) was used for gene interaction relationship mapping.Results: We filtered 586 DEGs in ACC and 616 DEGs in PFC for further analysis. By constructing the Co-expression network, we found that the gene connectivity was significantly reduced under disease conditions (P=0.04 in PFC and P=1.227e-09 in ACC). Crosstalk analysis showed that CD19, PTDSS2 and NDST2 were significantly differentially expressed in ACC and PFC of MDD patients. Among them, CD19 and PTDSS2 have been targeted by several drugs in the Drugbank database. KEGG pathway analysis demonstrated that the function of CD19 and PTDSS2 were enriched with the pathway of Glycerophospholipid metabolism and T cell receptor signaling pathway. Conclusion: Co-expression network and tissue comparing analysis can identify signaling pathways and cross talk genes related to MDD, which may provide novel insight for understanding the molecular mechanisms of MDD.

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