Dataset Information

Polymorphisms in melatonin synthesis pathways: possible influences on depression.

ABSTRACT: BACKGROUND:It has been reported that rs4446909, a single nucleotide polymorphism (SNP) in the promoter of acetylserotonin methyltransferase (ASMT), influences the expression of the ASMT enzyme. The common G allele is associated with lower ASMT activity, and therefore, diminishes conversion of N-acetylserotonin to melatonin. The G allele was associated with recurrent depressive disorder in a Polish group. ASMT might also affect bipolar relapse, given evidence that N-acetylserotonin might stimulate TRKB receptors, and TRKB may influence mood relapse in bipolar disorder. Additionally, arylalkylamine N-acetyltransferase (AANAT) polymorphisms have been reported associated with depression, perhaps through their influence upon N-acetylserotonin or melatonin synthesis. RESULTS:To replicate and further explore these ideas, rs4446909 was genotyped in four research groups, as part of a panel of 610 SNPs surveyed by an Illumina Golden Gate assay. In 768 cases with delayed sleep phase disorder or matched controls, rs4446909 was indeed associated with the depressive symptoms on a self-report scale (P = 0.01, R2 = 0.007). However, there was no significant association of rs4446909 with self-reported depression in a sleep clinic patient group or with two groups of elderly men and women from multicenter studies, nor was the response to lithium treatment associated with rs4446909 in bipolar patients. No associations of two AANAT SNPs with depression were found. CONCLUSIONS:The evidence did not support a strong influence of rs4446909 upon mood, but the partial replication may be consistent with a modest effect. It is possible that larger or younger subject groups with improved phenotype ascertainment might demonstrate more persuasive replication.

SUBMITTER: Kripke DF

PROVIDER: S-EPMC3177871 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Polymorphisms in melatonin synthesis pathways: possible influences on depression.

Kripke Daniel F DF Nievergelt Caroline M CM Tranah Greg J GJ Murray Sarah S SS McCarthy Michael J MJ Rex Katharine M KM Parimi Neeta N Kelsoe John R JR

Journal of circadian rhythms 20110809

<h4>Background</h4>It has been reported that rs4446909, a single nucleotide polymorphism (SNP) in the promoter of acetylserotonin methyltransferase (ASMT), influences the expression of the ASMT enzyme. The common G allele is associated with lower ASMT activity, and therefore, diminishes conversion of N-acetylserotonin to melatonin. The G allele was associated with recurrent depressive disorder in a Polish group. ASMT might also affect bipolar relapse, given evidence that N-acetylserotonin might ...[more]

PMID: 21827647

Similar Datasets

Project description:Intervention 1: Intervention group: Treatment with melatonin will be started on the evening of the first chemotherapy dose and continue through 1 month following the last dose of chemotherapy or 6 months after starting melatonin (each one goes earlier). During this period, patients will consume 20 mg of melatonin (4 capsules, each one contains 5mg melatonin) every evening. Melatonin capsule will be supplied by Zahravi Pharmaceutical Company. Intervention 2: Control group: Treatment with melatonin will be started on the evening of the first chemotherapy dose and continue through 1 month following the last dose of chemotherapy or 6 months after starting melatonin/placebo (each one goes earlier). During this period, patients will consume 4 capsules of placebo every evening. Placebo capsules will be supplied by Zahravi Pharmaceutical Company and will be the same as melatonin. Primary outcome(s): Percent of grade 2 and 3 neuropathy according to National Cancer Institute’s Common Toxicity Criteria for adverse events (NCI-CTCAE V.4) will be compered among the two study groups (case and control), as the main outcome of the study. Timepoint: Prior to the start of study; during the chemotherapy (prior to receiving each cycle); 1 month after receiving the last dose of chemotherapy or 6 months after initiation of melatonin (each one happens earlier). Method of measurement: National Cancer Institute’s Common Toxicity Criteria for adverse events (NCI-CTCAE V.4) scale will be used by the oncologist to evaluate severity of neuropathy in the patients. According to this scale severity of neuropathy will be classified from 1 to 5. Study Design: Randomization: Randomized, Blinding: Double blinded, Placebo: Used, Assignment: Parallel, Purpose: Prevention, Randomization description: Randomization will be done by block-permutation method, considering 8 blocks, each one consisting 10 patients. Random Allocation software will be used to allocate patients to drug or placebo group. Randomization and allocation will be done by one of the researchers who has no role in the treatment and evaluation of the patients, and also analysis of data, Blinding description: Randomization and allocation will be done by one of the researchers who has no role in the treatment and evaluation of the patients, and also analysis of data. Drug (melatonin) and placebo packaging will be similar and will not be distinguishable by physician and patients who receive them. During the study, melatonin and placebo will be supplied by the same company.

Dataset Information

Polymorphisms in melatonin synthesis pathways: possible influences on depression.

Publications

Polymorphisms in melatonin synthesis pathways: possible influences on depression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets