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Associations of depression status with plasma levels of candidate lipid and amino acid metabolites: a meta-analysis of individual data from three independent samples of US postmenopausal women.

ABSTRACT: Recent animal and small clinical studies have suggested depression is related to altered lipid and amino acid profiles. However, this has not been examined in a population-based sample, particularly in women. We identified multiple metabolites associated with depression as potential candidates from prior studies. Cross-sectional data from three independent samples of postmenopausal women were analyzed, including women from the Women's Health Initiative-Observational Study (WHI-OS, n = 926), the WHI-Hormone Trials (WHI-HT; n = 1,325), and the Nurses' Health Study II Mind-Body Study (NHSII-MBS; n = 218). Positive depression status was defined as having any of the following: elevated depressive symptoms, antidepressant use, or depression history. Plasma metabolites were measured using liquid chromatography-tandem mass spectrometry (21 phosphatidylcholines (PCs), 7 lysophosphatidylethanolamines, 5 ceramides, 3 branched chain amino acids, and 9 neurotransmitters). Associations between depression status and metabolites were evaluated using multivariable linear regression; results were pooled by random-effects meta-analysis with multiple testing adjustment using the false discovery rate (FDR). Prevalence rates of positive depression status were 24.4% (WHI-OS), 25.7% (WHI-HT), and 44.7% (NHSII-MBS). After multivariable adjustment, positive depression status was associated with higher levels of glutamate and PC 36 : 1/38 : 3, and lower levels of tryptophan and GABA-to-glutamate and GABA-to-glutamine ratio (FDR-p < 0.05). Positive associations with LPE 18 : 0/18 : 1 and inverse associations with valine and serotonin were also observed, although these associations did not survive FDR adjustment. Associations of positive depression status with several candidate metabolites including PC 36 : 1/38 : 3 and amino acids involved in neurotransmission suggest potential depression-related metabolic alterations in postmenopausal women, with possible implications for later chronic disease.

SUBMITTER: Huang T

PROVIDER: S-EPMC7914294 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCholine plays an integral role in one-carbon metabolism in the body, but it is unclear whether genetic polymorphisms are associated with variations in plasma choline and its metabolites.ObjectivesThis study aimed to evaluate the association of genetic variants in choline and one-carbon metabolism with plasma choline and its metabolites.MethodsWe analyzed data from 1423 postmenopausal women in a case-control study nested within the Women's Health Initiative Observational Study. Plasma concentrations of choline, betaine, dimethylglycine (DMG), and trimethylamine N-oxide were determined in 12-h fasting blood samples collected at baseline (1993-1998). Candidate and tagging single-nucleotide polymorphisms (SNPs) were genotyped in betaine-homocysteine S-methyltransferase (BHMT), BHMT2, 5,10-methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate dehydrogenase (NADP+ dependent 1) (MTHFD1), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR). Linear regression was used to derive percentage difference in plasma concentrations per variant allele, adjusting for confounders, including B-vitamin biomarkers. Potential effect modification by plasma vitamin B-12, vitamin B-6, and folate concentrations and folic-acid fortification periods was examined.ResultsThe candidate SNP BHMT R239Q (rs3733890) was associated with lower concentrations of plasma betaine and DMG concentrations (-4.00% and -6.75% per variant allele, respectively; both nominal P < 0.05). Another candidate SNP, BHMT2 rs626105 A>G, was associated with higher plasma DMG concentration (13.0%; P < 0.0001). Several tagSNPs in these 2 genes were associated with plasma concentrations after correction for multiple comparisons. Vitamin B-12 status was a significant effect modifier of the association between the genetic variant BHMT2 rs626105 A>G and plasma DMG concentration.ConclusionsGenetic variations in metabolic enzymes were associated with plasma concentrations of choline and its metabolites. Our findings contribute to the knowledge on the variation in blood nutrient concentrations in postmenopausal women.

Project description:ImportanceDuring the past decade, cannabis use among US adults has increased markedly, with a parallel increase in suicidality (ideation, plan, attempt, and death). However, associations between cannabis use and suicidality among young adults are poorly understood.ObjectiveTo determine whether cannabis use and cannabis use disorder (CUD) are associated with a higher prevalence of suicidality among young adults with or without depression and to assess whether these associations vary by sex.Design, setting, and participantsThis survey study examined data from 281 650 adults aged 18 to 34 years who participated in the National Surveys on Drug Use and Health. Data were collected from January 1, 2008, to December 31, 2019.ExposuresPrevalence of past-year daily or near-daily cannabis use (≥300 days in the past year), CUD, and major depressive episode (MDE). Past-year CUD and MDE were based on DSM-IV diagnostic criteria.Main outcomes and measuresPast-year suicidal ideation, plan, and attempt.ResultsAmong the 281 650 adults aged 18 to 34 (men, 49.9% [95% CI, 49.6%-50.2%]; women, 50.1% [95% CI, 49.8%-50.4%]) included in the analysis, past-year suicidal ideation and plan along with daily cannabis use increased among all examined sociodemographic subgroups (except daily cannabis use among current high-school students), and past-year suicide attempt increased among most subgroups. National trends in adjusted prevalence of past-year suicidal ideation, plan, and attempt varied by daily and nondaily cannabis use and CUD among adults with or without MDE. After controlling for MDE, CUD, cannabis use status, and potential confounding factors, the adjusted prevalence of suicidal ideation, plan, and attempt increased 1.4 to 1.6 times from the 2008-2009 to 2018-2019 periods (adjusted risk ratio [ARR] for suicidal ideation, 1.4 [95% CI, 1.3-1.5]; ARR for suicide plan, 1.6 [95% CI, 1.5-1.9]; ARR for suicide attempt, 1.4 [95% CI, 1.2-1.7]), with 2008 to 2009 as the reference period. Past-year CUD, daily cannabis use, and nondaily cannabis use were associated with a higher prevalence of past-year suicidal ideation, plan, and attempt in both sexes (eg, among individuals without MDE, prevalence of suicidal ideation for those with vs without CUD was 13.9% vs 3.5% among women and 9.9% vs 3.0% among men; P < .001), but significantly more so in women than men (eg, suicide plan among those with CUD and MDE was 52% higher for women [23.7%] than men [15.6%]; P < .001).Conclusions and relevanceFrom 2008 to 2019, suicidal ideation, plan, and attempt increased 40% to 60% over increases ascribed to cannabis use and MDE. Future research is needed to examine this increase in suicidality and to determine whether it is due to cannabis use or overlapping risk factors.

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Associations of depression status with plasma levels of candidate lipid and amino acid metabolites: a meta-analysis of individual data from three independent samples of US postmenopausal women.

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