Plasma lipidomic profile of depressive symptoms: a longitudinal study in a large sample of community-dwelling American Indians in the strong heart study

Miao, Guanhong; Deen, Jason F.; Struzeski, Joseph B.; Chen, Mingjing; Zhang, Ying; Cole, Shelley A.; Fretts, Amanda M.; Lee, Elisa T.; Howard, Barbara V.; Fiehn, Oliver; Zhao, Jinying

doi:10.1038/s41380-023-01948-w

Cited by 12 publications

(9 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggest that the vinylether bond is critical for relieving anxiety when AA is bound to sn-2. Our hypothesis is supported by previous studies demonstrating that plasma levels of ether-linked PC are inversely correlated with melancholia and depression in humans [8,30], and that cytidine diphosphate-choline supplementation in a mouse model of inflammatory bowel disease improves anxiety-like behaviors and reduces PC degradation in the prefrontal cortex, possibly through restoring gut microbiome imbalances and lipid metabolism disruptions in the brain [31]. Although it has been reported that free AA in plasma inversely correlates with anxious distress dimension scores [8], diacyl and plasmanyl PC with AA did not affect anxiety behaviors in the present The anxiolytic effect of PC(P-18:0/20:4) may therefore not be attributable to the function of free AA.…”

Section: Phospholipid Moieties Reduce Anxiety-like Behaviorssupporting

confidence: 89%

Solitary and Synergistic Effects of Different Hydrophilic and Hydrophobic Phospholipid Moieties on Rat Behaviors

Kikuchi,

Iwasaki,

Yoshioka

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

Glycerophospholipids have hydrophobic and hydrophilic moieties. Previous studies suggest that phospholipids with different moieties have different effects on rodent behavior; however, the relationship between chemical structures and behavioral effects remains unclear. To clarify the functions of phospholipid moieties, we injected male rats with phospholipids with different moieties and conducted behavioral tests. Exploratory activity was reduced by phosphatidylethanolamine (PE)(18:0/22:6) but not PE(18:0/18:0) or PE(18:0/20:4). Conversely, exploratory activity was increased by plasmanyl PE(16:0/22:6), which harbors an alkyl–ether linkage, but not by phosphatidylcholine (PC)(16:0/22:6) or plasmanyl PC(16:0/22:6). Docosahexaenoic acid (DHA)(22:6) and an alkyl–ether linkage in PE were thus postulated to be involved in exploratory activity. Anxiety-like behavior was reduced by plasmenyl PC(18:0/20:4), which harbors a vinyl–ether linkage, but not by PC(18:0/20:4) or plasmanyl PC(18:0/20:4), suggesting the anxiolytic effects of vinyl–ether linkage. The activation of social interaction was suppressed by PE(18:0/18:0), PE(18:0/22:6), PC(16:0/22:6), plasmanyl PE(16:0/22:6), and plasmanyl PC(16:0/22:6) but not by PE(18:0/20:4), plasmenyl PE(18:0/20:4), or plasmanyl PC(18:0/22:6). DHA may suppress social interaction, whereas arachidonic acid(20:4) or a combination of alkyl–ether linkage and stearic acid(18:0) may restore social deficits. Our findings indicate the characteristic effects of different phospholipid moieties on rat behavior, and may help to elucidate patterns between chemical structures and their effects.

show abstract

Section: Phospholipid Moieties Reduce Anxiety-like Behaviorssupporting

confidence: 89%

Solitary and Synergistic Effects of Different Hydrophilic and Hydrophobic Phospholipid Moieties on Rat Behaviors

Kikuchi,

Iwasaki,

Yoshioka

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…These findings corroborate previous studies demonstrating that some PCs and PEs, such as, PC(32:0), PC(16:0/22:5), PC(14:0/22:6), PE(o‐36:4), and PE(38:2), were associated with CVD in other racial and ethnic groups. 5 , 6 , 8 , 23 In addition, some PCs and PEs (eg, PC(36:1), PC(38:3), PC(36:3) A, and PE(16:0/22:5)) identified in the present study were also associated with risks of diabetes, 19 chronic kidney disease, 24 depressive symptoms, 25 or all‐cause mortality 26 in our previous studies of the same group of American Indian participants. Moreover, these results support previous studies showing that altered levels of PCs in either plasma or atherosclerotic plaque tissues were associated with coronary atherosclerosis.…”

Section: Discussionsupporting

confidence: 52%

“… 33 Perturbed ACs have been associated with a wide range of metabolic disorders including CVD, 34 diabetes, 35 and depressive symptoms. 25 …”

Section: Discussionmentioning

confidence: 99%

Longitudinal Lipidomic Signature of Coronary Heart Disease in American Indian People

Miao,

Pechlaner,

Fiehn

et al. 2024

JAHA

Self Cite

View full text Add to dashboard Cite

Background Dyslipidemia is an independent risk factor for coronary heart disease (CHD). Standard lipid panel cannot capture the complexity of the blood lipidome (ie, all molecular lipids in the blood). To date, very few large‐scale epidemiological studies have assessed the full spectrum of the blood lipidome on risk of CHD, especially in a longitudinal setting. Methods and Results Using an untargeted liquid chromatography–mass spectrometry, we repeatedly measured 1542 lipid species from 1835 unique American Indian participants who attended 2 clinical visits (≈5.5 years apart) and followed up to 17.8 years in the Strong Heart Family Study (SHFS). We first identified baseline lipid species associated with risk of CHD, followed by replication in a European population. The model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, low‐density lipoprotein cholesterol, estimated glomerular filtration rate, education, and physical activity at baseline. We then examined the longitudinal association between changes in lipid species and changes in cardiovascular risk factors during follow‐up. Multiple testing was controlled by the false discovery rate. We found that baseline levels of multiple lipid species (eg, phosphatidylcholines, phosphatidylethanolamines, and ceramides) were associated with the risk of CHD and improved the prediction accuracy over conventional risk factors in American Indian people. Some identified lipids in American Indian people were replicated in European people. Longitudinal changes in multiple lipid species (eg, acylcarnitines, phosphatidylcholines, and triacylglycerols) were associated with changes in cardiovascular risk factors. Conclusions Baseline plasma lipids and their longitudinal changes over time are associated with risk of CHD. These findings provide novel insights into the role of dyslipidemia in CHD.

show abstract

“…Currently, the primary clinical use of the PPARA agonists is for dyslipidemia 77 and interestingly peripheral lipid alterations are commonly observed in MDD 78–80 . The FADS locus (includes FADS1, FADS2 and FADS3 ) is the most pleiotropic regulator of peripheral metabolite levels, with significant genetic associations for 79 metabolites, including 75 lipid species 25 .…”

Section: Discussionmentioning

confidence: 99%

Mechanistic convergence of depression and suicidality on astrocyte fatty acid metabolism

Fitzgerald

O’Toole

Pokhvisneva

et al. 2023

Preprint

View full text Add to dashboard Cite

Genome-wide association studies (GWAS) show conceptual promise to identify novel mechanisms of major depressive disorder (MDD), but have not yet achieved this potential. One explanation is that MDD risk acts through complex expression networks, and GWAS-identified genes represent important components of these networks but in isolation are insufficient for their functional annotation. In this study, we aimed to identify and characterize the expression networks through which GWAS-identified MDD risk genes operate. We generated and characterized seeded co-expression networks of 252 MDD risk genes over 11 brain regions. We used principal component regression and Mendelian randomization to identify a relation between the networks of two such genes (FADS1 and ZKSCAN8) and suicidal ideation. These networks were primarily expressed in astrocytes, enriched for functions related to fatty acid metabolism, and could define MDD-altered astrocyte states. We then identified FGFR3 to EPHA4 signaling as a putative downstream effector of these astrocyte states on synaptic function. Finally through transcriptomic and genetic analyses, we identify PPARA as a putative therapeutic target of these mechanisms in MDD. Our study defines a tractable pathway to translate genetic findings into therapeutically actionable mechanisms.

show abstract

Plasma lipidomic profile of depressive symptoms: a longitudinal study in a large sample of community-dwelling American Indians in the strong heart study

Cited by 12 publications

References 79 publications

Solitary and Synergistic Effects of Different Hydrophilic and Hydrophobic Phospholipid Moieties on Rat Behaviors

Solitary and Synergistic Effects of Different Hydrophilic and Hydrophobic Phospholipid Moieties on Rat Behaviors

Longitudinal Lipidomic Signature of Coronary Heart Disease in American Indian People

Mechanistic convergence of depression and suicidality on astrocyte fatty acid metabolism

Contact Info

Product

Resources

About