T126. Short- Vs Medium + Long-Chain Plasma Acylcarnitine in Phenotypes of Major Depression at Baseline and After Citalopram/Escitalopram Treatment

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Background

Metabolic signatures that align with depression phenotypes could better characterize the neurobiology of major depressive disorder (MDD) and its heterogeneity. We aimed to identify metabolomic markers of MDD phenotypes and their change after SSRI-treatment.

Methods

We evaluated metabolic profiles from the Mayo-Clinic-Pharmacogenomics-Research-Network (PGRN) of 240 subjects with MDD. Targeted metabolomics were quantified using the AbsoluteIDQ®p180-Kit, which measures 186 endogenous metabolites. Metabolites were compared in three depression phenotypes [core depression (CD), anxiety (A), neurovegetative symptom of melancholia (NVSM)], classified by Hamilton Depression Rating Scale sub-scores at baseline and after 8 weeks of treatment with citalopram or

Results

Baseline to 8-week change in small chain acylcarnitines significantly increased, driven primarily by a significant increase in the CD phenotype patients (n=31, C0(log2[FC]=0.14, p=0.045); C3(log2[FC]=0.24, p=0.027). The mean medium/long chain acylcarnitines significantly decreased after treatment, driven primarily by decreases in the NVSM phenotype patients (n=17, C8 (log2[FC]=-0.88, p<0.001); C16(log2[FC]=-0.6, p<0.001)). Pairwise differential abundance analysis at week 8 revealed that levels

Conclusions

Altered acyl-carnitine profiles in clinical MDD phenotypes suggested that beta oxidation and mitochondrial energetics status could provide insights into disease heterogeneity and may help guide efforts toward MDD subclassification.

Supported By

Dr Ahmed Research reported in this publication was supported by National Institute of General Medical Sciences of the National Institutes of Health under award number T32 GM008685.

Keywords

Metabolomics, Major Depressive Disorder (MDD), SSRI, Acylcarnitines, Phenotype

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