Amino acid metabolism, lipid metabolism, and oxidative stress are associated with post-stroke depression: a metabonomics study

Background: Post-stroke depression (PSD) is a mood disorder characterized by depression and anhedonia caused by stroke. Metabolomics identified metabolites associated with PSD, but previous studies are based on gas chromatography (GC)/mass spectrometry (MS). This study aimed to perform a liquid chromatography (LC)-MS-based metabolomics study of the plasma metabolite profiles between patients with PSD and controls.

Methods: This was a prospective study of patients with stroke enrolled between July and December 2017 at the Second Affiliated Hospital of Nanchang University. Patients were grouped as Hamilton Depression Rating Scale > 7 (PSD) or < 7 (controls). Metabonomics profiling of plasma sampled was conducted by LC-MS. By combining multivariable and univariable statistical analyses, significant differential metabolites between the two groups were screened. The threshold for significant differences was VIP ≥1 and P < 0.05. Log₂FC is the logarithm of the mean ratio between the two groups.

Results: There were no significant difference with respect to age, NIHSS score, and MMSE between the two groups (all P > 0.05). There were six differential metabolites between the PSD and stroke groups, of which three metabolites were increased and three were decreased. Compared with the control group, p-chlorophenylalanine (Log₂FC = 1.37, P = 0.03), phenylacetyl glutamine (Log₂FC = 0.21, P = 0.048), and DHA (Log₂FC = 0.77, P = 0.01) levels were higher in the PSD group, while betaine (trimethylglycine) (Log₂FC = - 0.79, P = 0.04), palmitic acid (Log₂FC = - 0.51, P = 0.001), and MHPG-SO₄ (Log₂FC = - 2.37, P = 0.045) were decreased.

Conclusion: Plasma metabolomics showed that amino acid metabolism (phenylacetyl glutamine, p-chlorophenylalanine, trimethylglycine), lipid metabolism (DHA, palmitic acid, trimethylglycine), and oxidative stress (DHA, palmitic acid, trimethylglycine) were associated with PSD. These results could help to reveal the pathophysiological mechanism of PSD and eventually identify treatment targets.

Keywords: Amino acid metabolism; Lipid metabolism; Liquid chromatography-mass spectrometry; Metabonomics; Oxidative stress; Post-stroke depression.