Maternal serum amino acids and hydroxylated sphingomyelins at pregnancy are associated with anxiety symptoms during pregnancy and throughout the first year after delivery

Background: Studies suggest an interplay between maternal metabolome and mental health. Objective: We investigated the association of maternal serum metabolome at pregnancy with anxiety scores during pregnancy and throughout the first year postpartum. Methods: A prospective cohort of Brazilian women collected 119 serum metabolome at pregnancy (28-38 weeks) and anxiety scores measured by the State-Trait Anxiety Inventory (STAI) at pregnancy (n =118), 1 (n =83), 6 (n =68), and 12 (n =57) months postpartum. Targeted metabolomics quantified metabolites belonging to amino acids (AA), biogenic amines/amino acid-related compounds, acylcarnitines, lysophosphatidylcholines, diacyl phosphatidylcholines, alkyl:acyl phosphatidylcholines, non-hydroxylated and hydroxylated sphingomyelins [SM (OH)], and hexoses classes. Linear mixed-effect models were used to evaluate the association of metabolites and STAI scores. Hierarchical clustering and principal component analyses were employed to identify clusters and metabolites, which drove their main differences. Multiple comparison-adjusted p-values (q-value) <= 0.05 were considered significant. Results: AA (beta = 1.44) and SM(OH) (beta = 1.49) classes showed an association with STAI scores trajectory (q- value =0.047). Two clusters were identified based on these classes. Women in cluster 2 had decreased AA and SM(OH) concentrations and higher STAI scores (worse symptoms) trajectory (beta =2.28; p-value =0.041). Isoleucine, leucine, valine, SM(OH) 22:1, 22:2, and 24:1 drove the main differences between the clusters. Limitations: The target semiquantitative metabolome analysis and small sample size limited our conclusions. Conclusions: Our results suggest that AA and SM(OH) during pregnancy play a role in anxiety symptoms throughout the first year postpartum.