Temporal variations in serum metabolites of bipolar disorder around the summer solstice: A targeted metabolomics study

Bipolar disorder (BD) is a severe mood disorder characterized by seasonal variations, but the underlying metabolite changes are not well understood. This study employed targeted metabolomics to examine serum metabolite changes in 9 BD patients and 9 healthy controls (HCs) at 6 time points: 15 d before, on, and 15 d after the spring equinox and summer solstice. In the summer, 4 metabolites in HCs and 25 in BD showed time effects, with phenylalanine (Phe) -alanine-betaine showing interaction effects; however, none were significant after false discovery rate (FDR) correction. Analysis across the spring and summer revealed significant time effects in 48 metabolites in HCs and 201 in BD, with Phe showing notable interactions. In the spring, Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale scores, retardation, sleep disturbance, and psychic anxiety factors correlated positively with Homoarginine (HArg), Phe, and lactate. In the summer, Young Mania Rating Scale (YMRS) was positively associated with 3-hydroxyphenylacetic acid and negatively with Harg, glutamine, and citrate; sleep disturbance was positively linked to sarcosine, and retardation factor negatively linked to HArg. These seasonal changes in BD metabolites were primarily linked to the biosynthetic pathways of phenylalanine, tyrosine, and tryptophan. Further research is needed to understand how these metabolic shifts influence BD episodes.