Correlations between cerebrospinal fluid and plasma levels of GABA, glutamate, dopamine, and related metabolites, and their concentrations across neurological disorders.

BACKGROUND: Neurotransmitters play critical roles in both central and peripheral nervous system function. However, the correlation between cerebrospinal fluid (CSF) and plasma levels of neurotransmitters remains incompletely understood, limiting the interpretation of peripheral measurements as surrogates for central neurochemical changes. This study aimed to investigate the correlations between CSF and plasma levels of GABA, glutamate, dopamine, and related metabolites, and to explore their expressions across common neurological disorders in a real-world clinical setting. METHODS: A total of 181 paired CSF and plasma samples from patients with neurological disorders and 67 plasma samples from healthy controls were analyzed. Concentrations of GABA, betaine, L-DOPA, histamine, glutamine, glutamate, dopamine, and choline were quantified using LC-MS/MS. Correlations between CSF and plasma concentrations were assessed using Pearson correlation analysis. Age- and sex-related effects were evaluated in healthy controls, and differences among disease groups were analyzed after classifying patients into neurodegenerative diseases (NDDs), CNS demyelinating diseases (CNS DDs), CNS tumors, and CNS infections. RESULTS: GABA, histamine, betaine, glutamate, and choline exhibited higher concentrations in plasma than in CSF, whereas glutamine concentrations were higher in CSF. Except for betaine and glutamate, all other neurotransmitters showed statistically significant but weak CSF-plasma correlations (r = 0.15-0.7, p < 0.05). In healthy controls, plasma histamine, betaine, glutamate, and choline levels were higher in males. Plasma GABA levels in all disease groups were consistently lower than controls, and plasma glutamine levels in NDDs, CNS DDs, and CNS tumors were significantly higher than those in controls. By contrast, there were no significant differences in CSF levels among different disease groups, except that glutamate was higher in the CNS tumor group than in the other disease groups. CONCLUSIONS: Most plasma neurotransmitters and their metabolites do not reliably reflect their CSF levels, which may provide important context for interpreting peripheral neurotransmitter biomarkers in CNS diseases.