Antipsychotic Treatment-Associated Modulation of ABC Transporter Genes (ABCC1, ABCB1, and ABCA2) in Schizophrenia: A Longitudinal Expression Study.

BACKGROUND

ATP-binding cassette (ABC) transporters regulate xenobiotic efflux, oxidative stress responses, and blood-brain barrier (BBB) homeostasis. Dysregulation of transporters such as ABCC1, ABCB1, and ABCA2 has been linked to neuropsychiatric disorders, yet their expression patterns in schizophrenia and their modulation by antipsychotic treatment remain unclear. This study investigated longitudinal changes in the expression of these genes in schizophrenia patients before and after antipsychotic therapy, compared with healthy controls.

METHODS

Sixty individuals with schizophrenia and sixty matched healthy controls were included. Serum samples were obtained from patients during the acute pre-treatment phase and after clinical improvement following antipsychotic therapy. Gene expression of ABCC1, ABCB1, and ABCA2 was measured by RT-qPCR (normalized to ACTB). Log2 fold-change (log2FC) values relative to controls were calculated. Group differences were assessed with Mann-Whitney U and Wilcoxon signed-rank tests, and associations with clinical severity were analyzed using correlations with Positive and Negative Syndrome Scale (PANSS) scores.

RESULTS

In the acute phase, ABCC1 and ABCB1 expression were significantly downregulated in schizophrenia compared with controls (both p < 0.001). Antipsychotic treatment produced significant increases in both genes, though expression remained below control levels. ABCA2 showed no baseline differences but exhibited marked upregulation after treatment (p < 0.001). Higher baseline ABCC1 expression was associated with greater pre-treatment symptom severity, whereas higher baseline ABCB1 expression was associated with, rather than predicted, poorer clinical improvement. No significant correlations were found for ABCA2.

CONCLUSIONS

These findings demonstrate distinct, gene-specific alterations in ABC transporter expression in schizophrenia. ABCC1 and ABCB1 appear suppressed during acute illness and partially restored with antipsychotic therapy, while ABCA2 shows a strong treatment-related upregulation. ABC transporter expression-particularly ABCB1-may provide preliminary molecular insight into treatment-related variability, although biomarker utility cannot be established from the present data. Longitudinal pharmacogenomic studies are needed to clarify their clinical relevance.