Decreased N-acetylaspartate plus N-acetyl-aspartyl-glutamate levels in the caudate of schizophrenia patients with tardive dyskinesia

Tardive dyskinesia (TD) may reflect an intrinsic neurobiological vulnerability associated with schizophrenia, yet metabolic alterations in the caudate nucleu, a key brain region regulating involuntary movements-remain poorly characterized by proton magnetic resonance spectroscopy (1 H-MRS). We investigated the relationship between caudate nucleus metabolite concentrations and TD symptoms using 1 H-MRS. We recruited 117 patients with schizophrenia, including 67 patients with TD and 50 patients without TD (NT). We also recruited 41 healthy controls (HCs). Absolute metabolite concentrations of N-acetylaspartate plus N-acetyl-aspartyl-glutamate (tNAA), creatine (Cr) and glutamine plus glutamate (Glx) in the caudate nucleus were quantified using a 3.0-T MRI scanner with water signal referencing. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Abnormal Involuntary Movement Scale (AIMS). Among-group differences were analyzed using analysis of covariance with sex, age and years of education as covariates, followed by Bonferroni correction for multiple comparisons. After correction, the adjusted p-value was 0.017. Regression analysis was performed on metabolic indexes in the TD group with disease duration as a covariate. No significant differences in age, sex, or education level were observed among the groups. Additionally, no significant differences in PANSS scores or antipsychotic medication dosage were observed between the TD and NT groups. The TD group exhibited a significantly longer disease duration than the NT group (p < 0.05). Absolute tNAA levels—a marker of neuronal integrity—were significantly lower in the TD group than in the NT group (p < 0.05), while Cr (involved in energy metabolism) and Glx (involved in excitatory neurotransmission) levels did not significantly differ. These findings suggest reduced neuronal viability in the caudate nucleus in TD, though the clinical implications warrant further investigation.