Metabolite Changes Common in Tardive Dyskinesia

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Researchers found changes in 57 metabolites among patients with tardive dyskinesia, indicating their potential impact on disease development and as a biomarker.

Many recent studies on tardive dyskinesia have focused on treatment, including deep brain stimulation and vesicular monoamine transporter type 2 inhibitors. A study published in Schizophrenia Bulletin takes a step back, looking at metabolomics and potential diagnostic biomarkers for the condition.

“The pathogenesis of tardive dyskinesia (TD) remains unclear, involving multiple biological pathways,” researchers wrote. “This study aimed to explore biomarkers of TD through untargeted metabolomics for the early identification of TD.”

The study team recruited 84 patients with schizophrenia who also had TD and 160 patients with schizophrenia who did not have TD. The TD diagnosis was based on Schooler–Kane criteria, while the severity of TD and psychiatric symptoms were evaluated with the Abnormal Involuntary Movement Scale and the Positive and Negative Syndrome Scale. They obtained fasting blood samples from all participants and conducted an untargeted metabolomics analysis using ultra-high-performance liquid chromatography-high resolution mass spectrometry. Researchers analyzed the data using orthogonal partial least squares discriminant analysis and receiver-operating characteristic curves.

Significant Changes in 57 Metabolites

According to the study results, this methodology enabled the quantification and profiling of 699 metabolites.

Of these, 57 metabolites demonstrated significant changes (variable importance of projection, >1; false discovery rate-adjusted P<0.05) that mainly involved amino acids and lipids. These alterations primarily impacted the phenylalanine, tyrosine, and tryptophan pathways (impact=0.5; P=0.025) and the phenylalanine metabolism pathway (impact=0.36; P=0.050).

Metabolites found to be negatively related to the total abnormal involuntary movement scale score included:

• N-Acetyl-l-phenylalanine (B=2.249; t=4.56; P<0.001; 95% CI, 1.302–3.286)
• Succinylcarnitine AcCa(4:0-DC) (B=1.009; t=3.07; P=0.002; 95% CI, 0.362–1.656)

Further, five differential metabolites had area under the curve (AUC) values of greater than 0.7 for the diagnosis of TD, with a combined diagnostic capability exceeding 0.8 (AUC=0.817; 95% CI, 0.759–0.875).

Importance of Amino Acids & Lipids

Overall, the findings indicate that disturbances in amino acid and lipid metabolism are predominant in TD, according to the study results.

“Amino acids and lipid metabolites may be involved in the development of TD,” researchers wrote. “Additionally, a biomarker panel composed of amino acids and lipids can be used for the differential diagnosis of TD.”