Certain blood biochemical markers may have an important role in the pathogenesis of schizophrenia (SCH) combined with tardive dyskinesia (TD) and may be helpful in the diagnosis of SCH with TD, according to findings published in Disease Markers.

“Because the pathogenesis of TD is uncertain, most studies have focused on one possible pathogenesis and have not integrated all the many factors that may be involved in the pathogenesis,” Qian Wu, PhD, of Pingdingshan University in China, and colleagues wrote. “This has led to the neglect of the role of oxidative stress factors when considering the dopamine hypothesis and the influence of inflammatory factors when considering oxidative stress mechanisms.”

Dr. Wu and colleagues noted that examining whether blood biomarkers of patients with SCH who also have TD can be used as diagnostic markers of TD “is of great significance.” The researchers analyzed this question in 121 patients with SCH and TD and 118 patients with SCH between January 2010 and August 2021. Oxidative stress factors measured included superoxide dismutase1 (SOD1), glutathione peroxidase1 (GPX1), malondialdehyde1 (MDA1), catalase activity1 (CAT1), and brain-derived neurotrophic factor 1 (BDNF1); certain inflammatory cytokines, including interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), serum tumor necrosis factor (TNF-α), prolactin, estrogen, and cortisol, were also examined.

Significant Differences in Patient Demographics & Blood Biomarkers

Investigators observed statistically significant differences in age, gender, years of education, diabetes, total disease course, delusions (P1) total score, blunted affect (N1) total score, somatic concern (G1) total score, and Positive and Negative Syndrome Scale (PANSS) score between the TD and SCH groups. Age, diabetes incidence, total disease course, and P1, N1, G1, and PANSS scores in the TD group were significantly higher than in the SCH group. Compared with SCH, TD occurred more frequently in males than in females, and individuals in the TD group had fewer years of education than those in the SCH group.

“Age and female [sex] were immutable risk factors for the development of TD,” Dr. Wu and colleagues wrote.

The researchers found that GPX1, MDA1, and CAT1 were statistically different between the TD and SCH groups, but there was no statistical difference in the blood level of SOD1 and BDNF1 between the TD and the SCH groups. The MDA1 value in the TD group was significantly greater in the SCH group, whereas the GPX1 and CAT1 values in participants with SCH were significantly higher than those in participants with TD.

In the analysis of blood levels for IL-2, IL-6, IL-8, and TNF-α, significant differences were observed between patients in the TD group and patients in the SCH group. Specifically, the TNF-α level in the TD group was significantly lower than that in the SCH group, but there were no significant differences in the levels of IL-2, IL-6, and IL-8 between the two groups.

Study Limitations & Directions for Future Research

Dr. Wu and colleagues acknowledged several limitations of their research, including the possible impact of long-term antipsychotic medication use on blood biochemical markers.

“We paid more attention to the blood biochemical markers of patients in our study, but TD is with obvious behavioral abnormalities, and we can pay more attention to the correlation between blood biochemical markers and the severity of abnormal behavior in future studies,” the study authors wrote.

They also noted that the cognitive status of patients with TD is correlated with blood biochemical markers, indicating that the role of such markers in the pathophysiological mechanism of TD warrants further investigation.