Mitochondrial Damage of Lymphocytes in Patients with Acute Relapse of Schizophrenia: A Correlational Study with Efficacy and Clinical Symptoms

Abstract

Objective Accumulating evidence has demonstrated that schizophrenia is associated with mitochondrial and immune abnormalities. In this pilot case–control study, we investigated the level of mitochondrial impairment in lymphocytes in patients with acute relapse of schizophrenia and explored the correlation between the level of mitochondrial damage and symptoms or treatment response. Methods Lymphocytic mitochondrial damage was detected using mitochondrial fluorescence staining and flow cytometry in 37 patients (at admission and discharge) and 24 controls. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression Scale (CGI-S). Results The levels of mitochondrial damage in CD3+ T, CD4+ T, and CD8+ T lymphocytes of the patients with schizophrenia at admission were significantly higher than those of the controls (p<0.05) and did not return to normal at discharge (p>0.05). The mitochondrial damage of T cells significantly improved at discharge for responsive patients only, as compared with that at admission (P<0.05). However, no significant difference was found in mitochondrial damage in CD19+ B cells between patients and healthy controls, or between admission and discharge (p>0.05). Furthermore, the reduction in mitochondrial damage of CD3, CD4, and CD8 lymphocytes was positively correlated with the reduction of the score of the PANSS positive scale at discharge (p<0.05), while no significant correlation was found between the level of mitochondrial damage in lymphocytes and the scores of PANSS and CGI-S. Conclusion Acute relapse of schizophrenia might be associated with higher levels of mitochondrial damage in peripheral blood T lymphocytes. The degree of recovery of mitochondrial impairment in the T cells may be used as a predictor of treatment response in schizophrenia. As this is a pilot study, the conclusion still needs further verification in large-scale studies.

Altered mitochondrial lymphocyte in overweight schizophrenia patients treated with atypical antipsychotics and its association with cognitive function

“…Some studies suggest that the elevated CD4+/CD8+ ratio may be linked to negative symptoms in schizophrenia (such as attention deficits and emotional blunting) ( 43 ), with a weaker association observed with positive symptoms (such as hallucinations and delusions), which contrasts with our research findings. Conversely, other studies have not identified any correlation between this ratio and specific symptom types ( 13 ). Similarly, research findings regarding the relationship between age and the T lymphocyte mitochondrial CD4+/CD8+ ratio are also subject to controversy.…”

“…Mitochondria, the energy-producing centers within cells, are crucial for normal cellular functioning. Some studies have indicated impaired lymphocyte mitochondrial function in patients receiving treatment with atypical antipsychotic medications( 13 ). Furthermore, the metabolic syndrome induced by medication may contribute to lymphocyte mitochondrial damage ( 8 ).…”

Analysis of mitochondrial function in lymphocytes obtained from COVID-19 patients

“…The SCMM exhibited a good performance in predicting the response to treatment for schizophrenia. 16 In addition, lymphocyte dysfunction occurs in T cells during the early stages of sepsis. SCMM-CD4 is more effective for diagnosing sepsis at an early stage than the traditional biomarker PCT, and the diagnostic value of PCT, when combined with SCMM-CD4, is superior to that observed for SCMM-CD4 alone during early sepsis.…”

Microglia and Other Cellular Mediators of Immunological Dysfunction in Schizophrenia: A Narrative Synthesis of Clinical Findings

“…However, their findings on the expression of dopamine receptors D (DRD) 2 and 4 were inconsistent, likely due to methodological differences (mRNA expression vs. flow cytometry) [ 173 , 174 ]. T-cell-specific oxidative damage in SCZ has also been quantified and showed an increase in mitochondrial dysfunction across different T cell subsets from patients with acute relapse compared to HCs [ 175 ]. Furthermore, this cellular pathology appears to be associated with positive symptoms [ 175 ].…”

“…T-cell-specific oxidative damage in SCZ has also been quantified and showed an increase in mitochondrial dysfunction across different T cell subsets from patients with acute relapse compared to HCs [ 175 ]. Furthermore, this cellular pathology appears to be associated with positive symptoms [ 175 ]. Lastly, T cell methylation profile and repertoire were reportedly associated with distinct SCZ subtypes.…”