The Perspectives of Early Diagnosis of Schizophrenia Through the Detection of Epigenomics-Based Biomarkers in iPSC-Derived Neurons

Abstract

The lack of early diagnostic biomarkers for schizophrenia greatly limits treatment options that deliver therapeutic agents to affected cells at a timely manner. While previous schizophrenia biomarker research has identified various biological signals that are correlated with certain diseases, their reliability and practicality as an early diagnostic tool remains unclear. In this article, we discuss the use of atypical epigenetic and/or consequent transcriptional alterations (ETAs) as biomarkers of early-stage schizophrenia. Furthermore, we review the viability of discovering and applying these biomarkers through the use of cutting-edge technologies such as human induced pluripotent stem cell (iPSC)-derived neurons, brain models, and single-cell level analyses.

Results from PSIPROSPER: A multicenter retrospective study to analyze the impact of treatment with paliperidone palmitate 1-month on clinical outcomes and hospital resource utilization in adult patients with schizophrenia in Portugal

“…The mean disease duration (4.9 years) at the start of treatment with PP1M and the median time between first symptoms and diagnosis (1.1 years) are also aligned with expectations. However, the median time from first symptoms to diagnosis is still higher than desirable, significantly delaying the start of the treatment, which negatively impacts treatment outcomes ( 14 – 16 ). Misdiagnosis usually happens due to the diagnosis of a myriad of other mental disorders ( 37 ).…”

“…As in other mental disorders, the outcome and impact of schizophrenia can be positively influenced by early diagnosis and the subsequent treatment initiation ( 1 , 14 – 16 ). The treatment for schizophrenia has improved significantly in recent times.…”

Potential diagnostic biomarkers for schizophrenia

“…Despite these challenges, the ability of human induced pluripotent stem cells (hiPSCs) recapitulates transcriptomic changes of brain development during differentiation to neural cell types while retaining patient-specific genetic backgrounds have allowed for the in vitro study of SCH. The hiPSCs can provide insight into the cellular mechanisms underlying SCH [ 196 ], and utilization of single-cell level analyses in combination with organoid technology was proposed to discover epigenetic and/or consequent transcriptional alterations [ 197 ]-based biomarkers in diagnosing SCH [ 198 , 199 ] ( Table 5 ).…”