Epigenetic clock analysis of blood samples in drug-naive first-episode schizophrenia patients

Abstract

Background Schizophrenia (SCZ) is a severe and chronic psychiatric disorder with premature age-related physiological changes. However, numerous previous studies examined the epigenetic age acceleration in SCZ patients and yielded inconclusive results. In this study, we propose to explore the epigenetic age acceleration in drug-naive first-episode SCZ (FSCZ) patients and investigate whether epigenetic age acceleration is associated with antipsychotic treatment, psychotic symptoms, cognition, and subcortical volumes. Methods We assessed the epigenetic age in 38 drug-naive FSCZ patients and 38 healthy controls by using three independent clocks, including Horvath, Hannum and Levine algorithms. The epigenetic age measurements in SCZ patients were repeated after receiving 8 weeks risperidone monotherapy. Results Our findings showed significantly positive correlations between epigenetic ages assessed by three clocks and chronological age in both FSCZ patients and healthy controls. Compared with healthy controls, drug-naive FSCZ patients have a significant epigenetic age deceleration in Horvath clock (p = 0.01), but not in Hannum clock (p = 0.07) and Levine clock (p = 0.43). The epigenetic ages of Hannum clock (p = 0.002) and Levine clock (p = 0.01) were significantly accelerated in SCZ patients after 8-week risperidone treatment. However, no significant associations between epigenetic age acceleration and psychotic symptoms, cognitive function, as well as subcortical volumes were observed in FSCZ patients. Conclusion These results demonstrate that distinct epigenetic clocks are sensitive to different aspects of aging process. Further investigations with comprehensive epigenetic clock analyses and large samples are required to confirm our findings.

Exploring neuroadaptive cellular pathways in chronic morphine exposure: An in‐vitro analysis of cabergoline and Mdivi‐1 co‐treatment effects on the autophagy–apoptosis axis

“…This signaling pathway, in conjunction with CREB, regulates the expression of BDNF. Activation of BDNF in neurons is induced by the upstream phosphorylation of PI3K and its effector AKT 86 . Notably, p‐Akt is consistently expressed in U‐87 MG cells, 87 leading us to suggest that the persistent in‐vitro BDNF expression in U87‐MG cells under different treatments may be linked to the BDNF/PI3K/AKT/CREB signaling pathways, reflecting this cell line's resistance characteristics.…”

“…Activation of BDNF in neurons is induced by the upstream phosphorylation of PI3K and its effector AKT. 86 Notably, p-Akt is consistently expressed in U-87 MG cells, 87 leading us to suggest that the persistent in-vitro BDNF expression in U87-MG cells under different treatments may be linked to the BDNF/ PI3K/AKT/CREB signaling pathways, reflecting this cell line's resistance characteristics. In contrast, the SK-N-MC model, which is more susceptible to morphine's effects, demonstrates a significant suppressive impact on BDNF expression.…”

Polygenic risk for schizophrenia, social dispositions, and pace of epigenetic aging: Results from the Young Finns Study

“…The onset of schizophrenia may have effects on epigenetic aging via multiple mechanisms. Specifically, the onset of the disorder commonly results in sick leaves, antipsychotic medications, unemployment periods, and narrowed social network that, in turn, seems to correlate with pace of epigenetic aging on the basis of preliminary evidence (Beach et al., 2022 ; Das, 2022 ; Du et al., 2022 ; Freni‐Sterrantino et al., 2022 ; Li et al., 2023 ).…”