ArticleFrontiers in psychiatry2022
Clozapine Long-Term Treatment Might Reduce Epigenetic Age Through Hypomethylation of Longevity Regulatory Pathways Genes.
Article in Frontiers in psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it, 7 citations in OpenAlex.
- DNA methylation and histone modifications associated with antipsychotic treatment: a systematic review.Molecular psychiatry · 2025Pooled it
- Antipsychotic use in bipolar disorder: clinical and genomic correlates- a Mayo clinic bipolar disorder biobank study.International journal of bipolar disorders · 2025Article
- Antipsychotic Use in Bipolar Disorder: Clinical and Genomic Correlates- A Mayo Clinic Bipolar Disorder Biobank Study.Research square · 2025Article
- A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan.Nature aging · 2025Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Long-term studies have shown significantly lower mortality rates in patients with continuous clozapine (CLZ) treatment than other antipsychotics. We aimed to evaluate epigenetic age and DNA methylome differences between CLZ-treated patients and those without psychopharmacological treatment. The DNA methylome was analyzed using the Infinium MethylationEPIC BeadChip in 31 CLZ-treated patients with psychotic disorders and 56 patients with psychiatric disorders naive to psychopharmacological treatment. Delta age (Δage) was calculated as the difference between predicted epigenetic age and chronological age. CLZ-treated patients were stratified by sex, age, and years of treatment. Differential methylation sites between both groups were determined using linear regression models. The Δage in CLZ-treated patients was on average lower compared with drug-naive patients for the three clocks analyzed; however, after data-stratification, this difference remained only in male patients. Additional differences were observed in Hannum and Horvath clocks when comparing chronological age and years of CLZ treatment. We identified 44,716 differentially methylated sites, of which 87.7% were hypomethylated in CLZ-treated patients, and enriched in the longevity pathway genes. Moreover, by protein-protein interaction, AMPK and insulin signaling pathways were found enriched. CLZ could promote a lower Δage in individuals with long-term treatment and modify the DNA methylome of the longevity-regulating pathways genes.
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