Progress Report
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Realization of a society where child abuse, depression and suicide are “zero”[2] Development of indicators evaluating biological impacts of abuse, depression, and suicide
Progress until FY2025
1. Outline of the project
We will obtain genome-wide DNA methylation data from peripheral samples of children and young adults with a history of childhood maltreatment (with and without suicidal ideation/behavior), as well as from healthy controls. We will examine whether the “epigenome-level biological aging” signature identified in our previous study of young suicide decedents is (i) elevated in individuals with maltreatment compared to controls, and (ii) further accentuated among those with both maltreatment and suicidal ideation/behavior.
In addition, we will use a novel positron emission tomography (PET) tracer for in vivo visualization of AMPA receptors in the human brain, which we developed (Miyazaki et al., Nature Medicine, 2020). Using this AMPA-PET approach, we will assess AMPA receptor density in young adults with childhood maltreatment and compare these data with age-matched healthy control datasets (already established) to identify brain regions where AMPA receptor density is altered in association with maltreatment and suicidal behavior.
2. Outcome so far
Interim analyses using blood samples from children with a history of maltreatment and healthy controls have shown that epigenetic age is advanced in maltreated children compared with controls, with more pronounced acceleration among those with suicidal ideation or behavior. We are also steadily developing a new epigenetic age algorithm that sensitively captures biological health status in young Japanese individuals.
We have further found that, in young patients with depression experiencing psychological stress, care-based interventions can shift blood-based epigenetic age toward rejuvenation within only a few months. This finding provides important evidence that the health-damaging biological aging observed in maltreated children and young people with suicidality may be reversible through appropriate care.
In addition, we have observed increased AMPA receptor density across broad brain regions in many young individuals with histories of maltreatment and severe suicidality. This increase was particularly marked in cases with the most severe childhood adversity. These changes differ from those we have observed in patients with other psychiatric or physical disorders, suggesting that they may represent brain alterations specific to young people with maltreatment histories and suicidality. If similar patterns are confirmed in additional cases, this may lead to the discovery of a distinct brain mechanism underlying maltreatment-related suicide risk in youth.
3. Future plans
We have established a multicenter framework for consent and sample collection, enabling construction of one of the largest epigenomic datasets in Asia on maltreatment and suicidality in youth. AMPA-PET analyses will be conducted in a subset.
These efforts aim to develop biomarkers of biological aging and mental health status. Epigenomic findings are being advanced toward productization in collaboration with industry partners.
In parallel, working with experts in digital technology and ELSI, we will carefully develop systems for biomarker-based detection of severe stress in children, ensuring appropriate consideration of both benefits and risks.
Principal investigators (PIs)
OTSUKA Ikuo (Kobe University)
MIYAZAKI Tomoyuki (Yokohama City University)