Progress Report
Realization of a society where child abuse and suicide are zero[2] Brain AMPA receptor data and epigenome data for abuse and suicidality
Progress until FY2024
1. Outline of the project
By using the positron emission tomography (PET) tracer technology for alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors recognition for human living brain, which we developed for the first time worldwide (Miyazaki et al., Nature Medicine 2020), we aim to perform AMPA-PET imaging on young adults who have experienced abuse in childhood and analyze the densities of AMPA receptors in their brains. We compare these with AMPA-PET data from sex/age-matched healthy controls (already constructed) and identify the brain regions where AMPA receptor levels differ in relation to histories of abuse and suicidal tendency. Through these efforts, we aim to clarify the brain mechanisms underlying the emotional instability leading to suicide from the biological effects of abuse history in childhood. We also aim to obtain comprehensive DNA methylation data for the same individuals and examine the relationship between AMPA-PET and epigenome data.
2. Outcome so far
We conducted AMPA-PET scans on three young individuals whose childhood adversity was most severe and strong suicidal tendencies. In all cases, we observed increased AMPA receptor density across the entire brain, with the most pronounced increase seen in the individual with the highest adversity score. This pattern differs from findings in other psychiatric or physical conditions and may reflect unique brain changes specific to youth with a history of abuse and suicidality.
If similar trends are observed in additional cases, it may lead to a new understanding that specific brain alterations are associated with early-life adversity and suicide risk in young people.
Early traumatic experiences may impact the biological system (HPA axis) responsible for stress responses, leading to long-term effects on brain development. Given the variability in abuse and psychological symptoms, additional data—including brain function beyond AMPA-PET, epigenomic information, and animal model results—must be collected to elucidate underlying mechanisms and identify robust biomarkers.
3. Future plans
Visualization and Classification of Brain and Mental Health
We are conducting AMPA-PET imaging in youth with a history of abuse or suicidal tendencies—an internationally rare study—to identify brain changes specific to these risks. By integrating epigenomic, EEG, and MRI data, we aim to clarify mechanisms of depression/suicide risk and contribute to the development of new treatments.
Broadening Inclusion Criteria and Strengthening Recruitment
To improve feasibility and clinical relevance, we are expanding participant criteria beyond those with recent suicide attempts, enabling more diverse data collection and practical biomarker development.
Scientific Validation and Method Optimization
The PET tracer 11C-K2, developed to visualize AMPA receptor distribution, is being evaluated for accuracy and safety. To validate observed changes in individuals with adverse experiences, we are introducing rodent models of early-life stress and facilitating interdisciplinary discussions with domestic and international experts to ensure methodological robustness and applicability.
- Principal investigators (PIs)
- MIYAZAKI Tomoyuki (Yokohama City University)
- OTSUKA Ikuo (Kobe University)