Progress Report
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Realization of a society where child abuse, depression and suicide are “zero”[1] Elucidation of the Biological Mechanisms Underlying Stress and Resilience
Progress until FY2025
1. Outline of the project
This research and development project aims to clarify the differences in how stress is experienced and how it affects individuals ("stress quality") based on the body's internal mechanisms. It also aims to elucidate the mechanisms behind the decline in the ability to adapt to stress (resilience). Specifically, we will compare blood samples from children and young adults with depressive or suicidal tendencies against those of healthy individuals to analyze cellular and genetic differences, while also investigating the impact of stress on the brain and blood using mouse experiments. Furthermore, we position autism spectrum disorder as a developmental vulnerability model for early-life adversity and investigate how childhood experiences influence the immune system and neural circuit formation. Through this approach, we aim to visualize objective indicators of stress, thereby establishing a foundation for future early detection, prevention, and appropriate support interventions.

2. Outcome so far
We analyzed the blood of young people experiencing severe stress or suicidal tendencies in detail at the single-cell level. As a result, we found that changes such as excessive inflammatory responses were occurring in the immune cells that protect the body from foreign threats. Furthermore, within "NK cells," a type of immune cell, we identified a substance that serves as a specific indicator (biomarker) to objectively identify these mental states. This groundbreaking discovery, which views mental health issues as an immune abnormality, has been filed for a patent as an early detection technology (Patent Application 2026-070783).
Additionally, experiencing prolonged stress can lead to depressed moods and increased anxiety. Through mouse experiments, we discovered that "neutrophils," a type of white blood cell, are deeply involved in this process. It is believed that neutrophils, which become abnormally activated by stress, weaken the barrier function protecting the brain, thereby causing adverse effects on the mind and behavior.

Moreover, using both child/adolescent and adult cohorts with autism spectrum disorder, we identified shared immune abnormalities involving T cells, NK cells, and macrophages associated with early-life adversity. These findings are expected to support the social implementation of immune and neural circuit biomarkers that reflect developmental vulnerability.
3. Future plans
Moving forward, we will collaborate with multiple facilities to validate the specifically identified biomarker using testing methods widely adopted in clinical settings, thereby enhancing its reproducibility as an indicator. Furthermore, by comparing it with other psychiatric disorders and examining changes in the marker before and after treatment, we will explore its potential not only for early detection but also as a novel therapeutic target. In parallel, we will extend the immune and neural circuit markers identified in autism spectrum disorder to children and young people with adverse childhood experience. At the same time, as basic research, we will newly introduce genetically modified mice and fully utilize the latest brain imaging analysis to more thoroughly elucidate the mechanisms by which immune cell abnormalities adversely affect the mind and behavior. Through such a smooth bridge from basic research to clinical application, we will contribute to the establishment of specific technologies to accurately assess the "quality" of each individual's stress and proactively prevent suicide, ultimately realizing a society where everyone can live a healthy life.


Principal investigators (PIs)
FURUYASHIKI Tomoyuki (Institute of Science Tokyo)
MAKINODAN Manabu (Kumamoto University)