Millions of people live through early life stress (abuse, neglect, parental divorce), and it raises the risk of depression, anxiety, diabetes, and addiction. Until now it was unclear exactly how such experiences change the brain: in some studies the amygdala of stress survivors was larger, in others smaller, in still others no different. Part of the contradiction comes from the fact that people were examined at different ages, and animals at different life stages. This work is the first to compare data from rats, adolescents, and older adults using the same method of volume measurement, and it shows that the direction of change depends on age.
Researchers measured amygdala volume in three groups. Wistar rats (34 individuals) were subjected to chronic immobilization for three hours a day starting on day 45 of life, then scanned on a 7-tesla MRI at three points: before stress, immediately after, and one month later. In 1208 adolescents from the European IMAGEN cohort, childhood trauma was assessed with the CTQ questionnaire and amygdala volume was tracked from age 14 to 23. In 25,000 adults from UK Biobank (ages 40-69), amygdala volume was linked to answers about adverse childhood experiences. In all cases, MRI and statistical models accounting for age and sex were used.
In rats after chronic stress, the amygdala grew faster than in control animals, especially in the basolateral and central nuclei. In adolescents with high childhood trauma scores, amygdala volume increased more steeply from age 14 to 23 (β = 2.38, p = .013). In adults from UK Biobank, by contrast, high early stress went hand in hand with smaller amygdala volume (β = −0.018, p = .0016), and the effect was localized in the right and left hemispheres. These data add up to a single picture: stress accelerates amygdala maturation in youth, and by adulthood leads to its reduction relative to the norm.
The work explains why previous studies produced contradictory results: they caught people at different points along the same trajectory. The "amygdala burnout" model suggests that early stress makes this structure grow faster, but then its volume drops below the level of people without stress. This is consistent with a meta-analysis that found a U-shaped relationship between age and the direction of change. For science, it means that when studying the consequences of stress, one must account for age at the time of measurement, not simply the presence or absence of adverse experiences.
Longitudinal data on people over 40 are still lacking: it is unknown exactly how amygdala volume changes after the peak. Three possible scenarios: a sharp drop, convergence with the norm, or parallel decline. To choose among them, repeated MRI scans of the same people over decades are needed. It is also important to find out what role stress in adult life plays: it may amplify or, conversely, smooth out the effects of childhood experiences.
The results matter for psychiatry and developmental neuroscience: they clarify exactly when the brain is most sensitive to stress and help interpret neuroimaging data in patients with depression and anxiety disorders. For social policy, this is one more argument in favor of early help for children from disadvantaged families.
Collect longitudinal data on amygdala volume in people over 40 with a known history of childhood stress. Test how additional stressors in adult life affect the volume trajectory.
In the neuroscience of stress, the question of which cellular mechanisms underlie the volume change remains open: dendrite growth, an increase in the number of synapses, or neurogenesis. It is also unclear why some people are more vulnerable to early stress than others, and how this relates to genetics and epigenetics.
In normal development, the human amygdala increases in volume by 40% between ages 8 and 18, and a third of that growth comes from the maturation of neurons in the basolateral nucleus. In rats after chronic stress, the volume of this region grows even faster, visible within just a few weeks.
Daniel Keyes's novel Flowers for Algernon shows how accelerated intellectual development turns into its rapid decline. The "amygdala burnout" model draws a similar trajectory for the emotional brain: early stress speeds up growth but drains the resource.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.