For this study, the researchers focused on 536 men and women ages 18 to 22 who had completed questionnaires and brain imaging scans as part of the Duke Neurogenetics Study in the U.S. Based on their responses to a childhood trauma questionnaire, 299 people had experienced a high level of childhood trauma or early-life stress, including emotional abuse, physical abuse, emotional neglect, physical neglect and/or sexual abuse. Another 237 people had low levels of early-life stress.
The link between stress and depression was clear. People who had experienced significant early-life stress had higher levels of depression and anxiety symptoms as adults, and were more likely to be diagnosed with major depressive disorder than people who had experienced relatively low early-life stress.
To investigate the impact of stress on the brain, the researchers used a new way of studying brain anatomy in relation to stress, called whole-brain structural covariance, which captures coordinated structural changes, or “structural synchrony,” between brain regions. Each study participant had completed a magnetic resonance imaging (MRI) scan, which shows brain structure. Using this data, the researchers analyzed 56 brain regions to identify coordinated structural changes in people who had experienced significant early-life stress. These changes were compared to people with low early-life stress.
The researchers found a notable change related to the amygdala, the brain region involved in emotional responses, particularly fear or the response to threatening situations. In terms of the overall brain anatomy, the amygdala showed greater structural coordination with more brain regions – eight in the significant stress group versus three in the comparison group – and with regions involved in motivation and regulating emotions. At the same time, there was less coordination across brain regions as a whole.
“The amygdala is becoming a stronger brain network hub and possibly a stronger driver of behaviour among people with high levels of childhood stress or trauma,” says Dr. Yuliya Nikolova, Scientist in the Campbell Institute at CAMH. “The simultaneous loss of structural synchrony among other brain regions may be a trade-off.” The researchers believe these combined changes may contribute to the higher rates of depression in young adults with a history of early life stress.
Another novel aspect of the study is that the researchers showed similar findings using structural covariance in preclinical models exposed to stress. This approach better enables the researchers to understand when, how and why changes occur. In other analyses, the researchers identified that four brain regions – including the amygdala – became larger as a percentage of the whole brain in preclinical models exposed to stress.
In addition, a protein in the amygdala — called postsynaptic density protein-95 — was seen to increase in preclinical models exposed to stress relative to the comparison group. This cellular change is promising because it may point to an underlying biological mechanism that contributes to the changes in brain structure.
The researchers’ long-term goal is to identify opportunities to intervene to prevent depression. “If repeated stressful life events are inducing structural and cellular changes, if we know what these changes are, we can aim to block them before the cumulative effects on the brain occur,” says Dr. Banasr.
In the Summer 2018 Issue of CAMH Discovers Quarterly: