The Effect of Genetic Risk and Maternal Behavior on Children’s Amygdala Connectivity

Post by Shireen Parimoo

What's the science?

Depression and anxiety are internalizing disorders, which means that their symptoms are primarily experienced internally (e.g. sadness, loneliness) rather than being directed externally (e.g. impulsive behavior, bullying). Adverse childhood experiences like negative parental behavior are associated with a higher incidence of internalizing symptoms and depression later in life. Depression has also been linked to disrupted functioning of the amygdala and the hypothalamic-pituitary-adrenal (HPA) axis, a set of brain regions that control the body’s reaction to stress. Together, negative childhood experiences and having certain genes associated with the HPA axis are related to having depression, but the mechanism of this interaction is unclear. This week in NeuroImage, Pozzi and colleagues used functional magnetic resonance imaging (fMRI) to delineate the relationship between HPA genetic risk, parental behavior, amygdala activation, and children’s depressive symptoms.

How did they do it?

Eighty children aged 8 - 9 years old participated in a longitudinal study with two time points. At the first time point, the authors recorded interactions between the children and their mother and 18 months later, the children performed an emotional processing task while undergoing fMRI scanning. The mother-child interactions were each 15 minutes long and consisted of an event-planning interaction and a problem-solving interaction. The mothers’ behavior was categorized into negative (e.g. anger) and positive (e.g. listening) behavior during each interaction. Saliva samples were also collected at the first time point to assess genetic risk, yielding a composite HPA genetic risk score based on the number of HPA-related genes that they possessed.

At the second time point, children completed questionnaires assessing internalizing symptoms, depression, and anxiety, while their mothers completed questionnaires assessing maternal depression and their children’s internalizing symptoms. The children also completed an emotional face-matching task in which they had to match the gender of an angry or fearful target face with one of two other faces. In the control condition, participants matched shapes instead of faces. The authors first examined task-related activity in the amygdala when participants performed the face compared to the shape matching task. They then performed a generalized psychophysiological interaction (gPPI) analysis to determine how the connectivity between the amygdala and other regions of the brain were related to the interaction between genetic risk, child functioning, and maternal behavior.

What did they find?

There were no direct associations between amygdala activation during the emotional face-matching task, and the interaction between genetic risk, and maternal behavior. Genetic risk moderated the relationship between negative maternal behaviors and brain connectivity. Specifically, higher genetic risk was linked to greater amygdala connectivity with the right superior frontal gyrus when mothers exhibited more negative behaviors during the problem-solving task. Conversely, if mothers exhibited more negative behaviors but the child’s genetic risk was low, the connectivity between the amygdala and the right superior frontal gyrus was also lower. During the event planning task, negative maternal behavior was associated with greater connectivity between the amygdala and the postcentral gyrus in the presence of high genetic risk, but reduced amygdala connectivity with fronto-parietal regions when genetic risk was low. This suggests that how mothers interact with their children affects the children’s amygdala’s connectivity in different ways depending on the level of genetic risk for HPA axis dysregulation.

Finally, genetic risk was not directly associated with children’s internalizing or depressive symptoms. However, there was an indirect relationship between genetic risk and child functioning that was mediated by the amygdala’s connectivity to the precuneus. Higher genetic risk was linked to more internalizing symptoms in children via higher amygdala-precuneus connectivity.

What's the impact?

This study is the first to show that genetic risk influences the effect that negative maternal behavior has on brain activity (connectivity) related to children’s emotion processing. The results further illustrate that altered brain functioning underlies the interaction between genetic risk factors and depressive symptoms. These findings provide deeper insight into how genetic and environmental variables might contribute to the development of internalizing disorders such as depression and anxiety.

Pozzi et al. Interaction between hypothalamic-pituitary-adrenal axis genetic variation and maternal behavior in the prediction of amygdala connectivity in children. NeuroImage (2019). Access the original scientific publication here.