Pubertal testosterone influences threat-related amygdala-orbitofrontal cortex coupling

Abstract

Growing evidence indicates that normative pubertal maturation is associated with increased threat reactivity, and this developmental shift has been implicated in the increased rates of adolescent affective disorders. However, the neural mechanisms involved in this pubertal increase in threat reactivity remain unknown. Research in adults indicates that testosterone transiently decreases amygdala-orbitofrontal cortex (OFC) coupling. Consequently, we hypothesized that increased pubertal testosterone disrupts amygdala-OFC coupling, which may contribute to developmental increases in threat reactivity in some adolescents. Hypotheses were tested in a longitudinal study by examining the impact of testosterone on functional connectivity. Findings were consistent with hypotheses and advance our understanding of normative pubertal changes in neural systems instantiating affect/motivation. Finally, potential novel insights into the neurodevelopmental pathways that may contribute to adolescent vulnerability to behavioral and emotional problems are discussed.

Keywords: OFC; amygdale; connectivity; puberty; testosterone; threat.

Fig. 1

Decreased threat-related coupling with amygdala over time in participants with large increases in testosterone. Note: OFC = orbitofrontal cortex. The left images display two views of regions of OFC that exhibited decreased threat-related coupling with left (blue) and right (red; overlap = purple) amygdala in individuals with large increases in testosterone over time. Also pictured is a representative coronal slice that shows the average location of the amygdala seed regions. The scatterplot on the top right illustrates the relationship between change in testosterone over time (x-axis, z-scored within gender) and change in threat-related left amygdala–OFC coupling (y-axis, mean change in coupling β-value, converted to z-scores). The bar graph in the bottom right illustrates this relationship broken down by time point and by size of testosterone increase (determined by median split). Error bars represent 95% confidence intervals. The graphs for the coupling with right amygdala exhibited extremely similar patterns.

Fig. 2

Within gender threat-related coupling between left amygdala and OFC. Note: OFC = orbitofrontal cortex. The scatterplot illustrates the relationship between change in testosterone over time (x-axis) and change in threat-related left amygdala–OFC coupling (y-axis, mean change in coupling β-value, converted to z-scores) plotted separately for each gender (boys = filled diamonds and a solid line; girls = open circles and a dotted line).