Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Early life stress (ELS) can precipitate psychopathology by affecting amygdala function.
• The hypothalamic-pituitary-adrenal (HPA) axis plays a crucial role in mediating the effects of stress.
• Genetic variations in the HPA axis may influence individual vulnerability to ELS.

Purpose of the Study:

• To investigate the interaction between ELS and HPA axis genetic variation on threat-related amygdala function.
• To examine the association between this interaction and psychopathology symptoms.
• To explore potential neural mechanisms underlying the relationship between HPA axis genetics, ELS, and anxiety.

Main Methods:

• Utilized data from 308 college students (Duke Neurogenetics Study).
• Assessed ELS and anxiety/depression symptoms via questionnaires.
• Measured HPA axis genetic variation using a biologically-informed multilocus profile score (BIMPS).
• Acquired BOLD fMRI data during an emotional face matching task.

Main Results:

• The interaction between HPA axis BIMPS and ELS significantly predicted right amygdala reactivity to threat (empirical-p=0.016).
• Higher BIMPS individuals with ELS showed increased threat-related amygdala reactivity.
• Higher BIMPS correlated with greater anxious arousal, but amygdala function did not mediate this.

Conclusions:

• Polygenic variation in the HPA axis may moderate the impact of ELS on amygdala function.
• This interaction confers risk for anxiety symptomatology.
• Neural mechanisms linking HPA axis BIMPS and anxiety symptoms require further investigation.