A neural biomarker of psychological vulnerability to future life stress

Abstract

We all experience a host of common life stressors such as the death of a family member, medical illness, and financial uncertainty. While most of us are resilient to such stressors, continuing to function normally, for a subset of individuals, experiencing these stressors increases the likelihood of developing treatment-resistant, chronic psychological problems, including depression and anxiety. It is thus paramount to identify predictive markers of risk, particularly those reflecting fundamental biological processes that can be targets for intervention and prevention. Using data from a longitudinal study of 340 healthy young adults, we demonstrate that individual differences in threat-related amygdala reactivity predict psychological vulnerability to life stress occurring as much as 1 to 4 years later. These results highlight a readily assayed biomarker, threat-related amygdala reactivity, which predicts psychological vulnerability to commonly experienced stressors and represents a discrete target for intervention and prevention.

Fig. 1. Model A: All participants completing a post-scanning assessment (n=340)

A) Participants underwent a baseline fMRI scan to measure threat-related amygdala reactivity. The main effect of task (fearful and angry faces>shapes) elicited bilateral amygdala reactivity (thresholded at p<.05 corrected). (B) Participants were invited to complete an online assessment every 3 months post-scanning. The green boxes indicate the baseline scanning assessment and the blue boxes indicate online assessments. For Model A, life stress at Time 2 (as measured by the Life Events Scale for Students) and internalizing symptoms at Time 2 (as measured by the Mood and Anxiety Symptom Questionnaire) were taken from the most recent assessment completed by each participant, as indicated by the red boxes. (C) Depressive and anxiety symptoms at Time 2 are plotted as a function of the parameter estimates of threat-related amygdala reactivity and life stress post-scanning (groups divided into terciles). Dotted lines indicate 95% confidence bands. Internalizing symptoms were predicted by a significant interaction between amygdala reactivity and life stress experienced post-scanning, B=2.01, SE=.7, t(339)=3.08, p=.002. See also Table S1 and Figure S1.

Fig. 2. Model B: All participants completing an assessment at least 1-year post-scanning (n=192)

(A) For Model B, we selected data from all participants who completed a follow-up assessment at least 1 year post-scanning. (B) Internalizing symptoms at Time 2 as a function of amygdala reactivity and life stress experienced post-scanning. Internalizing symptoms were predicted by a significant interaction between amygdala reactivity and life stress experienced post-scanning, B=1.75, SE=.8, t(191)=2.33, p=.02. See also Table S3 and Figure S2.

Fig. 3. Model C: Predicting symptoms reported approximately 1 year post-scanning from amygdala reactivity at baseline and life stress reported between the scanning session and 1 year post-scanning (n=99)

(A) For Model C, to obtain a prospective assessment of life stress, we selected depression and anxiety symptoms from the assessment completed approximately 1 year post-scanning (range: 365-455 days) and a mean stress score from all assessments completed before then. (B) Internalizing symptoms at Time 2 as a function of amygdala reactivity and life stress experienced post-scanning (groups created by median split). Internalizing symptoms were predicted by a significant interaction between amygdala reactivity and life stress experienced post-scanning, B=5.56, SE=1.9, t(98)=2.96, p=.003. See also Table S3 and Figure S3.