Mild early‐life stress exaggerates the impact of acute stress on corticolimbic resting‐state functional connectivity

Abstract

Abundant evidence shows that early‐life stress (ELS) predisposes for the development of stress‐related psychopathology when exposed to stressors later in life, but the underlying mechanisms remain unclear. To study predisposing effects of mild ELS on stress sensitivity, we examined in a healthy human population the impact of a history of ELS on acute stress‐related changes in corticolimbic circuits involved in emotional processing (i.e., amygdala, hippocampus and ventromedial prefrontal cortex [vmPFC]). Healthy young male participants (n = 120) underwent resting‐state functional magnetic resonance imaging (fMRI) in two separate sessions (stress induction vs. control). The Childhood Trauma Questionnaire (CTQ) was administered to index self‐reported ELS, and stress induction was verified using salivary cortisol, blood pressure, heart rate and subjective affect. Our findings show that self‐reported ELS was negatively associated with baseline cortisol, but not with the acute stress‐induced cortisol response. Critically, individuals with more self‐reported ELS exhibited an exaggerated reduction of functional connectivity in corticolimbic circuits under acute stress. A mediation analysis showed that the association between ELS and stress‐induced changes in amygdala–hippocampal connectivity became stronger when controlling for basal cortisol. Our findings show, in a healthy sample, that the effects of mild ELS on functioning of corticolimbic circuits only become apparent when exposed to an acute stressor and may be buffered by adaptations in hypothalamic–pituitary–adrenal axis function. Overall, our findings might reveal a potential mechanism whereby even mild ELS might confer vulnerability to exposure to stressors later in adulthood.

Nuclei-specific hypothalamus networks predict a dimensional marker of stress in humans

“…The hippocampus is affected by stress, in particular early life adversity, which can have lasting effects on its structure and function 75 , 76 . It is therefore an important subcortical region not included a priori here.…”

EJN stress, brain and behaviour special issue

“…One is certainly the timing of the stressful challenge and the context. Especially early in life exposure to adversity has lasting impacts on brain and behaviour (Čater & Majdič, 2021; Clinton et al, 2021; Roque et al, 2021; Wang et al, 2021), specifically also with regard to addiction and reward circuitry (Roque et al, 2021; Rudolph et al, 2020; Levis et al, 2021; Mooney‐Leber et al, 2021), pain responding (Melchior et al, 2021), epigenetic programming (Alyamani et al, 2021; Womersley et al, 2021), neuroinflammation (Friend et al, 2020; Marsland et al, 2021) and in interaction with the metabolic regulation (Berry et al, 2021). Beyond this, it is even unclear how ‘normative’ developmental experiences contribute to stress‐related behaviours (Farber et al, 2020), but it may be that broader environmental factors, such as access to green space, may contribute to resilience and reduced stress responding (Rojas‐Carvajal et al, 2021).…”