Employing a developmental psychopathology framework, we tested the utility of the hormesis model in examining the strengthening of children and youth through limited levels of adversity in relation to internalizing and externalizing outcomes within a brain-by-development context.

Analyzing data from the Adolescent Brain and Cognitive Development study (N = 11,878), we formed latent factors of threat, deprivation, and unpredictability. We examined linear and nonlinear associations between adversity dimensions and youth psychopathology symptoms and how change of resting-state functional connectivity (rsFC) in the default mode network (DMN) from Time 1 to Time 5 moderates these associations.

A cubic association was found between threat and youth internalizing problems; low-to-moderate family conflict levels reduced these problems. Deprivation also displayed a cubic relation with youth externalizing problems, with moderate deprivation levels associated with fewer problems. Unpredictability linearly increased both problem types. Change in DMN rsFC significantly moderated the cubic link between threat levels and internalizing problems, with declining DMN rsFC levels from Time 1 to Time 5 facilitating hormesis. Hormetic effects peaked earlier, emphasizing the importance of sensitive periods and developmental timing of outcomes related to earlier experiences.

Strengthening through limited environmental adversity is crucial for developing human resilience. Understanding this process requires considering both linear and nonlinear adversity-psychopathology associations. Testing individual differences by brain and developmental context will inform preventive intervention programming.

Patients with geriatric depression exhibit a spectrum of symptoms ranging from mild to severe cognitive impairment which could potentially lead to the development of Alzheimer’s disease (AD). The aim of the study is to assess the alterations of the default mode network (DMN) in remitted geriatric depression (RGD) patients and whether it could serve as an underlying neuropathological mechanism associated with the risk of progression of AD.

Cross-sectional study.

A total of 154 participants, comprising 66 RGD subjects (which included 27 patients with comorbid amnestic mild cognitive impairment [aMCI] and 39 without aMCI [RGD]), 45 aMCI subjects without a history of depression (aMCI), and 43 matched healthy comparisons (HC), were recruited.

All participants completed neuropsychological tests and underwent resting-state functional magnetic resonance imaging (fMRI). Posterior cingulate cortex (PCC)-seeded DMN functional connectivity (FC) along with cognitive function were compared among the four groups, and correlation analyses were conducted.

In contrast to HC, RGD, aMCI, and RGD-aMCI subjects showed significant impairment across all domains of cognitive functions except for attention. Furthermore, compared with HC, there was a similar and significant decrease in PCC-seed FC in the bilateral medial superior frontal gyrus (M-SFG) in the RGD, aMCI, and RGD-aMCI groups.

The aberrations in rsFC of the DMN were associated with cognitive deficits in RGD patients and might potentially reflect an underlying neuropathological mechanism for the increased risk of developing AD. Therefore, altered connectivity in the DMN could serve as a potential neural marker for the conversion of geriatric depression to AD.