Interplay of early negative life events, development of orbitofrontal cortical thickness and depression in young adulthood

Abstract

BackgroundEarly negative life events (NLE) have long‐lasting influences on neurodevelopment and psychopathology. Reduced orbitofrontal cortex (OFC) thickness was frequently associated with NLE and depressive symptoms. OFC thinning might mediate the effect of NLE on depressive symptoms, although few longitudinal studies exist. Using a complete longitudinal design with four time points, we examined whether NLE during childhood and early adolescence predict depressive symptoms in young adulthood through accelerated OFC thinning across adolescence.MethodsWe acquired structural MRI from 321 participants at two sites across four time points from ages 14 to 22. We measured NLE with the Life Events Questionnaire at the first time point and depressive symptoms with the Center for Epidemiologic Studies Depression Scale at the fourth time point. Modeling latent growth curves, we tested whether OFC thinning mediates the effect of NLE on depressive symptoms.ResultsA higher burden of NLE, a thicker OFC at the age of 14, and an accelerated OFC thinning across adolescence predicted young adults' depressive symptoms. We did not identify an effect of NLE on OFC thickness nor OFC thickness mediating effects of NLE on depressive symptoms.ConclusionsUsing a complete longitudinal design with four waves, we show that NLE in childhood and early adolescence predict depressive symptoms in the long term. Results indicate that an accelerated OFC thinning may precede depressive symptoms. Assessment of early additionally to acute NLEs and neurodevelopment may be warranted in clinical settings to identify risk factors for depression.

How early environment influences the developing brain and long‐term mental health

“…Less is known about whether the accumulation of more common, less severe negative experiences also constitute risk factors for depression throughout life. In the longitudinal IMAGEN Consortium cohort (N = 321), Backhausen et al (2024) studied the impact of commonly encountered negative life events in childhood, ranging from illness and death in the family to social and school problems, on depressed mood in young adulthood. Negative life events prior to age 14 were found to cumulatively impact on depressive mood in young adulthood, up to 8 years later.…”

“…However, this study lacked a prospective component, thereby leaving causal inference to speculation. Future research that combines these multimodal environment-sensitive brain patterns with the prospective design of Backhausen et al (2024), would be ideally suited to better understand the longitudinal dynamics, chronicity, and possible causality of environmental influences on brain and mental health throughout development.…”

“…In the longitudinal study by Backhausen et al. ( 2024 ), OFC thickness was measured four times between age 14 and 22, and showed the expected developmental trajectory of thinning, attributable to synaptic pruning. A thicker OFC at age 14, and a steeper pattern of cortical thinning over time, were associated with more depressed mood at age 22.…”

“…The first paper, by Backhausen et al (2024), investigated longitudinal links between negative life events in childhood, prefrontal cortex development, and depressive mood in young adulthood. The second article, by Norbom et al (2024), identified anatomical brain patterns in children that are associated with their parent's income levels and educational attainment, and that may be potential markers of resilience to socio-economic adversity.…”

“…The first paper, by Backhausen et al. ( 2024) , investigated longitudinal links between negative life events in childhood, prefrontal cortex development, and depressive mood in young adulthood. The second article, by Norbom et al.…”