In a recent study published in the journal JCPP’s progress, a group of researchers investigated whether early negative life events (NLEs) predict depressive symptoms in young adulthood through accelerated thinning of the orbitofrontal cortex (OFC) through adolescence. They used a comprehensive longitudinal study designed with four time points.
background
NLEs in childhood and adolescence, such as accidents, illnesses, and social or academic challenges, can affect brain structure and increase the risk of major depressive disorder (MDD) in adulthood.
Although severe NLE is associated with changes in OFC, there are limited studies on the effects of NLE on cortical thickness (CT) and surface area (SA). To disentangle the complex interplay between early NLE, OFC thickness development, and the onset of depressive symptoms in adulthood, especially given the limited longitudinal data and mixed results of the current study, Further research is needed.
About research
The study included 534 adolescent participants initially enrolled at two sites in the IMAGEN project.
These participants were evaluated at four different stages, starting at age 14 and then at ages 14, 16, 19, and 22. The final sample included 321 participants due to dropouts and incomplete questionnaire responses. This group was primarily white and well-educated. Exclusion criteria included serious psychiatric, neurological, or medical conditions.
At the participants’ initial examination, a modified form of the Life Events Questionnaire was administered to determine the level of exposure to NLEs. The questionnaire identified 39 potential life events, and participants rated their emotional responses to these events. This method allowed the creation of a score that reflected the severity and impact of NLE.
At the final assessment, participants completed the Center for Epidemiological Studies Depression Scale (CES-D) to assess symptoms of depression. This measure focused on the frequency of depressive symptoms experienced in the previous week.
Magnetic resonance imaging (MRI) scans were performed at each evaluation stage using a Siemens Trio 3T whole-body MR tomography machine, with various adjustments and updates of the machine at different sites and time points. The scan captured high-resolution T1-weighted images.
This study focused on cortical thickness (CT) of the orbitofrontal cortex (OFC), considering its association with NLE and depressive symptoms. Image processing and quality control were carefully handled using FreeSurfer 6.0.0 software and additional manual checks. This careful approach ensured the reliability of the data used in the study.
The statistical analysis was performed in two major steps. First, we compared multiple unconditional latent growth curve models (LGCMs) to understand changes in OFC thickness over time. The best model was selected based on various statistical criteria.
We then constructed a multiple mediator model and introduced depressive symptoms and early NLE into the analysis. This model considered direct and indirect paths between these variables and adjusted for gender, location, and emotional symptoms at initial assessment. The model was processed using Mplus version 8.7, employing full information maximum likelihood estimation to account for missing data.
research result
In the present study, a significant proportion of participants reported experiencing at least one initial NLE before the first assessment (319 of 321, >99%), with a median NLE score of 6.
By the fourth assessment, the majority of these individuals (243 of 321, approximately 76%) had subclinical levels of depression, as indicated by a score of less than 16 on the CES-D (median = 9). He showed symptoms of illness. Emotional symptoms, which serve as an early indicator of depressive symptoms, initially showed relatively low scores (median = 2).
Although individual and mean trajectories showed a nearly linear decline throughout adolescence, OFC thickness showed large interindividual variability. A linear model with a homoscedastic residual structure was determined to be optimal for modeling longitudinal thinning of the OFC. This model showed a good fit to the data, showing an average decrease in her OFC thickness across adolescence.
The multimediator model used initial NLE as a predictor, along with control variables (gender, region, affective symptoms at first assessment) for OFC thickness and depressive symptoms’ latent intercept and slope, and these growth factors and predictors Regression analysis was performed based on the factors. This model showed a significant direct path from his NLE in early life to depressive symptoms in young adulthood, but no significant indirect path through OFC thickness.
Interestingly, greater baseline OFC thickness and accelerated OFC thinning were associated with increased depressive symptoms.
Gender and site also influenced OFC thickness. Men had thicker initial OFCs compared to women, and participants at site 2 had thinner OFCs than participants at site 1, showing more pronounced thinning. However, gender and site did not significantly affect depressive symptoms, and early affective symptoms did not affect OFC thickness or reduction. Symptoms of depression in young adulthood.