Abstract: Objective: White matter microstructure alterations have recently been associated with adolescence depressive episodes, but it is unknown whether they predate depression. We investigated whether subthreshold-depression in adolescence is associated with white matter microstructure variations and whether they relate to depression outcome.
Method: Adolescents with subthreshold-depression (n=96) and healthy controls (n=336), drawn from a community-based cohort, were compared using diffusion tensor imaging and whole-brain tractbased spatial statistics (TBSS) at age 14 to assess white matter microstructure. They were followedup at age 16 to assess depression. Probabilistic tractography was used to reconstruct white matter streamlines from the TBSS analysis resulting regions, and along bundles implicated in emotion regulation, the uncinate fasciculus and the cingulum. We searched for mediating effects of white matter microstructure on the relationship between baseline subthreshold-depression and depression at follow-up, and then explored the specificity of the findings.
Results: Lower fractional anisotropy (FA) and higher radial diffusivity were found in the anterior corpus callosum in the adolescents with subthreshold-depression. Tractography analysis showed that they also had lower FA in the right cingulum streamlines, along with lower FA and higher mean diffusivity in tracts connecting the corpus callosum to the anterior cingulate cortex. The relation between baseline subthreshold-depression and follow-up depression was mediated by FA values in the latter tracts, and lower FA values in those tracts distinctively predicted higher individual risk for depression.
Conclusions: Early FA variations in tracts projecting from the corpus callosum to the anterior cingulate cortex might denote higher risk of transition to depression in adolescents.
Abstract: Here we report the first and most robust evidence about how sleep habits are associated with regional brain grey matter volumes and school grade average in early adolescence. Shorter time in bed during weekdays, and later weekend sleeping hours correlate with smaller brain grey matter volumes in frontal, anterior cingulate, and precuneus cortex regions. Poor school grade average associates with later weekend bedtime and smaller grey matter volumes in medial brain regions. The medial prefrontal - anterior cingulate cortex appears most tightly related to the adolescents’ variations in sleep habits, as its volume correlates inversely with both weekend bedtime and wake up time, and also with poor school performance. These findings suggest that sleep habits, notably during the weekends, have an alarming link with both the structure of the adolescent brain and school performance, and thus highlight the need for informed interventions.
Abstract: Negative life events (NLE) contribute to anxiety and depression disorders, but their relationship with brain functioning in adolescence has rarely been studied. We hypothesized that neural response to social threat would relate to NLE in the frontal–limbic emotional regions. Participants (N = 685) were drawn from the Imagen database of 14-year-old community adolescents recruited in schools. They underwent functional MRI while viewing angry and neutral faces, as a probe to neural response to social threat. Lifetime NLEs were assessed using the ‘distress’, ‘family’ and ‘accident’ subscales from a life event dimensional questionnaire. Relationships between NLE subscale scores and neural response were investigated. Links of NLE subscales scores with anxiety or depression outcomes at the age of 16 years were also investigated. Lifetime ‘distress’ positively correlated with ventral-lateral orbitofrontal and temporal cortex activations during angry face processing. ‘Distress’ scores correlated with the probabilities of meeting criteria for Generalized Anxiety Disorder or Major Depressive Disorder at the age of 16 years. Lifetime ‘family’ and ‘accident’ scores did not relate with neural response or follow-up conditions, however. Thus, different types of NLEs differentially predicted neural responses to threat during adolescence, and differentially predicted a de novo internalizing condition 2 years later. The deleterious effect of self-referential NLEs is suggested.
Neuroimaging findings have been reported in regions of the brain associated with emotion in both adults and adolescents with depression, but few studies have investigated whether such brain alterations can be detected in adolescents with subthreshold depression, a condition at risk for major depressive disorder. In this study, we searched for differences in brain structure at age 14 years in adolescents with subthreshold depression and their relation to depression at age 16 years.
High-resolution structural magnetic resonance imaging was used to assess adolescents with self-reported subthreshold depression (n = 119) and healthy control adolescents (n = 461), all recruited from a community-based sample. Regional gray and white matter volumes were compared across groups using whole-brain voxel-based morphometry. The relationship between subthreshold depression at baseline and depression outcome was explored using causal mediation analyses to search for mediating effects of regional brain volumes.
Adolescents with subthreshold depression had smaller gray matter volume in the ventromedial prefrontal and rostral anterior cingulate cortices and caudates, and smaller white matter volumes in the anterior limb of internal capsules, left forceps minor, and right cingulum. In girls, but not in boys, the relation between subthreshold depression at baseline and high depression score at follow-up was mediated by medial–prefrontal gray matter volume.
Subthreshold depression in early adolescence might be associated with smaller gray and white matter volumes in regions of the frontal–striatal–limbic affective circuit, and the occurrence of depression in girls with subthreshold depression might be influenced by medial–prefrontal gray matter volume. However, these findings should be interpreted with caution because of the limitations of the clinical assessment methods.
Abstract: Resilience is the capacity of individuals to resist mental disorders despite exposure to stress. Little is known about its neural underpinnings. The putative variation of white-matter microstructure with resilience in adolescence, a critical period for brain maturation and onset of high-prevalence mental disorders, has not been assessed by diffusion tensor imaging (DTI). Lower fractional anisotropy (FA) though, has been reported in the corpus callosum (CC), the brain's largest white-matter structure, in psychiatric and stress-related conditions. We hypothesized that higher FA in the CC would characterize stress-resilient adolescents.