Neural correlates of three types of negative life events during angry face processing in adolescents.

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

Early variations in white matter microstructure and depression outcome in adolescents with subthreshold-depression

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

Early variations in white matter microstructure and depression outcome in adolescents with subthreshold-depression

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

Depression, Cognitive Functions, and Impaired Functioning in Middle-Aged Adults From the CONSTANCES Cohort

International audienceOBJECTIVE:This large-scale population-based prospective study examined the association between depressive symptoms and cognitive performance at baseline with later functioning in middle-aged adults.METHODS:The Center for Epidemiologic Studies Depression Scale, the Digit Symbol Substitution Test (DSST), the Trail Making Test B (TMT-B), and the Semantic Verbal Fluency test (SVF) were completed at baseline by 7,426 participants aged ≥ 45 years from February 2012 to December 2013. Role limitations and social functioning were later assessed with the second version of the 12-Item Short Form Health Survey. The association between depressive symptoms and cognitive performance at baseline with functioning at follow-up was examined using general linear models and mediation analyses including sex, age, education, alcohol intake, and cannabis use as covariates.RESULTS:Altered functioning at follow-up was predicted by depressive symptoms (β per standard deviation [95% confidence intervals]: -1.10 [-1.16 to -1.03] and -1.02 [-1.08, -0.96] for role limitations and social functioning, respectively) and DSST, TMT-B, and SVF performance (for role limitations: 0.11 [0.09 to 0.14], -0.11 [-0.13 to -0.08], and 0.03 [0.01 to 0.06], respectively; for social functioning: 0.10 [0.07 to 0.12], -0.08 [-0.11 to -0.06], and 0.04 [0.01 to 0.05], respectively) at baseline. Depressive symptoms were associated with poorer cognitive performance at baseline (-0.19 [-0.25 to -0.13], 0.15 [0.08 to 0.21], and -0.11 [-0.17 to -0.04], respectively). Cognitive performance accounted for only 0.3%-1.4% of the relationship between depressive symptoms and functioning. In contrast, depressive symptoms accounted for 19.5%-43.7% of the association between cognitive performance and functioning.CONCLUSIONS:In middle-aged adults from the general population, cognitive impairment is unlikely to substantially explain the association between depressive symptoms and later role limitations and social functioning

Cardiovascular risk goes up as your mood goes down: Interaction of depression and socioeconomic status in determination of cardiovascular risk in the CONSTANCES cohort

International audienceBACKGROUND - Recent evidence suggests that the association of psychological variables with the risk of coronary heart disease (CHD) might depend upon socioeconomic status (SES). However, it is unclear whether the association between depressive symptoms and CHD risk might differ according to three SES indicators (education, occupational status and household monthly income). METHODS - Among 34,836 working participants of the French CONSTANCES cohort (16,221 men, mean age [SD]: 44.0 [10.4] years) without history of cardiovascular disease, depressive symptoms were assessed with the Center of Epidemiologic Studies Depression scale (CES-D). The Framingham risk equation calibrated to the French population estimated the participant's 10-year risk of CHD. Associations between depressive symptoms and CHD risk were estimated using linear regression models in SES strata. RESULTS - The estimated 10-year risk of CHD was 16.9% in men and 1.8% in women. In men, the increased CHD risk in those with (versus without) depressive symptoms was more pronounced as occupational status decreased, being 0.65% (−0.57; 1.88), 1.58% (0.50; 2.66) and 3.19% (1.30; 5.07) higher in individuals of high, medium and low occupational status, respectively (p for interaction: 0.01). In contrast, effect modification by education or household income was less evident, despite similar trends. In women, no effect modification was found whatever the SES indicator. CONCLUSIONS - Depressive symptoms and 10-year estimated CHD risk were more tightly linked in individuals of lower SES, at least in men. Occupational status was the SES indicator that displays the most obvious effect modification on this association

The brain’s response to reward anticipation and depression in adolescence: dimensionality, specificity and longitudinal predictions in a community-based sample

International audienceOBJECTIVE: The authors examined whether alterations in the brain's reward network operate as a mechanism across the spectrum of risk for depression. They then tested whether these alterations are specific to anhedonia as compared with low mood and whether they are predictive of depressive outcomes.METHOD: Functional MRI was used to collect blood-oxygen-level-dependent (BOLD) responses to anticipation of reward in the monetary incentive task in 1,576 adolescents in a community-based sample. Adolescents with current subthreshold depression and clinical depression were compared with matched healthy subjects. In addition, BOLD responses were compared across adolescents with anhedonia, low mood, or both symptoms, cross-sectionally and longitudinally.RESULTS: Activity in the ventral striatum was reduced in participants with subthreshold and clinical depression relative to healthy comparison subjects. Low ventral striatum activation predicted transition to subthreshold or clinical depression in previously healthy adolescents at 2-year follow-up. Brain responses during reward anticipation decreased in a graded manner between healthy adolescents, adolescents with current or future subthreshold depression, and adolescents with current or future clinical depression. Low ventral striatum activity was associated with anhedonia but not low mood; however, the combined presence of both symptoms showed the strongest reductions in the ventral striatum in all analyses.CONCLUSIONS: The findings suggest that reduced striatal activation operates as a mechanism across the risk spectrum for depression. It is associated with anhedonia in healthy adolescents and is a behavioral indicator of positive valence systems, consistent with predictions based on the Research Domain Criteria

Sex effects on structural maturation of the limbic system and outcomes on emotional regulation during adolescence

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Irregular sleep habits, regional grey matter volumes, and psychological functioning in adolescents

International audienceChanging sleep rhythms in adolescents often lead to sleep deficits and a delay in sleep timing between weekdays and weekends. The adolescent brain, and in particular the rapidly developing structures involved in emotional control, are vulnerable to external and internal factors. In our previous study in adolescents at age 14, we observed a strong relationship between weekend sleep schedules and regional medial prefrontal cortex grey matter volumes. Here, we aimed to assess whether this relationship remained in this group of adolescents of the general population at the age of 16 (n = 101; mean age 16.8 years; 55% girls). We further examined grey matter volumes in the hippocampi and the amygdalae, calculated with voxel-based morphometry. In addition, we investigated the relationships between sleep habits, assessed with self-reports, and regional grey matter volumes, and psychological functioning, assessed with the Strengths and Difficulties Questionnaire and tests on working memory and impulsivity. Later weekend wake-up times were associated with smaller grey matter volumes in the medial prefrontal cortex and the amygdalae, and greater weekend delays in wake-up time were associated with smaller grey matter volumes in the right hippocampus and amygdala. The medial prefrontal cortex region mediated the correlation between weekend wake up time and externalising symptoms. Paying attention to regular sleep habits during adolescence could act as a protective factor against the emergence of psychopathology via enabling favourable brain development

Longitudinal associations between adolescent catch-up sleep, white-matter maturation and internalizing problems

International audienceSleep is an important contributor for neural maturation and emotion regulation during adolescence, with long-term effects on a range of white matter tracts implicated in affective processing in at-risk populations. We investigated the effects of adolescent sleep patterns on longitudinal changes in white matter development and whether this is related to the emergence of emotional (internalizing) problems. Sleep patterns and internalizing problems were assessed using self-report questionnaires in adolescents recruited in the general population followed up from age 14-19 years (N = 111 White matter structure was measured using diffusion tensor imaging (DTI) and estimated using fractional anisotropy (FA). We found that longitudinal increases in time in bed (TIB) on weekends and increases in TIB-variability between weekdays to weekend, were associated with an increase in FA in various interhemispheric and cortico-striatal tracts. Extracted FA values from left superior longitudinal fasciculus mediated the relationship between increases in TIB on weekends and a decrease in internalizing problems. These results imply that while insufficient sleep might have potentially harmful effects on long-term white matter development and internalizing problems, longer sleep duration on weekends (catch-up sleep) might be a natural counteractive and protective strategy