Etude en imagerie par résonance magnétique des substrats neuro-anatomiques de la dépression sub-syndromique chez l'adolescent

Neuroimaging findings have been reported in emotional regions in both adults and adolescents with depression but it still remains unknown whether such brain alterations can be detected before depression onset or reflect disease progression. Although subthreshold-depression in adolescence is a condition at risk for Major Depressive Disorder, not all youths with subthreshold depression will develop full-syndrome depression. Thus, studying brain correlates of subthreshold-depression in adolescence may inform on the pathophysiology of depression. We used clinical and, T1 weighted and diffusion magnetic resonance imaging data from the IMAGEN study, an European and population-based cohort of 2131 adolescents recruited from secondary schools at age 14 and followed-up at age 16. Regional gray and white matter morphometry and white matter microstructure were compared between adolescents with subthreshold-depression and healthy control adolescents. Macro and micro structural brain changes were found in adolescents with subthreshold-depression in regions involved in Major Depressive Disorder. The relation between subthreshold-depression at baseline and clinical depression at follow-up was mediated by lower medial-prefrontal gray matter volume in girls and by lower fractional anisotropy in tracts projecting from the corpus callosum to the anterior cingulate cortex in both sexes. The findings suggest that subthreshold-depression in early adolescence is associated with structural volumetric and connectivity changes in emotion-regulation circuits, and that some of these changes might denote high risk for later clinical depression.Des anomalies macro et micro-structurales des réseaux cérébraux impliqués dans la régulation émotionnelle ont été observées chez des adolescents et des adultes présentant un trouble dépressif majeur. Cependant, on ignore si ces anomalies se développent au fur et à mesure de la maladie dépressive ou si elles sont présentes avant. La dépression sub-syndromique de l’adolescent étant associée à un risque élevé, mais non systématique, de développer ultérieurement un trouble dépressif majeur, l'étude des corrélats neuro-anatomiques qui lui sont associées pourrait apporter des informations sur la physiopathologie de la dépression. Nous avons utilisé les données cliniques et d’Imagerie par Résonance Magnétique pondérée en T1 et en diffusion de l’étude européenne IMAGEN portant sur 2131 adolescents recrutés en population générale à 14 ans, puis réévalués à 16 ans, afin de comparer les données d’adolescents présentant une dépression sub-syndromique à celles d’adolescents non déprimés. Nous avons mis en évidence des changements structuraux chez des adolescents présentant une dépression sub-syndromique dans des régions impliquées dans la dépression. La relation entre dépression sub-syndromique à 14 ans et dépression clinique à 16 ans était en partie expliquée par un plus petit volume de cortex préfrontal médian chez les filles et par de plus faibles valeurs de fraction d’anisotropie dans les faisceaux connectant le corps calleux au cortex cingulaire antérieur chez les deux sexes. A l’adolescence, des changements cérébraux dans des régions impliquées dans la régulation émotionnelle semblent être associés à un risque accru de transition vers des formes syndromiques de dépression

Sleep habits, academic performance, and the adolescent brain structure

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.Peer reviewe

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

Resilience and corpus callosum microstructure in adolescence

Background. 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. Method. Three groups of adolescents recruited from the community were compared: resilient with low risk of mental disorder despite high exposure to lifetime stress (n = 55), at-risk of mental disorder exposed to the same level of stress (n = 68), and controls (n = 123). Personality was assessed by the NEO-Five Factor Inventory (NEO-FFI). Voxelwise statistics of DTI values in CC were obtained using tract-based spatial statistics. Regional projections were identified by probabilistic tractography. Results. Higher FA values were detected in the anterior CC of resilient compared to both non-resilient and control adolescents. FA values varied according to resilience capacity. Seed regional changes in anterior CC projected onto anterior cingulate and frontal cortex. Neuroticism and three other NEO-FFI factor scores differentiated non-resilient participants from the other two groups. Conclusion. High FA was detected in resilient adolescents in an anterior CC region projecting to frontal areas subserving cognitive resources. Psychiatric risk was associated with personality characteristics. Resilience in adolescence may be related to white-matter microstructure

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

Neuropsychosocial profiles of current and future adolescent alcohol misusers

A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models1 can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers2 in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence3. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms4. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions

Differential predictors for alcohol use in adolescents as a function of familial risk

Abstract: Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions