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

Changing 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.Peer reviewe

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

Though adolescence is a time of emerging sex differences in emotions, sex-related differences in the anatomy of the maturing brain has been under-explored over this period. The aim of this study was to investigate whether puberty and sexual differentiation in brain maturation could explain emotional differences between girls and boys during adolescence. We adapted a dedicated longitudinal pipeline to process structural and diffusion images from 335 typically developing adolescents between 14 and 16 years. We used voxel-based and Regions of Interest approaches to explore sex and puberty effects on brain and behavioral changes during adolescence. Sexual differences in brain maturation were characterized by amygdala and hippocampal volume increase in boys and decrease in girls. These changes were mediating the sexual differences in positive emotional regulation as illustrated by positive attributes increase in boys and decrease in girls. Moreover, the differential maturation rates between the limbic system and the prefrontal cortex highlighted the delayed maturation in boys compared to girls. This is the first study to show the sex effects on the differential cortico/subcortical maturation rates and the interaction between sex and puberty in the limbic system maturation related to positive attributes, reported as being protective from emotional disorders.Peer reviewe

The empirical replicability of task-based fMRI as a function of sample size

Replicating results (i.e. obtaining consistent results using a new independent dataset) is an essential part of good science. As replicability has consequences for theories derived from empirical studies, it is of utmost importance to better understand the underlying mechanisms influencing it. A popular tool for non-invasive neuroimaging studies is functional magnetic resonance imaging (fMRI). While the effect of underpowered studies is well documented, the empirical assessment of the interplay between sample size and replicability of results for task-based fMRI studies remains limited. In this work, we extend existing work on this assessment in two ways. Firstly, we use a large database of 1400 subjects performing four types of tasks from the IMAGEN project to subsample a series of independent samples of increasing size. Secondly, replicability is evaluated using a multi-dimensional framework consisting of 3 different measures: (un)conditional test-retest reliability, coherence and stability. We demonstrate not only a positive effect of sample size, but also a trade-off between spatial resolution and replicability. When replicability is assessed voxelwise or when observing small areas of activation, a larger sample size than typically used in fMRI is required to replicate results. On the other hand, when focussing on clusters of voxels, we observe a higher replicability. In addition, we observe variability in the size of clusters of activation between experimental paradigms or contrasts of parameter estimates within these

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

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

Background Early 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. Methods We 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. Results A 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. Conclusions Using 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

Personality, attentional biases towards emotional faces and symptoms of mental disorders in an adolescent sample

Objective To investigate the role of personality factors and attentional biases towards emotional faces, in establishing concurrent and prospective risk for mental disorder diagnosis in adolescence. Method Data were obtained as part of the IMAGEN study, conducted across 8 European sites, with a community sample of 2257 adolescents. At 14 years, participants completed an emotional variant of the dot-probe task, as well two personality measures, namely the Substance Use Risk Profile Scale and the revised NEO Personality Inventory. At 14 and 16 years, participants and their parents were interviewed to determine symptoms of mental disorders. Results Personality traits were general and specific risk indicators for mental disorders at 14 years. Increased specificity was obtained when investigating the likelihood of mental disorders over a 2-year period, with the Substance Use Risk Profile Scale showing incremental validity over the NEO Personality Inventory. Attentional biases to emotional faces did not characterise or predict mental disorders examined in the current sample. Discussion Personality traits can indicate concurrent and prospective risk for mental disorders in a community youth sample, and identify at-risk youth beyond the impact of baseline symptoms. This study does not support the hypothesis that attentional biases mediate the relationship between personality and psychopathology in a community sample. Task and sample characteristics that contribute to differing results among studies are discussed

The relationship between negative life events and cortical structural connectivity in adolescents

Adolescence is a crucial period for physical and psychological development. The impact of negative life events represents a risk factor for the onset of neuropsychiatric disorders. This study aims to investigate the relationship between negative life events and structural brain connectivity, considering both graph theory and connectivity strength. A group (n = 487) of adolescents from the IMAGEN Consortium was divided into Low and High Stress groups. Brain networks were extracted at an individual level, based on morphological similarity between grey matter regions with regions defined using an atlas-based region of interest (ROI) approach. Between-group comparisons were performed with global and local graph theory measures in a range of sparsity levels. The analysis was also performed in a larger sample of adolescents (n = 976) to examine linear correlations between stress level and network measures. Connectivity strength differences were investigated with network-based statistics. Negative life events were not found to be a factor influencing global network measures at any sparsity level. At local network level, between-group differences were found in centrality measures of the left somato-motor network (a decrease of betweenness centrality was seen at sparsity 5%), of the bilateral central visual and the left dorsal attention network (increase of degree at sparsity 10% at sparsity 30% respectively). Network-based statistics analysis showed an increase in connectivity strength in the High stress group in edges connecting the dorsal attention, limbic and salience networks. This study suggests negative life events alone do not alter structural connectivity globally, but they are associated to connectivity properties in areas involved in emotion and attention.</p

Ventral striatum connectivity during reward anticipation in adolescent smokers

Substance misusers, including adolescent smokers, often have reduced reward system activity during processing of non-drug rewards. Using a psychophysiological interaction approach, we examined functional connectivity with the ventral striatum during reward anticipation in a large (N = 206) sample of adolescent smokers. Increased smoking frequency was associated with (1) increased connectivity with regions involved in saliency and valuation, including the orbitofrontal cortex and (2) reduced connectivity between the ventral striatum and regions associated with inhibition and risk aversion, including the right inferior frontal gyrus. These results demonstrate that functional connectivity during reward processing is relevant to adolescent addiction

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

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

Drinking Motives, Personality Traits, Life Stressors - Identifying Pathways to Harmful Alcohol Use in Adolescence Using a Panel Network Approach

BACKGROUND AND AIMS: Models of alcohol use risk suggest that drinking motives represent the most proximal risk factors on which more distal factors converge. However, little is known about how distinct risk factors influence each other and alcohol use on different temporal scales (within a given moment vs. over time). We aimed to estimate the dynamic associations of distal (personality and life stressors) and proximal (drinking motives) risk factors, and their relationship to alcohol use in adolescence and early adulthood using a novel graphical vector autoregressive (GVAR) panel network approach.DESIGN, SETTING, AND CASES: We estimated panel networks on data from the IMAGEN study, a longitudinal European cohort study following adolescents across three waves (ages 16, 19, 22). Our sample consisted of 1829 adolescents (51% females) who reported alcohol use on at least one assessment wave.MEASUREMENTS: Risk factors included personality traits (NEO-FFI: neuroticism, extraversion, openness, agreeableness, and conscientiousness; SURPS: impulsivity and sensation seeking), stressful life events (LEQ: sum scores of stressful life events), and drinking motives (DMQ: social, enhancement, conformity, coping anxiety, coping depression). We assessed alcohol use (AUDIT: quantity and frequency) and alcohol-related problems (AUDIT: related problems).FINDINGS: Within a given moment, social (partial correlation (pcor) =0.17) and enhancement motives (pcor=0.15) co-occurred most strongly with drinking quantity and frequency, while coping depression motives (pcor=0.13), openness (pcor=0.05), and impulsivity (pcor=0.09) were related to alcohol-related problems. The temporal network showed no predictive associations between distal risk factors and drinking motives. Social motives (beta=0.21), previous alcohol use (beta=0.11), and openness (beta=0.10) predicted alcohol-related problems over time (all p&lt;0.01).CONCLUSIONS: Heavy and frequent alcohol use, along with social drinking motives, appear to be key targets for preventing the development of alcohol-related problems throughout late adolescence. We found no evidence for personality traits and life stressors predisposing towards distinct drinking motives over time.</p