Search

Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cortical thickness development and aging trajectories unfold along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distributions of dopaminergic receptors, inhibitory neurons, glial cell populations, and brain-metabolic features explain up to 50% of the variance associated with a lifespan model of regional cortical thickness trajectories. In contrast, modeled cortical thickness change patterns during adulthood are best explained by cholinergic and glutamatergic neurotransmitter receptor and transporter distributions. These relationships are supported by developmental gene expression trajectories and translate to individual longitudinal data from over 8000 adolescents, explaining up to 59% of developmental change at cohort- and 18% at single-subject level. Integrating neurobiological brain atlases with normative modeling and population neuroimaging provides a biologically meaningful path to understand brain development and aging in living humans. The neurobiology of human brain development and aging is hard to study in vivo. The authors report on distinct spatial associations between brain morphology and cellular as well as molecular brain properties throughout neurodevelopment and aging. [ABSTRACT FROM AUTHOR]

Adolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to limited large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages, and the neurobiological basis underlying individual heterogeneity remains poorly understood. Here we identify, using the IMAGEN adolescent cohort followed up over 9 years (14–23 y), three groups of adolescents characterized by distinct developmental patterns of whole-brain gray matter volume (GMV). Group 1 show continuously decreasing GMV associated with higher neurocognitive performances than the other two groups during adolescence. Group 2 exhibit a slower rate of GMV decrease and lower neurocognitive performances compared with Group 1, which was associated with epigenetic differences and greater environmental burden. Group 3 show increasing GMV and lower baseline neurocognitive performances due to a genetic variation. Using the UK Biobank, we show these differences may be attenuated in mid-to-late adulthood. Our study reveals clusters of adolescent neurodevelopment based on GMV and the potential long-term impact. Longitudinal analysis of neuroimaging data are useful for analysing heterogeneity in adolescent brain development. Here the authors cluster adolescent participants of the IMAGEN study into groups based on gray matter volume developmental patterns and investigate genome-wide and epigenome-wide associations with these groups. [ABSTRACT FROM AUTHOR]

Adolescent subcortical structural brain development might underlie psychopathological symptoms, which often emerge in adolescence. At the same time, sex differences exist in psychopathology, which might be mirrored in underlying sex differences in structural development. However, previous studies showed inconsistencies in subcortical trajectories and potential sex differences. Therefore, we aimed to investigate the subcortical structural trajectories and their sex differences across adolescence using for the first time a single cohort design, the same quality control procedure, software, and a general additive mixed modeling approach. We investigated two large European sites from ages 14 to 24 with 503 participants and 1408 total scans from France and Germany as part of the IMAGEN project including four waves of data acquisition. We found significantly larger volumes in males versus females in both sites and across all seven subcortical regions. Sex differences in age‐related trajectories were observed across all regions in both sites. Our findings provide further evidence of sex differences in longitudinal adolescent brain development of subcortical regions and thus might eventually support the relationship of underlying brain development and different adolescent psychopathology in boys and girls. [ABSTRACT FROM AUTHOR]

A growing number of evidence supports a continued distribution of autistic traits in the general population. However, brain maturation trajectories of autistic traits as well as the influence of sex on these trajectories remain largely unknown. We investigated the association of autistic traits in the general population, with longitudinal gray matter (GM) maturation trajectories during the critical period of adolescence. We assessed 709 community-based adolescents (54.7% women) at age 14 and 22. After testing the effect of sex, we used whole-brain voxel-based morphometry to measure longitudinal GM volumes changes associated with autistic traits measured by the Social Responsiveness Scale (SRS) total and sub-scores. In women, we observed that the SRS was associated with slower GM volume decrease globally and in the left parahippocampus and middle temporal gyrus. The social communication sub-score correlated with slower GM volume decrease in the left parahippocampal, superior temporal gyrus, and pallidum; and the social cognition sub-score correlated with slower GM volume decrease in the left middle temporal gyrus, the right ventromedial prefrontal and orbitofrontal cortex. No longitudinal association was found in men. Autistic traits in young women were found to be associated with specific brain trajectories in regions of the social brain and the reward circuit known to be involved in Autism Spectrum Disorder. These findings support both the hypothesis of an earlier GM maturation associated with autistic traits in adolescence and of protective mechanisms in women. They advocate for further studies on brain trajectories associated with autistic traits in women. [ABSTRACT FROM AUTHOR]

Smoking of cigarettes among young adolescents is a pressing public health issue. However, the neural mechanisms underlying smoking initiation and sustenance during adolescence, especially the potential causal interactions between altered brain development and smoking behaviour, remain elusive. Here, using large longitudinal adolescence imaging genetic cohorts, we identify associations between left ventromedial prefrontal cortex (vmPFC) gray matter volume (GMV) and subsequent self-reported smoking initiation, and between right vmPFC GMV and the maintenance of smoking behaviour. Rule-breaking behaviour mediates the association between smaller left vmPFC GMV and smoking behaviour based on longitudinal cross-lagged analysis and Mendelian randomisation. In contrast, smoking behaviour associated longitudinal covariation of right vmPFC GMV and sensation seeking (especially hedonic experience) highlights a potential reward-based mechanism for sustaining addictive behaviour. Taken together, our findings reveal vmPFC GMV as a possible biomarker for the early stages of nicotine addiction, with implications for its prevention and treatment. The relationship between brain development and smoking behaviour is not well understood. Here, the authors show an association between volume of the left ventromedial prefrontal cortex and smoking initiation in adolescents. [ABSTRACT FROM AUTHOR]

The functional neuroanatomy and connectivity of reward processing in adults are well documented, with relatively less research on adolescents, a notable gap given this developmental period's association with altered reward sensitivity. Here, a large sample (n = 1,510) of adolescents performed the monetary incentive delay (MID) task during functional magnetic resonance imaging. Probabilistic maps identified brain regions that were reliably responsive to reward anticipation and receipt, and to prediction errors derived from a computational model. Psychophysiological interactions analyses were used to examine functional connections throughout reward processing. Bilateral ventral striatum, pallidum, insula, thalamus, hippocampus, cingulate cortex, midbrain, motor area, and occipital areas were reliably activated during reward anticipation. Bilateral ventromedial prefrontal cortex and bilateral thalamus exhibited positive and negative activation, respectively, during reward receipt. Bilateral ventral striatum was reliably active following prediction errors. Previously, individual differences in the personality trait of sensation seeking were shown to be related to individual differences in sensitivity to reward outcome. Here, we found that sensation seeking scores were negatively correlated with right inferior frontal gyrus activity following reward prediction errors estimated using a computational model. Psychophysiological interactions demonstrated widespread cortical and subcortical connectivity during reward processing, including connectivity between reward‐related regions with motor areas and the salience network. Males had more activation in left putamen, right precuneus, and middle temporal gyrus during reward anticipation. In summary, we found that, in adolescents, different reward processing stages during the MID task were robustly associated with distinctive patterns of activation and of connectivity. [ABSTRACT FROM AUTHOR]

Objective: White matter microstructure alterations have recently been associated with depressive episodes during adolescence, but it is unknown whether they predate depression. The authors 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 control subjects (N=336) drawn from a community-based cohort were compared using diffusion tensor imaging and whole brain tract-based spatial statistics (TBSS) at age 14 to assess white matter microstructure. They were followed up at age 16 to assess depression. Probabilistic tractography was used to reconstruct white matter streamlines spreading from the regions identified in the TBSS analysis and along bundles implicated in emotion regulation, the uncinate fasciculus and the cingulum. The authors 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 subthreshold depression at baseline and depression at follow-up 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 may denote a higher risk of transition to depression in adolescents. [ABSTRACT FROM AUTHOR]

Sleep 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Despite calls for integration of neurobiological methods into research on youth resilience (high competence despite high adversity), we know little about structural brain correlates of resilient functioning. The aim of the current study was to test for brain regions uniquely associated with positive functioning in the context of adversity, using detailed phenotypic classification. Methods: 1,870 European adolescents (Mage = 14.56 years, SDage = 0.44 years, 51.5% female) underwent MRI scanning and completed behavioral and psychological measures of stressful life events, academic competence, social competence, rule-abiding conduct, personality, and alcohol use. Results: The interaction of competence and adversity identified two regions centered on the right middle and superior frontal gyri; grey matter volumes in these regions were larger in adolescents experiencing adversity who showed positive adaptation. Differences in these regions among competence/adversity subgroups were maintained after controlling for several covariates and were robust to alternative operationalization decisions for key constructs. Conclusions: We demonstrate structural brain correlates of adolescent resilience, and suggest that right prefrontal structures are implicated in adaptive functioning for youth who have experienced adversity. [ABSTRACT FROM AUTHOR]

Adolescence is a common time for initiation of alcohol use and alcohol use disorders. Importantly, the neuro-anatomical foundation for later alcohol-related problems may already manifest pre-natally, particularly due to smoking and alcohol consumption during pregnancy. In this context, cortical gyrification is an interesting marker of neuronal development but has not been investigated as a risk factor for adolescent alcohol use. On magnetic resonance imaging scans of 595 14-year-old adolescents from the IMAGEN sample, we computed whole-brain mean curvature indices to predict change in alcohol-related problems over the following 2 years. Change of alcohol use-related problems was significantly predicted from mean curvature in left orbitofrontal cortex (OFC). Less gyrification of OFC was associated with an increase in alcohol use-related problems over the next 2 years. Moreover, lower gyrification in left OFC was related to pre-natal alcohol exposure, whereas maternal smoking during pregnancy had no effect. Current alcohol use-related problems of the biological mother had no effect on offsprings' OFC gyrification or drinking behaviour. The data support the idea that alcohol consumption during pregnancy mediates the development of neuro-anatomical phenotypes, which in turn constitute a risk factor for increasing problems due to alcohol consumption in a vulnerable stage of life. Maternal smoking during pregnancy or current maternal alcohol/nicotine consumption had no significant effect. The OFC mediates behaviours known to be disturbed in addiction, namely impulse control and reward processing. The results stress the importance of pre-natal alcohol exposure for later increases in alcohol use-related problems, mediated by structural brain characteristics. [ABSTRACT FROM AUTHOR]

The impulsive behavior that is often characteristic of adolescence may reflect underlying neurodevelopmental processes. Moreover, impulsivity is a multi-dimensional construct, and it is plausible that distinct brain networks contribute to its different cognitive, clinical and behavioral aspects. As these networks have not yet been described, we identified distinct cortical and subcortical networks underlying successful inhibitions and inhibition failures in a large sample (n = 1,896) of 14-year-old adolescents. Different networks were associated with drug use (n = 1,593) and attention-deficit hyperactivity disorder symptoms (n = 342). Hypofunctioning of a specific orbitofrontal cortical network was associated with likelihood of initiating drug use in early adolescence. Right inferior frontal activity was related to the speed of the inhibition process (n = 826) and use of illegal substances and associated with genetic variation in a norepinephrine transporter gene (n = 819). Our results indicate that both neural endophenotypes and genetic variation give rise to the various manifestations of impulsive behavior. [ABSTRACT FROM AUTHOR]

In the last decade, several studies have described the typical brain white matter maturation in children and adolescents. Diffusion tensor imaging (DTI) is the most frequent MRI technique used to investigate the structural changes across development. However, few previous studies have used the magnetization transfer ratio (MTR), which gives a closer measure of myelin content. Here, we employed both techniques for the same sample of 176 typically developing children from 7 to 14 years of age. We investigated the associations between DTI parameters and MTR measure, to assess the myelination in the brain in development. Secondly, we investigated age-effects on DTI parameters (fractional anisotropy, axial, radial and mean diffusivities) and MTR. No significant correlations between MTR and DTI parameters were observed. In addition, a significant age-effect was detected for DTI data but was not visible for MTR data. Thereby, changes in white matter at this age might be primarily correlated with microstructural changes. [ABSTRACT FROM AUTHOR]

Background: Voxel-based analysis of diffusion tensor magnetic resonance imaging (DTI) data was used to examine white matter integrity in adolescents with early-onset schizophrenia (EOS), defined as schizophrenia beginning before the 18th birthday. Methods: Nineteen patients with EOS, aged 13 to 19, were compared with 20 healthy volunteers matched for age, gender, and parental socioeconomic status. Diffusion tensor magnetic resonance imaging data were acquired on a GE Signa NVi 1.5 Tesla system (General Electric, Milwaukee, Wisconsin). Maps of fractional anisotropy (FA) were registered into standard space, and group differences were examined using a nonparametric statistical approach. Results: In comparison with healthy participants, EOS patients had significantly lower FA in the white matter of the parietal association cortex bilaterally and in the left middle cerebellar penduncle. No areas with significantly higher FA in patients were identified. Conclusions: Parietal and cerebellar white matter abnormalities may contribute to the emergence of psychotic symptoms in adolescence. [Copyright &y& Elsevier]

Eating disorders are common in adolescence and are devastating and strongly comorbid with other psychiatric disorders. Yet little is known about their etiology, knowing which would aid in developing effective preventive measures. Longitudinal assessments of disordered eating behaviors (DEBs)—binge-eating, purging, and dieting—and comorbid psychopathology were measured in 1386 adolescents from the IMAGEN study. Development of DEBs and associated mental health problems was investigated by comparing participants who reported symptoms at ages 16 or 19 years, but not at age 14 years, with asymptomatic control participants. Voxel-based morphometry and psychopathological differences at age 14 were investigated to identify risk factors for the development of DEBs and associated mental health problems. DEBs and depressive symptoms developed together. Emotional and behavioral problems, including symptoms of attention-deficit/hyperactivity disorder and conduct disorder, predated their development. Alterations in frontostriatal brain areas also predated the development of DEBs and depressive symptoms. Specifically, development of binge-eating was predicted by higher gray matter volumes in the right putamen/globus pallidus at age 14. Conversely, development of purging and depressive symptoms was predicted by lower volumes in the medial orbitofrontal, dorsomedial, and dorsolateral prefrontal cortices. Lower gray matter volumes in the orbitofrontal and anterior cingulate cortices mediated the relationship between attention-deficit/hyperactivity disorder and conduct disorder symptoms and future purging and depressive symptoms. These findings suggest that alterations in frontal brain circuits are part of the shared etiology among eating disorders, attention-deficit/hyperactivity disorder, conduct disorder, and depression and highlight the importance of a transdiagnostic approach to treating these conditions. [ABSTRACT FROM AUTHOR]

Binge eating and other forms of disordered eating behavior (DEB) are associated with failed inhibitory control. This study investigated the neural correlates of failed inhibitory control as a potential biomarker for DEB. The study used prospective longitudinal data from the European IMAGEN study adolescent cohort. Participants completed baseline assessments (questionnaires and a brain scan [functional magnetic resonance imaging]) at 14 years of age and a follow-up assessment (questionnaires) at 16 years of age. Self-reported binge eating and/or purging were used to indicate presence of DEB. Neural correlates of failed inhibition were assessed using the stop signal task. Participants were categorized as healthy control subjects (reported no DEB at both time points), maintainers (reported DEB at both time points), recoverers (reported DEB at baseline only), and developers (reported DEB at follow-up only). Forty-three individuals per group with complete scanning data were matched on gender, age, puberty, and intelligence (N = 172). At baseline, despite similar task performance, incorrectly responding to stop signals (failed inhibitory control) was associated with greater recruitment of the medial prefrontal cortex and anterior cingulate cortex in the developers compared with healthy control subjects and recoverers. Greater recruitment of the medial prefrontal and anterior cingulate regions during failed inhibition accords with abnormal evaluation of errors contributing to DEB development. As this precedes symptom onset and is evident despite normal task performance, neural responses during failed inhibition may be a useful biomarker of vulnerability for DEB. This study highlights the potential value of prospective neuroimaging studies for identifying markers of illness before the emergence of behavior changes. [ABSTRACT FROM AUTHOR]

High adolescent alcohol consumption is predictive for alcohol problems later in life. To tailor interventions, early identification of risk groups for adolescent alcohol consumption is important. The IMAGEN dataset was utilized to investigate predictors for problematic alcohol consumption at age 18-20 years as a function self and parental personality and drug-related measures as well as life-events and cognitive variables all assessed at age 14 years (N = 1404). For this purpose the binary partitioning algorithm ctree was used in an explorative analysis. The algorithm recursively selects significant input variables and splits the outcome variable based on these, yielding a conditional inference tree. Four significant split variables, namely Place of residence, the Disorganization subscale of the Temperament and Character Inventory, Sex, and the Sexuality subscale of the life-events questionnaire were found to distinguish between adolescents scoring high or low on the Alcohol Use Disorders Identification Test about five years later (all p < 0.001). The analyis adds to the literature on predictors of adolescent drinking problems using a large European sample. The identified split variables could easily be collected in community samples. If their validity is proven in independent samples, they could facilitate intervention studies in the field of adolescent alcohol prevention. [ABSTRACT FROM AUTHOR]