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.
Objective:Adolescents are particularly vulnerable to addiction, and in the case of smoking, this often leads to long-lasting nicotine dependence. The authors investigated a possible neural mechanism ...underlying this vulnerability.
Method:Functional MRI was performed during reward anticipation in 43 adolescent smokers and 43 subjects matched on age, gender, and IQ. The authors also assessed group differences in novelty seeking, impulsivity, and reward delay discounting.
Results:In relation to the comparison subjects, the adolescent smokers showed greater reward delay discounting and higher scores for novelty seeking. Neural responses in the ventral striatum during reward anticipation were significantly lower in the smokers than in the comparison subjects, and in the smokers this response was correlated with smoking frequency. Notably, the lower response to reward anticipation in the ventral striatum was also observed in smokers (N=14) who had smoked on fewer than 10 occasions.
Conclusions:The present findings suggest that a lower response to reward anticipation in the ventral striatum may be a vulnerability factor for the development of early nicotine use.
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.
Data from genome-wide association studies (GWASs) have been used to estimate the heritability of human complex traits in recent years. Existing methods are based on the linear mixed model, with the ...assumption that the genetic effects are random variables, which is opposite to the fixed effect assumption embedded in the framework of quantitative genetics theory. Moreover, heritability estimators provided by existing methods may have large standard errors, which calls for the development of reliable and accurate methods to estimate heritability.
In this paper, we first investigate the influences of the fixed and random effect assumption on heritability estimation, and prove that these two assumptions are equivalent under mild conditions in the theoretical aspect. Second, we propose a two-stage strategy by first performing sparse regularization via cross-validated elastic net, and then applying variance estimation methods to construct reliable heritability estimations. Results on both simulated data and real data show that our strategy achieves a considerable reduction in the standard error while reserving the accuracy.
The proposed strategy allows for a reliable and accurate heritability estimation using GWAS data. It shows the promising future that reliable estimations can still be obtained with even a relatively restricted sample size, and should be especially useful for large-scale heritability analyses in the genomics era.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Moment-to-moment reaction time variability on tasks of attention, often quantified by intra-individual response variability (IRV), provides a good indication of the degree to which an individual is ...vulnerable to lapses in sustained attention. Increased IRV is a hallmark of several disorders of attention, including Attention-Deficit/Hyperactivity Disorder (ADHD). Here, task-based fMRI was used to provide the first examination of how average brain activation and functional connectivity patterns in adolescents are related to individual differences in sustained attention as measured by IRV. We computed IRV in a large sample of adolescents (n = 758) across 'Go' trials of a Stop Signal Task (SST). A data-driven, multi-step analysis approach was used to identify networks associated with low IRV (i.e., good sustained attention) and high IRV (i.e., poorer sustained attention). Low IRV was associated with greater functional segregation (i.e., stronger negative connectivity) amongst an array of brain networks, particularly between cerebellum and motor, cerebellum and prefrontal, and occipital and motor networks. In contrast, high IRV was associated with stronger positive connectivity within the motor network bilaterally and between motor and parietal, prefrontal, and limbic networks. Consistent with these observations, a separate sample of adolescents exhibiting elevated ADHD symptoms had increased fMRI activation and stronger positive connectivity within the same motor network denoting poorer sustained attention, compared to a matched asymptomatic control sample. With respect to the functional connectivity signature of low IRV, there were no statistically significant differences in networks denoting good sustained attention between the ADHD symptom group and asymptomatic control group. We propose that sustained attentional processes are facilitated by an array of neural networks working together, and provide an empirical account of how the functional role of the cerebellum extends to cognition in adolescents. This work highlights the involvement of motor cortex in the integrity of sustained attention, and suggests that atypically strong connectivity within motor networks characterizes poor attentional capacity in both typically developing and ADHD symptomatic adolescents.
The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic ...factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.
Background
Stress exposure in childhood and adolescence has been linked to reductions in cortical structures and cognitive functioning. However, to date, most of these studies have been ...cross‐sectional, limiting the ability to make long‐term inferences, given that most cortical structures continue to develop through adolescence.
Methods
Here, we used a subset of the IMAGEN population cohort sample (N = 502; assessment ages: 14, 19, and 22 years; mean age: 21.945 years; SD = 0.610) to understand longitudinally the long‐term interrelations between stress, cortical development, and cognitive functioning. To these ends, we first used a latent change score model to examine four bivariate relations – assessing individual differences in change in the relations between adolescent stress exposure and volume, surface area, and cortical thickness of cortical structures, as well as cognitive outcomes. Second, we probed for indirect neurocognitive effects linking stress to cortical brain structures and cognitive functions using rich longitudinal mediation modeling.
Results
Latent change score modeling showed that greater baseline adolescence stress at age 14 predicted a small reduction in the right anterior cingulate volume (Std. β = −.327, p = .042, 95% CI −0.643, −0.012) and right anterior cingulate surface area (Std. β = −.274, p = .038, 95% CI −0.533, −0.015) across ages 14–22. These effects were very modest in nature and became nonsignificant after correcting for multiple comparisons. Our longitudinal analyses found no evidence of indirect effects in the two neurocognitive pathways linking adolescent stress to brain and cognitive outcomes.
Conclusion
Findings shed light on the impact of stress on brain reductions, particularly in the prefrontal cortex that have consistently been implicated in the previous cross‐sectional studies. However, the magnitude of effects observed in our study is smaller than that has been reported in past cross‐sectional work. This suggests that the potential impact of stress during adolescence on brain structures may likely be more modest than previously noted.
Period (Per) genes are involved in regulation of the circadian clock and are thought to modulate several brain functions. We demonstrate that Per2(Brdm1) mutant mice, which have a deletion in the PAS ...domain of the Per2 protein, show alterations in the glutamatergic system. Lowered expression of the glutamate transporter Eaat1 is observed in these animals, leading to reduced uptake of glutamate by astrocytes. As a consequence, glutamate levels increase in the extracellular space of Per2(Brdm1) mutant mouse brains. This is accompanied by increased alcohol intake in these animals. In humans, variations of the PER2 gene are associated with regulation of alcohol consumption. Acamprosate, a drug used to prevent craving and relapse in alcoholic patients is thought to act by dampening a hyper-glutamatergic state. This drug reduced augmented glutamate levels and normalized increased alcohol consumption in Per2(Brdm1) mutant mice. Collectively, these data establish glutamate as a link between dysfunction of the circadian clock gene Per2 and enhanced alcohol intake.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Comorbidity is the rule rather than the exception for childhood and adolescent onset mental disorders, but we cannot predict its occurrence and do not know the neural mechanisms underlying ...comorbidity. We investigate if the effects of comorbid internalizing and externalizing disorders on anatomical differences represent a simple aggregate of the effects on each disorder and if these comorbidity-associated cortical surface differences relate to a distinct genetic underpinning.
We studied the cortical surface area (SA) and thickness (CT) of 11,878 preadolescents (9-10 years) from the Adolescent Brain and Cognitive Development Study. Linear mixed models were implemented in comparative and association analyses among internalizing (dysthymia, major depressive disorder, disruptive mood dysregulation disorder, agoraphobia, panic disorder, specific phobia, separation anxiety disorder, social anxiety disorder, generalized anxiety disorder, post-traumatic stress disorder), externalizing (attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder) diagnostic groups, a group with comorbidity of the two and a healthy control group. Genome-wide association analysis (GWAS) and cell type specificity analysis were performed on 4468 unrelated European participants from this cohort.
Smaller cortical surface area but higher thickness was noted across patient groups when compared to controls. Children with comorbid internalizing and externalizing disorders had more pronounced areal reduction than those without comorbidity, indicating an additive burden. In contrast, cortical thickness had a non-linear effect with comorbidity: the comorbid group had no significant CT differences, while those patient groups without comorbidity had significantly higher thickness compare to healthy controls. Distinct biological pathways were implicated in regional SA and CT differences. Specifically, CT differences were associated with immune-related processes implicating astrocytes and oligodendrocytes, while SA-related differences related mainly to inhibitory neurons.
The emergence of comorbidity across distinct clusters of psychopathology is unlikely to be due to a simple additive neurobiological effect alone. Distinct developmental risk moderated by immune-related adaptation processes, with unique genetic and cell-specific factors, may contribute to underlying SA and CT differences. Children with the highest risk but lowest resilience, both captured in their developmental morphometry, may develop a comorbid illness pattern.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anxiety and depression in children and adolescents warrant special attention as a public health concern given their devastating and long-term effects on development and mental health. Multiple ...factors, ranging from genetic vulnerabilities to environmental stressors, influence the risk for the disorders. This study aimed to understand how environmental factors and genomics affect children and adolescents anxiety and depression across three cohorts: Adolescent Brain and Cognitive Development Study (US, age of 9-10; N=11,875), Consortium on Vulnerability to Externalizing Disorders and Addictions (INDIA, age of 6-17; N=4,326) and IMAGEN (EUROPE, age of 14; N=1888). We performed data harmonization and identified the environmental impact on anxiety/depression using a linear mixed-effect model, recursive feature elimination regression, and the LASSO regression model. Subsequently, genome-wide association analyses with consideration of significant environmental factors were performed for all three cohorts by mega-analysis and meta-analysis, followed by functional annotations. The results showed that multiple environmental factors contributed to the risk of anxiety and depression during development, where early life stress and school support index had the most significant and consistent impact across all three cohorts. In both meta, and mega-analysis, SNP rs79878474 in chr11p15 emerged as a particularly promising candidate associated with anxiety and depression, despite not reaching genomic significance. Gene set analysis on the common genes mapped from top promising SNPs of both meta and mega analyses found significant enrichment in regions of chr11p15 and chr3q26, in the function of potassium channels and insulin secretion, in particular Kv3, Kir-6.2, SUR potassium channels encoded by the KCNC1, KCNJ11, and ABCCC8 genes respectively, in chr11p15. Tissue enrichment analysis showed significant enrichment in the small intestine, and a trend of enrichment in the cerebellum. Our findings provide evidences of consistent environmental impact from early life stress and school support index on anxiety and depression during development and also highlight the genetic association between mutations in potassium channels, which support the stress-depression connection via hypothalamic-pituitary-adrenal axis, along with the potential modulating role of potassium channels.
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