Chronic peer victimization has long-term impacts on mental health; however, the biological mediators of this adverse relationship are unknown. We sought to determine whether adolescent brain ...development is involved in mediating the effect of peer victimization on psychopathology. We included participants (n = 682) from the longitudinal IMAGEN study with both peer victimization and neuroimaging data. Latent profile analysis identified groups of adolescents with different experiential patterns of victimization. We then associated the victimization trajectories and brain volume changes with depression, generalized anxiety, and hyperactivity symptoms at age 19. Repeated measures ANOVA revealed time-by-victimization interactions on left putamen volume (F = 4.38, p = 0.037). Changes in left putamen volume were negatively associated with generalized anxiety (t = -2.32, p = 0.020). Notably, peer victimization was indirectly associated with generalized anxiety via decreases in putamen volume (95% CI = 0.004-0.109). This was also true for the left caudate (95% CI = 0.002-0.099). These data suggest that the experience of chronic peer victimization during adolescence might induce psychopathology-relevant deviations from normative brain development. Early peer victimization interventions could prevent such pathological changes.
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 versus 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.
We estimated panel networks on data from the IMAGEN study, a longitudinal European cohort study following adolescents across three waves (aged 16, 19 and 22 years). Our sample consisted of 1829 adolescents (51% females) who reported alcohol use on at least one assessment wave.
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 drinking motives questionnaire (DMQ): social, enhancement, conformity, coping anxiety and coping depression. We assessed alcohol use alcohol use disorders identification test (AUDIT): quantity and frequency and alcohol-related problems (AUDIT: related problems).
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 < 0.01).
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.
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.
Background
While drinking alcohol, one must choose between the immediate rewarding effects and the delayed reward of a healthier lifestyle. Individuals differ in their devaluation of a delayed reward ...based on the time required to receive it, i.e., delay discounting (DD). Previous studies have shown that adolescents discount more steeply than adults and that steeper DD is associated with heavier alcohol use in both groups.
Methods
In a large‐scale longitudinal study, we investigated whether higher rates of DD are an antecedent or a consequence of alcohol use during adolescent development. As part of the IMAGEN project, 2220 adolescents completed the Monetary Choice Questionnaire as a DD measure, the Alcohol Use Disorders Identification Test, and the Timeline Follow Back interview at ages 14, 16, 18, and 22. Bivariate latent growth curve models were applied to investigate the relationship between DD and drinking. To explore the consequences of drinking, we computed the cumulative alcohol consumption and correlated it with the development of discounting. A subsample of 221 participants completed an intertemporal choice task (iTeCh) during functional magnetic resonance imaging at ages 14, 16, and 18. Repeated‐measures ANOVA was used to differentiate between high‐risk and low‐risk drinkers on the development of neural processing during intertemporal choices.
Results
Overall, high rates of DD at age 14 predicted a greater increase in drinking over 8 years. In contrast, on average, moderate alcohol use did not affect DD from ages 14 to 22. Of note, we found indicators for less brain activity in top‐down control areas during intertemporal choices in the participants who drank more.
Conclusions
Steep DD was shown to be a predictor rather than a consequence of alcohol use in low‐level drinking adolescents. Important considerations for future longitudinal studies are the sampling strategies to be used and the reliability of the assessments.
In a longitudinal study, we investigated adolescents from age 14 to 22 to clarify whether drinking is a cause or a consequence of delay discounting (DD), both measured by questionnaires. A subsample completed a DD task during fMRI. Steeper DD at age 14 was associated with higher increase of drinking. Decision‐related signal in medial frontal gyrus (MFG) was higher in those who drank less initially, and insula signal was higher in those who showed less increase of drinking.
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.
Mental disorders represent an increasing personal and financial burden and yet treatment development has stagnated in recent decades. Current disease classifications do not reflect psychobiological ...mechanisms of psychopathology, nor the complex interplay of genetic and environmental factors, likely contributing to this stagnation. Ten years ago, the longitudinal IMAGEN study was designed to comprehensively incorporate neuroimaging, genetics, and environmental factors to investigate the neural basis of reinforcement-related behavior in normal adolescent development and psychopathology. In this article, we describe how insights into the psychobiological mechanisms of clinically relevant symptoms obtained by innovative integrative methodologies applied in IMAGEN have informed our current and future research aims. These aims include the identification of symptom groups that are based on shared psychobiological mechanisms and the development of markers that predict disease course and treatment response in clinical groups. These improvements in precision medicine will be achieved, in part, by employing novel methodological tools that refine the biological systems we target. We will also implement our approach in low- and medium-income countries to understand how distinct environmental, socioeconomic, and cultural conditions influence the development of psychopathology. Together, IMAGEN and related initiatives strive to reduce the burden of mental disorders by developing precision medicine approaches globally.
Abnormalities across different domains of neuropsychological functioning may constitute a risk factor for heavy drinking during adolescence and for developing alcohol use disorders later in life. ...However, the exact nature of such multi‐domain risk profiles is unclear, and it is further unclear whether these risk profiles differ between genders. We combined longitudinal and cross‐sectional analyses on the large IMAGEN sample (N ≈ 1000) to predict heavy drinking at age 19 from gray matter volume as well as from psychosocial data at age 14 and 19—for males and females separately. Heavy drinking was associated with reduced gray matter volume in 19‐year‐olds' bilateral ACC, MPFC, thalamus, middle, medial and superior OFC as well as left amygdala and anterior insula and right inferior OFC. Notably, this lower gray matter volume associated with heavy drinking was stronger in females than in males. In both genders, we observed that impulsivity and facets of novelty seeking at the age of 14 and 19, as well as hopelessness at the age of 14, are risk factors for heavy drinking at the age of 19. Stressful life events with internal (but not external) locus of control were associated with heavy drinking only at age 19. Personality and stress assessment in adolescents may help to better target counseling and prevention programs. This might reduce heavy drinking in adolescents and hence reduce the risk of early brain atrophy, especially in females. In turn, this could additionally reduce the risk of developing alcohol use disorders later in adulthood.
Heavy drinking was associated with reduced gray matter volume in 19‐year‐olds' bilateral ACC, MPFC, thalamus, middle, medial and superior OFC as well as left amygdala and anterior insula and right inferior OFC. Notably, females drove this effect much stronger than males. In both genders, we observed that impulsivity and facets of novelty seeking at age 14 and 19, as well as hopelessness at age 14, are risk factors for heavy drinking at age 19.
Research in adolescent depression has found aberrant intrinsic functional connectivity (iFC) among the ventral striatum (VS) and several brain regions implicated in reward processing. The present ...study probes this question by taking advantage of the availability of data from a large youth cohort, the IMAGEN Consortium.
iFC data from 303 adolescents (48% of them female) were used to examine associations of VS connectivity at baseline (at age 14) with depressive disorders at baseline and at 2-year (N=250) and 4-year (N=219) follow-ups. Eleven regions of interest, key nodes of the reward system, were used to probe the reward network and calculate the connectivity strength of the VS within this network (VS connectivity
). The main analyses assessed associations of VS connectivity
with depressive disorders, anhedonia, and low mood using logistic regression. Autoregressive models accounting for carryover effects over time were conducted to further evaluate these brain-behavior associations.
Higher right VS connectivity
was associated with higher probability of depressive disorders at baseline (odds ratio=2.65, 95% CI=1.40, 5.05). This finding was confirmed in the autoregressive model, adjusting for carryover effects of the depressive disorders across the three time points. VS connectivity
was not predictive of depressive disorders at follow-up assessments. Longitudinal associations between VS connectivity
and anhedonia emerged in the structural equation model: left VS connectivity
was associated with anhedonia at 2 years (odds ratio=2.20, 95% CI=1.54, 3.14), and right VS connectivity
was linked to anhedonia at 4 years (odds ratio=1.87, 95% CI=1.09, 3.21). VS connectivity
did not predict low mood at any time point in the structural equation model.
The connectivity strength of the VS within the reward network showed distinct patterns of association with depressive disorders and anhedonia from mid to late adolescence, suggesting that the role of this circuitry in depression changes with age. This study replicates, in an independent sample, the association between the VS and depression previously reported in younger adolescents. The findings suggest a role of VS connectivity
in anhedonia but not in low mood.
Hemispheric lateralization and its origins have been of great interest in neuroscience for over a century. The left-right asymmetry in cortical thickness may stem from differential maturation of the ...cerebral cortex in the two hemispheres. Here, we investigated the spatial pattern of hemispheric differences in cortical thinning during adolescence, and its relationship with the density of neurotransmitter receptors and homotopic functional connectivity. Using longitudinal data from IMAGEN study (N = 532), we found that many cortical regions in the frontal and temporal lobes thinned more in the right hemisphere than in the left. Conversely, several regions in the occipital and parietal lobes thinned less in the right (vs. left) hemisphere. We then revealed that regions thinning more in the right (vs. left) hemispheres had higher density of neurotransmitter receptors and transporters in the right (vs. left) side. Moreover, the hemispheric differences in cortical thinning were predicted by homotopic functional connectivity. Specifically, regions with stronger homotopic functional connectivity showed a more symmetrical rate of cortical thinning between the left and right hemispheres, compared with regions with weaker homotopic functional connectivity. Based on these findings, we suggest that the typical patterns of hemispheric differences in cortical thinning may reflect the intrinsic organization of the neurotransmitter systems and related patterns of homotopic functional connectivity.
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.
The development of seven subcortical regions from age 14 to 24 was modeled using general additive mixed models in two large European samples. Age trajectories showed sex differences in structural brain development in all subcortical regions of interest. This might be related to different adolescent psychopathology in boys and girls.
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