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.

Emotions and worries during 1.5 years of the COVID-19 pandemic - how adults with and without mental health conditions coped with the crisis.

BACKGROUND: During the COVID 19 pandemic, there were social restrictions with severe mental stress for a long time. Most studies on mental health consequences of the pandemic focused primarily on the beginning of the pandemic. The present study on families of patients or study participants of a child and adolescent psychiatry aimed to examine long-term profiles of emotions and worries in adults with and without mental health condition (mhc) during the first 1.5 years of the COVID-19 pandemic. METHODS: We surveyed emotions and worries of 128 adults with (n = 32) and without (n = 96) pre-pandemic mhc over a 1.5-year study period from spring 2020 until summer/autumn 2021. Emotions and worries were captured at four time points: [i] pre-pandemic, [ii] spring 2020 (first lockdown was implemented), [iii] December 2020 (hard lockdown at Christmas time) and [iv] summer/autumn 2021 (considerable ease of regulations); [i] pre-pandemic and [iii] December 2020 were measured retrospectively). First, we run non-parametric tests to compare emotions and worries between adults with and without pre-pandemic mhc at the four time points. Next, we conducted latent profile analysis to identify subgroups from the total sample who share similar trajectories of emotions and worries. Finally, a logistic regression analysis was run to examine whether socio-demographic and psycho-social factors were related to identified trajectories of emotions and worries. RESULTS: Adults without pre-pandemic mhc reported a strong worsening of emotions and worries at the beginning of the pandemic and a lower worsening during the course, while adults with pre-pandemic mhc reported a constant worsening of emotions and worries. The latent profile analysis revealed three profiles of adults who show either i) an adaption, ii) no adaption or iii) a continuous high condition. With increasing age, higher perceived stress and pre-pandemic mhc, the likelihood of an adaption was increased. CONCLUSION: The results of the present study suggested that adults (both with and without pre-pandemic mhc) coped the crisis with different strategies and that most of them returned to their initial, pre-pandemic levels of emotions and worries when social restrictions were considerably eased or stopped.

Adolescent to young adult longitudinal development of subcortical volumes in two European sites with four waves.

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.

App-Based Mindfulness Meditation Training and an Audiobook Intervention Reduce Symptom Severity but Do Not Modify Backward Inhibition in Adolescent Obsessive-Compulsive Disorder: Evidence from an EEG Study.

(1) Background: 1-2% of children and adolescents are affected by Obsessive-Compulsive Disorder (OCD). The rigid, repetitive features of OCD and an assumed disability to inhibit recent mental representations are assumed to have led to a paradoxical advantage in that the Backward Inhibition (BI) effect was recently found to be lower in adolescents with OCD as compared to healthy controls. It was hypothesized that app-based mindfulness meditation training could reduce the disability to inhibit recent mental representations and thus increase the BI-effect by adapting cognitive flexibility and inhibition abilities according to healthy controls. (2) Methods: 58 adolescents (10-19 years) with OCD were included in the final sample of this interviewer-blind, randomized controlled study. Participants were allocated to an intervention group (app-based mindfulness meditation training) or an (active) control group (app-based audiobook) for eight weeks. Symptom (CY-BOCS), behavioral (reaction times and mean accuracy), and neurophysiological changes (in EEG) of the BI-effect were analyzed in a pre-post design. (3) Results: The intervention and the control group showed an intervention effect (Reliable Change Index: 67%) with a significant symptom reduction. Contrary to the hypothesis, the BI-effect did not differ between pre vs. post app-based mindfulness meditation training. In addition, as expected the audiobook application showed no effects. Thus, we observed no intervention-specific differences with respect to behavioral (reaction times and mean accuracy) or with respect to neurophysiological (perceptual [P1], attentional [N1], conflict monitoring [N2] or updating and response selection [P3]) processes. However, in an exploratory approach, we revealed that the BI-effect decreased in participants who did not benefit from using an app, regardless of group. (4) Conclusions: Both listening to an app-based mindfulness meditation training and to an audiobook reduce symptom severity in adolescent OCD as measured by the CY-BOCS; however, they have no specific effect on BI. The extent of the baseline BI-effect might be considered as an intra-individual component to predict the benefit of both mindfulness meditation training and listening to an audiobook.

Is loss avoidance differentially rewarding in adolescents versus adults? Differences in ventral striatum and anterior insula activation during the anticipation of potential monetary losses.

Avoiding loss is a crucial, adaptive guide to human behavior. While previous developmental research has primarily focused on gaining rewards, less attention has been paid to loss processing and its avoidance. In daily life, it is often unknown how likely an action will result in a loss, making the role of uncertainty in loss processing particularly important. By using functional magnetic resonance imaging, we investigated the influence of varying outcome probabilities (12%, 34%, and 67%) on brain regions implicated in loss processing (ventral striatum (VS), anterior insula (AI)) by comparing 28 adolescents (10-18 years) and 24 adults (22-32 years) during the anticipation of potential monetary loss.Overall, results revealed slower RTs in adolescents compared to adults with both groups being faster in the experimental (monetary condition) vs. control trials (verbal condition). Fastest RTs were observed for the 67% outcome probability in both age groups. An age group × outcome probability interaction effect revealed the greatest differences between the groups for the 12% vs. the 67% outcome probability. Neurally, both age groups demonstrated a higher percent signal change in the VS and AI during the anticipation of potential monetary loss versus the verbal condition. However, adults demonstrated an even greater activation of VS and AI than adolescents during the anticipation of potential monetary loss, but not during the verbal condition. This may indicate that adolescents differ from adults regarding their experience of avoiding losing monetary rewards.

Adolescent to young adult longitudinal development across 8 years for matching emotional stimuli during functional magnetic resonance imaging.

We investigated development from adolescence to young adulthood of neural bottom-up and top-down processes using a functional magnetic resonance imaging task on emotional attention. We followed 249 participants from age 14-22 in up to four waves resulting in 687 total scans of a matching task in which participants decided whether two pictures were the same including distracting emotional or neutral scenes. We applied generalized additive mixed models and a reliability approach for longitudinal analysis. Reaction times and error rates decreased longitudinally. For top-down processing, we found a longitudinal increase for the bilateral inferior frontal gyrus (IFG) for negative stimuli and in the left IFG also for positive and neutral stimuli. For bottom-up activation in the bilateral amygdala, we found a relative stability for negative and neutral stimuli. For positive stimuli, there was an increase starting in the twenties. Results show ongoing behavioral and top-down prefrontal development relatively independent from emotional valence. Amygdala bottom-up activation remained stable except for positive stimuli. Current findings add to the sparse literature on longitudinal top-down and bottom-up development into young adulthood and emphasize the role of reliability. These findings might help to characterize healthy in contrast to dysfunctional development of emotional attention.

Best Practices in Structural Neuroimaging of Neurodevelopmental Disorders.

Structural magnetic resonance imaging (sMRI) offers immense potential for increasing our understanding of how anatomical brain development relates to clinical symptoms and functioning in neurodevelopmental disorders. Clinical developmental sMRI may help identify neurobiological risk factors or markers that may ultimately assist in diagnosis and treatment. However, researchers and clinicians aiming to conduct sMRI studies of neurodevelopmental disorders face several methodological challenges. This review offers hands-on guidelines for clinical developmental sMRI. First, we present brain morphometry metrics and review evidence on typical developmental trajectories throughout adolescence, together with atypical trajectories in selected neurodevelopmental disorders. Next, we discuss challenges and good scientific practices in study design, image acquisition and analysis, and recent options to implement quality control. Finally, we discuss choices related to statistical analysis and interpretation of results. We call for greater completeness and transparency in the reporting of methods to advance understanding of structural brain alterations in neurodevelopmental disorders.

Ventral Striatal Activation During Reward Anticipation of Different Reward Probabilities in Adolescents and Adults.

Adolescence has been linked to an enhanced tolerance of uncertainty and risky behavior and is possibly connected to an increased response toward rewards. However, previous research has produced inconsistent findings. To investigate whether these findings are due to different reward probabilities used in the experimental design, we extended a monetary incentive delay (MID) task by including three different reward probabilities. Using functional magnetic resonance imaging, 25 healthy adolescents and 22 adults were studied during anticipation of rewards in the VS. Differently colored cue stimuli indicated either a monetary or verbal trial and symbolized different reward probabilities, to which the participants were blinded. Results demonstrated faster reaction times for lower reward probabilities (33%) in both age groups. Adolescents were slower through all conditions and had less activation on a neural level. Imaging results showed a three-way interaction between age group x condition x reward probability with differences in percent signal change between adolescents and adults for the high reward probabilities (66%, 88%) while adolescents demonstrated differences for the lowest (33%). Therefore, previous inconsistent findings could be due to different reward probabilities, which makes examining these crucial for a better understanding of adolescent and adult behavior.

Neuroimaging evidence for structural correlates in adolescents resilient to polysubstance use: A five-year follow-up study.

Early initiation of polysubstance use (PSU) is a strong predictor of subsequent addiction, however scarce individuals present resilience capacity. This neuroimaging study aimed to investigate structural correlates associated with cessation or reduction of PSU and determine the extent to which brain structural features accounted for this resilient outcome. Participants from a European community-based cohort self-reported their alcohol, tobacco and cannabis use frequency at ages 14, 16 and 19 and had neuroimaging sessions at ages 14 and 19. We included three groups in the study: the resilient-to-PSU participants showed PSU at 16 and/or 14 but no more at 19 (n = 18), the enduring polysubstance users at 19 displayed PSU continuation from 14 or 16 (n = 193) and the controls were abstinent or low drinking participants (n = 460). We conducted between-group comparisons of grey matter volumes on whole brain using voxel-based morphometry and regional fractional anisotropy using tract-based spatial statistics. Random-forests machine-learning approach generated individual-level PSU-behavior predictions based on personality and neuroimaging features. Adolescents resilient to PSU showed significant larger grey matter volumes in the bilateral cingulate gyrus compared with enduring polysubstance users and controls at ages 19 and 14 (p<0.05 corrected) but no difference in fractional anisotropy. The larger cingulate volumes and personality trait "openness to experience" were the best precursors of resilience to PSU. Early in adolescence, a larger cingulate gyrus differentiated adolescents resilient to PSU, and this feature was critical in predicting this outcome. This study encourages further research into the neurobiological bases of resilience to addictive behaviors.

Do ADHD-impulsivity and BMI have shared polygenic and neural correlates?

There is an extensive body of literature linking ADHD to overweight and obesity. Research indicates that impulsivity features of ADHD account for a degree of this overlap. The neural and polygenic correlates of this association have not been thoroughly examined. In participants of the IMAGEN study, we found that impulsivity symptoms and body mass index (BMI) were associated (r = 0.10, n = 874, p = 0.014 FWE corrected), as were their respective polygenic risk scores (PRS) (r = 0.17, n = 874, p = 6.5 × 10-6 FWE corrected). We then examined whether the phenotypes of impulsivity and BMI, and the PRS scores of ADHD and BMI, shared common associations with whole-brain grey matter and the Monetary Incentive Delay fMRI task, which associates with reward-related impulsivity. A sparse partial least squared analysis (sPLS) revealed a shared neural substrate that associated with both the phenotypes and PRS scores. In a last step, we conducted a bias corrected bootstrapped mediation analysis with the neural substrate score from the sPLS as the mediator. The ADHD PRS associated with impulsivity symptoms (b = 0.006, 90% CIs = 0.001, 0.019) and BMI (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. The BMI PRS associated with BMI (b = 0.014, 95% CIs = 0.003, 0.033) and impulsivity symptoms (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. A common neural substrate may (in part) underpin shared genetic liability for ADHD and BMI and the manifestation of their (observable) phenotypic association.

The impact of emotional congruent and emotional neutral context on recognizing complex emotions in older adults.

Adding context information has been shown to attenuate the age-related decline of emotion recognition. Specifically, older adults might benefit from emotional congruent context information due to their greater social knowledge. Contrary, emotional neutral context information might impair older adults' performance more due to their decline of inhibitory abilities. Our aim was to examine the age-related decline of complex emotion recognition across three context conditions (emotional congruent, emotional neutral and no context). We hypothesized that emotional congruent context will help older adults to perform at the same level as younger adults and expected worse performance of older adults in the emotional neutral and no context conditions. Twenty-eight older and 28 younger adults watched film clips with complex emotions preceded by a fixation cross (no context), emotional congruent context or emotional neutral context. Emotional neutral context affected older adults' performance more negatively than young adults', whereas emotional congruent improved performance of both young and older adults to a similar extent. Results suggest that emotional congruent context does not eliminate the overall age-related deficit in complex emotion recognition. In contrast, this deficit might be intensified by emotional neutral context.

Distinct brain structure and behavior related to ADHD and conduct disorder traits.

Attention-Deficit/Hyperactivity Disorder (ADHD) and conduct disorder (CD) exemplify top-down dysregulation conditions that show a large comorbidity and shared genetics. At the same time, they entail two different types of symptomology involving mainly non-emotional or emotional dysregulation. Few studies have tried to separate the specific biology underlying these two dimensions. It has also been suggested that both types of conditions consist of extreme cases in the general population where the symptoms are widely distributed. Here we test whether brain structure is specifically associated to ADHD or CD symptoms in a general population of adolescents (n = 1093) being part of the IMAGEN project. Both ADHD symptoms and CD symptoms were related to similar and overlapping MRI findings of a smaller structure in prefrontal and anterior cingulate cortex. However, our regions of interest (ROI) approach indicated that gray matter volume (GMV) and surface area (SA) in dorsolateral/dorsomedial prefrontal cortex and caudal anterior cingulate cortex were negatively associated to ADHD symptoms when controlling for CD symptoms while rostral anterior cingulate cortex GMV was negatively associated to CD symptoms when controlling for ADHD symptoms. The structural findings were mirrored in performance of neuropsychological tests dependent on prefrontal and anterior cingulate regions, showing that while performance on the Stop Signal test was specifically related to the ADHD trait, delayed discounting and working memory were related to both ADHD and CD traits. These results point towards a partially domain specific and dimensional capacity in different top-down regulatory systems associated with ADHD and CD symptoms.

Association of Gray Matter and Personality Development With Increased Drunkenness Frequency During Adolescence.

Importance: Alcohol abuse correlates with gray matter development in adolescents, but the directionality of this association remains unknown. Objective: To investigate the directionality of the association between gray matter development and increase in frequency of drunkenness among adolescents. Design, Setting, and Participants: This cohort study analyzed participants of IMAGEN, a multicenter brain imaging study of healthy adolescents in 8 European sites in Germany (Mannheim, Dresden, Berlin, and Hamburg), the United Kingdom (London and Nottingham), Ireland (Dublin), and France (Paris). Data from the second follow-up used in the present study were acquired from January 1, 2013, to December 31, 2016, and these data were analyzed from January 1, 2016, to March 31, 2018. Analyses were controlled for sex, site, socioeconomic status, family history of alcohol dependency, puberty score, negative life events, personality, cognition, and polygenic risk scores. Personality and frequency of drunkenness were assessed at age 14 years (baseline), 16 years (first follow-up), and 19 years (second follow-up). Structural brain imaging scans were acquired at baseline and second follow-up time points. Main Outcomes and Measures: Increases in drunkenness frequency were measured by latent growth modeling, a voxelwise hierarchical linear model was used to observe gray matter volume, and tensor-based morphometry was used for gray matter development. The hypotheses were formulated before the data analyses. Results: A total of 726 adolescents (mean [SD] age at baseline, 14.4 [0.38] years; 418 [58%] female) were included. The increase in drunkenness frequency was associated with accelerated gray matter atrophy in the left posterior temporal cortex (peak: t1,710 = -5.8; familywise error (FWE)-corrected P = 7.2 × 10-5; cluster: 6297 voxels; P = 2.7 × 10-5), right posterior temporal cortex (cluster: 2070 voxels; FWE-corrected P = .01), and left prefrontal cortex (peak: t1,710 = -5.2; FWE-corrected P = 2 × 10-3; cluster: 10 624 voxels; P = 1.9 × 10-7). According to causal bayesian network analyses, 73% of the networks showed directionality from gray matter development to drunkenness increase as confirmed by accelerated gray matter atrophy in late bingers compared with sober controls (n = 20 vs 60; ß = 1.25; 95% CI, -2.15 to -0.46; t1,70 = 0.3; P = .004), the association of drunkenness increase with gray matter volume at age 14 years (ß = 0.23; 95% CI, 0.01-0.46; t1,584 = 2; P = .04), the association between gray matter atrophy and alcohol drinking units (ß = -0.0033; 95% CI, -6 × 10-3 to -5 × 10-4; t1,509 = -2.4; P = .02) and drunkenness frequency at age 23 years (ß = -0.16; 95% CI, -0.28 to -0.03; t1,533 = -2.5; P = .01), and the linear exposure-response curve stratified by gray matter atrophy and not by increase in frequency of drunkenness. Conclusions and Relevance: This study found that gray matter development and impulsivity were associated with increased frequency of drunkenness by sex. These results suggest that neurotoxicity-related gray matter atrophy should be interpreted with caution.

Cannabis-Associated Psychotic-like Experiences Are Mediated by Developmental Changes in the Parahippocampal Gyrus.

OBJECTIVE: Cannabis consumption during adolescence has been reported as a risk factor for psychotic-like experiences (PLEs) and schizophrenia. However, brain developmental processes associated with cannabis-related PLEs are still poorly described. METHOD: A total of 706 adolescents from the general population who were recruited by the IMAGEN consortium had structural magnetic resonance imaging scans at both 14 and 19 years of age. We used deformation-based morphometry to map voxelwise brain changes between the two time points, using the pairwise algorithm in SPM12b. We used an a priori region-of-interest approach focusing on the hippocampus/parahippocampus to perform voxelwise linear regressions. Lifetime cannabis consumption was assessed using the European School Survey Project on Alcohol and other Drugs (ESPAD), and PLEs were assessed with the Comprehensive Assessment Psychotic-like experiences (CAPE) tool. We first tested whether hippocampus/parahippocampus development was associated with PLEs. Then we formulated and tested an a priori simple mediation model in which uncus development mediates the association between lifetime cannabis consumption and PLEs. RESULTS: We found that PLEs were associated with reduced expansion within a specific region of the right hippocampus/parahippocampus formation, the uncus (p = .002 at the cluster level, p = .018 at the peak level). The partial simple mediation model revealed a significant total effect from lifetime cannabis consumption to PLEs (b = 0.069, 95% CI = 0.04-0.1, p =2 × 10-16), as well as a small yet significant, indirect effect of right uncus development (0.004; 95% CI = 0.0004-0.01, p = .026). CONCLUSION: We show here that the uncus development is involved in the cerebral basis of PLEs in a population-based sample of healthy adolescents.

Altered brain morphology in boys with attention deficit hyperactivity disorder with and without comorbid conduct disorder/oppositional defiant disorder.

About 50% of attention deficit hyperactivity disorder (ADHD) patients suffer from comorbidity with oppositional defiant disorder/conduct disorder (ODD/CD). Most previous studies on structural morphology did not differentiate between pure (ADHD-only) and comorbid ADHD (ADHD+ODD/CD). Therefore, we aimed to investigate the structural profile of ADHD-only versus ADHD+ODD/CD spanning the indices subcortical and cortical volume, cortical thickness, and surface area. We predicted a reduced total gray matter, striatal, and cerebellar volume in both patient groups and a reduced amygdalar and hippocampal volume for ADHD+ODD/CD. We also explored alterations in prefrontal volume, thickness, and surface area. We acquired structural images from an adolescent sample ranging from 11 to 17 years, matched with regard to age, pubertal status, and IQ-including 36 boys with ADHD-only, 26 boys with ADHD+ODD/CD, and 30 typically developing (TD) boys. We analyzed structural data with FreeSurfer. We found reductions in total gray matter and total surface area for both patient groups. Boys with ADHD+ODD/CD had a thicker cortex than the other groups in a right rostral middle frontal cluster, which was related to stronger ODD/CD symptoms, even when controlling for ADHD symptoms. No group differences in local cortical volume or surface area emerged. We demonstrate the necessity to carefully differentiate between ADHD and ADHD+ODD/CD. The increased rostral middle frontal thickness might hint at a delayed adolescent cortical thinning in ADHD+ODD/CD. Patients with the double burden ADHD and ODD or CD seem to be even more affected than patients with pure ADHD.

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.

Adolescent Basic Facial Emotion Recognition Is Not Influenced by Puberty or Own-Age Bias.

Basic facial emotion recognition is suggested to be negatively affected by puberty onset reflected in a "pubertal dip" in performance compared to pre- or post-puberty. However, findings remain inconclusive. Further, research points to an own-age bias, i.e., a superior emotion recognition for peer faces. We explored adolescents' ability to recognize specific emotions. Ninety-five children and adolescents, aged 8-17 years, judged whether the emotions displayed by adolescent or adult faces were angry, sad, neutral, or happy. We assessed participants a priori by pubertal status while controlling for age. Results indicated no "pubertal dip", but decreasing reaction times across adolescence. No own-age bias was found. Taken together, basic facial emotion recognition does not seem to be disrupted during puberty as compared to pre- and post-puberty.

Anterior insula hyperactivation in ADHD when faced with distracting negative stimuli.

Patients with attention deficit hyperactivity disorder (ADHD) suffer from poor emotion regulation that might arise from problems in the distribution of attentional resources when confronted with emotional distractors. Previous studies investigating the neurocognitive basis of these problems remain inconclusive. Moreover, most of these studies did not exclude participants with comorbidity, particularly of conduct or oppositional defiant disorder. The aim of this study was to assess alterations in fronto-limbic activation in ADHD adolescents specifically during negative distractors in an emotional attention task. For this purpose, we used functional magnetic resonance imaging to assess 25 boys with noncomorbid ADHD and 25 typically developing (TD) boys while they performed an emotional attention task with positive, negative, and neutral emotional distractors. Boys with ADHD had increased activation relative to TD boys specifically during the negative valenced stimuli in an emotional processing network comprising left anterior insula reaching into the inferior frontal gyrus. The findings suggest altered salience processing in ADHD of negative valenced emotional stimuli that may lead to higher distractibility in ADHD specifically when faced with negative emotional distractors.

Methylation of OPRL1 mediates the effect of psychosocial stress on binge drinking in adolescents.

BACKGROUND: Nociceptin is a key regulator linking environmental stress and alcohol drinking. In a genome-wide methylation analysis, we recently identified an association of a methylated region in the OPRL1 gene with alcohol-use disorders. METHODS: Here, we investigate the biological basis of this observation by analysing psychosocial stressors, methylation of the OPRL1 gene, brain response during reward anticipation and alcohol drinking in 660 fourteen-year-old adolescents of the IMAGEN study. We validate our findings in marchigian sardinian (msP) alcohol-preferring rats that are genetically selected for increased alcohol drinking and stress sensitivity. RESULTS: We found that low methylation levels in intron 1 of OPRL1 are associated with higher psychosocial stress and higher frequency of binge drinking, an effect mediated by OPRL1 methylation. In individuals with low methylation of OPRL1, frequency of binge drinking is associated with stronger BOLD response in the ventral striatum during reward anticipation. In msP rats, we found that stress results in increased alcohol intake and decreased methylation of OPRL1 in the nucleus accumbens. CONCLUSIONS: Our findings describe an epigenetic mechanism that helps to explain how psychosocial stress influences risky alcohol consumption and reward processing, thus contributing to the elucidation of biological mechanisms underlying risk for substance abuse.

Test-retest reliability of longitudinal task-based fMRI: Implications for developmental studies.

Great advances have been made in functional Magnetic Resonance Imaging (fMRI) studies, including the use of longitudinal design to more accurately identify changes in brain development across childhood and adolescence. While longitudinal fMRI studies are necessary for our understanding of typical and atypical patterns of brain development, the variability observed in fMRI blood-oxygen-level dependent (BOLD) signal and its test-retest reliability in developing populations remain a concern. Here we review the current state of test-retest reliability for child and adolescent fMRI studies (ages 5-18 years) as indexed by intraclass correlation coefficients (ICC). In addition to highlighting ways to improve fMRI test-retest reliability in developmental cognitive neuroscience research, we hope to open a platform for dialogue regarding longitudinal fMRI study designs, analyses, and reporting of results.