Hemispheric asymmetry in cortical thinning reflects intrinsic organization of the neurotransmitter systems and homotopic functional connectivity.

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.

Coupled changes between ruminating thoughts and resting-state brain networks during the transition into adulthood.

Perseverative negative thoughts, known as rumination, might arise from emotional challenges and preclude mental health when transitioning into adulthood. Due to its multifaceted nature, rumination can take several ruminative response styles, that diverge in manifestations, severity, and mental health outcomes. Still, prospective ruminative phenotypes remain elusive insofar. Longitudinal study designs are ideal for stratifying ruminative response styles, especially with resting-state functional MRI whose setup naturally elicits people's ruminative traits. Here, we considered self-rated questionnaires on rumination and psychopathology, along with resting-state functional MRI data in 595 individuals assessed at age 18 and 22 from the IMAGEN cohort. We conducted independent component analysis to characterize eight single static resting-state functional networks in each subject and session and furthermore conducted a dynamic analysis, tackling the time variations of functional networks during the entire scanning time. We then investigated their longitudinal mediation role between changes in three ruminative response styles (reflective pondering, brooding, and depressive rumination) and changes in internalizing and co-morbid externalizing symptoms. Four static and two dynamic networks longitudinally differentiated these ruminative styles and showed complemental sensitivity to internalizing and co-morbid externalizing symptoms. Among these networks, the right frontoparietal network covaried with all ruminative styles but did not play any mediation role towards psychopathology. The default mode, the salience, and the limbic networks prospectively stratified these ruminative styles, suggesting that maladaptive ruminative styles are associated with altered corticolimbic function. For static measures, only the salience network played a longitudinal causal role between brooding rumination and internalizing symptoms. Dynamic measures highlighted the default-mode mediation role between the other ruminative styles and co-morbid externalizing symptoms. In conclusion, we identified the ruminative styles' psychometric and neural outcome specificities, supporting their translation into applied research on young adult mental healthcare.

Genetics impact risk of Alzheimer's disease through mechanisms modulating structural brain morphology in late life.

BACKGROUND: Alzheimer's disease (AD)-related neuropathological changes can occur decades before clinical symptoms. We aimed to investigate whether neurodevelopment and/or neurodegeneration affects the risk of AD, through reducing structural brain reserve and/or increasing brain atrophy, respectively. METHODS: We used bidirectional two-sample Mendelian randomisation to estimate the effects between genetic liability to AD and global and regional cortical thickness, estimated total intracranial volume, volume of subcortical structures and total white matter in 37 680 participants aged 8-81 years across 5 independent cohorts (Adolescent Brain Cognitive Development, Generation R, IMAGEN, Avon Longitudinal Study of Parents and Children and UK Biobank). We also examined the effects of global and regional cortical thickness and subcortical volumes from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium on AD risk in up to 37 741 participants. RESULTS: Our findings show that AD risk alleles have an age-dependent effect on a range of cortical and subcortical brain measures that starts in mid-life, in non-clinical populations. Evidence for such effects across childhood and young adulthood is weak. Some of the identified structures are not typically implicated in AD, such as those in the striatum (eg, thalamus), with consistent effects from childhood to late adulthood. There was little evidence to suggest brain morphology alters AD risk. CONCLUSIONS: Genetic liability to AD is likely to affect risk of AD primarily through mechanisms affecting indicators of brain morphology in later life, rather than structural brain reserve. Future studies with repeated measures are required for a better understanding and certainty of the mechanisms at play.

Anxiety onset in adolescents: a machine-learning prediction.

Recent longitudinal studies in youth have reported MRI correlates of prospective anxiety symptoms during adolescence, a vulnerable period for the onset of anxiety disorders. However, their predictive value has not been established. Individual prediction through machine-learning algorithms might help bridge the gap to clinical relevance. A voting classifier with Random Forest, Support Vector Machine and Logistic Regression algorithms was used to evaluate the predictive pertinence of gray matter volumes of interest and psychometric scores in the detection of prospective clinical anxiety. Participants with clinical anxiety at age 18-23 (N = 156) were investigated at age 14 along with healthy controls (N = 424). Shapley values were extracted for in-depth interpretation of feature importance. Prospective prediction of pooled anxiety disorders relied mostly on psychometric features and achieved moderate performance (area under the receiver operating curve = 0.68), while generalized anxiety disorder (GAD) prediction achieved similar performance. MRI regional volumes did not improve the prediction performance of prospective pooled anxiety disorders with respect to psychometric features alone, but they improved the prediction performance of GAD, with the caudate and pallidum volumes being among the most contributing features. To conclude, in non-anxious 14 year old adolescents, future clinical anxiety onset 4-8 years later could be individually predicted. Psychometric features such as neuroticism, hopelessness and emotional symptoms were the main contributors to pooled anxiety disorders prediction. Neuroanatomical data, such as caudate and pallidum volume, proved valuable for GAD and should be included in prospective clinical anxiety prediction in adolescents.

Cognitive and brain development is independently influenced by socioeconomic status and polygenic scores for educational attainment.

Genetic factors and socioeconomic status (SES) inequalities play a large role in educational attainment, and both have been associated with variations in brain structure and cognition. However, genetics and SES are correlated, and no prior study has assessed their neural associations independently. Here we used a polygenic score for educational attainment (EduYears-PGS), as well as SES, in a longitudinal study of 551 adolescents to tease apart genetic and environmental associations with brain development and cognition. Subjects received a structural MRI scan at ages 14 and 19. At both time points, they performed three working memory (WM) tasks. SES and EduYears-PGS were correlated (r = 0.27) and had both common and independent associations with brain structure and cognition. Specifically, lower SES was related to less total cortical surface area and lower WM. EduYears-PGS was also related to total cortical surface area, but in addition had a regional association with surface area in the right parietal lobe, a region related to nonverbal cognitive functions, including mathematics, spatial cognition, and WM. SES, but not EduYears-PGS, was related to a change in total cortical surface area from age 14 to 19. This study demonstrates a regional association of EduYears-PGS and the independent prediction of SES with cognitive function and brain development. It suggests that the SES inequalities, in particular parental education, are related to global aspects of cortical development, and exert a persistent influence on brain development during adolescence.

Associations of delay discounting and drinking trajectories from ages 14 to 22.

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.

The Human Brain Is Best Described as Being on a Female/Male Continuum: Evidence from a Neuroimaging Connectivity Study.

Psychological androgyny has long been associated with greater cognitive flexibility, adaptive behavior, and better mental health, but whether a similar concept can be defined using neural features remains unknown. Using the neuroimaging data from 9620 participants, we found that global functional connectivity was stronger in the male brain before middle age but became weaker after that, when compared with the female brain, after systematic testing of potentially confounding effects. We defined a brain gender continuum by estimating the likelihood of an observed functional connectivity matrix to represent a male brain. We found that participants mapped at the center of this continuum had fewer internalizing symptoms compared with those at the 2 extreme ends. These findings suggest a novel hypothesis proposing that there exists a neuroimaging concept of androgyny using the brain gender continuum, which may be associated with better mental health in a similar way to psychological androgyny.

Identifying biological markers for improved precision medicine in psychiatry.

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.

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.

Neuropsychosocial profiles of current and future adolescent alcohol misusers.

A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.

Heavy drinking in adolescents is associated with change in brainstem microstructure and reward sensitivity.

Heavy drinker adolescents: altered brainstem microstructure.

The cortical-cerebellar circuit is vulnerable to heavy drinking (HD) in adults. We hypothesized early microstructural modifications of the pons/midbrain region, containing core structures of the reward system, in HD adolescents. Thirty-two otherwise symptom-free HDs at age 14 (HD14) and 24 abstainers becoming HDs at age 16 (HD16) were identified in the community with the Alcohol Use Disorders Identification Test (AUDIT) and compared with abstainers. The monetary incentive delay (MID) task assessed reward-sensitive performance. Voxelwise statistics of diffusion tensor imaging (DTI) values in the thalamo-ponto-mesencephalic region were obtained using tract-based spatial statistics. Projections between the ventral tegmental area (VTA) and the nucleus accumbens (NAcc) were identified by probabilistic tractography. Lower fraction of anisotropy and higher radial diffusivity (RD) values were detected in the upper dorsal pons of HD14 adolescents, and a trend for higher RD in HD16, compared with abstainers. When expecting reward, HD14 had higher MID task success scores than abstainers, and success scores were higher with a lower number of tracts in all adolescents. In symptom-free community adolescents, a region of lower white matter (WM) integrity in the pons at age 14 was associated with current HD and predicted HD at age 16. HD was related to reward sensitivity.

The initiation of cannabis use in adolescence is predicted by sex-specific psychosocial and neurobiological features.

Cannabis use initiated during adolescence might precipitate negative consequences in adulthood. Thus, predicting adolescent cannabis use prior to any exposure will inform the aetiology of substance abuse by disentangling predictors from consequences of use. In this prediction study, data were drawn from the IMAGEN sample, a longitudinal study of adolescence. All selected participants (n = 1,581) were cannabis-naïve at age 14. Those reporting any cannabis use (out of six ordinal use levels) by age 16 were included in the outcome group (N = 365, males n = 207). Cannabis-naïve participants at age 14 and 16 were included in the comparison group (N = 1,216, males n = 538). Psychosocial, brain and genetic features were measured at age 14 prior to any exposure. Cross-validated regularized logistic regressions for each use level by sex were used to perform feature selection and obtain prediction error statistics on independent observations. Predictors were probed for sex- and drug-specificity using post-hoc logistic regressions. Models reliably predicted use as indicated by satisfactory prediction error statistics, and contained psychosocial features common to both sexes. However, males and females exhibited distinct brain predictors that failed to predict use in the opposite sex or predict binge drinking in independent samples of same-sex participants. Collapsed across sex, genetic variation on catecholamine and opioid receptors marginally predicted use. Using machine learning techniques applied to a large multimodal dataset, we identified a risk profile containing psychosocial and sex-specific brain prognostic markers, which were likely to precede and influence cannabis initiation.

Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence.

BACKGROUND: Abnormalities in reward circuit function are considered a core feature of addiction. Yet, it is still largely unknown whether these abnormalities stem from chronic drug use, a genetic predisposition, or both. METHODS: In the present study, we investigated this issue using a large sample of adolescent children by applying structural equation modeling to examine the effects of several dopaminergic polymorphisms of the D1 and D2 receptor type on the reward function of the ventral striatum (VS) and orbital frontal cortex (OFC), and whether this relationship predicted the propensity to engage in early alcohol misuse behaviors at 14 years of age and again at 16 years of age. RESULTS: The results demonstrated a regional specificity with which the functional polymorphism rs686 of the D1 dopamine receptor (DRD1) gene and Taq1A of the ANKK1 gene influenced medial and lateral OFC activation during reward anticipation, respectively. Importantly, our path model revealed a significant indirect relationship between the rs686 of the DRD1 gene and early onset of alcohol misuse through a medial OFC × VS interaction. CONCLUSIONS: These findings highlight the role of D1 and D2 in adjusting reward-related activations within the mesocorticolimbic circuitry, as well as in the susceptibility to early onset of alcohol misuse.

Risk profiles for heavy drinking in adolescence: differential effects of gender.

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.

Overdominant Effect of a CHRNA4 Polymorphism on Cingulo-Opercular Network Activity and Cognitive Control.

The nicotinic system plays an important role in cognitive control and is implicated in several neuropsychiatric conditions. However, the contributions of genetic variability in this system to individuals' cognitive control abilities are poorly understood and the brain processes that mediate such genetic contributions remain largely unidentified. In this first large-scale neuroimaging genetics study of the human nicotinic receptor system (two cohorts, males and females, fMRI total N = 1586, behavioral total N = 3650), we investigated a common polymorphism of the high-affinity nicotinic receptor α4ß2 (rs1044396 on the CHRNA4 gene) previously implicated in behavioral and nicotine-related studies (albeit with inconsistent major/minor allele impacts). Based on our prior neuroimaging findings, we expected this polymorphism to affect neural activity in the cingulo-opercular (CO) network involved in core cognitive control processes including maintenance of alertness. Consistent across the cohorts, all cortical areas of the CO network showed higher activity in heterozygotes compared with both types of homozygotes during cognitive engagement. This inverted U-shaped relation reflects an overdominant effect; that is, allelic interaction (cumulative evidence p = 1.33 * 10-5). Furthermore, heterozygotes performed more accurately in behavioral tasks that primarily depend on sustained alertness. No effects were observed for haplotypes of the surrounding CHRNA4 region, supporting a true overdominant effect at rs1044396. As a possible mechanism, we observed that this polymorphism is an expression quantitative trait locus modulating CHRNA4 expression levels. This is the first report of overdominance in the nicotinic system. These findings connect CHRNA4 genotype, CO network activation, and sustained alertness, providing insights into how genetics shapes individuals' cognitive control abilities.SIGNIFICANCE STATEMENT The nicotinic acetylcholine system plays a central role in neuromodulatory regulation of cognitive control processes and is dysregulated in several neuropsychiatric disorders. Despite this functional importance, no large-scale neuroimaging genetics studies have targeted the contributions of genetic variability in this system to human brain activity. Here, we show the impact of a common polymorphism of the high-affinity nicotinic receptor α4ß2 that is consistent across brain activity and behavior in two large human cohorts. We report a hitherto unknown overdominant effect (allelic interaction) at this locus, where the heterozygotes show higher activity in the cingulo-opercular network underlying alertness maintenance and higher behavioral alertness performance than both homozygous groups. This gene-brain-behavior relationship informs about the biological basis of interindividual differences in cognitive control.

Individual differences in stop-related activity are inflated by the adaptive algorithm in the stop signal task.

Research using the Stop Signal Task employing an adaptive algorithm to accommodate individual differences often report inferior performance on the task in individuals with ADHD, OCD, and substance use disorders compared to non-clinical controls. Furthermore, individuals with deficits in inhibitory control tend to show reduced neural activity in key inhibitory regions during successful stopping. However, the adaptive algorithm systematically introduces performance-related differences in objective task difficulty that may influence the estimation of individual differences in stop-related neural activity. This report examines the effect that these algorithm-related differences have on the measurement of neural activity during the stop signal task. We compared two groups of subjects (n = 210) who differed in inhibitory ability using both a standard fMRI analysis and an analysis that resampled trials to remove the objective task difficulty confound. The results show that objective task difficulty influences the magnitude of between-group differences and that controlling for difficulty attenuates stop-related activity differences between superior and poor inhibitors. Specifically, group differences in the right inferior frontal gyrus, right middle occipital gyrus, and left inferior frontal gyrus are diminished when differences in objective task difficulty are controlled for. Also, when objective task difficulty effects are exaggerated, group differences in stop related activity emerge in other regions of the stopping network. The implications of these effects for how we interpret individual differences in activity levels are discussed.

Amygdala and regional volumes in treatment-resistant versus nontreatment-resistant depression patients.

BACKGROUND: Although treatment-resistant and nontreatment-resistant depressed patients show structural brain anomalies relative to healthy controls, the difference in regional volumetry between these two groups remains undocumented. METHODS: A whole-brain voxel-based morphometry (VBM) analysis of regional volumes was performed in 125 participants' magnetic resonance images obtained on a 1.5 Tesla scanner; 41 had treatment-resistant depression (TRD), 40 nontreatment-resistant depression (non-TRD), and 44 were healthy controls. The groups were comparable for age and gender. Bipolar/unipolar features as well as pharmacological treatment classes were taken into account as covariates. RESULTS: TRD patients had higher gray matter (GM) volume in the left and right amygdala than non-TRD patients. No difference was found between the TRD bipolar and the TRD unipolar patients, or between the non-TRD bipolar and non-TRD unipolar patients. An exploratory analysis showed that lithium-treated patients in both groups had higher GM volume in the superior and middle frontal gyri in both hemispheres. CONCLUSIONS: Higher GM volume in amygdala detected in TRD patients might be seen in perspective with vulnerability to chronicity, revealed by medication resistance.

The role of the cannabinoid receptor in adolescents' processing of facial expressions.

The processing of emotional faces is an important prerequisite for adequate social interactions in daily life, and might thus specifically be altered in adolescence, a period marked by significant changes in social emotional processing. Previous research has shown that the cannabinoid receptor CB1R is associated with longer gaze duration and increased brain responses in the striatum to happy faces in adults, yet, for adolescents, it is not clear whether an association between CBR1 and face processing exists. In the present study we investigated genetic effects of the two CB1R polymorphisms, rs1049353 and rs806377, on the processing of emotional faces in healthy adolescents. They participated in functional magnetic resonance imaging during a Faces Task, watching blocks of video clips with angry and neutral facial expressions, and completed a Morphed Faces Task in the laboratory where they looked at different facial expressions that switched from anger to fear or sadness or from happiness to fear or sadness, and labelled them according to these four emotional expressions. A-allele versus GG-carriers in rs1049353 displayed earlier recognition of facial expressions changing from anger to sadness or fear, but not for expressions changing from happiness to sadness or fear, and higher brain responses to angry, but not neutral, faces in the amygdala and insula. For rs806377 no significant effects emerged. This suggests that rs1049353 is involved in the processing of negative facial expressions with relation to anger in adolescence. These findings add to our understanding of social emotion-related mechanisms in this life period.

New evidence of factor structure and measurement invariance of the SDQ across five European nations.

The main purpose of the present study was to analyse the internal structure and to test the measurement invariance of the Strengths and Difficulties Questionnaire (SDQ), self-reported version, in five European countries. The sample consisted of 3012 adolescents aged between 12 and 17 years (M = 14.20; SD = 0.83). The five-factor model (with correlated errors added), and the five-factor model (with correlated errors added) with the reverse-worded items allowed to cross-load on the Prosocial subscale, displayed adequate goodness of-fit indices. Multi-group confirmatory factor analysis showed that the five-factor model (with correlated errors added) had partial strong measurement invariance by countries. A total of 11 of the 25 items were non-invariant across samples. The level of internal consistency of the Total difficulties score was 0.84, ranging between 0.69 and 0.78 for the SDQ subscales. The findings indicate that the SDQ's subscales need to be modified in various ways for screening emotional and behavioural problems in the five European countries that were analysed.

Dimensions of manic symptoms in youth: psychosocial impairment and cognitive performance in the IMAGEN sample.

BACKGROUND: It has been reported that mania may be associated with superior cognitive performance. In this study, we test the hypothesis that manic symptoms in youth separate along two correlated dimensions and that a symptom constellation of high energy and cheerfulness is associated with superior cognitive performance. METHOD: We studied 1755 participants of the IMAGEN study, of average age 14.4 years (SD = 0.43), 50.7% girls. Manic symptoms were assessed using the Development and Wellbeing Assessment by interviewing parents and young people. Cognition was assessed using the Wechsler Intelligence Scale For Children (WISC-IV) and a response inhibition task. RESULTS: Manic symptoms in youth formed two correlated dimensions: one termed exuberance, characterized by high energy and cheerfulness and one of undercontrol with distractibility, irritability and risk-taking behavior. Only the undercontrol, but not the exuberant dimension, was independently associated with measures of psychosocial impairment. In multivariate regression models, the exuberant, but not the undercontrolled, dimension was positively and significantly associated with verbal IQ by both parent- and self-report; conversely, the undercontrolled, but not the exuberant, dimension was associated with poor performance in a response inhibition task. CONCLUSIONS: Our findings suggest that manic symptoms in youth may form dimensions with distinct correlates. The results are in keeping with previous findings about superior performance associated with mania. Further research is required to study etiological differences between these symptom dimensions and their implications for clinical practice.