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  • Gowland, Penny  (3)
  • Itterman, Bernd  (3)
  • 1
    In: Molecular Psychiatry, Springer Science and Business Media LLC, Vol. 25, No. 11 ( 2020-11), p. 2648-2671
    Abstract: Imaging genetics offers the possibility of detecting associations between genotype and brain structure as well as function, with effect sizes potentially exceeding correlations between genotype and behavior. However, study results are often limited due to small sample sizes and methodological differences, thus reducing the reliability of findings. The IMAGEN cohort with 2000 young adolescents assessed from the age of 14 onwards tries to eliminate some of these limitations by offering a longitudinal approach and sufficient sample size for analyzing gene-environment interactions on brain structure and function. Here, we give a systematic review of IMAGEN publications since the start of the consortium. We then focus on the specific phenotype ‘drug use’ to illustrate the potential of the IMAGEN approach. We describe findings with respect to frontocortical, limbic and striatal brain volume, functional activation elicited by reward anticipation, behavioral inhibition, and affective faces, and their respective associations with drug intake. In addition to describing its strengths, we also discuss limitations of the IMAGEN study. Because of the longitudinal design and related attrition, analyses are underpowered for (epi-) genome-wide approaches due to the limited sample size. Estimating the generalizability of results requires replications in independent samples. However, such densely phenotyped longitudinal studies are still rare and alternative internal cross-validation methods (e.g., leave-one out, split-half) are also warranted. In conclusion, the IMAGEN cohort is a unique, very well characterized longitudinal sample, which helped to elucidate neurobiological mechanisms involved in complex behavior and offers the possibility to further disentangle genotype × phenotype interactions.
    Type of Medium: Online Resource
    ISSN: 1359-4184 , 1476-5578
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 1502531-7
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  • 2
    In: Human Brain Mapping, Wiley, Vol. 39, No. 8 ( 2018-08), p. 3263-3276
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1065-9471 , 1097-0193
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1492703-2
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  • 3
    In: Journal of Child Psychology and Psychiatry, Wiley, Vol. 55, No. 12 ( 2014-12), p. 1380-1389
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0021-9630 , 1469-7610
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 1470297-6
    SSG: 5,2
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