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1. Drinking motives, personality traits and life stressors-identifying pathways to harmful alcohol use in adolescence using a panel network approach

Author: Freichel, René, Pfirrmann, Janine, Cousjin, Janna, de Jong, Peter, Franken, Ingmar, Banaschewski, Tobias, Bokde, Arun L W, Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Heinz, Andreas, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H, Smolka, Michael N, Vaidya, Nilakshi, Whelan, Robert, Schumann, Gunter, Walter, Henrik, Veer, Ilya M, Wiers, Reinout W, Consortium, IMAGEN, Freichel, René, Pfirrmann, Janine, Cousjin, Janna, de Jong, Peter, Franken, Ingmar, Banaschewski, Tobias, Bokde, Arun L W, Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Heinz, Andreas, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H, Smolka, Michael N, Vaidya, Nilakshi, Whelan, Robert, Schumann, Gunter, Walter, Henrik, Veer, Ilya M, Wiers, Reinout W, and Consortium, IMAGEN
Abstract: Background and aims: 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. Design, setting and cases: 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. Measurements: 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). Findings: 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 probl
Published: 2023

2. Visual deep learning of unprocessed neuroimaging characterises dementia subtypes and generalises across non-stereotypic samples

Author: Moguilner, Sebastian, Whelan, Robert, Adams, Hieab, Valcour, Victor, Tagliazucchi, Enzo, Ibáñez, Agustín, Moguilner, Sebastian, Whelan, Robert, Adams, Hieab, Valcour, Victor, Tagliazucchi, Enzo, and Ibáñez, Agustín
Abstract: Background: Dementia's diagnostic protocols are mostly based on standardised neuroimaging data collected in the Global North from homogeneous samples. In other non-stereotypical samples (participants with diverse admixture, genetics, demographics, MRI signals, or cultural origins), classifications of disease are difficult due to demographic and region-specific sample heterogeneities, lower quality scanners, and non-harmonised pipelines. Methods: We implemented a fully automatic computer-vision classifier using deep learning neural networks. A DenseNet was applied on raw (unpreprocessed) data from 3000 participants (behavioural variant frontotemporal dementia-bvFTD, Alzheimer's disease-AD, and healthy controls; both male and female as self-reported by participants). We tested our results in demographically matched and unmatched samples to discard possible biases and performed multiple out-of-sample validations. Findings: Robust classification results across all groups were achieved from standardised 3T neuroimaging data from the Global North, which also generalised to standardised 3T neuroimaging data from Latin America. Moreover, DenseNet also generalised to non-standardised, routine 1.5T clinical images from Latin America. These generalisations were robust in samples with heterogenous MRI recordings and were not confounded by demographics (i.e., were robust in both matched and unmatched samples, and when incorporating demographic variables in a multifeatured model). Model interpretability analysis using occlusion sensitivity evidenced core pathophysiological regions for each disease (mainly the hippocampus in AD, and the insula in bvFTD) demonstrating biological specificity and plausibility. Interpretation: The generalisable approach outlined here could be used in the future to aid clinician decision-making in diverse samples. Funding: The specific funding of this article is provided in the acknowledgements section.
Published: 2023

3. A biologically informed polygenic score of neuronal plasticity moderates the association between cognitive aptitudes and cortical thickness in adolescents

Author: Navarri, Xavier, Vosberg, Daniel E., Shin, Jean, Richer, Louis, Leonard, Gabriel, Pike, G. Bruce, Banaschewski, Tobias, Bokde, Arun L.W., Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Brühl, Rüdiger, Martinot, Jean-Luc, Paillère Martinot, Marie-Laure, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H., Smolka, Michael N., Vaidya, Nilakshi, Walter, Henrik, Whelan, Robert, Schumann, Gunter, Pausova, Zdenka, Paus, Tomáš, Navarri, Xavier, Vosberg, Daniel E., Shin, Jean, Richer, Louis, Leonard, Gabriel, Pike, G. Bruce, Banaschewski, Tobias, Bokde, Arun L.W., Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Brühl, Rüdiger, Martinot, Jean-Luc, Paillère Martinot, Marie-Laure, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H., Smolka, Michael N., Vaidya, Nilakshi, Walter, Henrik, Whelan, Robert, Schumann, Gunter, Pausova, Zdenka, and Paus, Tomáš
Abstract: Although many studies of the adolescent brain identified positive associations between cognitive abilities and cortical thickness, little is known about mechanisms underlying such brain-behavior relationships. With experience-induced plasticity playing an important role in shaping the cerebral cortex throughout life, it is likely that some of the inter-individual variations in cortical thickness could be explained by genetic variations in relevant molecular processes, as indexed by a polygenic score of neuronal plasticity (PGS-NP). Here, we studied associations between PGS-NP, cognitive abilities, and thickness of the cerebral cortex, estimated from magnetic resonance images, in the Saguenay Youth Study (SYS, 533 females, 496 males: age=15.0 ± 1.8 years of age; cross-sectional), and the IMAGEN Study (566 females, 556 males; between 14 and 19 years; longitudinal). Using Gene Ontology, we first identified 199 genes implicated in neuronal plasticity, which mapped to 155,600 single nucleotide polymorphisms (SNPs). Second, we estimated their effect sizes from an educational attainment meta-GWAS to build a PGS-NP. Third, we examined a possible moderating role of PGS-NP in the relationship between performance intelligence quotient (PIQ), and its subtests, and the thickness of 34 cortical regions. In SYS, we observed a significant interaction between PGS-NP and object assembly vis-à-vis thickness in male adolescents (p = 0.026). A median-split analysis showed that, in males with a ‘high’ PGS-NP, stronger associations between object assembly and thickness were found in regions with larger age-related changes in thickness (r = 0.55, p = 0.00075). Although the interaction between PIQ and PGS-NP was non-significant (p = 0.064), we performed a similar median-split analysis. Again, in the high PGS-NP males, positive associations between PIQ and thickness were observed in regions with larger age-related changes in thickness (r = 0.40, p = 0.018). In the IMAGEN cohort, we did not r
Published: 2023
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4. Independent contribution of polygenic risk for schizophrenia and cannabis use in predicting psychotic-like experiences in young adulthood: Testing gene × environment moderation and mediation

Author: Hersenen-Medisch 1, TN groep Adan, Onderzoeksgroep 2, Onderzoek, Brain, Neurogenetica, Elkrief, Laurent, Lin, Bochao, Marchi, Mattia, Afzali, Mohammad H., Banaschewski, Tobias, Bokde, Arun L.W., Quinlan, Erin Burke, Desrivières, Sylvane, Flor, Herta, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean Luc, Martinot, Marie Laure Paillère, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomáš, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Schumann, Gunter, Luykx, Jurjen, Boks, Marco P., Conrod, Patricia J., Hersenen-Medisch 1, TN groep Adan, Onderzoeksgroep 2, Onderzoek, Brain, Neurogenetica, Elkrief, Laurent, Lin, Bochao, Marchi, Mattia, Afzali, Mohammad H., Banaschewski, Tobias, Bokde, Arun L.W., Quinlan, Erin Burke, Desrivières, Sylvane, Flor, Herta, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean Luc, Martinot, Marie Laure Paillère, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomáš, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Schumann, Gunter, Luykx, Jurjen, Boks, Marco P., and Conrod, Patricia J.
Published: 2023

5. A stable and replicable neural signature of lifespan adversity in the adult brain

Author: Holz, Nathalie E; https://orcid.org/0000-0002-6225-9267, Zabihi, Mariam; https://orcid.org/0000-0002-7083-2318, Kia, Seyed Mostafa; https://orcid.org/0000-0002-7128-814X, Monninger, Maximillian, Aggensteiner, Pascal-M; https://orcid.org/0000-0002-1048-9044, Siehl, Sebastian; https://orcid.org/0000-0002-8933-7552, Floris, Dorothea L, Bokde, Arun L W; https://orcid.org/0000-0003-0114-4914, Desrivières, Sylvane; https://orcid.org/0000-0002-9120-7060, Flor, Herta; https://orcid.org/0000-0003-4809-5398, Grigis, Antoine, Garavan, Hugh, Gowland, Penny; https://orcid.org/0000-0002-4900-4817, Heinz, Andreas; https://orcid.org/0000-0001-5405-9065, Brühl, Rüdiger; https://orcid.org/0000-0003-0111-5996, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère; https://orcid.org/0000-0002-0452-2450, Orfanos, Dimitri Papadopoulos; https://orcid.org/0000-0002-1242-8990, Paus, Tomáš, Poustka, Luise; https://orcid.org/0000-0002-7738-4394, Fröhner, Juliane H; https://orcid.org/0000-0002-8493-6396, Smolka, Michael N; https://orcid.org/0000-0001-5398-5569, Vaidya, Nilakshi, Walter, Henrik; https://orcid.org/0000-0002-9403-6121, Whelan, Robert; https://orcid.org/0000-0002-2790-7281, Schumann, Gunter; https://orcid.org/0000-0002-7740-6469, Meyer-Lindenberg, Andreas; https://orcid.org/0000-0001-5619-1123, Brandeis, Daniel, Buitelaar, Jan K; https://orcid.org/0000-0001-8288-7757, Nees, Frauke, et al, Holz, Nathalie E; https://orcid.org/0000-0002-6225-9267, Zabihi, Mariam; https://orcid.org/0000-0002-7083-2318, Kia, Seyed Mostafa; https://orcid.org/0000-0002-7128-814X, Monninger, Maximillian, Aggensteiner, Pascal-M; https://orcid.org/0000-0002-1048-9044, Siehl, Sebastian; https://orcid.org/0000-0002-8933-7552, Floris, Dorothea L, Bokde, Arun L W; https://orcid.org/0000-0003-0114-4914, Desrivières, Sylvane; https://orcid.org/0000-0002-9120-7060, Flor, Herta; https://orcid.org/0000-0003-4809-5398, Grigis, Antoine, Garavan, Hugh, Gowland, Penny; https://orcid.org/0000-0002-4900-4817, Heinz, Andreas; https://orcid.org/0000-0001-5405-9065, Brühl, Rüdiger; https://orcid.org/0000-0003-0111-5996, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère; https://orcid.org/0000-0002-0452-2450, Orfanos, Dimitri Papadopoulos; https://orcid.org/0000-0002-1242-8990, Paus, Tomáš, Poustka, Luise; https://orcid.org/0000-0002-7738-4394, Fröhner, Juliane H; https://orcid.org/0000-0002-8493-6396, Smolka, Michael N; https://orcid.org/0000-0001-5398-5569, Vaidya, Nilakshi, Walter, Henrik; https://orcid.org/0000-0002-9403-6121, Whelan, Robert; https://orcid.org/0000-0002-2790-7281, Schumann, Gunter; https://orcid.org/0000-0002-7740-6469, Meyer-Lindenberg, Andreas; https://orcid.org/0000-0001-5619-1123, Brandeis, Daniel, Buitelaar, Jan K; https://orcid.org/0000-0001-8288-7757, Nees, Frauke, and et al
Abstract: Environmental adversities constitute potent risk factors for psychiatric disorders. Evidence suggests the brain adapts to adversity, possibly in an adversity-type and region-specific manner. However, the long-term effects of adversity on brain structure and the association of individual neurobiological heterogeneity with behavior have yet to be elucidated. Here we estimated normative models of structural brain development based on a lifespan adversity profile in a longitudinal at-risk cohort aged 25 years (n = 169). This revealed widespread morphometric changes in the brain, with partially adversity-specific features. This pattern was replicated at the age of 33 years (n = 114) and in an independent sample at 22 years (n = 115). At the individual level, greater volume contractions relative to the model were predictive of future anxiety. We show a stable neurobiological signature of adversity that persists into adulthood and emphasize the importance of considering individual-level rather than group-level predictions to explain emerging psychopathology.
Published: 2023

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

Author: Fröhner, Juliane H., Ripke, Stephan, Jurk, Sarah, Li, Shu-Chen, Banaschewski, Tobias, Bokde, Arun L.W., Quinlan, Erin Burke, Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Heinz, Andreas, Brühl, Rügiger, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère, Artiges, Eric, Ness, Frauke, Orfanos, Dimitri Papadopoulos, Poustka, Luise, Hohmann, Sarah, Walter, Henrik, Whelan, Robert, Schumann, Gunter, Smolka, Michael N., Fröhner, Juliane H., Ripke, Stephan, Jurk, Sarah, Li, Shu-Chen, Banaschewski, Tobias, Bokde, Arun L.W., Quinlan, Erin Burke, Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Heinz, Andreas, Brühl, Rügiger, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère, Artiges, Eric, Ness, Frauke, Orfanos, Dimitri Papadopoulos, Poustka, Luise, Hohmann, Sarah, Walter, Henrik, Whelan, Robert, Schumann, Gunter, and Smolka, Michael N.
Abstract: 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.
Published: 2022

7. Multi-feature computational framework for combined signatures of dementia in underrepresented settings.

Author: Moguilner, Sebastian, Moguilner, Sebastian, Birba, Agustina, Fittipaldi, Sol, Gonzalez-Campo, Cecilia, Tagliazucchi, Enzo, Reyes, Pablo, Matallana, Diana, Parra, Mario, Slachevsky, Andrea, Farías, Gonzalo, Cruzat, Josefina, García, Adolfo, Eyre, Harris, La Joie, Renaud, Rabinovici, Gil, Whelan, Robert, Ibáñez, Agustín, Moguilner, Sebastian, Moguilner, Sebastian, Birba, Agustina, Fittipaldi, Sol, Gonzalez-Campo, Cecilia, Tagliazucchi, Enzo, Reyes, Pablo, Matallana, Diana, Parra, Mario, Slachevsky, Andrea, Farías, Gonzalo, Cruzat, Josefina, García, Adolfo, Eyre, Harris, La Joie, Renaud, Rabinovici, Gil, Whelan, Robert, and Ibáñez, Agustín
Abstract: Objective.The differential diagnosis of behavioral variant frontotemporal dementia (bvFTD) and Alzheimers disease (AD) remains challenging in underrepresented, underdiagnosed groups, including Latinos, as advanced biomarkers are rarely available. Recent guidelines for the study of dementia highlight the critical role of biomarkers. Thus, novel cost-effective complementary approaches are required in clinical settings.Approach. We developed a novel framework based on a gradient boosting machine learning classifier, tuned by Bayesian optimization, on a multi-feature multimodal approach (combining demographic, neuropsychological, magnetic resonance imaging (MRI), and electroencephalography/functional MRI connectivity data) to characterize neurodegeneration using site harmonization and sequential feature selection. We assessed 54 bvFTD and 76 AD patients and 152 healthy controls (HCs) from a Latin American consortium (ReDLat).Main results. The multimodal model yielded high area under the curve classification values (bvFTD patients vs HCs: 0.93 (±0.01); AD patients vs HCs: 0.95 (±0.01); bvFTD vs AD patients: 0.92 (±0.01)). The feature selection approach successfully filtered non-informative multimodal markers (from thousands to dozens).Results. Proved robust against multimodal heterogeneity, sociodemographic variability, and missing data.Significance. The model accurately identified dementia subtypes using measures readily available in underrepresented settings, with a similar performance than advanced biomarkers. This approach, if confirmed and replicated, may potentially complement clinical assessments in developing countries.
Published: 2022

8. Assessing general versus specific liability for externalizing problems in adolescence: Concurrent and prospective prediction of symptoms of conduct disorder, ADHD, and substance use.

Author: Perkins, Emily, Perkins, Emily, Foell, Jens, Drislane, Laura, Brislin, Sarah, Frick, Paul, Yancey, James, Soto, Elia, Ganley, Colleen, Keel, Pamela, Sica, Claudio, Flor, Herta, Nees, Frauke, Banaschewski, Tobias, Bokde, Arun, Desrivières, Sylvane, Grigis, Antoine, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Paillère Martinot, Marie-Laure, Artiges, Eric, Papadopoulos Orfanos, Dimitri, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane, Smolka, Michael, Walter, Henrik, Whelan, Robert, Schumann, Gunter, Patrick, Christopher, Joyner, Keanan, Perkins, Emily, Perkins, Emily, Foell, Jens, Drislane, Laura, Brislin, Sarah, Frick, Paul, Yancey, James, Soto, Elia, Ganley, Colleen, Keel, Pamela, Sica, Claudio, Flor, Herta, Nees, Frauke, Banaschewski, Tobias, Bokde, Arun, Desrivières, Sylvane, Grigis, Antoine, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Paillère Martinot, Marie-Laure, Artiges, Eric, Papadopoulos Orfanos, Dimitri, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane, Smolka, Michael, Walter, Henrik, Whelan, Robert, Schumann, Gunter, Patrick, Christopher, and Joyner, Keanan
Abstract: This study explored the generality versus specificity of two trait-liability factors for externalizing problems-disinhibition and callousness-in the concurrent and prospective prediction of symptoms of conduct disorder, attention-deficit/hyperactivity disorder (ADHD), and substance use (i.e., alcohol use disorder and history of illicit substance use). Disinhibition involves an impulsive, unrestrained cognitive-behavioral style; callousness entails a dispositional lack of social-emotional sensitivity. Participants were European adolescents from the multisite IMAGEN project who completed questionnaires and clinical interviews at ages 14 (N = 1,504, Mage = 14.41, 51.13% female) and 16 (N = 1,407, Mage = 16.46, 51.88% female). Disinhibition was related concurrently and prospectively to greater symptoms of conduct disorder, ADHD, and alcohol use disorder; higher scores on a general externalizing factor; and greater likelihood of having tried an illicit substance. Callousness was selectively related to greater conduct disorder symptoms. These findings indicate disinhibition confers broad liability for externalizing spectrum disorders, perhaps due to its affiliated deficits in executive function. In contrast, callousness appears to represent more specific liability for antagonistic (aggressive/exploitative) forms of externalizing, as exemplified by antisocial behavior. Results support the utility of developmental-ontogenetic and hierarchical-dimensional models of psychopathology and have important implications for early assessment of risk for externalizing problems. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Published: 2022

9. Neuroanatomical markers of psychotic experiences in adolescents: A machine-learning approach in a longitudinal population-based sample

Author: Beeldverwerking ISI, Brain, Cancer, Kenney, Joanne P M, Milena Rueda-Delgado, Laura, Hanlon, Erik O, Jollans, Lee, Kelleher, Ian, Healy, Colm, Dooley, Niamh, McCandless, Conor, Frodl, Thomas, Leemans, Alexander, Lebel, Catherine, Whelan, Robert, Cannon, Mary, Beeldverwerking ISI, Brain, Cancer, Kenney, Joanne P M, Milena Rueda-Delgado, Laura, Hanlon, Erik O, Jollans, Lee, Kelleher, Ian, Healy, Colm, Dooley, Niamh, McCandless, Conor, Frodl, Thomas, Leemans, Alexander, Lebel, Catherine, Whelan, Robert, and Cannon, Mary
Published: 2022

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

Author: Fröhner, Juliane H., Ripke, Stephan, Jurk, Sarah, Li, Shu-Chen, Banaschewski, Tobias, Bokde, Arun L.W., Quinlan, Erin Burke, Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Heinz, Andreas, Brühl, Rügiger, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère, Artiges, Eric, Ness, Frauke, Orfanos, Dimitri Papadopoulos, Poustka, Luise, Hohmann, Sarah, Walter, Henrik, Whelan, Robert, Schumann, Gunter, Smolka, Michael N., Fröhner, Juliane H., Ripke, Stephan, Jurk, Sarah, Li, Shu-Chen, Banaschewski, Tobias, Bokde, Arun L.W., Quinlan, Erin Burke, Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Heinz, Andreas, Brühl, Rügiger, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère, Artiges, Eric, Ness, Frauke, Orfanos, Dimitri Papadopoulos, Poustka, Luise, Hohmann, Sarah, Walter, Henrik, Whelan, Robert, Schumann, Gunter, and Smolka, Michael N.
Abstract: 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.
Published: 2022

11. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group.

Author: Jia, Tianye, Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J, Bastin, Mark E, Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil PS, Roiz Santiañez, Roberto, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Tordesillas Gutiérrez, Diana, Van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun LW, Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Büchel, Christian, Burke Quinlan, Erin, Cahn, Wiepke, de Zubicaray, Greig I, Ehrlich, Stefan, Ekström, Tomas J, Flor, Herta, Fröhner, Juliane H, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B, Martin, Nicholas G, Martinot, Jean-Luc, Mather, Karen A, McMahon, Katie L, McRae, Allan F, Nees, Frauke, Papadopoulos Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Sämann, Philipp G, Schofield, Peter R, Smolka, Michael N, Stein, Dan J, Strike, Lachlan T, Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M, Wen, Wei, Whelan, Robert, Apostolova, Liana G, Binder, Elisabeth B, Boomsma, Dorret I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J, Hulshoff Pol, Hilleke, Ophoff, Roel A, Pausova, Zdenka, Sachdev, Perminder S, Saykin, Andrew, Wright, Margaret J, Thompson, Paul M, Schumann, Gunter, Desrivières, Sylvane, Jia, Tianye, Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J, Bastin, Mark E, Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil PS, Roiz Santiañez, Roberto, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Tordesillas Gutiérrez, Diana, Van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun LW, Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Büchel, Christian, Burke Quinlan, Erin, Cahn, Wiepke, de Zubicaray, Greig I, Ehrlich, Stefan, Ekström, Tomas J, Flor, Herta, Fröhner, Juliane H, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B, Martin, Nicholas G, Martinot, Jean-Luc, Mather, Karen A, McMahon, Katie L, McRae, Allan F, Nees, Frauke, Papadopoulos Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Sämann, Philipp G, Schofield, Peter R, Smolka, Michael N, Stein, Dan J, Strike, Lachlan T, Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M, Wen, Wei, Whelan, Robert, Apostolova, Liana G, Binder, Elisabeth B, Boomsma, Dorret I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J, Hulshoff Pol, Hilleke, Ophoff, Roel A, Pausova, Zdenka, Sachdev, Perminder S, Saykin, Andrew, Wright, Margaret J, Thompson, Paul M, Schumann, Gunter, and Desrivières, Sylvane
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Published: 2021

12. Development of Proteomic Prediction Models for Transition to Psychotic Disorder in the Clinical High-Risk State and Psychotic Experiences in Adolescence

Author: Mongan, David, Focking, Melanie, Healy, Colm, Susai, Subash Raj, Heurich, Meike, Wynne, Kieran, Nelson, Barnaby, McGorry, Patrick D., Amminger, G. Paul, Nordentoft, Merete, Krebs, Marie-Odile, Riecher-Rossler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus, Borgwardt, Stefan, Ruhrmann, Stephan, Sachs, Gabriele, Pantelis, Christos, van der Gaag, Mark, de Haan, Lieuwe, Valmaggia, Lucia, Pollak, Thomas A., Kempton, Matthew J., Rutten, Bart P. F., Whelan, Robert, Cannon, Mary, Zammit, Stan, Cagney, Gerard, Cotter, David R., McGuire, Philip, Mongan, David, Focking, Melanie, Healy, Colm, Susai, Subash Raj, Heurich, Meike, Wynne, Kieran, Nelson, Barnaby, McGorry, Patrick D., Amminger, G. Paul, Nordentoft, Merete, Krebs, Marie-Odile, Riecher-Rossler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus, Borgwardt, Stefan, Ruhrmann, Stephan, Sachs, Gabriele, Pantelis, Christos, van der Gaag, Mark, de Haan, Lieuwe, Valmaggia, Lucia, Pollak, Thomas A., Kempton, Matthew J., Rutten, Bart P. F., Whelan, Robert, Cannon, Mary, Zammit, Stan, Cagney, Gerard, Cotter, David R., and McGuire, Philip
Abstract: Question Can plasma proteomic biomarkers aid prediction of transition to psychotic disorder in people at clinical high risk (CHR) of psychosis and adolescent psychotic experiences in the general population? Findings In this diagnostic study of 133 individuals at CHR in EU-GEI and 121 individuals from the general population in ALSPAC, models were developed based on baseline proteomic data, with excellent predictive performance for transition to psychotic disorder in individuals at CHR. In a general population sample, models based on proteomic data at age 12 years had fair predictive performance for psychotic experiences at age 18 years. Meaning Predictive models based on proteomic biomarkers may contribute to personalized prognosis and stratification strategies in individuals at risk of psychosis. This diagnostic study investigates whether proteomic biomarkers may aid the prediction of transition to psychotic disorder in the clinical high-risk state and adolescent psychotic experiences in the general population. Importance Biomarkers that are predictive of outcomes in individuals at risk of psychosis would facilitate individualized prognosis and stratification strategies. Objective To investigate whether proteomic biomarkers may aid prediction of transition to psychotic disorder in the clinical high-risk (CHR) state and adolescent psychotic experiences (PEs) in the general population. Design, Setting, and Participants This diagnostic study comprised 2 case-control studies nested within the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and the Avon Longitudinal Study of Parents and Children (ALSPAC). EU-GEI is an international multisite prospective study of participants at CHR referred from local mental health services. ALSPAC is a United Kingdom-based general population birth cohort. Included were EU-GEI participants who met CHR criteria at baseline and ALSPAC participants who did not report PEs at age 12 years. D
Published: 2021

13. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

Author: Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J., Bastin, Mark E., Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P.S., Roiz Santiañez, Roberto, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Tordesillas Gutiérrez, Diana, van’t Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L.W., Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Büchel, Christian, Burke Quinlan, Erin, Cahn, Wiepke, de Zubicaray, Greig I., Ehrlich, Stefan, Ekström, Tomas J., Flor, Herta, Fröhner, Juliane H., Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B., Martin, Nicholas G., Martinot, Jean Luc, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Nees, Frauke, Papadopoulos Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Sämann, Philipp G., Schofield, Peter R., Smolka, Michael N., Stein, Dan J., Strike, Lachlan T., Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M., Wen, Wei, Whelan, Robert, Apostolova, Liana G., Binder, Elisabeth B., Boomsma, Dorret I., Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J., Hulshoff Pol, Hilleke, Ophoff, Roel A., Pausova, Zdenka, Sachdev, Perminder S., Saykin, Andrew, Wright, Margaret J., Thompson, Paul M., Schumann, Gunter, Desrivières, Sylvane, Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J., Bastin, Mark E., Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P.S., Roiz Santiañez, Roberto, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Tordesillas Gutiérrez, Diana, van’t Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L.W., Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Büchel, Christian, Burke Quinlan, Erin, Cahn, Wiepke, de Zubicaray, Greig I., Ehrlich, Stefan, Ekström, Tomas J., Flor, Herta, Fröhner, Juliane H., Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B., Martin, Nicholas G., Martinot, Jean Luc, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Nees, Frauke, Papadopoulos Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Sämann, Philipp G., Schofield, Peter R., Smolka, Michael N., Stein, Dan J., Strike, Lachlan T., Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M., Wen, Wei, Whelan, Robert, Apostolova, Liana G., Binder, Elisabeth B., Boomsma, Dorret I., Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J., Hulshoff Pol, Hilleke, Ophoff, Roel A., Pausova, Zdenka, Sachdev, Perminder S., Saykin, Andrew, Wright, Margaret J., Thompson, Paul M., Schumann, Gunter, and Desrivières, Sylvane
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Published: 2021

14. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes : findings from the ENIGMA Epigenetics Working Group

Author: Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J., Bastin, Mark E., Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P. S., Santianez, Roberto Roiz, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Gutierrez, Diana Tordesillas, van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L. W., Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Buchel, Christian, Quinlan, Erin Burke, Cahn, Wiepke, de Zubicaray, Greig, I, Ehrlich, Stefan, Ekstrom, Tomas J., Flor, Herta, Frohner, Juliane H., Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B., Martin, Nicholas G., Martinot, Jean-Luc, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Samann, Philipp G., Schofield, Peter R., Smolka, Michael N., Stein, Dan J., Strike, Lachlan T., Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M., Wen, Wei, Whelan, Robert, Apostolova, Liana G., Binder, Elisabeth B., Boomsma, Dorret, I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J., Pol, Hilleke Hulshoff, Ophoff, Roel A., Pausova, Zdenka, Sachdev, Perminder S., Saykin, Andrew, Wright, Margaret J., Thompson, Paul M., Schumann, Gunter, Desrivieres, Sylvane, Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J., Bastin, Mark E., Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P. S., Santianez, Roberto Roiz, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Gutierrez, Diana Tordesillas, van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L. W., Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Buchel, Christian, Quinlan, Erin Burke, Cahn, Wiepke, de Zubicaray, Greig, I, Ehrlich, Stefan, Ekstrom, Tomas J., Flor, Herta, Frohner, Juliane H., Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B., Martin, Nicholas G., Martinot, Jean-Luc, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Samann, Philipp G., Schofield, Peter R., Smolka, Michael N., Stein, Dan J., Strike, Lachlan T., Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M., Wen, Wei, Whelan, Robert, Apostolova, Liana G., Binder, Elisabeth B., Boomsma, Dorret, I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J., Pol, Hilleke Hulshoff, Ophoff, Roel A., Pausova, Zdenka, Sachdev, Perminder S., Saykin, Andrew, Wright, Margaret J., Thompson, Paul M., Schumann, Gunter, and Desrivieres, Sylvane
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Published: 2021
Full Text: View/download PDF

15. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes : findings from the ENIGMA Epigenetics Working Group

Author: Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J., Bastin, Mark E., Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P. S., Santianez, Roberto Roiz, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Gutierrez, Diana Tordesillas, van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L. W., Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Buchel, Christian, Quinlan, Erin Burke, Cahn, Wiepke, de Zubicaray, Greig, I, Ehrlich, Stefan, Ekstrom, Tomas J., Flor, Herta, Frohner, Juliane H., Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B., Martin, Nicholas G., Martinot, Jean-Luc, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Samann, Philipp G., Schofield, Peter R., Smolka, Michael N., Stein, Dan J., Strike, Lachlan T., Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M., Wen, Wei, Whelan, Robert, Apostolova, Liana G., Binder, Elisabeth B., Boomsma, Dorret, I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J., Pol, Hilleke Hulshoff, Ophoff, Roel A., Pausova, Zdenka, Sachdev, Perminder S., Saykin, Andrew, Wright, Margaret J., Thompson, Paul M., Schumann, Gunter, Desrivieres, Sylvane, Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J., Bastin, Mark E., Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P. S., Santianez, Roberto Roiz, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Gutierrez, Diana Tordesillas, van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L. W., Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Buchel, Christian, Quinlan, Erin Burke, Cahn, Wiepke, de Zubicaray, Greig, I, Ehrlich, Stefan, Ekstrom, Tomas J., Flor, Herta, Frohner, Juliane H., Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B., Martin, Nicholas G., Martinot, Jean-Luc, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Samann, Philipp G., Schofield, Peter R., Smolka, Michael N., Stein, Dan J., Strike, Lachlan T., Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M., Wen, Wei, Whelan, Robert, Apostolova, Liana G., Binder, Elisabeth B., Boomsma, Dorret, I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J., Pol, Hilleke Hulshoff, Ophoff, Roel A., Pausova, Zdenka, Sachdev, Perminder S., Saykin, Andrew, Wright, Margaret J., Thompson, Paul M., Schumann, Gunter, and Desrivieres, Sylvane
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Published: 2021
Full Text: View/download PDF

16. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes : findings from the ENIGMA Epigenetics Working Group

Author: Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J., Bastin, Mark E., Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P. S., Santianez, Roberto Roiz, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Gutierrez, Diana Tordesillas, van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L. W., Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Buchel, Christian, Quinlan, Erin Burke, Cahn, Wiepke, de Zubicaray, Greig, I, Ehrlich, Stefan, Ekstrom, Tomas J., Flor, Herta, Frohner, Juliane H., Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B., Martin, Nicholas G., Martinot, Jean-Luc, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Samann, Philipp G., Schofield, Peter R., Smolka, Michael N., Stein, Dan J., Strike, Lachlan T., Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M., Wen, Wei, Whelan, Robert, Apostolova, Liana G., Binder, Elisabeth B., Boomsma, Dorret, I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J., Pol, Hilleke Hulshoff, Ophoff, Roel A., Pausova, Zdenka, Sachdev, Perminder S., Saykin, Andrew, Wright, Margaret J., Thompson, Paul M., Schumann, Gunter, Desrivieres, Sylvane, Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J., Bastin, Mark E., Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P. S., Santianez, Roberto Roiz, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Gutierrez, Diana Tordesillas, van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L. W., Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Buchel, Christian, Quinlan, Erin Burke, Cahn, Wiepke, de Zubicaray, Greig, I, Ehrlich, Stefan, Ekstrom, Tomas J., Flor, Herta, Frohner, Juliane H., Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B., Martin, Nicholas G., Martinot, Jean-Luc, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Samann, Philipp G., Schofield, Peter R., Smolka, Michael N., Stein, Dan J., Strike, Lachlan T., Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M., Wen, Wei, Whelan, Robert, Apostolova, Liana G., Binder, Elisabeth B., Boomsma, Dorret, I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J., Pol, Hilleke Hulshoff, Ophoff, Roel A., Pausova, Zdenka, Sachdev, Perminder S., Saykin, Andrew, Wright, Margaret J., Thompson, Paul M., Schumann, Gunter, and Desrivieres, Sylvane
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Published: 2021
Full Text: View/download PDF

17. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group.

Author: Jia, Tianye, Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J, Bastin, Mark E, Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil PS, Roiz Santiañez, Roberto, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Tordesillas Gutiérrez, Diana, Van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun LW, Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Büchel, Christian, Burke Quinlan, Erin, Cahn, Wiepke, de Zubicaray, Greig I, Ehrlich, Stefan, Ekström, Tomas J, Flor, Herta, Fröhner, Juliane H, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B, Martin, Nicholas G, Martinot, Jean-Luc, Mather, Karen A, McMahon, Katie L, McRae, Allan F, Nees, Frauke, Papadopoulos Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Sämann, Philipp G, Schofield, Peter R, Smolka, Michael N, Stein, Dan J, Strike, Lachlan T, Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M, Wen, Wei, Whelan, Robert, Apostolova, Liana G, Binder, Elisabeth B, Boomsma, Dorret I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J, Hulshoff Pol, Hilleke, Ophoff, Roel A, Pausova, Zdenka, Sachdev, Perminder S, Saykin, Andrew, Wright, Margaret J, Thompson, Paul M, Schumann, Gunter, Desrivières, Sylvane, Jia, Tianye, Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J, Bastin, Mark E, Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil PS, Roiz Santiañez, Roberto, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Tordesillas Gutiérrez, Diana, Van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun LW, Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Büchel, Christian, Burke Quinlan, Erin, Cahn, Wiepke, de Zubicaray, Greig I, Ehrlich, Stefan, Ekström, Tomas J, Flor, Herta, Fröhner, Juliane H, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B, Martin, Nicholas G, Martinot, Jean-Luc, Mather, Karen A, McMahon, Katie L, McRae, Allan F, Nees, Frauke, Papadopoulos Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Sämann, Philipp G, Schofield, Peter R, Smolka, Michael N, Stein, Dan J, Strike, Lachlan T, Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M, Wen, Wei, Whelan, Robert, Apostolova, Liana G, Binder, Elisabeth B, Boomsma, Dorret I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J, Hulshoff Pol, Hilleke, Ophoff, Roel A, Pausova, Zdenka, Sachdev, Perminder S, Saykin, Andrew, Wright, Margaret J, Thompson, Paul M, Schumann, Gunter, and Desrivières, Sylvane
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Published: 2021

18. Reward Processing in Novelty Seekers: A Transdiagnostic Psychiatric Imaging Biomarker.

Author: Qi, Shile, Qi, Shile, Schumann, Gunter, Bustillo, Juan, Turner, Jessica A, Jiang, Rongtao, Zhi, Dongmei, Fu, Zening, Mayer, Andrew R, Vergara, Victor M, Silva, Rogers F, Iraji, Armin, Chen, Jiayu, Damaraju, Eswar, Ma, Xiaohong, Yang, Xiao, Stevens, Michael, Mathalon, Daniel H, Ford, Judith M, Voyvodic, James, Mueller, Bryon A, Belger, Aysenil, Potkin, Steven G, Preda, Adrian, Zhuo, Chuanjun, Xu, Yong, Chu, Congying, Banaschewski, Tobias, Barker, Gareth J, Bokde, Arun LW, Quinlan, Erin Burke, Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Martinot, Jean-Luc, Paillère Martinot, Marie-Laure, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomáš, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H, Smolka, Michael N, Walter, Henrik, Whelan, Robert, Calhoun, Vince D, Sui, Jing, IMAGEN Consortium, Qi, Shile, Qi, Shile, Schumann, Gunter, Bustillo, Juan, Turner, Jessica A, Jiang, Rongtao, Zhi, Dongmei, Fu, Zening, Mayer, Andrew R, Vergara, Victor M, Silva, Rogers F, Iraji, Armin, Chen, Jiayu, Damaraju, Eswar, Ma, Xiaohong, Yang, Xiao, Stevens, Michael, Mathalon, Daniel H, Ford, Judith M, Voyvodic, James, Mueller, Bryon A, Belger, Aysenil, Potkin, Steven G, Preda, Adrian, Zhuo, Chuanjun, Xu, Yong, Chu, Congying, Banaschewski, Tobias, Barker, Gareth J, Bokde, Arun LW, Quinlan, Erin Burke, Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Martinot, Jean-Luc, Paillère Martinot, Marie-Laure, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomáš, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H, Smolka, Michael N, Walter, Henrik, Whelan, Robert, Calhoun, Vince D, Sui, Jing, and IMAGEN Consortium
Abstract: BackgroundDysfunctional reward processing is implicated in multiple mental disorders. Novelty seeking (NS) assesses preference for seeking novel experiences, which is linked to sensitivity to reward environmental cues.MethodsA subset of 14-year-old adolescents (IMAGEN) with the top 20% ranked high-NS scores was used to identify high-NS-associated multimodal components by supervised fusion. These features were then used to longitudinally predict five different risk scales for the same and unseen subjects (an independent dataset of subjects at 19 years of age that was not used in predictive modeling training at 14 years of age) (within IMAGEN, n ≈1100) and even for the corresponding symptom scores of five types of patient cohorts (non-IMAGEN), including drinking (n = 313), smoking (n = 104), attention-deficit/hyperactivity disorder (n = 320), major depressive disorder (n = 81), and schizophrenia (n = 147), as well as to classify different patient groups with diagnostic labels.ResultsMultimodal biomarkers, including the prefrontal cortex, striatum, amygdala, and hippocampus, associated with high NS in 14-year-old adolescents were identified. The prediction models built on these features are able to longitudinally predict five different risk scales, including alcohol drinking, smoking, hyperactivity, depression, and psychosis for the same and unseen 19-year-old adolescents and even predict the corresponding symptom scores of five types of patient cohorts. Furthermore, the identified reward-related multimodal features can classify among attention-deficit/hyperactivity disorder, major depressive disorder, and schizophrenia with an accuracy of 87.2%.ConclusionsAdolescents with higher NS scores can be used to reveal brain alterations in the reward-related system, implicating potential higher risk for subsequent development of multiple disorders. The identified high-NS-associated multimodal reward-related signatures may serve as a transdiag
Published: 2021

19. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes : findings from the ENIGMA Epigenetics Working Group

Author: Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J., Bastin, Mark E., Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P. S., Santianez, Roberto Roiz, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Gutierrez, Diana Tordesillas, van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L. W., Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Buchel, Christian, Quinlan, Erin Burke, Cahn, Wiepke, de Zubicaray, Greig, I, Ehrlich, Stefan, Ekstrom, Tomas J., Flor, Herta, Frohner, Juliane H., Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B., Martin, Nicholas G., Martinot, Jean-Luc, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Samann, Philipp G., Schofield, Peter R., Smolka, Michael N., Stein, Dan J., Strike, Lachlan T., Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M., Wen, Wei, Whelan, Robert, Apostolova, Liana G., Binder, Elisabeth B., Boomsma, Dorret, I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J., Pol, Hilleke Hulshoff, Ophoff, Roel A., Pausova, Zdenka, Sachdev, Perminder S., Saykin, Andrew, Wright, Margaret J., Thompson, Paul M., Schumann, Gunter, Desrivieres, Sylvane, Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J., Bastin, Mark E., Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P. S., Santianez, Roberto Roiz, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Gutierrez, Diana Tordesillas, van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L. W., Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Buchel, Christian, Quinlan, Erin Burke, Cahn, Wiepke, de Zubicaray, Greig, I, Ehrlich, Stefan, Ekstrom, Tomas J., Flor, Herta, Frohner, Juliane H., Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B., Martin, Nicholas G., Martinot, Jean-Luc, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Samann, Philipp G., Schofield, Peter R., Smolka, Michael N., Stein, Dan J., Strike, Lachlan T., Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M., Wen, Wei, Whelan, Robert, Apostolova, Liana G., Binder, Elisabeth B., Boomsma, Dorret, I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J., Pol, Hilleke Hulshoff, Ophoff, Roel A., Pausova, Zdenka, Sachdev, Perminder S., Saykin, Andrew, Wright, Margaret J., Thompson, Paul M., Schumann, Gunter, and Desrivieres, Sylvane
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Published: 2021
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20. Development of Proteomic Prediction Models for Transition to Psychotic Disorder in the Clinical High-Risk State and Psychotic Experiences in Adolescence

Author: Mongan, David, Focking, Melanie, Healy, Colm, Susai, Subash Raj, Heurich, Meike, Wynne, Kieran, Nelson, Barnaby, McGorry, Patrick D., Amminger, G. Paul, Nordentoft, Merete, Krebs, Marie-Odile, Riecher-Rossler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus, Borgwardt, Stefan, Ruhrmann, Stephan, Sachs, Gabriele, Pantelis, Christos, van der Gaag, Mark, de Haan, Lieuwe, Valmaggia, Lucia, Pollak, Thomas A., Kempton, Matthew J., Rutten, Bart P. F., Whelan, Robert, Cannon, Mary, Zammit, Stan, Cagney, Gerard, Cotter, David R., McGuire, Philip, Mongan, David, Focking, Melanie, Healy, Colm, Susai, Subash Raj, Heurich, Meike, Wynne, Kieran, Nelson, Barnaby, McGorry, Patrick D., Amminger, G. Paul, Nordentoft, Merete, Krebs, Marie-Odile, Riecher-Rossler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus, Borgwardt, Stefan, Ruhrmann, Stephan, Sachs, Gabriele, Pantelis, Christos, van der Gaag, Mark, de Haan, Lieuwe, Valmaggia, Lucia, Pollak, Thomas A., Kempton, Matthew J., Rutten, Bart P. F., Whelan, Robert, Cannon, Mary, Zammit, Stan, Cagney, Gerard, Cotter, David R., and McGuire, Philip
Abstract: Question Can plasma proteomic biomarkers aid prediction of transition to psychotic disorder in people at clinical high risk (CHR) of psychosis and adolescent psychotic experiences in the general population? Findings In this diagnostic study of 133 individuals at CHR in EU-GEI and 121 individuals from the general population in ALSPAC, models were developed based on baseline proteomic data, with excellent predictive performance for transition to psychotic disorder in individuals at CHR. In a general population sample, models based on proteomic data at age 12 years had fair predictive performance for psychotic experiences at age 18 years. Meaning Predictive models based on proteomic biomarkers may contribute to personalized prognosis and stratification strategies in individuals at risk of psychosis. This diagnostic study investigates whether proteomic biomarkers may aid the prediction of transition to psychotic disorder in the clinical high-risk state and adolescent psychotic experiences in the general population. Importance Biomarkers that are predictive of outcomes in individuals at risk of psychosis would facilitate individualized prognosis and stratification strategies. Objective To investigate whether proteomic biomarkers may aid prediction of transition to psychotic disorder in the clinical high-risk (CHR) state and adolescent psychotic experiences (PEs) in the general population. Design, Setting, and Participants This diagnostic study comprised 2 case-control studies nested within the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and the Avon Longitudinal Study of Parents and Children (ALSPAC). EU-GEI is an international multisite prospective study of participants at CHR referred from local mental health services. ALSPAC is a United Kingdom-based general population birth cohort. Included were EU-GEI participants who met CHR criteria at baseline and ALSPAC participants who did not report PEs at age 12 years. D
Published: 2021

21. Development of Proteomic Prediction Models for Transition to Psychotic Disorder in the Clinical High-Risk State and Psychotic Experiences in Adolescence

Author: Mongan, David, Föcking, Melanie, Healy, Colm, Susai, Subash Raj, Heurich, Meike, Wynne, Kieran, Nelson, Barnaby, McGorry, Patrick D., Amminger, G. Paul, Nordentoft, Merete, Krebs, Marie Odile, Riecher-Rössler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus, Borgwardt, Stefan, Ruhrmann, Stephan, Sachs, Gabriele, Pantelis, Christos, Van Der Gaag, Mark, De Haan, Lieuwe, Valmaggia, Lucia, Pollak, Thomas A., Kempton, Matthew J., Rutten, Bart P.F., Whelan, Robert, Cannon, Mary, Zammit, Stan, Cagney, Gerard, Cotter, David R., McGuire, Philip, Mongan, David, Föcking, Melanie, Healy, Colm, Susai, Subash Raj, Heurich, Meike, Wynne, Kieran, Nelson, Barnaby, McGorry, Patrick D., Amminger, G. Paul, Nordentoft, Merete, Krebs, Marie Odile, Riecher-Rössler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus, Borgwardt, Stefan, Ruhrmann, Stephan, Sachs, Gabriele, Pantelis, Christos, Van Der Gaag, Mark, De Haan, Lieuwe, Valmaggia, Lucia, Pollak, Thomas A., Kempton, Matthew J., Rutten, Bart P.F., Whelan, Robert, Cannon, Mary, Zammit, Stan, Cagney, Gerard, Cotter, David R., and McGuire, Philip
Abstract: Importance: Biomarkers that are predictive of outcomes in individuals at risk of psychosis would facilitate individualized prognosis and stratification strategies. Objective: To investigate whether proteomic biomarkers may aid prediction of transition to psychotic disorder in the clinical high-risk (CHR) state and adolescent psychotic experiences (PEs) in the general population. Design, Setting, and Participants: This diagnostic study comprised 2 case-control studies nested within the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and the Avon Longitudinal Study of Parents and Children (ALSPAC). EU-GEI is an international multisite prospective study of participants at CHR referred from local mental health services. ALSPAC is a United Kingdom-based general population birth cohort. Included were EU-GEI participants who met CHR criteria at baseline and ALSPAC participants who did not report PEs at age 12 years. Data were analyzed from September 2018 to April 2020. Main Outcomes and Measures: In EU-GEI, transition status was assessed by the Comprehensive Assessment of At-Risk Mental States or contact with clinical services. In ALSPAC, PEs at age 18 years were assessed using the Psychosis-Like Symptoms Interview. Proteomic data were obtained from mass spectrometry of baseline plasma samples in EU-GEI and plasma samples at age 12 years in ALSPAC. Support vector machine learning algorithms were used to develop predictive models. Results: The EU-GEI subsample (133 participants at CHR (mean [SD] age, 22.6 [4.5] years; 68 [51.1%] male) comprised 49 (36.8%) who developed psychosis and 84 (63.2%) who did not. A model based on baseline clinical and proteomic data demonstrated excellent performance for prediction of transition outcome (area under the receiver operating characteristic curve [AUC], 0.95; positive predictive value [PPV], 75.0%; and negative predictive value [NPV], 98.6%). Functional analysis of differentially e
Published: 2021

22. Development of Proteomic Prediction Models for Transition to Psychotic Disorder in the Clinical High-Risk State and Psychotic Experiences in Adolescence

Author: Mongan, David, Föcking, Melanie, Healy, Colm, Susai, Subash Raj, Heurich, Meike, Wynne, Kieran, Nelson, Barnaby, McGorry, Patrick D., Amminger, G. Paul, Nordentoft, Merete, Krebs, Marie Odile, Riecher-Rössler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus, Borgwardt, Stefan, Ruhrmann, Stephan, Sachs, Gabriele, Pantelis, Christos, Van Der Gaag, Mark, De Haan, Lieuwe, Valmaggia, Lucia, Pollak, Thomas A., Kempton, Matthew J., Rutten, Bart P.F., Whelan, Robert, Cannon, Mary, Zammit, Stan, Cagney, Gerard, Cotter, David R., McGuire, Philip, Mongan, David, Föcking, Melanie, Healy, Colm, Susai, Subash Raj, Heurich, Meike, Wynne, Kieran, Nelson, Barnaby, McGorry, Patrick D., Amminger, G. Paul, Nordentoft, Merete, Krebs, Marie Odile, Riecher-Rössler, Anita, Bressan, Rodrigo A., Barrantes-Vidal, Neus, Borgwardt, Stefan, Ruhrmann, Stephan, Sachs, Gabriele, Pantelis, Christos, Van Der Gaag, Mark, De Haan, Lieuwe, Valmaggia, Lucia, Pollak, Thomas A., Kempton, Matthew J., Rutten, Bart P.F., Whelan, Robert, Cannon, Mary, Zammit, Stan, Cagney, Gerard, Cotter, David R., and McGuire, Philip
Abstract: Importance: Biomarkers that are predictive of outcomes in individuals at risk of psychosis would facilitate individualized prognosis and stratification strategies. Objective: To investigate whether proteomic biomarkers may aid prediction of transition to psychotic disorder in the clinical high-risk (CHR) state and adolescent psychotic experiences (PEs) in the general population. Design, Setting, and Participants: This diagnostic study comprised 2 case-control studies nested within the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) and the Avon Longitudinal Study of Parents and Children (ALSPAC). EU-GEI is an international multisite prospective study of participants at CHR referred from local mental health services. ALSPAC is a United Kingdom-based general population birth cohort. Included were EU-GEI participants who met CHR criteria at baseline and ALSPAC participants who did not report PEs at age 12 years. Data were analyzed from September 2018 to April 2020. Main Outcomes and Measures: In EU-GEI, transition status was assessed by the Comprehensive Assessment of At-Risk Mental States or contact with clinical services. In ALSPAC, PEs at age 18 years were assessed using the Psychosis-Like Symptoms Interview. Proteomic data were obtained from mass spectrometry of baseline plasma samples in EU-GEI and plasma samples at age 12 years in ALSPAC. Support vector machine learning algorithms were used to develop predictive models. Results: The EU-GEI subsample (133 participants at CHR (mean [SD] age, 22.6 [4.5] years; 68 [51.1%] male) comprised 49 (36.8%) who developed psychosis and 84 (63.2%) who did not. A model based on baseline clinical and proteomic data demonstrated excellent performance for prediction of transition outcome (area under the receiver operating characteristic curve [AUC], 0.95; positive predictive value [PPV], 75.0%; and negative predictive value [NPV], 98.6%). Functional analysis of differentially e
Published: 2021

23. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes : findings from the ENIGMA Epigenetics Working Group

Author: Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J., Bastin, Mark E., Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P. S., Santianez, Roberto Roiz, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Gutierrez, Diana Tordesillas, van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L. W., Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Buchel, Christian, Quinlan, Erin Burke, Cahn, Wiepke, de Zubicaray, Greig, I, Ehrlich, Stefan, Ekstrom, Tomas J., Flor, Herta, Frohner, Juliane H., Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B., Martin, Nicholas G., Martinot, Jean-Luc, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Samann, Philipp G., Schofield, Peter R., Smolka, Michael N., Stein, Dan J., Strike, Lachlan T., Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M., Wen, Wei, Whelan, Robert, Apostolova, Liana G., Binder, Elisabeth B., Boomsma, Dorret, I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J., Pol, Hilleke Hulshoff, Ophoff, Roel A., Pausova, Zdenka, Sachdev, Perminder S., Saykin, Andrew, Wright, Margaret J., Thompson, Paul M., Schumann, Gunter, Desrivieres, Sylvane, Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J., Bastin, Mark E., Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P. S., Santianez, Roberto Roiz, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Gutierrez, Diana Tordesillas, van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L. W., Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Buchel, Christian, Quinlan, Erin Burke, Cahn, Wiepke, de Zubicaray, Greig, I, Ehrlich, Stefan, Ekstrom, Tomas J., Flor, Herta, Frohner, Juliane H., Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B., Martin, Nicholas G., Martinot, Jean-Luc, Mather, Karen A., McMahon, Katie L., McRae, Allan F., Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Samann, Philipp G., Schofield, Peter R., Smolka, Michael N., Stein, Dan J., Strike, Lachlan T., Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M., Wen, Wei, Whelan, Robert, Apostolova, Liana G., Binder, Elisabeth B., Boomsma, Dorret, I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J., Pol, Hilleke Hulshoff, Ophoff, Roel A., Pausova, Zdenka, Sachdev, Perminder S., Saykin, Andrew, Wright, Margaret J., Thompson, Paul M., Schumann, Gunter, and Desrivieres, Sylvane
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Published: 2021
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24. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

Author: Onderzoeksgroep 1, Brain, Onderzoek, Hersenen-Bedrijfsvoering, Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J, Bastin, Mark E, Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P S, Roiz Santiañez, Roberto, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Tordesillas Gutiérrez, Diana, Van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L W, Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Büchel, Christian, Burke Quinlan, Erin, Cahn, Wiepke, de Zubicaray, Greig I, Ehrlich, Stefan, Ekström, Tomas J, Flor, Herta, Fröhner, Juliane H, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B, Martin, Nicholas G, Martinot, Jean-Luc, Mather, Karen A, McMahon, Katie L, McRae, Allan F, Nees, Frauke, Papadopoulos Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Sämann, Philipp G, Schofield, Peter R, Smolka, Michael N, Stein, Dan J, Strike, Lachlan T, Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M, Wen, Wei, Whelan, Robert, Apostolova, Liana G, Binder, Elisabeth B, Boomsma, Dorret I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J, Hulshoff Pol, Hilleke, Ophoff, Roel A, Pausova, Zdenka, Sachdev, Perminder S, Saykin, Andrew, Wright, Margaret J, Thompson, Paul M, Schumann, Gunter, Desrivières, Sylvane, Onderzoeksgroep 1, Brain, Onderzoek, Hersenen-Bedrijfsvoering, Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J, Bastin, Mark E, Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P S, Roiz Santiañez, Roberto, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Tordesillas Gutiérrez, Diana, Van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L W, Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Büchel, Christian, Burke Quinlan, Erin, Cahn, Wiepke, de Zubicaray, Greig I, Ehrlich, Stefan, Ekström, Tomas J, Flor, Herta, Fröhner, Juliane H, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B, Martin, Nicholas G, Martinot, Jean-Luc, Mather, Karen A, McMahon, Katie L, McRae, Allan F, Nees, Frauke, Papadopoulos Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Sämann, Philipp G, Schofield, Peter R, Smolka, Michael N, Stein, Dan J, Strike, Lachlan T, Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M, Wen, Wei, Whelan, Robert, Apostolova, Liana G, Binder, Elisabeth B, Boomsma, Dorret I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J, Hulshoff Pol, Hilleke, Ophoff, Roel A, Pausova, Zdenka, Sachdev, Perminder S, Saykin, Andrew, Wright, Margaret J, Thompson, Paul M, Schumann, Gunter, and Desrivières, Sylvane
Published: 2021

25. The genetic architecture of the human cerebral cortex

Author: Grasby, Katrina L., Jahanshad, Neda, Painter, Jodie N., Colodro-Conde, Lucia, Bralten, Janita, Hibar, Derrek P., Lind, Penelope A., Pizzagalli, Fabrizio, Ching, Christopher R. K., McMahon, Mary Agnes B., Shatokhina, Natalia, Zsembik, Leo C. P., Thomopoulos, Sophia I., Zhu, Alyssa H., Strike, Lachlan T., Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio A. A., Alnaes, Dag, Amlien, Inge K., Andersson, Micael, Ard, Tyler, Armstrong, Nicola J., Ashley-Koch, Allison, Atkins, Joshua R., Bernard, Manon, Brouwer, Rachel M., Buimer, Elizabeth E. L., Bulow, Robin, Burger, Christian, Cannon, Dara M., Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W., Couvy-Duchesne, Baptiste, Dale, Anders M., Dalvie, Shareefa, de Araujo, Tania K., de Zubicaray, Greig I., de Zwarte, Sonja M. C., den Braber, Anouk, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah-Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O., Foley, Sonya F., Ford, Judith M., Fukunaga, Masaki, Garrett, Melanie E., Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Gurholt, Tiril P., Gutman, Boris A., Hansell, Narelle K., Harris, Mathew A., Harrison, Marc B., Haswell, Courtney C., Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J., Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke-Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E., Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R., Kramer, Bernd, Lam, Max, Lancaster, Thomas M., Lee, Phil H., Lett, Tristram A., Lewis, Lindsay B., Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F., Mathias, Samuel R., Melzer, Tracy R., Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Moreira, Jose C. V., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Loohuis, Loes M. Olde, Orfanos, Dimitri Papadopoulos, Pearson, John F., Pitcher, Toni L., Putz, Benno, Quide, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M., Reay, William R., Redlich, Ronny, Reinbold, Celine S., Repple, Jonathan, Richard, Genevieve, Riedel, Brandalyn C., Risacher, Shannon L., Rocha, Cristiane S., Mota, Nina R., Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J., Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R., Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sonderby, Ida E., Sprooten, Emma, Tansey, Katherine E., Teumer, Alexander, Thalamuthu, Anbupalam, Tordesillas-Gutierrez, Diana, Turner, Jessica A., Uhlmann, Anne, Vallerga, Costanza L., van der Meer, Dennis, van Donkelaar, Marjolein M. J., van Eijk, Liza, van Erp, Theo G. M., van Haren, Neeltje E. M., van Rooij, Daan, van Tol, Marie-Jose, Veldink, Jan H., Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., Witt, Stephanie H., Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L., Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P., Artiges, Eric, Assareh, Amelia A., Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L., Brown, Gregory G., Cichon, Sven, Curran, Joanne E., Davies, Gareth E., Degenhardt, Franziska, Dennis, Michelle F., Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P., Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A., Green, Robert C., Hausler, Alexander N., Heindel, Walter, Ho, Beng-Choon, Hoffmann, Wolfgang U., Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R., Jr., Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A., Kolskar, Knut, Koops, Sanne, Krug, Axel, Lim, Kelvin O., Luykx, Jurjen J., Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., Matthews, Sarah, Van Son, Jaqueline Mayoral, McEwen, Sarah C., Melle, Ingrid, Morris, Derek W., Mueller, Bryon A., Nauck, Matthias, Nordvik, Jan E., Noethen, Markus M., O'Leary, Daniel S., Opel, Nils, Martinot, Marie-Laure Paillere, Pike, G. Bruce, Preda, Adrian, Quinlan, Erin B., Rasser, Paul E., Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M., Tooney, Paul A., Torres, Fabio R., Veltman, Dick J., Voyvodic, James T., Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H. H., Bis, Joshua C., Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Ikram, M. Arfan, Launer, Lenore, Longstreth, W. T., Lopez, Oscar L., Mazoyer, Bernard, Mosley, Thomas H., Roshchupkin, Gennady V., Satizabal, Claudia L., Schmidt, Reinhold, Seshadri, Sudha, Yang, Qiong, Alvim, Marina K. M., Ames, David, Anderson, Tim J., Andreassen, Ole A., Arias-Vasquez, Alejandro, Bastin, Mark E., Baune, Bernhard T., Beckham, Jean C., Blangero, John, Boomsma, Dorret I., Brodaty, Henry, Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bustillo, Juan R., Cahn, Wiepke, Cairns, Murray J., Calhoun, Vince, Carr, Vaughan J., Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L., Cendes, Fernando, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C., Dannlowski, Udo, de Geus, Eco J. C., Deary, Ian J., Delanty, Norman, Depondt, Chantal, Desrivieres, Sylvane, Donohoe, Gary, Espeseth, Thomas, Fernandez, Guillen, Fisher, Simon E., Flor, Herta, Forstner, Andreas J., Francks, Clyde, Franke, Barbara, Glahn, David C., Gollub, Randy L., Grabe, Hans J., Gruber, Oliver, Haberg, Asta K., Hariri, Ahmad R., Hartman, Catharina A., Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans A., Hillegers, Manon H. J., Hoekstra, Pieter J., Holmes, Avram J., Hong, L. Elliot, Hopkins, William D., Pol, Hilleke E. Hulshoff, Jernigan, Terry L., Jonsson, Erik G., Kahn, Rene S., Kennedy, Martin A., Kircher, Tilo T. J., Kochunov, Peter, Kwok, John B. J., Le Hellard, Stephanie, Loughland, Carmel M., Martin, Nicholas G., Martinot, Jean-Luc, McDonald, Colm, McMahon, Katie L., Meyer-Lindenberg, Andreas, Michie, Patricia T., Morey, Rajendra A., Mowry, Bryan, Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A., Pantelis, Christos, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Polderman, Tinca J. C., Posthuma, Danielle, Rietschel, Marcella, Roffman, Joshua L., Rowland, Laura M., Sachdev, Perminder S., Samann, Philipp G., Schall, Ulrich, Schumann, Gunter, Scott, Rodney J., Sim, Kang, Sisodiya, Sanjay M., Smoller, Jordan W., Sommer, Iris E., St Pourcain, Beate, Stein, Dan J., Toga, Arthur W., Trollor, Julian N., Van der Wee, Nic J. A., van't Ent, Dennis, Volzke, Henry, Walter, Henrik, Weber, Bernd, Weinberger, Daniel R., Wright, Margaret J., Zhou, Juan, Stein, Jason L., Thompson, Paul M., Medland, Sarah E., Grasby, Katrina L., Jahanshad, Neda, Painter, Jodie N., Colodro-Conde, Lucia, Bralten, Janita, Hibar, Derrek P., Lind, Penelope A., Pizzagalli, Fabrizio, Ching, Christopher R. K., McMahon, Mary Agnes B., Shatokhina, Natalia, Zsembik, Leo C. P., Thomopoulos, Sophia I., Zhu, Alyssa H., Strike, Lachlan T., Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio A. A., Alnaes, Dag, Amlien, Inge K., Andersson, Micael, Ard, Tyler, Armstrong, Nicola J., Ashley-Koch, Allison, Atkins, Joshua R., Bernard, Manon, Brouwer, Rachel M., Buimer, Elizabeth E. L., Bulow, Robin, Burger, Christian, Cannon, Dara M., Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W., Couvy-Duchesne, Baptiste, Dale, Anders M., Dalvie, Shareefa, de Araujo, Tania K., de Zubicaray, Greig I., de Zwarte, Sonja M. C., den Braber, Anouk, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah-Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O., Foley, Sonya F., Ford, Judith M., Fukunaga, Masaki, Garrett, Melanie E., Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Gurholt, Tiril P., Gutman, Boris A., Hansell, Narelle K., Harris, Mathew A., Harrison, Marc B., Haswell, Courtney C., Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J., Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke-Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E., Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R., Kramer, Bernd, Lam, Max, Lancaster, Thomas M., Lee, Phil H., Lett, Tristram A., Lewis, Lindsay B., Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F., Mathias, Samuel R., Melzer, Tracy R., Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Moreira, Jose C. V., Muhleisen, Thomas W., Mueller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Loohuis, Loes M. Olde, Orfanos, Dimitri Papadopoulos, Pearson, John F., Pitcher, Toni L., Putz, Benno, Quide, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M., Reay, William R., Redlich, Ronny, Reinbold, Celine S., Repple, Jonathan, Richard, Genevieve, Riedel, Brandalyn C., Risacher, Shannon L., Rocha, Cristiane S., Mota, Nina R., Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J., Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R., Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sonderby, Ida E., Sprooten, Emma, Tansey, Katherine E., Teumer, Alexander, Thalamuthu, Anbupalam, Tordesillas-Gutierrez, Diana, Turner, Jessica A., Uhlmann, Anne, Vallerga, Costanza L., van der Meer, Dennis, van Donkelaar, Marjolein M. J., van Eijk, Liza, van Erp, Theo G. M., van Haren, Neeltje E. M., van Rooij, Daan, van Tol, Marie-Jose, Veldink, Jan H., Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., Witt, Stephanie H., Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L., Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P., Artiges, Eric, Assareh, Amelia A., Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L., Brown, Gregory G., Cichon, Sven, Curran, Joanne E., Davies, Gareth E., Degenhardt, Franziska, Dennis, Michelle F., Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P., Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A., Green, Robert C., Hausler, Alexander N., Heindel, Walter, Ho, Beng-Choon, Hoffmann, Wolfgang U., Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R., Jr., Jang, MiHyun, Jansen, Andreas, Kimbrel, Nathan A., Kolskar, Knut, Koops, Sanne, Krug, Axel, Lim, Kelvin O., Luykx, Jurjen J., Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., Matthews, Sarah, Van Son, Jaqueline Mayoral, McEwen, Sarah C., Melle, Ingrid, Morris, Derek W., Mueller, Bryon A., Nauck, Matthias, Nordvik, Jan E., Noethen, Markus M., O'Leary, Daniel S., Opel, Nils, Martinot, Marie-Laure Paillere, Pike, G. Bruce, Preda, Adrian, Quinlan, Erin B., Rasser, Paul E., Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M., Tooney, Paul A., Torres, Fabio R., Veltman, Dick J., Voyvodic, James T., Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H. H., Bis, Joshua C., Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Ikram, M. Arfan, Launer, Lenore, Longstreth, W. T., Lopez, Oscar L., Mazoyer, Bernard, Mosley, Thomas H., Roshchupkin, Gennady V., Satizabal, Claudia L., Schmidt, Reinhold, Seshadri, Sudha, Yang, Qiong, Alvim, Marina K. M., Ames, David, Anderson, Tim J., Andreassen, Ole A., Arias-Vasquez, Alejandro, Bastin, Mark E., Baune, Bernhard T., Beckham, Jean C., Blangero, John, Boomsma, Dorret I., Brodaty, Henry, Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Bustillo, Juan R., Cahn, Wiepke, Cairns, Murray J., Calhoun, Vince, Carr, Vaughan J., Caseras, Xavier, Caspers, Svenja, Cavalleri, Gianpiero L., Cendes, Fernando, Corvin, Aiden, Crespo-Facorro, Benedicto, Dalrymple-Alford, John C., Dannlowski, Udo, de Geus, Eco J. C., Deary, Ian J., Delanty, Norman, Depondt, Chantal, Desrivieres, Sylvane, Donohoe, Gary, Espeseth, Thomas, Fernandez, Guillen, Fisher, Simon E., Flor, Herta, Forstner, Andreas J., Francks, Clyde, Franke, Barbara, Glahn, David C., Gollub, Randy L., Grabe, Hans J., Gruber, Oliver, Haberg, Asta K., Hariri, Ahmad R., Hartman, Catharina A., Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans A., Hillegers, Manon H. J., Hoekstra, Pieter J., Holmes, Avram J., Hong, L. Elliot, Hopkins, William D., Pol, Hilleke E. Hulshoff, Jernigan, Terry L., Jonsson, Erik G., Kahn, Rene S., Kennedy, Martin A., Kircher, Tilo T. J., Kochunov, Peter, Kwok, John B. J., Le Hellard, Stephanie, Loughland, Carmel M., Martin, Nicholas G., Martinot, Jean-Luc, McDonald, Colm, McMahon, Katie L., Meyer-Lindenberg, Andreas, Michie, Patricia T., Morey, Rajendra A., Mowry, Bryan, Nyberg, Lars, Oosterlaan, Jaap, Ophoff, Roel A., Pantelis, Christos, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Polderman, Tinca J. C., Posthuma, Danielle, Rietschel, Marcella, Roffman, Joshua L., Rowland, Laura M., Sachdev, Perminder S., Samann, Philipp G., Schall, Ulrich, Schumann, Gunter, Scott, Rodney J., Sim, Kang, Sisodiya, Sanjay M., Smoller, Jordan W., Sommer, Iris E., St Pourcain, Beate, Stein, Dan J., Toga, Arthur W., Trollor, Julian N., Van der Wee, Nic J. A., van't Ent, Dennis, Volzke, Henry, Walter, Henrik, Weber, Bernd, Weinberger, Daniel R., Wright, Margaret J., Zhou, Juan, Stein, Jason L., Thompson, Paul M., and Medland, Sarah E.
Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
Published: 2020
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26. Early Life Glucocorticoid Exposure Modulates Immune Function in Zebrafish (Danio rerio) Larvae

Author: Bos, Ruud van den, Cromwijk, Suzanne, Tschigg, Katharina, Althuizen, Joep, Zethof, J, Whelan, Robert, Flik, G., Schaaf, M.J., Bos, Ruud van den, Cromwijk, Suzanne, Tschigg, Katharina, Althuizen, Joep, Zethof, J, Whelan, Robert, Flik, G., and Schaaf, M.J.
Abstract: Contains fulltext : 221464.pdf (publisher's version ) (Open Access)
Published: 2020

27. The genetic architecture of the human cerebral cortex

Author: Grasby, Katrina L., Jahanshad, Neda, Painter, Jodie N., Colodro-Conde, Lucía, Bralten, Janita, Hibar, Derrek P., Lind, Penelope A., Pizzagalli, Fabrizio, Ching, Christopher R.K., McMahon, Mary Agnes B., Shatokhina, Natalia, Zsembik, Leo C.P., Thomopoulos, Sophia I., Zhu, Alyssa H., Strike, Lachlan T., Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio A.A., Alnæs, Dag, Amlien, Inge K., Andersson, Micael, Ard, Tyler, Armstrong, Nicola J., Ashley-Koch, Allison, Atkins, Joshua R., Bernard, Manon, Brouwer, Rachel M., Buimer, Elizabeth E.L., Bülow, Robin, Bürger, Christian, Cannon, Dara M., Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W., Couvy-Duchesne, Baptiste, Dale, Anders M., Dalvie, Shareefa, de Araujo, Tânia K., de Zubicaray, Greig I., de Zwarte, Sonja M.C., den Braber, Anouk, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O., Foley, Sonya F., Ford, Judith M., Fukunaga, Masaki, Garrett, Melanie E., Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Gurholt, Tiril P., Gutman, Boris A., Hansell, Narelle K., Harris, Mathew A., Harrison, Marc B., Haswell, Courtney C., Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J., Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E., Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R., Krämer, Bernd, Lam, Max, Lancaster, Thomas M., Lee, Phil H., Lett, Tristram A., Lewis, Lindsay B., Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F., Mathias, Samuel R., Melzer, Tracy R., Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Moreira, Jose C.V., Mühleisen, Thomas W., Müller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M., Orfanos, Dimitri Papadopoulos, Pearson, John F., Pitcher, Toni L., Pütz, Benno, Quidé, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M., Reay, William R., Redlich, Ronny, Reinbold, Céline S., Repple, Jonathan, Richard, Geneviève, Riedel, Brandalyn C., Risacher, Shannon L., Rocha, Cristiane S., Mota, Nina R., Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J., Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R., Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E., Sprooten, Emma, Tansey, Katherine E., Teumer, Alexander, Thalamuthu, Anbupalam, Tordesillas-Gutiérrez, Diana, Turner, Jessica A., Uhlmann, Anne, Vallerga, Costanza L., van der Meer, Dennis, van Donkelaar, Marjolein M.J., van Eijk, Liza, van Erp, Theo G.M., van Haren, Neeltje E.M., van Rooij, Daan, van Tol, Marie José, Veldink, Jan H., Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., Witt, Stephanie H., Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L., Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P., Artiges, Eric, Assareh, Amelia A., Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L., Brown, Gregory G., Cichon, Sven, Curran, Joanne E., Davies, Gareth E., Degenhardt, Franziska, Dennis, Michelle F., Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P., Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A., Green, Robert C., Häusler, Alexander N., Heindel, Walter, Ho, Beng Choon, Hoffmann, Wolfgang U., Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R., Jang, Mi Hyun, Jansen, Andreas, Kimbrel, Nathan A., Kolskår, Knut, Koops, Sanne, Krug, Axel, Lim, Kelvin O., Luykx, Jurjen J., Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., Matthews, Sarah, van Son, Jaqueline Mayoral, McEwen, Sarah C., Melle, Ingrid, Morris, Derek W., Mueller, Bryon A., Nauck, Matthias, Nordvik, Jan E., Nöthen, Markus M., O'Leary, Daniel S., Opel, Nils, Martinot, Marie Laure Paillère, Bruce Pike, G., Preda, Adrian, Quinlan, Erin B., Rasser, Paul E., Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M., Tooney, Paul A., Torres, Fábio R., Veltman, Dick J., Voyvodic, James T., Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H.H., Bis, Joshua C., Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Arfan Ikram, M., Launer, Lenore, Longstreth, W. T., Lopez, Oscar L., Fisher, Simon E., Martin, Nicholas G., McMahon, Katie L., Wright, Margaret J., Thompson, Paul M., Medland, Sarah E., Grasby, Katrina L., Jahanshad, Neda, Painter, Jodie N., Colodro-Conde, Lucía, Bralten, Janita, Hibar, Derrek P., Lind, Penelope A., Pizzagalli, Fabrizio, Ching, Christopher R.K., McMahon, Mary Agnes B., Shatokhina, Natalia, Zsembik, Leo C.P., Thomopoulos, Sophia I., Zhu, Alyssa H., Strike, Lachlan T., Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio A.A., Alnæs, Dag, Amlien, Inge K., Andersson, Micael, Ard, Tyler, Armstrong, Nicola J., Ashley-Koch, Allison, Atkins, Joshua R., Bernard, Manon, Brouwer, Rachel M., Buimer, Elizabeth E.L., Bülow, Robin, Bürger, Christian, Cannon, Dara M., Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W., Couvy-Duchesne, Baptiste, Dale, Anders M., Dalvie, Shareefa, de Araujo, Tânia K., de Zubicaray, Greig I., de Zwarte, Sonja M.C., den Braber, Anouk, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O., Foley, Sonya F., Ford, Judith M., Fukunaga, Masaki, Garrett, Melanie E., Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L., Green, Melissa J., Groenewold, Nynke A., Grotegerd, Dominik, Gurholt, Tiril P., Gutman, Boris A., Hansell, Narelle K., Harris, Mathew A., Harrison, Marc B., Haswell, Courtney C., Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J., Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E., Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R., Krämer, Bernd, Lam, Max, Lancaster, Thomas M., Lee, Phil H., Lett, Tristram A., Lewis, Lindsay B., Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F., Mathias, Samuel R., Melzer, Tracy R., Milaneschi, Yuri, Mirza-Schreiber, Nazanin, Moreira, Jose C.V., Mühleisen, Thomas W., Müller-Myhsok, Bertram, Najt, Pablo, Nakahara, Soichiro, Nho, Kwangsik, Olde Loohuis, Loes M., Orfanos, Dimitri Papadopoulos, Pearson, John F., Pitcher, Toni L., Pütz, Benno, Quidé, Yann, Ragothaman, Anjanibhargavi, Rashid, Faisal M., Reay, William R., Redlich, Ronny, Reinbold, Céline S., Repple, Jonathan, Richard, Geneviève, Riedel, Brandalyn C., Risacher, Shannon L., Rocha, Cristiane S., Mota, Nina R., Salminen, Lauren, Saremi, Arvin, Saykin, Andrew J., Schlag, Fenja, Schmaal, Lianne, Schofield, Peter R., Secolin, Rodrigo, Shapland, Chin Yang, Shen, Li, Shin, Jean, Shumskaya, Elena, Sønderby, Ida E., Sprooten, Emma, Tansey, Katherine E., Teumer, Alexander, Thalamuthu, Anbupalam, Tordesillas-Gutiérrez, Diana, Turner, Jessica A., Uhlmann, Anne, Vallerga, Costanza L., van der Meer, Dennis, van Donkelaar, Marjolein M.J., van Eijk, Liza, van Erp, Theo G.M., van Haren, Neeltje E.M., van Rooij, Daan, van Tol, Marie José, Veldink, Jan H., Verhoef, Ellen, Walton, Esther, Wang, Mingyuan, Wang, Yunpeng, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., Witt, Stephanie H., Wittfeld, Katharina, Wolf, Christiane, Wolfers, Thomas, Wu, Jing Qin, Yasuda, Clarissa L., Zaremba, Dario, Zhang, Zuo, Zwiers, Marcel P., Artiges, Eric, Assareh, Amelia A., Ayesa-Arriola, Rosa, Belger, Aysenil, Brandt, Christine L., Brown, Gregory G., Cichon, Sven, Curran, Joanne E., Davies, Gareth E., Degenhardt, Franziska, Dennis, Michelle F., Dietsche, Bruno, Djurovic, Srdjan, Doherty, Colin P., Espiritu, Ryan, Garijo, Daniel, Gil, Yolanda, Gowland, Penny A., Green, Robert C., Häusler, Alexander N., Heindel, Walter, Ho, Beng Choon, Hoffmann, Wolfgang U., Holsboer, Florian, Homuth, Georg, Hosten, Norbert, Jack, Clifford R., Jang, Mi Hyun, Jansen, Andreas, Kimbrel, Nathan A., Kolskår, Knut, Koops, Sanne, Krug, Axel, Lim, Kelvin O., Luykx, Jurjen J., Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., Matthews, Sarah, van Son, Jaqueline Mayoral, McEwen, Sarah C., Melle, Ingrid, Morris, Derek W., Mueller, Bryon A., Nauck, Matthias, Nordvik, Jan E., Nöthen, Markus M., O'Leary, Daniel S., Opel, Nils, Martinot, Marie Laure Paillère, Bruce Pike, G., Preda, Adrian, Quinlan, Erin B., Rasser, Paul E., Ratnakar, Varun, Reppermund, Simone, Steen, Vidar M., Tooney, Paul A., Torres, Fábio R., Veltman, Dick J., Voyvodic, James T., Whelan, Robert, White, Tonya, Yamamori, Hidenaga, Adams, Hieab H.H., Bis, Joshua C., Debette, Stephanie, Decarli, Charles, Fornage, Myriam, Gudnason, Vilmundur, Hofer, Edith, Arfan Ikram, M., Launer, Lenore, Longstreth, W. T., Lopez, Oscar L., Fisher, Simon E., Martin, Nicholas G., McMahon, Katie L., Wright, Margaret J., Thompson, Paul M., and Medland, Sarah E.
Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
Published: 2020

28. Early Life Glucocorticoid Exposure Modulates Immune Function in Zebrafish (Danio rerio) Larvae

Author: Bos, Ruud van den, Cromwijk, Suzanne, Tschigg, Katharina, Althuizen, Joep, Zethof, J, Whelan, Robert, Flik, G., Schaaf, M.J., Bos, Ruud van den, Cromwijk, Suzanne, Tschigg, Katharina, Althuizen, Joep, Zethof, J, Whelan, Robert, Flik, G., and Schaaf, M.J.
Abstract: Contains fulltext : 221464.pdf (publisher's version ) (Open Access)
Published: 2020

29. Early Life Glucocorticoid Exposure Modulates Immune Function in Zebrafish (Danio rerio) Larvae

Author: Bos, Ruud van den, Cromwijk, Suzanne, Tschigg, Katharina, Althuizen, Joep, Zethof, J, Whelan, Robert, Flik, G., Schaaf, M.J., Bos, Ruud van den, Cromwijk, Suzanne, Tschigg, Katharina, Althuizen, Joep, Zethof, J, Whelan, Robert, Flik, G., and Schaaf, M.J.
Abstract: Contains fulltext : 221464.pdf (publisher's version ) (Open Access)
Published: 2020

30. Profiles of Psychological Flexibility: A Latent Class Analysis of the Acceptance and Commitment Therapy Model

Author: Tyndall, I, Waldeck, D, Pancani, L, Whelan, R, Roche, B, Pereira, A, Tyndall, Ian, Waldeck, Daniel, Pancani, Luca, Whelan, Robert, Roche, Bryan, Pereira, Antonina, Tyndall, I, Waldeck, D, Pancani, L, Whelan, R, Roche, B, Pereira, A, Tyndall, Ian, Waldeck, Daniel, Pancani, Luca, Whelan, Robert, Roche, Bryan, and Pereira, Antonina
Abstract: There exists uncertainty for clinicians over how the separate subcomponent processes of psychological flexibility, a core construct of the Acceptance and Commitment Therapy model, interact and influence distress experienced. The present study (N = 567) employed latent class analysis to (a) identify potential classes (i.e., subgroups) of psychological flexibility based on responses on measures of key subcomponent process and (b) examine whether such classes could reliably differentiate levels of self-reported psychological distress and positive and negative emotionality. We found three distinct classes: (a) High Psychological Flexibility, (b) Moderate Psychological Flexibility, and (c) Low Psychological Flexibility. Those in the Low Psychology Flexibility class reported highest levels of psychological distress, whereas those in the High Psychological Flexibility class reported lowest levels of psychological distress. This study provides a clearer view to clinicians of the profile of the broader spectrum of the psychological flexibility model to facilitate change in clients.
Published: 2020

31. Long inter-fire intervals do not guarantee a large seed bank in a serotinous shrub (Banksia spinulosa Sm.)

Author: Whelan, Robert J, Ayre, David J, Whelan, Robert J, and Ayre, David J
Abstract: © 2020 British Ecological Society It is often assumed that long-lived woody perennials with canopy-stored seed banks steadily accumulate seeds over time since fire. Trends in flowering and fruiting have usually been inferred from synchronic studies of sites of different post-fire ages or counting stored seeds in apparent age classes, and mostly in obligate-seeder species. Long-term longitudinal studies on a broader range of species are needed to fully understand the dynamics of flower and fruit production and accumulation of viable seeds. Key questions are as follows: What is the annual trend in flowering and cone production? Is this matched by accumulation of cones and seeds? How is seed germinability related to cone age at the time of a fire? We counted inflorescences and tagged cones produced annually by the resprouting shrub Banksia spinulosa in 315 plants over 13 years at one site and in 46 plants over 20 years at another. At the end of the study, we harvested all accumulated cones, burned them and assessed seed viability using germination trials. We detected enormous inter-plant variation in reproductive effort and output. 50% of inflorescences was produced by only 10%–15% of plants. There was a potential for accumulation of massive seed banks. However, (a) only 8%–10% of inflorescences became cones; (b) only 44%–50% of these were retained until harvest; (c) many retained cones suffered seed predation; and (d) viability of retained seeds declined with cone age. The result of these processes meant that the accumulated seed bank was only two to four seeds per plant, 82%–94% of the viable seeds had been produced in 6 years prior to harvest and only 12%–26% of plants contributed to this viable seed bank. Synthesis: Cone and seed losses and declining seed viability in B. spinulosa mean that almost all viable seeds come from the past few years of flowering even though apparently intact cones may be retained for decades. If this is typical for resprouting serotinous
Published: 2020

32. A consensus guide to capturing the ability to inhibit actions and impulsive behaviors in the stop-signal task

Author: Verbruggen, Frederick, Aron, Adam R, Band, Guido Ph, Beste, Christian, Bissett, Patrick G, Brockett, Adam T, Brown, Joshua W, Chamberlain, Samuel R, Chambers, Christopher D, Colonius, Hans, Colzato, Lorenza S, Corneil, Brian D, Coxon, James P, Dupuis, Annie, Eagle, Dawn M, Garavan, Hugh, Greenhouse, Ian, Heathcote, Andrew, Huster, René J, Jahfari, Sara, Kenemans, J Leon, Leunissen, Inge, Logan, Gordon D, Matzke, Dora, Morein-Zamir, Sharon, Murthy, Aditya, Li, Chiang-Shan R, Paré, Martin, Poldrack, Russell A, Ridderinkhof, K Richard, Robbins, Trevor W, Roesch, Matthew, Rubia, Katya, Schachar, Russell J, Schall, Jeffrey D, Stock, Ann-Kathrin, Swann, Nicole C, Thakkar, Katharine N, van der Molen, Maurits W, Vermeylen, Luc, Vink, Matthijs, Wessel, Jan R, Whelan, Robert, Zandbelt, Bram B, Boehler, C Nico, Verbruggen, Frederick, Aron, Adam R, Band, Guido Ph, Beste, Christian, Bissett, Patrick G, Brockett, Adam T, Brown, Joshua W, Chamberlain, Samuel R, Chambers, Christopher D, Colonius, Hans, Colzato, Lorenza S, Corneil, Brian D, Coxon, James P, Dupuis, Annie, Eagle, Dawn M, Garavan, Hugh, Greenhouse, Ian, Heathcote, Andrew, Huster, René J, Jahfari, Sara, Kenemans, J Leon, Leunissen, Inge, Logan, Gordon D, Matzke, Dora, Morein-Zamir, Sharon, Murthy, Aditya, Li, Chiang-Shan R, Paré, Martin, Poldrack, Russell A, Ridderinkhof, K Richard, Robbins, Trevor W, Roesch, Matthew, Rubia, Katya, Schachar, Russell J, Schall, Jeffrey D, Stock, Ann-Kathrin, Swann, Nicole C, Thakkar, Katharine N, van der Molen, Maurits W, Vermeylen, Luc, Vink, Matthijs, Wessel, Jan R, Whelan, Robert, Zandbelt, Bram B, and Boehler, C Nico
Abstract: Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions. The stop-signal task is an essential tool to determine how quickly response inhibition is implemented. Despite its apparent simplicity, there are many features (ranging from task design to data analysis) that vary across studies in ways that can easily compromise the validity of the obtained results. Our goal is to facilitate a more accurate use of the stop-signal task. To this end, we provide twelve easy-to-implement consensus recommendations and point out the problems that can arise when these are not followed. Furthermore we provide user-friendly open-source resources intended to inform statistical-power considerations, facilitate the correct implementation of the task, and assist in proper data analysis.
Published: 2019

33. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes : findings from the ENIGMA Epigenetics Working Group.

Author: Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J, Bastin, Mark E, Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P S, Roiz Santiañez, Roberto, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Tordesillas Gutiérrez, Diana, Van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L W, Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Büchel, Christian, Burke Quinlan, Erin, Cahn, Wiepke, de Zubicaray, Greig I, Ehrlich, Stefan, Ekström, Tomas J, Flor, Herta, Fröhner, Juliane H, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B, Martin, Nicholas G, Martinot, Jean-Luc, Mather, Karen A, McMahon, Katie L, McRae, Allan F, Nees, Frauke, Papadopoulos Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Sämann, Philipp G, Schofield, Peter R, Smolka, Michael N, Stein, Dan J, Strike, Lachlan T, Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M, Wen, Wei, Whelan, Robert, Apostolova, Liana G, Binder, Elisabeth B, Boomsma, Dorret I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J, Hulshoff Pol, Hilleke, Ophoff, Roel A, Pausova, Zdenka, Sachdev, Perminder S, Saykin, Andrew, Wright, Margaret J, Thompson, Paul M, Schumann, Gunter, Desrivières, Sylvane, Jia, Tianye, Chu, Congying, Liu, Yun, van Dongen, Jenny, Papastergios, Evangelos, Armstrong, Nicola J, Bastin, Mark E, Carrillo-Roa, Tania, den Braber, Anouk, Harris, Mathew, Jansen, Rick, Liu, Jingyu, Luciano, Michelle, Ori, Anil P S, Roiz Santiañez, Roberto, Ruggeri, Barbara, Sarkisyan, Daniil, Shin, Jean, Sungeun, Kim, Tordesillas Gutiérrez, Diana, Van't Ent, Dennis, Ames, David, Artiges, Eric, Bakalkin, Georgy, Banaschewski, Tobias, Bokde, Arun L W, Brodaty, Henry, Bromberg, Uli, Brouwer, Rachel, Büchel, Christian, Burke Quinlan, Erin, Cahn, Wiepke, de Zubicaray, Greig I, Ehrlich, Stefan, Ekström, Tomas J, Flor, Herta, Fröhner, Juliane H, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Hoare, Jacqueline, Ittermann, Bernd, Jahanshad, Neda, Jiang, Jiyang, Kwok, John B, Martin, Nicholas G, Martinot, Jean-Luc, Mather, Karen A, McMahon, Katie L, McRae, Allan F, Nees, Frauke, Papadopoulos Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Sämann, Philipp G, Schofield, Peter R, Smolka, Michael N, Stein, Dan J, Strike, Lachlan T, Teeuw, Jalmar, Thalamuthu, Anbupalam, Trollor, Julian, Walter, Henrik, Wardlaw, Joanna M, Wen, Wei, Whelan, Robert, Apostolova, Liana G, Binder, Elisabeth B, Boomsma, Dorret I, Calhoun, Vince, Crespo-Facorro, Benedicto, Deary, Ian J, Hulshoff Pol, Hilleke, Ophoff, Roel A, Pausova, Zdenka, Sachdev, Perminder S, Saykin, Andrew, Wright, Margaret J, Thompson, Paul M, Schumann, Gunter, and Desrivières, Sylvane
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Published: 2019
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34. The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking : A Translational Study

Author: Mueller, Christian P., Chu, Congying, Qin, Liya, Liu, Chunyu, Xu, Bing, Gao, He, Ruggeri, Barbara, Hieber, Saskia, Schneider, Julia, Jia, Tianye, Tay, Nicole, Akira, Shizuo, Satoh, Takashi, Banaschewski, Tobias, Bokde, Arun L. W., Bromberg, Uli, Buechel, Christian, Quinlan, Erin Burke, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Martinot, Marie-Laure Paillere, Artiges, Eric, Lemaitre, Herve, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Millenet, Sabina, Froehner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Bakalkin, Georgy, Liu, Yun, Desrivieres, Sylvane, Elliott, Paul, Eulenburg, Volker, Levy, Daniel, Crews, Fulton, Schumann, Gunter, Mueller, Christian P., Chu, Congying, Qin, Liya, Liu, Chunyu, Xu, Bing, Gao, He, Ruggeri, Barbara, Hieber, Saskia, Schneider, Julia, Jia, Tianye, Tay, Nicole, Akira, Shizuo, Satoh, Takashi, Banaschewski, Tobias, Bokde, Arun L. W., Bromberg, Uli, Buechel, Christian, Quinlan, Erin Burke, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Martinot, Marie-Laure Paillere, Artiges, Eric, Lemaitre, Herve, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Millenet, Sabina, Froehner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Bakalkin, Georgy, Liu, Yun, Desrivieres, Sylvane, Elliott, Paul, Eulenburg, Volker, Levy, Daniel, Crews, Fulton, and Schumann, Gunter
Abstract: Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-kappa B activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 x 10(-19)) and regional methylation (P = 5.90 x 10(-25)). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-kappa B. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.
Published: 2019
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35. Allele-Specific Methylation of SPDEF : A Novel Moderator of Psychosocial Stress and Substance Abuse

Author: Tay, Nicole, Macare, Christine, Liu, Yun, Ruggeri, Barbara, Jia, Tianye, Chu, Congying, Biondo, Francesca, Ing, Alex, Luo, Qiang, Sarkisyan, Daniil, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L. W., Bromberg, Uli, Büchel, Christian, Quinlan, Erin Burke, Desrivieres, Sylvane, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Frieling, Helge, Bleich, Stefan, Barker, Edward D., Syvänen, Ann-Christine, Rüegg, Joelle, Ekström, Tomas J., Bakalkin, Georgy, Schumann, Gunter, Tay, Nicole, Macare, Christine, Liu, Yun, Ruggeri, Barbara, Jia, Tianye, Chu, Congying, Biondo, Francesca, Ing, Alex, Luo, Qiang, Sarkisyan, Daniil, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L. W., Bromberg, Uli, Büchel, Christian, Quinlan, Erin Burke, Desrivieres, Sylvane, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Frieling, Helge, Bleich, Stefan, Barker, Edward D., Syvänen, Ann-Christine, Rüegg, Joelle, Ekström, Tomas J., Bakalkin, Georgy, and Schumann, Gunter
Abstract: Objective: Psychosocial stress is a key risk factor for substance abuse among adolescents. Recently, epigenetic processes such as DNA methylation have emerged as potential mechanisms that could mediate this relationship. The authors conducted a genome-wide methylation analysis to investigate whether differentially methylated regions are associated with psychosocial stress in an adolescent population. Methods: A methylome-wide analysis of differentially methylated regions was used to examine a sample of 1,287 14-year-old adolescents (50.7% of them female) from the European IMAGEN study. The Illumina 450k array was used to assess DNA methylation, pyrosequencing was used for technical replication, and linear regression analyses were used to identify associations with psychosocial stress and substance use (alcohol and tobacco). Findings were replicated by pyrosequencing a test sample of 413 participants from the IMAGEN study. Results: Hypermethylation in the sterile alpha motif/pointed domain containing the ETS transcription factor (SPDEF) gene locus was associated with a greater number of stressful life events in an allele-dependent way. Among individuals with the minor G-allele, SPDEF methylation moderated the association between psychosocial stress and substance abuse. SPDEF methylation interacted with lifetime stress in gray matter volume in the right cuneus, which in turn was associated with the frequency of alcohol and tobacco use. SPDEF was involved in the regulation of trans-genes linked to substance use. Conclusions: Taken together, the study findings describe a novel epigenetic mechanism that helps explain how psychosocial stress exposure influences adolescent substance abuse.
Published: 2019
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36. The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking : A Translational Study

Author: Mueller, Christian P., Chu, Congying, Qin, Liya, Liu, Chunyu, Xu, Bing, Gao, He, Ruggeri, Barbara, Hieber, Saskia, Schneider, Julia, Jia, Tianye, Tay, Nicole, Akira, Shizuo, Satoh, Takashi, Banaschewski, Tobias, Bokde, Arun L. W., Bromberg, Uli, Buechel, Christian, Quinlan, Erin Burke, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Martinot, Marie-Laure Paillere, Artiges, Eric, Lemaitre, Herve, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Millenet, Sabina, Froehner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Bakalkin, Georgy, Liu, Yun, Desrivieres, Sylvane, Elliott, Paul, Eulenburg, Volker, Levy, Daniel, Crews, Fulton, Schumann, Gunter, Mueller, Christian P., Chu, Congying, Qin, Liya, Liu, Chunyu, Xu, Bing, Gao, He, Ruggeri, Barbara, Hieber, Saskia, Schneider, Julia, Jia, Tianye, Tay, Nicole, Akira, Shizuo, Satoh, Takashi, Banaschewski, Tobias, Bokde, Arun L. W., Bromberg, Uli, Buechel, Christian, Quinlan, Erin Burke, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Martinot, Marie-Laure Paillere, Artiges, Eric, Lemaitre, Herve, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Millenet, Sabina, Froehner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Bakalkin, Georgy, Liu, Yun, Desrivieres, Sylvane, Elliott, Paul, Eulenburg, Volker, Levy, Daniel, Crews, Fulton, and Schumann, Gunter
Abstract: Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-kappa B activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 x 10(-19)) and regional methylation (P = 5.90 x 10(-25)). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-kappa B. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.
Published: 2019
Full Text: View/download PDF

37. A consensus guide to capturing the ability to inhibit actions and impulsive behaviors in the stop-signal task

Author: Leerstoel Kenemans, Leerstoel Kemner, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Afd Psychologische functieleer, Verbruggen, Frederick, Aron, Adam R, Band, Guido Ph, Beste, Christian, Bissett, Patrick G, Brockett, Adam T, Brown, Joshua W, Chamberlain, Samuel R, Chambers, Christopher D, Colonius, Hans, Colzato, Lorenza S, Corneil, Brian D, Coxon, James P, Dupuis, Annie, Eagle, Dawn M, Garavan, Hugh, Greenhouse, Ian, Heathcote, Andrew, Huster, René J, Jahfari, Sara, Kenemans, J Leon, Leunissen, Inge, Logan, Gordon D, Matzke, Dora, Morein-Zamir, Sharon, Murthy, Aditya, Li, Chiang-Shan R, Paré, Martin, Poldrack, Russell A, Ridderinkhof, K Richard, Robbins, Trevor W, Roesch, Matthew, Rubia, Katya, Schachar, Russell J, Schall, Jeffrey D, Stock, Ann-Kathrin, Swann, Nicole C, Thakkar, Katharine N, van der Molen, Maurits W, Vermeylen, Luc, Vink, Matthijs, Wessel, Jan R, Whelan, Robert, Zandbelt, Bram B, Boehler, C Nico, Leerstoel Kenemans, Leerstoel Kemner, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Afd Psychologische functieleer, Verbruggen, Frederick, Aron, Adam R, Band, Guido Ph, Beste, Christian, Bissett, Patrick G, Brockett, Adam T, Brown, Joshua W, Chamberlain, Samuel R, Chambers, Christopher D, Colonius, Hans, Colzato, Lorenza S, Corneil, Brian D, Coxon, James P, Dupuis, Annie, Eagle, Dawn M, Garavan, Hugh, Greenhouse, Ian, Heathcote, Andrew, Huster, René J, Jahfari, Sara, Kenemans, J Leon, Leunissen, Inge, Logan, Gordon D, Matzke, Dora, Morein-Zamir, Sharon, Murthy, Aditya, Li, Chiang-Shan R, Paré, Martin, Poldrack, Russell A, Ridderinkhof, K Richard, Robbins, Trevor W, Roesch, Matthew, Rubia, Katya, Schachar, Russell J, Schall, Jeffrey D, Stock, Ann-Kathrin, Swann, Nicole C, Thakkar, Katharine N, van der Molen, Maurits W, Vermeylen, Luc, Vink, Matthijs, Wessel, Jan R, Whelan, Robert, Zandbelt, Bram B, and Boehler, C Nico
Published: 2019

38. A consensus guide to capturing the ability to inhibit actions and impulsive behaviors in the stop-signal task

Author: Verbruggen, Frederick, Aron, Adam R, Band, Guido Ph, Beste, Christian, Bissett, Patrick G, Brockett, Adam T, Brown, Joshua W, Chamberlain, Samuel R, Chambers, Christopher D, Colonius, Hans, Colzato, Lorenza S, Corneil, Brian D, Coxon, James P, Dupuis, Annie, Eagle, Dawn M, Garavan, Hugh, Greenhouse, Ian, Heathcote, Andrew, Huster, René J, Jahfari, Sara, Kenemans, J Leon, Leunissen, Inge, Logan, Gordon D, Matzke, Dora, Morein-Zamir, Sharon, Murthy, Aditya, Li, Chiang-Shan R, Paré, Martin, Poldrack, Russell A, Ridderinkhof, K Richard, Robbins, Trevor W, Roesch, Matthew, Rubia, Katya, Schachar, Russell J, Schall, Jeffrey D, Stock, Ann-Kathrin, Swann, Nicole C, Thakkar, Katharine N, van der Molen, Maurits W, Vermeylen, Luc, Vink, Matthijs, Wessel, Jan R, Whelan, Robert, Zandbelt, Bram B, Boehler, C Nico, Verbruggen, Frederick, Aron, Adam R, Band, Guido Ph, Beste, Christian, Bissett, Patrick G, Brockett, Adam T, Brown, Joshua W, Chamberlain, Samuel R, Chambers, Christopher D, Colonius, Hans, Colzato, Lorenza S, Corneil, Brian D, Coxon, James P, Dupuis, Annie, Eagle, Dawn M, Garavan, Hugh, Greenhouse, Ian, Heathcote, Andrew, Huster, René J, Jahfari, Sara, Kenemans, J Leon, Leunissen, Inge, Logan, Gordon D, Matzke, Dora, Morein-Zamir, Sharon, Murthy, Aditya, Li, Chiang-Shan R, Paré, Martin, Poldrack, Russell A, Ridderinkhof, K Richard, Robbins, Trevor W, Roesch, Matthew, Rubia, Katya, Schachar, Russell J, Schall, Jeffrey D, Stock, Ann-Kathrin, Swann, Nicole C, Thakkar, Katharine N, van der Molen, Maurits W, Vermeylen, Luc, Vink, Matthijs, Wessel, Jan R, Whelan, Robert, Zandbelt, Bram B, and Boehler, C Nico
Abstract: Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions. The stop-signal task is an essential tool to determine how quickly response inhibition is implemented. Despite its apparent simplicity, there are many features (ranging from task design to data analysis) that vary across studies in ways that can easily compromise the validity of the obtained results. Our goal is to facilitate a more accurate use of the stop-signal task. To this end, we provide twelve easy-to-implement consensus recommendations and point out the problems that can arise when these are not followed. Furthermore we provide user-friendly open-source resources intended to inform statistical-power considerations, facilitate the correct implementation of the task, and assist in proper data analysis.
Published: 2019

39. A consensus guide to capturing the ability to inhibit actions and impulsive behaviors in the stop-signal task

Author: Leerstoel Kenemans, Leerstoel Kemner, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Afd Psychologische functieleer, Verbruggen, Frederick, Aron, Adam R, Band, Guido Ph, Beste, Christian, Bissett, Patrick G, Brockett, Adam T, Brown, Joshua W, Chamberlain, Samuel R, Chambers, Christopher D, Colonius, Hans, Colzato, Lorenza S, Corneil, Brian D, Coxon, James P, Dupuis, Annie, Eagle, Dawn M, Garavan, Hugh, Greenhouse, Ian, Heathcote, Andrew, Huster, René J, Jahfari, Sara, Kenemans, J Leon, Leunissen, Inge, Logan, Gordon D, Matzke, Dora, Morein-Zamir, Sharon, Murthy, Aditya, Li, Chiang-Shan R, Paré, Martin, Poldrack, Russell A, Ridderinkhof, K Richard, Robbins, Trevor W, Roesch, Matthew, Rubia, Katya, Schachar, Russell J, Schall, Jeffrey D, Stock, Ann-Kathrin, Swann, Nicole C, Thakkar, Katharine N, van der Molen, Maurits W, Vermeylen, Luc, Vink, Matthijs, Wessel, Jan R, Whelan, Robert, Zandbelt, Bram B, Boehler, C Nico, Leerstoel Kenemans, Leerstoel Kemner, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Afd Psychologische functieleer, Verbruggen, Frederick, Aron, Adam R, Band, Guido Ph, Beste, Christian, Bissett, Patrick G, Brockett, Adam T, Brown, Joshua W, Chamberlain, Samuel R, Chambers, Christopher D, Colonius, Hans, Colzato, Lorenza S, Corneil, Brian D, Coxon, James P, Dupuis, Annie, Eagle, Dawn M, Garavan, Hugh, Greenhouse, Ian, Heathcote, Andrew, Huster, René J, Jahfari, Sara, Kenemans, J Leon, Leunissen, Inge, Logan, Gordon D, Matzke, Dora, Morein-Zamir, Sharon, Murthy, Aditya, Li, Chiang-Shan R, Paré, Martin, Poldrack, Russell A, Ridderinkhof, K Richard, Robbins, Trevor W, Roesch, Matthew, Rubia, Katya, Schachar, Russell J, Schall, Jeffrey D, Stock, Ann-Kathrin, Swann, Nicole C, Thakkar, Katharine N, van der Molen, Maurits W, Vermeylen, Luc, Vink, Matthijs, Wessel, Jan R, Whelan, Robert, Zandbelt, Bram B, and Boehler, C Nico
Published: 2019

40. The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking : A Translational Study

Author: Mueller, Christian P., Chu, Congying, Qin, Liya, Liu, Chunyu, Xu, Bing, Gao, He, Ruggeri, Barbara, Hieber, Saskia, Schneider, Julia, Jia, Tianye, Tay, Nicole, Akira, Shizuo, Satoh, Takashi, Banaschewski, Tobias, Bokde, Arun L. W., Bromberg, Uli, Buechel, Christian, Quinlan, Erin Burke, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Martinot, Marie-Laure Paillere, Artiges, Eric, Lemaitre, Herve, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Millenet, Sabina, Froehner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Bakalkin, Georgy, Liu, Yun, Desrivieres, Sylvane, Elliott, Paul, Eulenburg, Volker, Levy, Daniel, Crews, Fulton, Schumann, Gunter, Mueller, Christian P., Chu, Congying, Qin, Liya, Liu, Chunyu, Xu, Bing, Gao, He, Ruggeri, Barbara, Hieber, Saskia, Schneider, Julia, Jia, Tianye, Tay, Nicole, Akira, Shizuo, Satoh, Takashi, Banaschewski, Tobias, Bokde, Arun L. W., Bromberg, Uli, Buechel, Christian, Quinlan, Erin Burke, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Martinot, Marie-Laure Paillere, Artiges, Eric, Lemaitre, Herve, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Millenet, Sabina, Froehner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Bakalkin, Georgy, Liu, Yun, Desrivieres, Sylvane, Elliott, Paul, Eulenburg, Volker, Levy, Daniel, Crews, Fulton, and Schumann, Gunter
Abstract: Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-kappa B activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 x 10(-19)) and regional methylation (P = 5.90 x 10(-25)). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-kappa B. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.
Published: 2019
Full Text: View/download PDF

41. The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking : A Translational Study

Author: Mueller, Christian P., Chu, Congying, Qin, Liya, Liu, Chunyu, Xu, Bing, Gao, He, Ruggeri, Barbara, Hieber, Saskia, Schneider, Julia, Jia, Tianye, Tay, Nicole, Akira, Shizuo, Satoh, Takashi, Banaschewski, Tobias, Bokde, Arun L. W., Bromberg, Uli, Buechel, Christian, Quinlan, Erin Burke, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Martinot, Marie-Laure Paillere, Artiges, Eric, Lemaitre, Herve, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Millenet, Sabina, Froehner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Bakalkin, Georgy, Liu, Yun, Desrivieres, Sylvane, Elliott, Paul, Eulenburg, Volker, Levy, Daniel, Crews, Fulton, Schumann, Gunter, Mueller, Christian P., Chu, Congying, Qin, Liya, Liu, Chunyu, Xu, Bing, Gao, He, Ruggeri, Barbara, Hieber, Saskia, Schneider, Julia, Jia, Tianye, Tay, Nicole, Akira, Shizuo, Satoh, Takashi, Banaschewski, Tobias, Bokde, Arun L. W., Bromberg, Uli, Buechel, Christian, Quinlan, Erin Burke, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Martinot, Marie-Laure Paillere, Artiges, Eric, Lemaitre, Herve, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Millenet, Sabina, Froehner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Bakalkin, Georgy, Liu, Yun, Desrivieres, Sylvane, Elliott, Paul, Eulenburg, Volker, Levy, Daniel, Crews, Fulton, and Schumann, Gunter
Abstract: Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-kappa B activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 x 10(-19)) and regional methylation (P = 5.90 x 10(-25)). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-kappa B. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.
Published: 2019
Full Text: View/download PDF

42. A consensus guide to capturing the ability to inhibit actions and impulsive behaviors in the stop-signal task

Author: Leerstoel Kenemans, Leerstoel Kemner, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Afd Psychologische functieleer, Verbruggen, Frederick, Aron, Adam R, Band, Guido Ph, Beste, Christian, Bissett, Patrick G, Brockett, Adam T, Brown, Joshua W, Chamberlain, Samuel R, Chambers, Christopher D, Colonius, Hans, Colzato, Lorenza S, Corneil, Brian D, Coxon, James P, Dupuis, Annie, Eagle, Dawn M, Garavan, Hugh, Greenhouse, Ian, Heathcote, Andrew, Huster, René J, Jahfari, Sara, Kenemans, J Leon, Leunissen, Inge, Logan, Gordon D, Matzke, Dora, Morein-Zamir, Sharon, Murthy, Aditya, Li, Chiang-Shan R, Paré, Martin, Poldrack, Russell A, Ridderinkhof, K Richard, Robbins, Trevor W, Roesch, Matthew, Rubia, Katya, Schachar, Russell J, Schall, Jeffrey D, Stock, Ann-Kathrin, Swann, Nicole C, Thakkar, Katharine N, van der Molen, Maurits W, Vermeylen, Luc, Vink, Matthijs, Wessel, Jan R, Whelan, Robert, Zandbelt, Bram B, Boehler, C Nico, Leerstoel Kenemans, Leerstoel Kemner, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Afd Psychologische functieleer, Verbruggen, Frederick, Aron, Adam R, Band, Guido Ph, Beste, Christian, Bissett, Patrick G, Brockett, Adam T, Brown, Joshua W, Chamberlain, Samuel R, Chambers, Christopher D, Colonius, Hans, Colzato, Lorenza S, Corneil, Brian D, Coxon, James P, Dupuis, Annie, Eagle, Dawn M, Garavan, Hugh, Greenhouse, Ian, Heathcote, Andrew, Huster, René J, Jahfari, Sara, Kenemans, J Leon, Leunissen, Inge, Logan, Gordon D, Matzke, Dora, Morein-Zamir, Sharon, Murthy, Aditya, Li, Chiang-Shan R, Paré, Martin, Poldrack, Russell A, Ridderinkhof, K Richard, Robbins, Trevor W, Roesch, Matthew, Rubia, Katya, Schachar, Russell J, Schall, Jeffrey D, Stock, Ann-Kathrin, Swann, Nicole C, Thakkar, Katharine N, van der Molen, Maurits W, Vermeylen, Luc, Vink, Matthijs, Wessel, Jan R, Whelan, Robert, Zandbelt, Bram B, and Boehler, C Nico
Published: 2019

43. A consensus guide to capturing the ability to inhibit actions and impulsive behaviors in the stop-signal task

Author: Verbruggen, Frederick, Aron, Adam R, Band, Guido Ph, Beste, Christian, Bissett, Patrick G, Brockett, Adam T, Brown, Joshua W, Chamberlain, Samuel R, Chambers, Christopher D, Colonius, Hans, Colzato, Lorenza S, Corneil, Brian D, Coxon, James P, Dupuis, Annie, Eagle, Dawn M, Garavan, Hugh, Greenhouse, Ian, Heathcote, Andrew, Huster, René J, Jahfari, Sara, Kenemans, J Leon, Leunissen, Inge, Logan, Gordon D, Matzke, Dora, Morein-Zamir, Sharon, Murthy, Aditya, Li, Chiang-Shan R, Paré, Martin, Poldrack, Russell A, Ridderinkhof, K Richard, Robbins, Trevor W, Roesch, Matthew, Rubia, Katya, Schachar, Russell J, Schall, Jeffrey D, Stock, Ann-Kathrin, Swann, Nicole C, Thakkar, Katharine N, van der Molen, Maurits W, Vermeylen, Luc, Vink, Matthijs, Wessel, Jan R, Whelan, Robert, Zandbelt, Bram B, Boehler, C Nico, Verbruggen, Frederick, Aron, Adam R, Band, Guido Ph, Beste, Christian, Bissett, Patrick G, Brockett, Adam T, Brown, Joshua W, Chamberlain, Samuel R, Chambers, Christopher D, Colonius, Hans, Colzato, Lorenza S, Corneil, Brian D, Coxon, James P, Dupuis, Annie, Eagle, Dawn M, Garavan, Hugh, Greenhouse, Ian, Heathcote, Andrew, Huster, René J, Jahfari, Sara, Kenemans, J Leon, Leunissen, Inge, Logan, Gordon D, Matzke, Dora, Morein-Zamir, Sharon, Murthy, Aditya, Li, Chiang-Shan R, Paré, Martin, Poldrack, Russell A, Ridderinkhof, K Richard, Robbins, Trevor W, Roesch, Matthew, Rubia, Katya, Schachar, Russell J, Schall, Jeffrey D, Stock, Ann-Kathrin, Swann, Nicole C, Thakkar, Katharine N, van der Molen, Maurits W, Vermeylen, Luc, Vink, Matthijs, Wessel, Jan R, Whelan, Robert, Zandbelt, Bram B, and Boehler, C Nico
Abstract: Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions. The stop-signal task is an essential tool to determine how quickly response inhibition is implemented. Despite its apparent simplicity, there are many features (ranging from task design to data analysis) that vary across studies in ways that can easily compromise the validity of the obtained results. Our goal is to facilitate a more accurate use of the stop-signal task. To this end, we provide twelve easy-to-implement consensus recommendations and point out the problems that can arise when these are not followed. Furthermore we provide user-friendly open-source resources intended to inform statistical-power considerations, facilitate the correct implementation of the task, and assist in proper data analysis.
Published: 2019

44. The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking : A Translational Study

Author: Mueller, Christian P., Chu, Congying, Qin, Liya, Liu, Chunyu, Xu, Bing, Gao, He, Ruggeri, Barbara, Hieber, Saskia, Schneider, Julia, Jia, Tianye, Tay, Nicole, Akira, Shizuo, Satoh, Takashi, Banaschewski, Tobias, Bokde, Arun L. W., Bromberg, Uli, Buechel, Christian, Quinlan, Erin Burke, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Martinot, Marie-Laure Paillere, Artiges, Eric, Lemaitre, Herve, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Millenet, Sabina, Froehner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Bakalkin, Georgy, Liu, Yun, Desrivieres, Sylvane, Elliott, Paul, Eulenburg, Volker, Levy, Daniel, Crews, Fulton, Schumann, Gunter, Mueller, Christian P., Chu, Congying, Qin, Liya, Liu, Chunyu, Xu, Bing, Gao, He, Ruggeri, Barbara, Hieber, Saskia, Schneider, Julia, Jia, Tianye, Tay, Nicole, Akira, Shizuo, Satoh, Takashi, Banaschewski, Tobias, Bokde, Arun L. W., Bromberg, Uli, Buechel, Christian, Quinlan, Erin Burke, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Martinot, Marie-Laure Paillere, Artiges, Eric, Lemaitre, Herve, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomas, Poustka, Luise, Millenet, Sabina, Froehner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Bakalkin, Georgy, Liu, Yun, Desrivieres, Sylvane, Elliott, Paul, Eulenburg, Volker, Levy, Daniel, Crews, Fulton, and Schumann, Gunter
Abstract: Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-kappa B activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 x 10(-19)) and regional methylation (P = 5.90 x 10(-25)). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-kappa B. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.
Published: 2019
Full Text: View/download PDF

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

Author: Ruggeri, Barbara, Macare, Christine, Stopponi, Serena, Jia, Tianye, Carvalho, Fabiana M, Robert, Gabriel, Banaschewski, Tobias, Bokde, Arun L W, Bromberg, Uli, Büchel, Christian, Cattrell, Anna, Conrod, Patricia J, Desrivières, Sylvane, Flor, Herta, Frouin, Vincent, Gallinat, Jürgen, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean Luc, Martinot, Marie-Laure Paillère, Nees, Frauke, Papadopoulos-Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Smolka, Michael N, Vetter, Nora C, Walter, Henrik, Whelan, Robert, Sommer, Wolfgang H, Bakalkin, Georgy, Ciccocioppo, Roberto, Schumann, Gunter, Ruggeri, Barbara, Macare, Christine, Stopponi, Serena, Jia, Tianye, Carvalho, Fabiana M, Robert, Gabriel, Banaschewski, Tobias, Bokde, Arun L W, Bromberg, Uli, Büchel, Christian, Cattrell, Anna, Conrod, Patricia J, Desrivières, Sylvane, Flor, Herta, Frouin, Vincent, Gallinat, Jürgen, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean Luc, Martinot, Marie-Laure Paillère, Nees, Frauke, Papadopoulos-Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Smolka, Michael N, Vetter, Nora C, Walter, Henrik, Whelan, Robert, Sommer, Wolfgang H, Bakalkin, Georgy, Ciccocioppo, Roberto, and Schumann, Gunter
Abstract: 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.
Published: 2018
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46. The Acceptance and Action Questionnaire-II (AAQ-II) as a measure of experiential avoidance: Concerns over discriminant validity

Author: Tyndall, Ian T., Waldeck, Daniel, Pancani, Luca, Whelan, Robert, Roche, Bryan, Dawson, David L., Tyndall, Ian T., Waldeck, Daniel, Pancani, Luca, Whelan, Robert, Roche, Bryan, and Dawson, David L.
Abstract: Psychological inflexibility and experiential avoidance are key constructs in the Acceptance and Commitment Therapy (ACT) model of behavior change. Wolgast (2014) questioned the construct validity of the Acceptance and Action Questionnaire-II (AAQ-II), the most used self-report instrument to assess the efficacy of ACT interventions. Wolgast suggested that the AAQ-II measured psychological distress rather than psychological inflexibility and experiential avoidance. The current study further examined the construct validity of the AAQ-II by conducting an online cross-sectional survey (n = 524), including separate measures of experiential avoidance and psychological distress. Confirmatory factor analyses indicated that items from the AAQ-II correlated more highly with measures of depression, anxiety, and stress than the Brief Experiential Avoidance Questionnaire (BEAQ). Implications include that, as broad measures of experiential avoidance, the AAQ-II and BEAQ may not measure the same construct. In terms of psychological distress, the BEAQ has greater discriminant validity than the AAQ-II, and perhaps an alternative instrument of psychological inflexibility might be needed to assess core outcomes in ACT intervention research.
Published: 2018

47. Profiles of Psychological Flexibility: A latent class analysis of the Acceptance and Commitment Therapy model

Author: Tyndall, Ian T., Waldeck, Daniel, Pancani, Luca, Whelan, Robert, Roche, Bryan, Pereira, Antonina, Tyndall, Ian T., Waldeck, Daniel, Pancani, Luca, Whelan, Robert, Roche, Bryan, and Pereira, Antonina
Abstract: There exists uncertainty for clinicians over how the separate sub-component processes of psychological flexibility, a core construct of the Acceptance and Commitment Therapy model, interact and influence distress experienced. The present study (N = 567) employed latent class analysis to (i) identify potential classes (i.e., subgroups) of psychological flexibility based on responses on measures of key sub-component process, and (ii) to examine whether such classes could reliably differentiate levels of self-reported psychological distress and positive and negative emotionality. We found three distinct classes: (i) High Psychological Flexibility, (ii) Moderate Psychological Flexibility, and (iii) Low Psychological Flexibility. Those in the Low Psychology Flexibility class reported highest levels of psychological distress, whereas those in the High Psychological Flexibility class subgroup reported lowest levels of psychological distress. This study provides a clearer view to clinicians of the profile of the broader spectrum of the psychological flexibility model to facilitate change in clients.
Published: 2018

48. The Acceptance and Action Questionnaire-II (AAQ-II) as a measure of experiential avoidance: Concerns over discriminant validity

Author: Tyndall, Ian T., Waldeck, Daniel, Pancani, Luca, Whelan, Robert, Roche, Bryan, Dawson, David L., Tyndall, Ian T., Waldeck, Daniel, Pancani, Luca, Whelan, Robert, Roche, Bryan, and Dawson, David L.
Abstract: Psychological inflexibility and experiential avoidance are key constructs in the Acceptance and Commitment Therapy (ACT) model of behavior change. Wolgast (2014) questioned the construct validity of the Acceptance and Action Questionnaire-II (AAQ-II), the most used self-report instrument to assess the efficacy of ACT interventions. Wolgast suggested that the AAQ-II measured psychological distress rather than psychological inflexibility and experiential avoidance. The current study further examined the construct validity of the AAQ-II by conducting an online cross-sectional survey (n = 524), including separate measures of experiential avoidance and psychological distress. Confirmatory factor analyses indicated that items from the AAQ-II correlated more highly with measures of depression, anxiety, and stress than the Brief Experiential Avoidance Questionnaire (BEAQ). Implications include that, as broad measures of experiential avoidance, the AAQ-II and BEAQ may not measure the same construct. In terms of psychological distress, the BEAQ has greater discriminant validity than the AAQ-II, and perhaps an alternative instrument of psychological inflexibility might be needed to assess core outcomes in ACT intervention research.
Published: 2018

49. Profiles of Psychological Flexibility: A latent class analysis of the Acceptance and Commitment Therapy model

Author: Tyndall, Ian T., Waldeck, Daniel, Pancani, Luca, Whelan, Robert, Roche, Bryan, Pereira, Antonina, Tyndall, Ian T., Waldeck, Daniel, Pancani, Luca, Whelan, Robert, Roche, Bryan, and Pereira, Antonina
Abstract: There exists uncertainty for clinicians over how the separate sub-component processes of psychological flexibility, a core construct of the Acceptance and Commitment Therapy model, interact and influence distress experienced. The present study (N = 567) employed latent class analysis to (i) identify potential classes (i.e., subgroups) of psychological flexibility based on responses on measures of key sub-component process, and (ii) to examine whether such classes could reliably differentiate levels of self-reported psychological distress and positive and negative emotionality. We found three distinct classes: (i) High Psychological Flexibility, (ii) Moderate Psychological Flexibility, and (iii) Low Psychological Flexibility. Those in the Low Psychology Flexibility class reported highest levels of psychological distress, whereas those in the High Psychological Flexibility class subgroup reported lowest levels of psychological distress. This study provides a clearer view to clinicians of the profile of the broader spectrum of the psychological flexibility model to facilitate change in clients.
Published: 2018

50. Genetic risk for schizophrenia and autism, social impairment and developmental pathways to psychosis

Author: Velthorst, Eva, Froudist-Walsh, Sean, Stahl, Eli, Ruderfer, Douglas, Ivanov, Ilyan, Buxbaum, Joseph, Banaschewski, Tobias, Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Burke Quinlan, Erin, Desrivières, Sylvane, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Paillère Martinot, Marie Laure, Artiges, Eric, Nees, Frauke, Papadopoulos Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Schumann, Gunter, Reichenberg, Abraham, Børglum, Anders D., Grove, Jakob, Mattheisen, Manuel, Werge, Thomas, Mortensen, Preben Bo, Pedersen, Marianne Giørtz, Pedersen, Carsten Bøcker, Mors, Ole, Nordentoft, Merete, Hougaard, David M., Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Hansen, Christine Søholm, Daly, Mark J., Neale, Benjamin M., Robinson, Elise B., Cerrato, Felecia, Dumont, Ashley, Goldstein, Jacqueline, Velthorst, Eva, Froudist-Walsh, Sean, Stahl, Eli, Ruderfer, Douglas, Ivanov, Ilyan, Buxbaum, Joseph, Banaschewski, Tobias, Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Burke Quinlan, Erin, Desrivières, Sylvane, Flor, Herta, Frouin, Vincent, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Paillère Martinot, Marie Laure, Artiges, Eric, Nees, Frauke, Papadopoulos Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Hohmann, Sarah, Fröhner, Juliane H., Smolka, Michael N., Walter, Henrik, Whelan, Robert, Schumann, Gunter, Reichenberg, Abraham, Børglum, Anders D., Grove, Jakob, Mattheisen, Manuel, Werge, Thomas, Mortensen, Preben Bo, Pedersen, Marianne Giørtz, Pedersen, Carsten Bøcker, Mors, Ole, Nordentoft, Merete, Hougaard, David M., Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Hansen, Christine Søholm, Daly, Mark J., Neale, Benjamin M., Robinson, Elise B., Cerrato, Felecia, Dumont, Ashley, and Goldstein, Jacqueline
Abstract: While psychotic experiences (PEs) are assumed to represent psychosis liability, general population studies have not been able to establish significant associations between polygenic risk scores (PRS) and PEs. Previous work suggests that PEs may only represent significant risk when accompanied by social impairment. Leveraging data from the large longitudinal IMAGEN cohort, including 2096 14-year old adolescents that were followed-up to age 18, we tested whether the association between polygenic risk and PEs is mediated by (increasing) impairments in social functioning and social cognitive processes. Using structural equation modeling (SEM) for the subset of participants (n = 643) with complete baseline and follow-up data, we examined pathways to PEs. We found that high polygenic risk for schizophrenia (p = 0.014), reduced brain activity to emotional stimuli (p = 0.009) and social impairments in late adolescence (p < 0.001; controlling for functioning in early adolescence) each independently contributed to the severity of PEs at age 18. The pathway between polygenic risk for autism spectrum disorder and PEs was mediated by social impairments in late adolescence (indirect pathway; p = 0.025). These findings point to multiple direct and indirect pathways to PEs, suggesting that different processes are in play, depending on genetic loading, and environment. Our results suggest that treatments targeting prevention of social impairment may be particularly promising for individuals at genetic risk for autism in order to minimize risk for psychosis.
Published: 2018

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