Publications by authors named "Vincent Frouin"

139 Publications

Region-specific expression of young small-scale duplications in the human central nervous system.

BMC Ecol Evol 2021 04 21;21(1):59. Epub 2021 Apr 21.

Centre National de Recherche en Génomique Humaine (CNRGH), Institut François Jacob, CEA, Université Paris-Saclay, Evry, France.

Background: The duplication of genes is one of the main genetic mechanisms that led to the gain in complexity of biological tissue. Although the implication of duplicated gene expression in brain evolution was extensively studied through comparisons between organs, their role in the regional specialization of the adult human central nervous system has not yet been well described.

Results: Our work explored intra-organ expression properties of paralogs through multiple territories of the human central nervous system (CNS) using transcriptome data generated by the Genotype-Tissue Expression (GTEx) consortium. Interestingly, we found that paralogs were associated with region-specific expression in CNS, suggesting their involvement in the differentiation of these territories. Beside the influence of gene expression level on region-specificity, we observed the contribution of both duplication age and duplication type to the CNS region-specificity of paralogs. Indeed, we found that small scale duplicated genes (SSDs) and in particular ySSDs (SSDs younger than the 2 rounds of whole genome duplications) were more CNS region-specific than other paralogs. Next, by studying the two paralogs of ySSD pairs, we observed that when they were region-specific, they tend to be specific to the same region more often than for other paralogs, showing the high co-expression of ySSD pairs. The extension of this analysis to families of paralogs showed that the families with co-expressed gene members (i.e. homogeneous families) were enriched in ySSDs. Furthermore, these homogeneous families tended to be region-specific families, where the majority of their gene members were specifically expressed in the same region.

Conclusions: Overall, our study suggests the involvement of ySSDs in the differentiation of human central nervous system territories. Therefore, we show the relevance of exploring region-specific expression of paralogs at the intra-organ level.
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http://dx.doi.org/10.1186/s12862-021-01794-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059171PMC
April 2021

Sex differences in neural correlates of common psychopathological symptoms in early adolescence.

Psychol Med 2021 Mar 26:1-11. Epub 2021 Mar 26.

Centre for Population Neuroscience and Stratified Medicine (PONS) and Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.

Background: Sex-related differences in psychopathology are known phenomena, with externalizing and internalizing symptoms typically more common in boys and girls, respectively. However, the neural correlates of these sex-by-psychopathology interactions are underinvestigated, particularly in adolescence.

Methods: Participants were 14 years of age and part of the IMAGEN study, a large (N = 1526) community-based sample. To test for sex-by-psychopathology interactions in structural grey matter volume (GMV), we used whole-brain, voxel-wise neuroimaging analyses based on robust non-parametric methods. Psychopathological symptom data were derived from the Strengths and Difficulties Questionnaire (SDQ).

Results: We found a sex-by-hyperactivity/inattention interaction in four brain clusters: right temporoparietal-opercular region (p < 0.01, Cohen's d = -0.24), bilateral anterior and mid-cingulum (p < 0.05, Cohen's d = -0.18), right cerebellum and fusiform (p < 0.05, Cohen's d = -0.20) and left frontal superior and middle gyri (p < 0.05, Cohen's d = -0.26). Higher symptoms of hyperactivity/inattention were associated with lower GMV in all four brain clusters in boys, and with higher GMV in the temporoparietal-opercular and cerebellar-fusiform clusters in girls.

Conclusions: Using a large, sex-balanced and community-based sample, our study lends support to the idea that externalizing symptoms of hyperactivity/inattention may be associated with different neural structures in male and female adolescents. The brain regions we report have been associated with a myriad of important cognitive functions, in particular, attention, cognitive and motor control, and timing, that are potentially relevant to understand the behavioural manifestations of hyperactive and inattentive symptoms. This study highlights the importance of considering sex in our efforts to uncover mechanisms underlying psychopathology during adolescence.
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http://dx.doi.org/10.1017/S0033291720005140DOI Listing
March 2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Transl Psychiatry 2021 03 22;11(1):182. Epub 2021 Mar 22.

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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http://dx.doi.org/10.1038/s41398-021-01213-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985307PMC
March 2021

Genome-wide haplotype association study in imaging genetics using whole-brain sulcal openings of 16,304 UK Biobank subjects.

Eur J Hum Genet 2021 Mar 4. Epub 2021 Mar 4.

Université Paris-Saclay, CEA, Neurospin, Gif-sur-Yvette, France.

Neuroimaging-genetics cohorts gather two types of data: brain imaging and genetic data. They allow the discovery of associations between genetic variants and brain imaging features. They are invaluable resources to study the influence of genetics and environment in the brain features variance observed in normal and pathological populations. This study presents a genome-wide haplotype analysis for 123 brain sulcus opening value (a measure of sulcal width) across the whole brain that include 16,304 subjects from UK Biobank. Using genetic maps, we defined 119,548 blocks of low recombination rate distributed along the 22 autosomal chromosomes and analyzed 1,051,316 haplotypes. To test associations between haplotypes and complex traits, we designed three statistical approaches. Two of them use a model that includes all the haplotypes for a single block, while the last approach considers each haplotype independently. All the statistics produced were assessed as rigorously as possible. Thanks to the rich imaging dataset at hand, we used resampling techniques to assess False Positive Rate for each statistical approach in a genome-wide and brain-wide context. The results on real data show that genome-wide haplotype analyses are more sensitive than single-SNP approach and account for local complex Linkage Disequilibrium (LD) structure, which makes genome-wide haplotype analysis an interesting and statistically sound alternative to the single-SNP counterpart.
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http://dx.doi.org/10.1038/s41431-021-00827-8DOI Listing
March 2021

Irregular sleep habits, regional grey matter volumes, and psychological functioning in adolescents.

PLoS One 2021 10;16(2):e0243720. Epub 2021 Feb 10.

National Institute of Health and Medical Research, INSERM U A10 "Trajectoires développementales & psychiatrie", University Paris-Saclay, Ecole Normale Supérieure Paris-Saclay, CNRS, Centre Borelli, Gif-sur-Yvette, France.

Changing sleep rhythms in adolescents often lead to sleep deficits and a delay in sleep timing between weekdays and weekends. The adolescent brain, and in particular the rapidly developing structures involved in emotional control, are vulnerable to external and internal factors. In our previous study in adolescents at age 14, we observed a strong relationship between weekend sleep schedules and regional medial prefrontal cortex grey matter volumes. Here, we aimed to assess whether this relationship remained in this group of adolescents of the general population at the age of 16 (n = 101; mean age 16.8 years; 55% girls). We further examined grey matter volumes in the hippocampi and the amygdalae, calculated with voxel-based morphometry. In addition, we investigated the relationships between sleep habits, assessed with self-reports, and regional grey matter volumes, and psychological functioning, assessed with the Strengths and Difficulties Questionnaire and tests on working memory and impulsivity. Later weekend wake-up times were associated with smaller grey matter volumes in the medial prefrontal cortex and the amygdalae, and greater weekend delays in wake-up time were associated with smaller grey matter volumes in the right hippocampus and amygdala. The medial prefrontal cortex region mediated the correlation between weekend wake up time and externalising symptoms. Paying attention to regular sleep habits during adolescence could act as a protective factor against the emergence of psychopathology via enabling favourable brain development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243720PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875363PMC
July 2021

Association between childhood trauma and risk for obesity: a putative neurocognitive developmental pathway.

BMC Med 2020 10 15;18(1):278. Epub 2020 Oct 15.

Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, 200433, People's Republic of China.

Background: Childhood trauma increases the risk for adult obesity through multiple complex pathways, and the neural substrates are yet to be determined.

Methods: Participants from three population-based neuroimaging cohorts, including the IMAGEN cohort, the UK Biobank (UKB), and the Human Connectome Project (HCP), were recruited. Voxel-based morphometry analysis of both childhood trauma and body mass index (BMI) was performed in the longitudinal IMAGEN cohort; validation of the findings was performed in the UKB. White-matter connectivity analysis was conducted to study the structural connectivity between the identified brain region and subdivisions of the hypothalamus in the HCP.

Results: In IMAGEN, a smaller frontopolar cortex (FPC) was associated with both childhood abuse (CA) (β = - .568, 95%CI - .942 to - .194; p = .003) and higher BMI (β = - .086, 95%CI - .128 to - .043; p < .001) in male participants, and these findings were validated in UKB. Across seven data collection sites, a stronger negative CA-FPC association was correlated with a higher positive CA-BMI association (β = - 1.033, 95%CI - 1.762 to - .305; p = .015). Using 7-T diffusion tensor imaging data (n = 156), we found that FPC was the third most connected cortical area with the hypothalamus, especially the lateral hypothalamus. A smaller FPC at age 14 contributed to higher BMI at age 19 in those male participants with a history of CA, and the CA-FPC interaction enabled a model at age 14 to account for some future weight gain during a 5-year follow-up (variance explained 5.8%).

Conclusions: The findings highlight that a malfunctioning, top-down cognitive or behavioral control system, independent of genetic predisposition, putatively contributes to excessive weight gain in a particularly vulnerable population, and may inform treatment approaches.
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http://dx.doi.org/10.1186/s12916-020-01743-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559717PMC
October 2020

Orbitofrontal cortex volume links polygenic risk for smoking with tobacco use in healthy adolescents.

Psychol Med 2020 Sep 3:1-8. Epub 2020 Sep 3.

Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, 95 East Zhongguancun Road, Beijing, 100190, China.

Background: Tobacco smoking remains one of the leading causes of preventable illness and death and is heritable with complex underpinnings. Converging evidence suggests a contribution of the polygenic risk for smoking to the use of tobacco and other substances. Yet, the underlying brain mechanisms between the genetic risk and tobacco smoking remain poorly understood.

Methods: Genomic, neuroimaging, and self-report data were acquired from a large cohort of adolescents from the IMAGEN study (a European multicenter study). Polygenic risk scores (PGRS) for smoking were calculated based on a genome-wide association study meta-analysis conducted by the Tobacco and Genetics Consortium. We examined the interrelationships among the genetic risk for smoking initiation, brain structure, and the number of occasions of tobacco use.

Results: A higher smoking PGRS was significantly associated with both an increased number of occasions of tobacco use and smaller cortical volume of the right orbitofrontal cortex (OFC). Furthermore, reduced cortical volume within this cluster correlated with greater tobacco use. A subsequent path analysis suggested that the cortical volume within this cluster partially mediated the association between the genetic risk for smoking and the number of occasions of tobacco use.

Conclusions: Our data provide the first evidence for the involvement of the OFC in the relationship between smoking PGRS and tobacco use. Future studies of the molecular mechanisms underlying tobacco smoking should consider the mediation effect of the related neural structure.
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http://dx.doi.org/10.1017/S0033291720002962DOI Listing
September 2020

Neural Correlates of Adolescent Irritability and Its Comorbidity With Psychiatric Disorders.

J Am Acad Child Adolesc Psychiatry 2020 12 27;59(12):1371-1379. Epub 2020 Aug 27.

Vermont Center on Behavior and Health, University of Vermont, Burlington.

Objective: Irritable mood, a common and impairing symptom in psychopathology, has been proposed to underlie the developmental link between oppositional problems in youth and depression in adulthood. We examined the neural correlates of adolescent irritability in IMAGEN, a sample of 2,024 14-year-old adolescents from 5 European countries.

Method: The Development and Well-Being Assessment (DAWBA) was used to assess attention-deficit/hyperactivity disorder, major depressive disorder, oppositional defiant disorder, and generalized anxiety disorder. Three items from the DAWBA, selected as close matches to the Affective Reactivity Index, were used to assess irritability. Structural magnetic resonance imaging was examined using whole-brain voxel-based morphometry analysis, and functional magnetic resonance imaging was examined during a stop signal task of inhibitory control. Imaging data were included in structural equation models to examine the direct and indirect associations between irritable mood and comorbid DSM diagnoses.

Results: Whole-brain voxelwise analysis showed that adolescent irritable mood was associated with less gray matter volume and less neural activation underlying inhibitory control in frontal and temporal cortical areas (cluster-correction at p < .05). Structural equation models suggested that part of the observed smaller gray matter volume was exclusively driven by irritability separate from direct relationships between generalized anxiety disorder (or attention-deficit/hyperactivity disorder, major depressive disorder, or oppositional defiant disorder) and gray matter volume.

Conclusion: This study identifies adolescent irritability as an independent construct and points to a neurobiological correlate to irritability that is an important contributing feature to many psychopathological disorders.
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http://dx.doi.org/10.1016/j.jaac.2019.11.028DOI Listing
December 2020

The IMAGEN study: a decade of imaging genetics in adolescents.

Mol Psychiatry 2020 11 29;25(11):2648-2671. Epub 2020 Jun 29.

Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany.

Imaging genetics offers the possibility of detecting associations between genotype and brain structure as well as function, with effect sizes potentially exceeding correlations between genotype and behavior. However, study results are often limited due to small sample sizes and methodological differences, thus reducing the reliability of findings. The IMAGEN cohort with 2000 young adolescents assessed from the age of 14 onwards tries to eliminate some of these limitations by offering a longitudinal approach and sufficient sample size for analyzing gene-environment interactions on brain structure and function. Here, we give a systematic review of IMAGEN publications since the start of the consortium. We then focus on the specific phenotype 'drug use' to illustrate the potential of the IMAGEN approach. We describe findings with respect to frontocortical, limbic and striatal brain volume, functional activation elicited by reward anticipation, behavioral inhibition, and affective faces, and their respective associations with drug intake. In addition to describing its strengths, we also discuss limitations of the IMAGEN study. Because of the longitudinal design and related attrition, analyses are underpowered for (epi-) genome-wide approaches due to the limited sample size. Estimating the generalizability of results requires replications in independent samples. However, such densely phenotyped longitudinal studies are still rare and alternative internal cross-validation methods (e.g., leave-one out, split-half) are also warranted. In conclusion, the IMAGEN cohort is a unique, very well characterized longitudinal sample, which helped to elucidate neurobiological mechanisms involved in complex behavior and offers the possibility to further disentangle genotype × phenotype interactions.
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http://dx.doi.org/10.1038/s41380-020-0822-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577859PMC
November 2020

Cortical signatures in behaviorally clustered autistic traits subgroups: a population-based study.

Transl Psychiatry 2020 06 27;10(1):207. Epub 2020 Jun 27.

Neurospin, Institut Joliot, CEA, Université Paris-Saclay, Gif-sur-Yvette, 91191, France.

Extensive heterogeneity in autism spectrum disorder (ASD) has hindered the characterization of consistent biomarkers, which has led to widespread negative results. Isolating homogenized subtypes could provide insight into underlying biological mechanisms and an overall better understanding of ASD. A total of 1093 participants from the population-based "Healthy Brain Network" cohort (Child Mind Institute in the New York City area, USA) were selected based on score availability in behaviors relevant to ASD, aged 6-18 and IQ >= 70. All participants underwent an unsupervised clustering analysis on behavioral dimensions to reveal subgroups with ASD traits, identified by the presence of social deficits. Analysis revealed three socially impaired ASD traits subgroups: (1) high in emotionally dysfunctional traits, (2) high in ADHD-like traits, and (3) high in anxiety and depressive symptoms. 527 subjects had good quality structural MRI T1 data. Site effects on cortical features were adjusted using the ComBat method. Neuroimaging analyses compared cortical thickness, gyrification, and surface area, and were controlled for age, gender, and IQ, and corrected for multiple comparisons. Structural neuroimaging analyses contrasting one combined heterogeneous ASD traits group against controls did not yield any significant differences. Unique cortical signatures, however, were observed within each of the three individual ASD traits subgroups versus controls. These observations provide evidence of ASD traits subtypes, and confirm the necessity of applying dimensional approaches to extract meaningful differences, thus reducing heterogeneity and paving the way to better understanding ASD traits.
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http://dx.doi.org/10.1038/s41398-020-00894-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320967PMC
June 2020

Imaging the aging brain: study design and baseline findings of the SENIOR cohort.

Alzheimers Res Ther 2020 06 26;12(1):77. Epub 2020 Jun 26.

NeuroSpin, Frédéric Joliot Life Sciences Institute, CEA, Paris-Saclay University, Gif-sur-Yvette, France.

Background: Current demographic trends point towards an aging society entailing increasing occurrence and burden of neurodegenerative diseases. In this context, understanding physiological aging and its turning point into neurodegeneration is essential for the development of possible biomarkers and future therapeutics of brain disease.

Methods: The SENIOR study represents a longitudinal, observational study including cognitively healthy elderlies aged between 50 and 70 years old at the time of inclusion, being followed annually over 10 years. Our multimodal protocol includes structural, diffusion, functional, and sodium magnetic resonance imaging (MRI) at 3 T and 7 T, positron emission tomography (PET), blood samples, genetics, audiometry, and neuropsychological and neurological examinations as well as assessment of neuronal risk factors.

Results: One hundred forty-two participants (50% females) were enrolled in the SENIOR cohort with a mean age of 60 (SD 6.3) years at baseline. Baseline results with multiple regression analyses reveal that cerebral white matter lesions can be predicted by cardiovascular and cognitive risk factors and age. Cardiovascular risk factors were strongly associated with juxtacortical and periventricular lesions. Intra-subject across-test variability as a measure of neuropsychological test performance and possible cognitive marker predicts white matter volume and is significantly associated with risk profile. Division of the cohort into subjects with a higher and lower risk profile shows significant differences in intra-subject across-test variability and volumes as well as cortical thickness of brain regions of the temporal lobe. There is no difference between the lower- and higher-risk groups in amyloid load using PET data from a subset of 81 subjects.

Conclusions: We here describe the study protocol and baseline findings of the SENIOR observational study which aim is the establishment of integrated, multiparametric maps of normal aging and the identification of early biomarkers for neurodegeneration. We show that intra-subject across-test variability as a marker of neuropsychological test performance as well as age, gender, and combined risk factors influence neuronal decline as represented by decrease in brain volume, cortical thickness, and increase in white matter lesions. Baseline findings will be used as underlying basis for the further implications of aging and neuronal degeneration as well as examination of brain aging under different aspects of brain pathology versus physiological aging.
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http://dx.doi.org/10.1186/s13195-020-00642-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320588PMC
June 2020

Multiway generalized canonical correlation analysis.

Biostatistics 2020 May 25. Epub 2020 May 25.

Laboratoire des Signaux et Systèmes (L2S), CNRS-CentraleSupélec, Université Paris-Saclay, 3 rue Joliot-Curie, 91192 Gif-sur-Yvette cedex, France and Institut du Cerveau, INSERM U1127, CNRS UMR 7225, Sorbonne Universitè, F-75013, Paris, France.

Regularized generalized canonical correlation analysis (RGCCA) is a general multiblock data analysis framework that encompasses several important multivariate analysis methods such as principal component analysis, partial least squares regression, and several versions of generalized canonical correlation analysis. In this article, we extend RGCCA to the case where at least one block has a tensor structure. This method is called multiway generalized canonical correlation analysis (MGCCA). Convergence properties of the MGCCA algorithm are studied, and computation of higher-level components are discussed. The usefulness of MGCCA is shown on simulation and on the analysis of a cognitive study in human infants using electroencephalography (EEG).
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http://dx.doi.org/10.1093/biostatistics/kxaa010DOI Listing
May 2020

Enhancer Locus in ch14q23.1 Modulates Brain Asymmetric Temporal Regions Involved in Language Processing.

Cereb Cortex 2020 09;30(10):5322-5332

UNATI, Neurospin, Institut Joliot, CEA, Université Paris-Saclay, Gif-sur-Yvette 91191, France.

Identifying the genes that contribute to the variability in brain regions involved in language processing may shed light on the evolution of brain structures essential to the emergence of language in Homo sapiens. The superior temporal asymmetrical pit (STAP), which is not observed in chimpanzees, represents an ideal phenotype to investigate the genetic variations that support human communication. The left STAP depth was significantly associated with a predicted enhancer annotation located in the 14q23.1 locus, between DACT1 and KIAA0586, in the UK Biobank British discovery sample (N = 16 515). This association was replicated in the IMAGEN cohort (N = 1726) and the UK Biobank non-British validation sample (N = 2161). This genomic region was also associated to a lesser extent with the right STAP depth and the formation of sulcal interruptions, "plis de passage," in the bilateral STAP but not with other structural brain MRI phenotypes, highlighting its notable association with the superior temporal regions. Diffusion MRI emphasized an association with the fractional anisotropy of the left auditory fibers of the corpus callosum and with networks involved in linguistic processing in resting-state functional MRI. Overall, this evidence demonstrates a specific relationship between this locus and the establishment of the superior temporal regions that support human communication.
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http://dx.doi.org/10.1093/cercor/bhaa112DOI Listing
September 2020

Clinical, molecular, and radiomic profile of gliomas with FGFR3-TACC3 fusions.

Neuro Oncol 2020 11;22(11):1614-1624

Inserm Unit 1127, Sorbonne University, Institute of the Brain and Spinal Cord, Paris, France.

Background: Actionable fibroblast growth factor receptor 3 (FGFR3)-transforming acidic coiled-coil protein 3 fusions (F3T3) are found in approximately 3% of gliomas, but their characteristics and prognostic significance are still poorly defined. Our goal was to characterize the clinical, radiological, and molecular profile of F3T3 positive diffuse gliomas.

Methods: We screened F3T3 fusion by real-time (RT)-PCR and FGFR3 immunohistochemistry in a large series of gliomas, characterized for main genetic alterations, histology, and clinical evolution. We performed a radiological and radiomic case control study, using an exploratory and a validation cohort.

Results: We screened 1162 diffuse gliomas (951 unselected cases and 211 preselected for FGFR3 protein immunopositivity), identifying 80 F3T3 positive gliomas. F3T3 was mutually exclusive with IDH mutation (P < 0.001) and EGFR amplification (P = 0.01), defining a distinct molecular cluster associated with CDK4 (P = 0.04) and MDM2 amplification (P = 0.03). F3T3 fusion was associated with longer survival for the whole series and for glioblastomas (median overall survival was 31.1 vs 19.9 mo, P = 0.02) and was an independent predictor of better outcome on multivariate analysis.F3T3 positive gliomas had specific MRI features, affecting preferentially insula and temporal lobe, and with poorly defined tumor margins. F3T3 fusion was correctly predicted by radiomics analysis on both the exploratory (area under the curve [AUC] = 0.87) and the validation MRI (AUC = 0.75) cohort. Using Cox proportional hazards models, radiomics predicted survival with a high C-index (0.75, SD 0.04), while the model combining clinical, genetic, and radiomic data showed the highest C-index (0.81, SD 0.04).

Conclusion: F3T3 positive gliomas have distinct molecular and radiological features, and better outcome.
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http://dx.doi.org/10.1093/neuonc/noaa121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690363PMC
November 2020

Neural Correlates of the Dual-Pathway Model for ADHD in Adolescents.

Am J Psychiatry 2020 09 7;177(9):844-854. Epub 2020 May 7.

Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China (Shen, Luo, Jia, Feng, Sahakian); State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science and Human Phenome Institute, Fudan University, Shanghai, China (Luo); Departments of Psychology and Psychiatry and the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, U.K. (Sahakian); Medical Research Council-Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Desrivières, Quinlan, Schumann); School of Mathematical Sciences, Fudan University, Shanghai, China (Zhao); Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (Banaschewski, Millenet, Nees); Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin (Bokde); University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Büchel); Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (Flor, Nees); Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany (Flor); Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel University, Kiel, Germany (Nees); NeuroSpin, Commissariat à l'Énergie Atomique, Université Paris-Saclay, Gif-sur-Yvette, France (Frouin, Orfanos); Departments of Psychiatry and Psychology, University of Vermont, Burlington (Garavan); Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, U.K. (Gowland); Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin (Heinz, Walter); Physikalisch-Technische Bundesanstalt Braunschweig and Berlin (Ittermann); Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 1000, Neuroimaging and Psychiatry, University Paris Sud-Paris Saclay, University Paris Descartes, Paris (Martinot, Artiges, Paillère-Martinot); Service Hospitalier Frédéric Joliot, Orsay, France (Martinot, Artiges); Maison de Solenn, Paris (Martinot); Groupe Hospitalier Nord Essonne, Department of Psychiatry, Orsay, France (Artiges); Assistance Publique-Hôpitaux de Paris, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris (Paillère-Martinot); Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto (Paus); Departments of Psychology and Psychiatry, University of Toronto, Toronto (Paus); Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Poustka); Clinic for Child and Adolescent Psychiatry, Medical University of Vienna, Vienna (Poustka); Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany (Fröhner, Smolka); School of Psychology and Global Brain Health Institute, Trinity College Dublin (Whelan); Developmental and Behavioral Pediatric Department and Child Primary Care Department, Ministry of Education-Shanghai Key Lab for Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China (Li, Sahakian); Department of Computer Science, University of Warwick, Coventry, U.K. (Feng); and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Feng).

Objective: The dual-pathway model has been proposed to explain the heterogeneity in symptoms of attention deficit hyperactivity disorder (ADHD) by two independent psychological pathways based on distinct brain circuits. The authors sought to test whether the hypothesized cognitive and motivational pathways have separable neural correlates.

Methods: In a longitudinal community-based cohort of 1,963 adolescents, the neuroanatomical correlates of ADHD were identified by a voxel-wise association analysis and then validated using an independent clinical sample (99 never-medicated patients with ADHD, 56 medicated patients with ADHD, and 267 healthy control subjects). The cognitive and motivational pathways were assessed by neuropsychological tests of working memory, intrasubject variability, stop-signal reaction time, and delay discounting. The associations were tested between the identified neuroanatomical correlates and both ADHD symptoms 2 years later and the polygenic risk score for ADHD.

Results: Gray matter volumes of both a prefrontal cluster and a posterior occipital cluster were negatively associated with inattention. Compared with healthy control subjects, never-medicated patients, but not medicated patients, had significantly lower gray matter volumes in these two clusters. Working memory and intrasubject variability were associated with the posterior occipital cluster, and delay discounting was independently associated with both clusters. The baseline gray matter volume of the posterior occipital cluster predicted the inattention symptoms in a 2-year follow-up and was associated with the genetic risk for ADHD.

Conclusions: The dual-pathway model has both shared and separable neuroanatomical correlates, and the shared correlate in the occipital cortex has the potential to serve as an imaging trait marker of ADHD, especially the inattention symptom domain.
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http://dx.doi.org/10.1176/appi.ajp.2020.19020183DOI Listing
September 2020

Social brain activation during mentalizing in a large autism cohort: the Longitudinal European Autism Project.

Mol Autism 2020 02 22;11(1):17. Epub 2020 Feb 22.

Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim / University of Heidelberg, Mannheim, Germany.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition with key deficits in social functioning. It is widely assumed that the biological underpinnings of social impairment are neurofunctional alterations in the "social brain," a neural circuitry involved in inferring the mental state of a social partner. However, previous evidence comes from small-scale studies and findings have been mixed. We therefore carried out the to-date largest study on neural correlates of mentalizing in ASD.

Methods: As part of the Longitudinal European Autism Project, we performed functional magnetic resonance imaging at six European sites in a large, well-powered, and deeply phenotyped sample of individuals with ASD (N = 205) and typically developing (TD) individuals (N = 189) aged 6 to 30 years. We presented an animated shapes task to assess and comprehensively characterize social brain activation during mentalizing. We tested for effects of age, diagnosis, and their association with symptom measures, including a continuous measure of autistic traits.

Results: We observed robust effects of task. Within the ASD sample, autistic traits were moderately associated with functional activation in one of the key regions of the social brain, the dorsomedial prefrontal cortex. However, there were no significant effects of diagnosis on task performance and no effects of age and diagnosis on social brain responses. Besides a lack of mean group differences, our data provide no evidence for meaningful differences in the distribution of brain response measures. Extensive control analyses suggest that the lack of case-control differences was not due to a variety of potential confounders.

Conclusions: Contrary to prior reports, this large-scale study does not support the assumption that altered social brain activation during mentalizing forms a common neural marker of ASD, at least with the paradigm we employed. Yet, autistic individuals show socio-behavioral deficits. Our work therefore highlights the need to interrogate social brain function with other brain measures, such as connectivity and network-based approaches, using other paradigms, or applying complementary analysis approaches to assess individual differences in this heterogeneous condition.
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http://dx.doi.org/10.1186/s13229-020-0317-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036196PMC
February 2020

Genome wide association study of incomplete hippocampal inversion in adolescents.

PLoS One 2020 28;15(1):e0227355. Epub 2020 Jan 28.

Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.

Incomplete hippocampal inversion (IHI), also called hippocampal malrotation, is an atypical presentation of the hippocampus present in about 20% of healthy individuals. Here we conducted the first genome-wide association study (GWAS) in IHI to elucidate the genetic underpinnings that may contribute to the incomplete inversion during brain development. A total of 1381 subjects contributed to the discovery cohort obtained from the IMAGEN database. The incidence rate of IHI was 26.1%. Loci with P<1e-5 were followed up in a validation cohort comprising 161 subjects from the PING study. Summary statistics from the discovery cohort were used to compute IHI heritability as well as genetic correlations with other traits. A locus on 18q11.2 (rs9952569; OR = 1.999; Z = 5.502; P = 3.755e-8) showed a significant association with the presence of IHI. A functional annotation of the locus implicated genes AQP4 and KCTD1. However, neither this locus nor the other 16 suggestive loci reached a significant p-value in the validation cohort. The h2 estimate was 0.54 (sd: 0.30) and was significant (Z = 1.8; P = 0.036). The top three genetic correlations of IHI were with traits representing either intelligence or education attainment and reached nominal P< = 0.013.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227355PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986744PMC
April 2020

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

JAMA Psychiatry 2020 04;77(4):409-419

Department of Psychiatry and Addictology, Medical Faculty, University of Montreal, Montréal, Québec, Canada.

Importance: Alcohol abuse correlates with gray matter development in adolescents, but the directionality of this association remains unknown.

Objective: To investigate the directionality of the association between gray matter development and increase in frequency of drunkenness among adolescents.

Design, Setting, And Participants: This cohort study analyzed participants of IMAGEN, a multicenter brain imaging study of healthy adolescents in 8 European sites in Germany (Mannheim, Dresden, Berlin, and Hamburg), the United Kingdom (London and Nottingham), Ireland (Dublin), and France (Paris). Data from the second follow-up used in the present study were acquired from January 1, 2013, to December 31, 2016, and these data were analyzed from January 1, 2016, to March 31, 2018. Analyses were controlled for sex, site, socioeconomic status, family history of alcohol dependency, puberty score, negative life events, personality, cognition, and polygenic risk scores. Personality and frequency of drunkenness were assessed at age 14 years (baseline), 16 years (first follow-up), and 19 years (second follow-up). Structural brain imaging scans were acquired at baseline and second follow-up time points.

Main Outcomes And Measures: Increases in drunkenness frequency were measured by latent growth modeling, a voxelwise hierarchical linear model was used to observe gray matter volume, and tensor-based morphometry was used for gray matter development. The hypotheses were formulated before the data analyses.

Results: A total of 726 adolescents (mean [SD] age at baseline, 14.4 [0.38] years; 418 [58%] female) were included. The increase in drunkenness frequency was associated with accelerated gray matter atrophy in the left posterior temporal cortex (peak: t1,710 = -5.8; familywise error (FWE)-corrected P = 7.2 × 10-5; cluster: 6297 voxels; P = 2.7 × 10-5), right posterior temporal cortex (cluster: 2070 voxels; FWE-corrected P = .01), and left prefrontal cortex (peak: t1,710 = -5.2; FWE-corrected P = 2 × 10-3; cluster: 10 624 voxels; P = 1.9 × 10-7). According to causal bayesian network analyses, 73% of the networks showed directionality from gray matter development to drunkenness increase as confirmed by accelerated gray matter atrophy in late bingers compared with sober controls (n = 20 vs 60; β = 1.25; 95% CI, -2.15 to -0.46; t1,70 = 0.3; P = .004), the association of drunkenness increase with gray matter volume at age 14 years (β = 0.23; 95% CI, 0.01-0.46; t1,584 = 2; P = .04), the association between gray matter atrophy and alcohol drinking units (β = -0.0033; 95% CI, -6 × 10-3 to -5 × 10-4; t1,509 = -2.4; P = .02) and drunkenness frequency at age 23 years (β = -0.16; 95% CI, -0.28 to -0.03; t1,533 = -2.5; P = .01), and the linear exposure-response curve stratified by gray matter atrophy and not by increase in frequency of drunkenness.

Conclusions And Relevance: This study found that gray matter development and impulsivity were associated with increased frequency of drunkenness by sex. These results suggest that neurotoxicity-related gray matter atrophy should be interpreted with caution.
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http://dx.doi.org/10.1001/jamapsychiatry.2019.4063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990803PMC
April 2020

Cortical Surfaces Mediate the Relationship Between Polygenic Scores for Intelligence and General Intelligence.

Cereb Cortex 2020 04;30(4):2707-2718

Holland Bloorview Kids Rehabilitation Hospital and Departments of Psychology and Psychiatry, Bloorview Research Institute, University of Toronto, Toronto, Ontario, M6A 2E1, Canada.

Recent large-scale, genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with general intelligence. The cumulative influence of these loci on brain structure is unknown. We examined if cortical morphology mediates the relationship between GWAS-derived polygenic scores for intelligence (PSi) and g-factor. Using the effect sizes from one of the largest GWAS meta-analysis on general intelligence to date, PSi were calculated among 10 P value thresholds. PSi were assessed for the association with g-factor performance, cortical thickness (CT), and surface area (SA) in two large imaging-genetics samples (IMAGEN N = 1651; IntegraMooDS N = 742). PSi explained up to 5.1% of the variance of g-factor in IMAGEN (F1,1640 = 12.2-94.3; P < 0.005), and up to 3.0% in IntegraMooDS (F1,725 = 10.0-21.0; P < 0.005). The association between polygenic scores and g-factor was partially mediated by SA and CT in prefrontal, anterior cingulate, insula, and medial temporal cortices in both samples (PFWER-corrected < 0.005). The variance explained by mediation was up to 0.75% in IMAGEN and 0.77% in IntegraMooDS. Our results provide evidence that cumulative genetic load influences g-factor via cortical structure. The consistency of our results across samples suggests that cortex morphology could be a novel potential biomarker for neurocognitive dysfunction that is among the most intractable psychiatric symptoms.
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http://dx.doi.org/10.1093/cercor/bhz270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175009PMC
April 2020

Sex effects on structural maturation of the limbic system and outcomes on emotional regulation during adolescence.

Neuroimage 2020 04 4;210:116441. Epub 2019 Dec 4.

Inserm, UMR 1000, Research Unit NeuroImaging and Psychiatry, Univ Paris Sud, Université Paris-Saclay, Université Paris Descartes, Digiteo Labs, Bâtiment 660, Gif-sur-Yvette, France; Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives, CNRS UMR 5293, Université de Bordeaux, Centre Broca Nouvelle-Aquitaine, Bordeaux, France. Electronic address:

Though adolescence is a time of emerging sex differences in emotions, sex-related differences in the anatomy of the maturing brain has been under-explored over this period. The aim of this study was to investigate whether puberty and sexual differentiation in brain maturation could explain emotional differences between girls and boys during adolescence. We adapted a dedicated longitudinal pipeline to process structural and diffusion images from 335 typically developing adolescents between 14 and 16 years. We used voxel-based and Regions of Interest approaches to explore sex and puberty effects on brain and behavioral changes during adolescence. Sexual differences in brain maturation were characterized by amygdala and hippocampal volume increase in boys and decrease in girls. These changes were mediating the sexual differences in positive emotional regulation as illustrated by positive attributes increase in boys and decrease in girls. Moreover, the differential maturation rates between the limbic system and the prefrontal cortex highlighted the delayed maturation in boys compared to girls. This is the first study to show the sex effects on the differential cortico/subcortical maturation rates and the interaction between sex and puberty in the limbic system maturation related to positive attributes, reported as being protective from emotional disorders.
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http://dx.doi.org/10.1016/j.neuroimage.2019.116441DOI Listing
April 2020

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

Mol Psychiatry 2019 Dec 6. Epub 2019 Dec 6.

University Medical Centre Hamburg-Eppendorf, House W34, 3.OG, Martinistr. 52, 20246, Hamburg, Germany.

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.
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http://dx.doi.org/10.1038/s41380-019-0605-zDOI Listing
December 2019

Identifying biological markers for improved precision medicine in psychiatry.

Mol Psychiatry 2020 02 1;25(2):243-253. Epub 2019 Nov 1.

PONS Research Group, Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Humboldt University, Berlin and Leibniz Institute for Neurobiology, Magdeburg, Germany.

Mental disorders represent an increasing personal and financial burden and yet treatment development has stagnated in recent decades. Current disease classifications do not reflect psychobiological mechanisms of psychopathology, nor the complex interplay of genetic and environmental factors, likely contributing to this stagnation. Ten years ago, the longitudinal IMAGEN study was designed to comprehensively incorporate neuroimaging, genetics, and environmental factors to investigate the neural basis of reinforcement-related behavior in normal adolescent development and psychopathology. In this article, we describe how insights into the psychobiological mechanisms of clinically relevant symptoms obtained by innovative integrative methodologies applied in IMAGEN have informed our current and future research aims. These aims include the identification of symptom groups that are based on shared psychobiological mechanisms and the development of markers that predict disease course and treatment response in clinical groups. These improvements in precision medicine will be achieved, in part, by employing novel methodological tools that refine the biological systems we target. We will also implement our approach in low- and medium-income countries to understand how distinct environmental, socioeconomic, and cultural conditions influence the development of psychopathology. Together, IMAGEN and related initiatives strive to reduce the burden of mental disorders by developing precision medicine approaches globally.
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http://dx.doi.org/10.1038/s41380-019-0555-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978138PMC
February 2020

Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition.

JAMA Psychiatry 2020 04;77(4):420-430

Department of Biological Psychology and Netherlands Twin Register, VU University Amsterdam, Amsterdam, the Netherlands.

Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.

Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.

Design, Setting, And Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.

Main Outcomes And Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.

Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.

Conclusions And Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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http://dx.doi.org/10.1001/jamapsychiatry.2019.3779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822096PMC
April 2020

Identification of neurobehavioural symptom groups based on shared brain mechanisms.

Nat Hum Behav 2019 12 7;3(12):1306-1318. Epub 2019 Oct 7.

NeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.

Most psychopathological disorders develop in adolescence. The biological basis for this development is poorly understood. To enhance diagnostic characterization and develop improved targeted interventions, it is critical to identify behavioural symptom groups that share neural substrates. We ran analyses to find relationships between behavioural symptoms and neuroimaging measures of brain structure and function in adolescence. We found two symptom groups, consisting of anxiety/depression and executive dysfunction symptoms, respectively, that correlated with distinct sets of brain regions and inter-regional connections, measured by structural and functional neuroimaging modalities. We found that the neural correlates of these symptom groups were present before behavioural symptoms had developed. These neural correlates showed case-control differences in corresponding psychiatric disorders, depression and attention deficit hyperactivity disorder in independent clinical samples. By characterizing behavioural symptom groups based on shared neural mechanisms, our results provide a framework for developing a classification system for psychiatric illness that is based on quantitative neurobehavioural measures.
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http://dx.doi.org/10.1038/s41562-019-0738-8DOI Listing
December 2019

"Plis de passage" Deserve a Role in Models of the Cortical Folding Process.

Brain Topogr 2019 11 3;32(6):1035-1048. Epub 2019 Oct 3.

Neurospin, CEA, Paris-Saclay University, 91191, Gif-sur-Yvette, France.

Cortical folding is a hallmark of brain topography whose variability across individuals remains a puzzle. In this paper, we call for an effort to improve our understanding of the pli de passage phenomenon, namely annectant gyri buried in the depth of the main sulci. We suggest that plis de passage could become an interesting benchmark for models of the cortical folding process. As an illustration, we speculate on the link between modern biological models of cortical folding and the development of the Pli de Passage Frontal Moyen (PPFM) in the middle of the central sulcus. For this purpose, we have detected nine interrupted central sulci in the Human Connectome Project dataset, which are used to explore the organization of the hand sensorimotor areas in this rare configuration of the PPFM.
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http://dx.doi.org/10.1007/s10548-019-00734-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882753PMC
November 2019

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

J Am Acad Child Adolesc Psychiatry 2020 05 18;59(5):642-649. Epub 2019 Jul 18.

Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Objective: Cannabis consumption during adolescence has been reported as a risk factor for psychotic-like experiences (PLEs) and schizophrenia. However, brain developmental processes associated with cannabis-related PLEs are still poorly described.

Method: A total of 706 adolescents from the general population who were recruited by the IMAGEN consortium had structural magnetic resonance imaging scans at both 14 and 19 years of age. We used deformation-based morphometry to map voxelwise brain changes between the two time points, using the pairwise algorithm in SPM12b. We used an a priori region-of-interest approach focusing on the hippocampus/parahippocampus to perform voxelwise linear regressions. Lifetime cannabis consumption was assessed using the European School Survey Project on Alcohol and other Drugs (ESPAD), and PLEs were assessed with the Comprehensive Assessment Psychotic-like experiences (CAPE) tool. We first tested whether hippocampus/parahippocampus development was associated with PLEs. Then we formulated and tested an a priori simple mediation model in which uncus development mediates the association between lifetime cannabis consumption and PLEs.

Results: We found that PLEs were associated with reduced expansion within a specific region of the right hippocampus/parahippocampus formation, the uncus (p = .002 at the cluster level, p = .018 at the peak level). The partial simple mediation model revealed a significant total effect from lifetime cannabis consumption to PLEs (b = 0.069, 95% CI = 0.04-0.1, p =2 × 10), as well as a small yet significant, indirect effect of right uncus development (0.004; 95% CI = 0.0004-0.01, p = .026).

Conclusion: We show here that the uncus development is involved in the cerebral basis of PLEs in a population-based sample of healthy adolescents.
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http://dx.doi.org/10.1016/j.jaac.2019.05.034DOI Listing
May 2020

[Care in an LTC unit: between psychosis, fantasy and challenge].

Soins Psychiatr 2019 May - Jun;40(322):18-21

Groupement hospitalier de Bretagne Sud, site de Quimperlé, pôle G, 20 bis avenue Général Leclerc, BP 134, 29391 Quimperlé cedex, France.

In nursing homes, residents with psychiatric disorders are cared for alongside other residents. While the clinical presentation is different to that of dementia, the caregivers need to adopt a new approach in order to provide the necessary long-term support. Their social representations of madness must also be questioned. The integration of psychotic residents into a nursing home must be anticipated and prepared through exchanges and interventions overseen jointly by the geriatric and psychiatric teams.
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http://dx.doi.org/10.1016/j.spsy.2019.04.003DOI Listing
July 2019

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

Mol Psychiatry 2021 03 21;26(3):1019-1028. Epub 2019 Jun 21.

Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.

There is an extensive body of literature linking ADHD to overweight and obesity. Research indicates that impulsivity features of ADHD account for a degree of this overlap. The neural and polygenic correlates of this association have not been thoroughly examined. In participants of the IMAGEN study, we found that impulsivity symptoms and body mass index (BMI) were associated (r = 0.10, n = 874, p = 0.014 FWE corrected), as were their respective polygenic risk scores (PRS) (r = 0.17, n = 874, p = 6.5 × 10 FWE corrected). We then examined whether the phenotypes of impulsivity and BMI, and the PRS scores of ADHD and BMI, shared common associations with whole-brain grey matter and the Monetary Incentive Delay fMRI task, which associates with reward-related impulsivity. A sparse partial least squared analysis (sPLS) revealed a shared neural substrate that associated with both the phenotypes and PRS scores. In a last step, we conducted a bias corrected bootstrapped mediation analysis with the neural substrate score from the sPLS as the mediator. The ADHD PRS associated with impulsivity symptoms (b = 0.006, 90% CIs = 0.001, 0.019) and BMI (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. The BMI PRS associated with BMI (b = 0.014, 95% CIs = 0.003, 0.033) and impulsivity symptoms (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. A common neural substrate may (in part) underpin shared genetic liability for ADHD and BMI and the manifestation of their (observable) phenotypic association.
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http://dx.doi.org/10.1038/s41380-019-0444-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910212PMC
March 2021

Neural Correlates of Failed Inhibitory Control as an Early Marker of Disordered Eating in Adolescents.

Biol Psychiatry 2019 06 25;85(11):956-965. Epub 2019 Mar 25.

Section of Eating Disorders, Department of Psychological Medicine, London, United Kingdom; South London & Maudsley National Health Service Foundation Trust, London, United Kingdom.

Background: Binge eating and other forms of disordered eating behavior (DEB) are associated with failed inhibitory control. This study investigated the neural correlates of failed inhibitory control as a potential biomarker for DEB.

Methods: The study used prospective longitudinal data from the European IMAGEN study adolescent cohort. Participants completed baseline assessments (questionnaires and a brain scan [functional magnetic resonance imaging]) at 14 years of age and a follow-up assessment (questionnaires) at 16 years of age. Self-reported binge eating and/or purging were used to indicate presence of DEB. Neural correlates of failed inhibition were assessed using the stop signal task. Participants were categorized as healthy control subjects (reported no DEB at both time points), maintainers (reported DEB at both time points), recoverers (reported DEB at baseline only), and developers (reported DEB at follow-up only). Forty-three individuals per group with complete scanning data were matched on gender, age, puberty, and intelligence (N = 172).

Results: At baseline, despite similar task performance, incorrectly responding to stop signals (failed inhibitory control) was associated with greater recruitment of the medial prefrontal cortex and anterior cingulate cortex in the developers compared with healthy control subjects and recoverers.

Conclusions: Greater recruitment of the medial prefrontal and anterior cingulate regions during failed inhibition accords with abnormal evaluation of errors contributing to DEB development. As this precedes symptom onset and is evident despite normal task performance, neural responses during failed inhibition may be a useful biomarker of vulnerability for DEB. This study highlights the potential value of prospective neuroimaging studies for identifying markers of illness before the emergence of behavior changes.
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http://dx.doi.org/10.1016/j.biopsych.2019.01.027DOI Listing
June 2019
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