@article {236, title = {Adult aggressive behavior in humans and biomarkers: a focus on lipids and methylation}, journal = {Journal of Pediatric and Neonatal Individualized Medicine (JPNIM)}, volume = {7}, year = {2018}, month = {04/2018}, abstract = {

Aggression shows large variation between individuals, with about 50\% explained by genetic factors. Biomarkers related to aggression have been reported for lipid metabolism and for epigenetic marks. Methylation and blood lipid levels are not independent and differential methylation can be a consequence of variation in blood lipid levels. We hypothesized that the methylation level of such loci in blood can inform us if aggression is associated with long-term exposure to lipid levels. If this is the case, we expect to find that loci where methylation levels are influenced by lipid levels to show differential methylation in aggressive individuals. Such loci might complement classic lipid level measures as a biomarker for lipid-related disturbances in aggression. As a first step, we examined the association of lipid levels and related biomarkers with aggression in a large adult population cohort (N = 5,588) and in 31 monozygotic (MZ) twin pairs who were discordant for aggression, as well as 12 extremely discordant MZ pairs. Biomarkers were not significantly associated with aggression in the population cohort. In the discordant MZ pairs we identified significant within-pair differences for glucose and marginally significant differences for lipids and cytokines, with the more aggressive twin showing lower levels of glucose and low density lipoprotein cholesterol and higher levels of fibrinogen, C-reactive protein and interleukin-6. The analysis of epigenetic data in the MZ pairs discordant for aggression did not show enrichment for lipid cytosine guanine dinucleotides (CpGs) and we observed no enrichment of lipid CpGs in an epigenome-wide association study of aggression in the population cohort. These results did not support the hypothesis that lipid CpGs show differential methylation in adult aggression. A next step will be to examine the role of biomarkers in aggression across the lifespan, including childhood, and to explore a more holistic biomarker approach, such as offered by metabolomics.

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}, keywords = {adult aggression, biomarkers, discordant twin pairs, epigenetics, lipids}, doi = {10.7363/070204}, url = {http://www.jpnim.com/index.php/jpnim/article/view/070204}, author = {Fiona Hagenbeek and Jenny van Dongen and Kluft, Cornelis and Thomas Hankemeier and Lannie Ligthart and Gonneke Willemsen and de Geus, Eco J.C. and Vink, Jacqueline M. and Meike Bartels and Dorret I. Boomsma} } @article {230, title = {Childhood aggression and the co-occurrence of behavioural and emotional problems: results across ages 3{\textendash}16~years from multiple raters in six cohorts in the EU-ACTION project}, journal = {European Child {\&} Adolescent Psychiatry}, year = {2018}, month = {May}, abstract = {

Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety\–depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child\&$\#$39;s age (ages 3 through 16\ years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5{\%} boys), 20,958 5- to 6-year-olds (49.6{\%} boys), 18,291 7- to 8-year-olds (49.0{\%} boys), 27,218 9- to 10-year-olds (49.4{\%} boys), 18,543 12- to 13-year-olds (48.9{\%} boys) and 10,088 15- to 16-year-olds (46.6{\%} boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and internalising domains. At each age, the co-occurrence was particularly prevalent for aggression and oppositional and ADHD-related problems, with correlations of around 0.5 in general. Aggression also showed substantial associations with anxiety\–depression and other internalizing symptoms (correlations around 0.4). Co-occurrence for self-reported problems was somewhat higher than for parental reports, but we found neither rater differences, nor differences across assessment instruments in co-occurrence patterns. There were large similarities in co-occurrence patterns across the different European countries. Finally, co-occurrence was generally stable across age and sex, and if any change was observed, it indicated stronger correlations when children grew older. We present an online tool to visualise these associations as a function of rater, gender, instrument and cohort. In addition, we present a description of the full EU-ACTION projects, its first results and the future perspectives.

Related interactive tool here.

}, issn = {1435-165X}, doi = {10.1007/s00787-018-1169-1}, url = {https://doi.org/10.1007/s00787-018-1169-1}, author = {Meike Bartels and Anne Hendriks and Matteo Mauri and Eva Krapohl and Alyce Whipp and Koen Bolhuis and Conde, Lucia Colodro and Luningham, Justin and Fung Ip, Hill and Fiona Hagenbeek and Roetman, Peter and Gatej, Raluca and Lamers, Audri and Michel G. Nivard and Jenny van Dongen and Lu, Yi and Christel Middeldorp and van Beijsterveldt, Toos and Vermeiren, Robert and Thomas Hankemeier and Kluft, Cees and Medland, Sarah and Lundstr{\"o}m, Sebastian and Richard J. Rose and Pulkkinen, Lea and Vuoksimaa, Eero and Korhonen, Tellervo and Martin, Nicholas G. and Gitta Lubke and Catrin Finkenauer and Vassilios Fanos and Henning Tiemeier and Lichtenstein, Paul and Robert Plomin and Kaprio, Jaakko and Dorret I. Boomsma} } @article {129, title = {Discovery of biochemical biomarkers for aggression: A role for metabolomics in psychiatry.}, journal = {Am J Med Genet B Neuropsychiatr Genet}, year = {2016}, month = {2016 Feb 23}, abstract = {

Human aggression encompasses a wide range of behaviors and is related to many psychiatric disorders. We introduce the different classification systems of aggression and related disorders as a basis for discussing biochemical biomarkers and then present an overview of studies in humans (published between 1990 and 2015) that reported statistically significant associations of biochemical biomarkers with aggression, DSM-IV disorders involving aggression, and their subtypes. The markers are of different types, including inflammation markers, neurotransmitters, lipoproteins, and hormones from various classes. Most studies focused on only a limited portfolio of biomarkers, frequently a specific class only. When integrating the data, it is clear that compounds from several biological pathways have been found to be associated with aggressive behavior, indicating complexity and the need for a broad approach. In the second part of the paper, using examples from the aggression literature and psychiatric metabolomics studies, we argue that a better understanding of aggression would benefit from a more holistic approach such as provided by metabolomics. \© 2016 Wiley Periodicals, Inc.

}, issn = {1552-485X}, doi = {10.1002/ajmg.b.32435}, author = {Fiona Hagenbeek and Kluft, Cornelis and Thomas Hankemeier and Meike Bartels and Draisma, Harmen H M and Christel Middeldorp and Berger, Ruud and Antonio Noto and Lussu, Milena and Pool, Ren{\'e} and Faa, Gavino and Dorret I. Boomsma} }