@article {426,
	title = {Urinary Amine and organic acid metabolites evaluated as markers for childhood aggression: The ACTION biomarker study},
	journal = {Frontiers in Psychiatry},
	volume = {11},
	year = {2020},
	pages = {165},
	abstract = {<p>Biomarkers are of interest as potential diagnostic and predictive instruments in personalized medicine. We present the first urinary metabolomics biomarker study of childhood aggression. We aim to examine the association of urinary metabolites and neurotransmitter ratios involved in key metabolic and neurotransmitter pathways in a large cohort of twins (N = 1,347) and clinic-referred children (N = 183) with an average age of 9.7 years. This study is part of ACTION (Aggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies), in which we developed a standardized protocol for large-scale collection of urine samples in children. Our analytical design consisted of three phases: a discovery phase in twins scoring low or high on aggression (N = 783); a replication phase in twin pairs discordant for aggression (N = 378); and a validation phase in clinical cases and matched twin controls (N = 367). In the discovery phase, 6 biomarkers were significantly associated with childhood aggression, of which the association of O-phosphoserine ($\beta$ = 0.36; SE = 0.09; p = 0.004), and gamma-L-glutamyl-L-alanine ($\beta$ = 0.32; SE = 0.09; p = 0.01) remained significant after multiple testing. Although non-significant, the directions of effect were congruent between the discovery and replication analyses for six biomarkers and two neurotransmitter ratios and the concentrations of 6 amines differed between low and high aggressive twins. In the validation analyses, the top biomarkers and neurotransmitter ratios, with congruent directions of effect, showed no significant associations with childhood aggression. We find suggestive evidence for associations of childhood aggression with metabolic dysregulation of neurotransmission, oxidative stress, and energy metabolism. Although replication is required, our findings provide starting points to investigate causal and pleiotropic effects of these dysregulations on childhood aggression.</p>
},
	keywords = {amines, biomarkers, childhood aggression, metabolites, metabolomics, neurotransmitters, organic acids, oxidative stress},
	doi = {10.3389/fpsyt.2020.00165},
	author = {Hagenbeek, Fiona A and Roetman, Peter J and Pool, Ren{\'e} and Kluft, Cornelis and Harms, Amy C and van Dongen, Jenny and Colins, Olivier F and Talens, Simone and van Beijsterveldt, Catharina E M and Vandenbosch, Marjolein M L J Z and de Zeeuw, Eveline L and D{\'e}jean, S{\'e}bastien and Fanos, Vassilios and Ehli, Erik A and Davies, Gareth E and Hottenga, Jouke Jan and Hankemeier, Thomas and Bartels, Meike and Vermeiren, Robert R J M and Boomsma, Dorret I}
}
@article {283,
	title = {Unraveling the Genetic and Environmental Relationship Between Well-Being and Depressive Symptoms Throughout the Lifespan},
	journal = {Frontiers in Psychiatry},
	volume = {9},
	year = {2018},
	pages = {261},
	abstract = {<p>Whether well-being and depressive symptoms can be considered as two sides of the same coin is widely debated. The aim of this study was to gain insight into the etiology of the association between well-being and depressive symptoms across the lifespan. In a large twin-design, including data from 43,427 twins between age 7 and 99, we estimated the association between well-being and depressive symptoms throughout the lifespan and assessed genetic and environmental contributions to the observed overlap. For both well-being (range 31\% \&ndash;47\%) and depressive symptoms (range 50\%-61\%), genetic factors explained a substantial part of the phenotypic variance across the lifespan. Phenotypic correlations between well-being and depressive symptoms across ages ranged from -.34 in childhood to -.49 in adulthood. In children, genetic effects explained 49\% of the phenotypic correlation while in adolescents and young adults, genetic effects explained 60\% to 77\% of the phenotypic correlations. Moderate to high genetic correlations (ranging from -0.60 to -0.66) were observed in adolescence and adulthood, while in childhood environmental correlations were substantial but genetic correlations small. Our results suggest that in childhood genetic and environmental effects are about equally important in explaining the relationship between well-being and depressive symptoms. From adolescence onwards, the role of genetic effects increases compared to environmental effects. These results provided more insights into the etiological underpinnings of well-being and depressive symptoms, possibly allowing to articulate better strategies for health promotion and resource allocation in the future.</p>
},
	issn = {1664-0640},
	doi = {10.3389/fpsyt.2018.00261},
	url = {https://www.frontiersin.org/article/10.3389/fpsyt.2018.00261},
	author = {Bart M. L. Baselmans and Willems, Yayouk E. and Catharina E. M. van Beijsterveldt and Lannie Ligthart and Gonneke Willemsen and Conor V Dolan and Dorret I. Boomsma and Meike Bartels}
}
