TY  - JOUR
A1  - Ziegler, Georg C.
A1  - Almos, Peter
A1  - McNeill, Rhiannon V.
A1  - Jansch, Charline
A1  - Lesch, Klaus‐Peter
T1  - Cellular effects and clinical implications of SLC2A3 copy number variation
JF  - Journal of Cellular Physiology
N2  - SLC2A3 encodes the predominantly neuronal glucose transporter 3 (GLUT3), which facilitates diffusion of glucose across plasma membranes. The human brain depends on a steady glucose supply for ATP generation, which consequently fuels critical biochemical processes, such as axonal transport and neurotransmitter release. Besides its role in the central nervous system, GLUT3 is also expressed in nonneural organs, such as the heart and white blood cells, where it is equally involved in energy metabolism. In cancer cells, GLUT3 overexpression contributes to the Warburg effect by answering the cell's increased glycolytic demands. The SLC2A3 gene locus at chromosome 12p13.31 is unstable and prone to non‐allelic homologous recombination events, generating multiple copy number variants (CNVs) of SLC2A3 which account for alterations in SLC2A3 expression. Recent associations of SLC2A3 CNVs with different clinical phenotypes warrant investigation of the potential influence of these structural variants on pathomechanisms of neuropsychiatric, cardiovascular, and immune diseases. In this review, we accumulate and discuss the evidence how SLC2A3 gene dosage may exert diverse protective or detrimental effects depending on the pathological condition. Cellular states which lead to increased energetic demand, such as organ development, proliferation, and cellular degeneration, appear particularly susceptible to alterations in SLC2A3 copy number. We conclude that better understanding of the impact of SLC2A3 variation on disease etiology may potentially provide novel therapeutic approaches specifically targeting this GLUT.
KW  - copy number variation
KW  - energy metabolism
KW  - glucose transporter
KW  - GLUT3
KW  - neurodegeneration
KW  - neurodevelopment
KW  - SLC2A3
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218009
VL  - 235
IS  - 12
SP  - 9021
EP  - 9036
ER  - 
TY  - JOUR
A1  - Opitz, Timm
A1  - Schuwerk, Tobias
A1  - Paulus, Markus
A1  - Kloo, Daniela
A1  - Osterhaus, Christopher
A1  - Lesch, Klaus‐Peter
A1  - Sodian, Beate
T1  - No links between genetic variation and developing theory of mind: A preregistered replication attempt of candidate gene studies
JF  - Developmental Science
N2  - Genetic variability is being discussed as a source of inter‐individual differences in Theory of Mind development. Previous studies documented an association between variations in DRD4 VNTR 48 bp, OXTR rs53576, COMT rs4680, and Theory of Mind task performance. As empirical evidence on these associations is sparse, we conducted a preregistered replication attempt of a study reporting a link between DRD4 VNTR 48 bp and false belief understanding in 50‐month‐old children [Lackner, C., Sabbagh, M. A., Hallinan, E., Liu, X., & Holden, J. J. (2012). Developmental Science, 15(2), 272–280.]. Additionally, we attempted a replication of studies on the role of OXTR rs53576 and COMT rs4680 in Theory of Mind. In both replication attempts, we did not find any evidence for associations between the sampled genetic markers and Theory of Mind ability in a series of analyses. Extending the replication attempt of Lackner et al., we employed longitudinal data from several tasks and measurement points, which allowed us to run follow‐up robustness checks with more reliable scores. These extensive analyses corroborated our null finding. This comprehensive non‐replication is important to balance current research on genetic markers of Theory of Mind. In a combined evaluation of our own and previous studies, we point to substantial methodological issues that research on the genetic basis of Theory of Mind development faces. We conclude that these limitations currently prevent firm conclusions on genetic influences on Theory of Mind development.
KW  - COMT
KW  - DRD4
KW  - false belief
KW  - OXTR
KW  - theory of mind
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238812
VL  - 24
IS  - 5
ER  - 
TY  - JOUR
A1  - Postema, Merel C.
A1  - Hoogman, Martine
A1  - Ambrosino, Sara
A1  - Asherson, Philip
A1  - Banaschewski, Tobias
A1  - Bandeira, Cibele E.
A1  - Baranov, Alexandr
A1  - Bau, Claiton H.D.
A1  - Baumeister, Sarah
A1  - Baur‐Streubel, Ramona
A1  - Bellgrove, Mark A.
A1  - Biederman, Joseph
A1  - Bralten, Janita
A1  - Brandeis, Daniel
A1  - Brem, Silvia
A1  - Buitelaar, Jan K.
A1  - Busatto, Geraldo F.
A1  - Castellanos, Francisco X.
A1  - Cercignani, Mara
A1  - Chaim‐Avancini, Tiffany M.
A1  - Chantiluke, Kaylita C.
A1  - Christakou, Anastasia
A1  - Coghill, David
A1  - Conzelmann, Annette
A1  - Cubillo, Ana I.
A1  - Cupertino, Renata B.
A1  - de Zeeuw, Patrick
A1  - Doyle, Alysa E.
A1  - Durston, Sarah
A1  - Earl, Eric A.
A1  - Epstein, Jeffery N.
A1  - Ethofer, Thomas
A1  - Fair, Damien A.
A1  - Fallgatter, Andreas J.
A1  - Faraone, Stephen V.
A1  - Frodl, Thomas
A1  - Gabel, Matt C.
A1  - Gogberashvili, Tinatin
A1  - Grevet, Eugenio H.
A1  - Haavik, Jan
A1  - Harrison, Neil A.
A1  - Hartman, Catharina A.
A1  - Heslenfeld, Dirk J.
A1  - Hoekstra, Pieter J.
A1  - Hohmann, Sarah
A1  - Høvik, Marie F.
A1  - Jernigan, Terry L.
A1  - Kardatzki, Bernd
A1  - Karkashadze, Georgii
A1  - Kelly, Clare
A1  - Kohls, Gregor
A1  - Konrad, Kerstin
A1  - Kuntsi, Jonna
A1  - Lazaro, Luisa
A1  - Lera‐Miguel, Sara
A1  - Lesch, Klaus‐Peter
A1  - Louza, Mario R.
A1  - Lundervold, Astri J.
A1  - Malpas, Charles B
A1  - Mattos, Paulo
A1  - McCarthy, Hazel
A1  - Namazova‐Baranova, Leyla
A1  - Nicolau, Rosa
A1  - Nigg, Joel T.
A1  - Novotny, Stephanie E.
A1  - Oberwelland Weiss, Eileen
A1  - O'Gorman Tuura, Ruth L.
A1  - Oosterlaan, Jaap
A1  - Oranje, Bob
A1  - Paloyelis, Yannis
A1  - Pauli, Paul
A1  - Picon, Felipe A.
A1  - Plessen, Kerstin J.
A1  - Ramos‐Quiroga, J. Antoni
A1  - Reif, Andreas
A1  - Reneman, Liesbeth
A1  - Rosa, Pedro G.P.
A1  - Rubia, Katya
A1  - Schrantee, Anouk
A1  - Schweren, Lizanne J.S.
A1  - Seitz, Jochen
A1  - Shaw, Philip
A1  - Silk, Tim J.
A1  - Skokauskas, Norbert
A1  - Soliva Vila, Juan C.
A1  - Stevens, Michael C.
A1  - Sudre, Gustavo
A1  - Tamm, Leanne
A1  - Tovar‐Moll, Fernanda
A1  - van Erp, Theo G.M.
A1  - Vance, Alasdair
A1  - Vilarroya, Oscar
A1  - Vives‐Gilabert, Yolanda
A1  - von Polier, Georg G.
A1  - Walitza, Susanne
A1  - Yoncheva, Yuliya N.
A1  - Zanetti, Marcus V.
A1  - Ziegler, Georg C.
A1  - Glahn, David C.
A1  - Jahanshad, Neda
A1  - Medland, Sarah E.
A1  - Thompson, Paul M.
A1  - Fisher, Simon E.
A1  - Franke, Barbara
A1  - Francks, Clyde
T1  - Analysis of structural brain asymmetries in attention‐deficit/hyperactivity disorder in 39 datasets
JF  - Journal of Child Psychology and Psychiatry
N2  - Objective
Some studies have suggested alterations of structural brain asymmetry in attention‐deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left‐right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.

Methods
We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.

Results
There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study‐wide correction for multiple testing.

Conclusion
Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.
KW  - attention‐deficit
KW  - hyperactivity disorder
KW  - brain asymmetry
KW  - brain laterality
KW  - structural MRI
KW  - large‐scale data
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239968
VL  - 62
IS  - 10
SP  - 1202
EP  - 1219
ER  -