TY  - JOUR
A1  - Jain, M.
A1  - Vélez, J. I.
A1  - Acosta, M. T.
A1  - Palacio, L. G.
A1  - Balog, J.
A1  - Roessler, E.
A1  - Pineda, D.
A1  - Londoño, A. C.
A1  - Palacio, J. D.
A1  - Arbelaez, A.
A1  - Lopera, F.
A1  - Elia, J.
A1  - Hakonarson, H.
A1  - Seitz, C.
A1  - Freitag, C. M.
A1  - Palmason, H.
A1  - Meyer, J.
A1  - Romanos, M.
A1  - Walitza, S.
A1  - Hemminger, U.
A1  - Warnke, A.
A1  - Romanos, J.
A1  - Renner, T.
A1  - Jacob, C.
A1  - Lesch, K.-P.
A1  - Swanson, J.
A1  - Castellanos, F. X.
A1  - Bailey-Wilson, J. E.
A1  - Arcos-Burgos, M.
A1  - Muenke, M.
T1  - A cooperative interaction between LPHN3 and 11q doubles the risk for ADHD
JF  - Molecular Psychiatry
N2  - In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P<1 × 10−8) and 11q and 17p (P<1 × 10−6). As we have identified that common variants of the LPHN3 gene were responsible for the 4q linkage signal, we focused on 4q–11q interaction to determine that single-nucleotide polymorphisms (SNPs) harbored in the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 genes, to double the risk of developing ADHD. This interaction not only explains genetic effects much better than taking each of these loci effects by separated but also differences in brain metabolism as depicted by proton magnetic resonance spectroscopy data and pharmacogenetic response to stimulant medication. These findings not only add information about how high order genetic interactions might be implicated in conferring susceptibility to develop ADHD but also show that future studies of the effects of genetic interactions on ADHD clinical information will help to shape predictive models of individual outcome.
KW  - ADHD
KW  - genetic interaction
KW  - LPHN3
KW  - NCAM1
KW  - DRD2
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125128
VL  - 17
ER  - 
TY  - JOUR
A1  - Bender, Stephan
A1  - Resch, Franz
A1  - Klein, Christoph
A1  - Renner, Tobias
A1  - Fallgatter, Andreas J.
A1  - Weisbrod, Matthias
A1  - Romanos, Marcel
T1  - Influence of Stimulant Medication and Response Speed on Lateralization of Movement-Related Potentials in Attention-Deficit/Hyperactivity Disorder
JF  - PLoS One
N2  - Background: Hyperactivity is one of the core symptoms in attention deficit hyperactivity disorder (ADHD). However, it remains unclear in which way the motor system itself and its development are affected by the disorder. Movement-related potentials (MRP) can separate different stages of movement execution, from the programming of a movement to motor post-processing and memory traces. Pre-movement MRP are absent or positive during early childhood and display a developmental increase of negativity. 
Methods: We examined the influences of response-speed, an indicator of the level of attention, and stimulant medication on lateralized MRP in 16 children with combined type ADHD compared to 20 matched healthy controls. 
Results: We detected a significantly diminished lateralisation of MRP over the pre-motor and primary motor cortex during movement execution (initial motor potential peak, iMP) in patients with ADHD. Fast reactions (indicating increased visuo-motor attention) led to increased lateralized negativity during movement execution only in healthy controls, while in children with ADHD faster reaction times were associated with more positive amplitudes. Even though stimulant medication had some effect on attenuating group differences in lateralized MRP, this effect was insufficient to normalize lateralized iMP amplitudes. 
Conclusions: A reduced focal (lateralized) motor cortex activation during the command to muscle contraction points towards an immature motor system and a maturation delay of the (pre-) motor cortex in children with ADHD. A delayed maturation of the neuronal circuitry, which involves primary motor cortex, may contribute to ADHD pathophysiology.
KW  - deficit-hyperactivity disorder
KW  - anticipatory mechanisms
KW  - motor preparation
KW  - TIC disorder
KW  - children
KW  - ADHD
KW  - methylphenidate
KW  - contingent negative-variation
KW  - continuous performance-test
KW  - slow cortical potentials
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135262
VL  - 7
IS  - 6
ER  -