We will apply now a new family based association strategy aimed to explain the genetic influence in suicidal behaviour by power based association test statistics (PBAT) in 336 bipolar patients assessed for suicidality within nuclear families.
Methods: By use of conditional power calculations, the approach screens all possible null hypotheses without biasing the nominal significance level, and it identifies the subset of phenotypes that has optimal power when tested for association by either univariate or multivariate family based association test (FBAT). Using this statistical
approach (PBAT) we investigated polymorphisms in serotonergic and noradrenergic genes, considering suicidal behaviour severity instead of the dichotomous phenotype (presence of suicide attempt).
Results: COMT Val/Met polymorphism was not associated with suicide with high confidence (power=91%). On the other Selleckchem Fludarabine hand, the analysis of the other 12 markers in the adrenergic and serotonergic genes revealed that the TH allele tended towards association with higher severity of suicidal behaviour (p=0.060) but the power obtained was very low.
Conclusions: The marginal finding of association between TH and severe
suicidal behaviour are convergent with previous reports. selleck screening library On the other hand, our sample has enough power to exclude the other polymorphisms investigated as major candidate for suicidality in bipolar disorder. (c) 2007 Elsevier Inc. All rights reserved.”
“Introduction: An earlier report suggested that mass amount of PET tracers could be an important factor in brain uptake mediated by P-glycoprotein. Thereby, this study investigated the influence of mass dose of laniquidar, desmethyl-loperamide and loperamide
on the P-glycoprotein-mediated brain uptake of respectively, [C-11]-laniquidar and [C-11]-N-desmethyl-loperamide check details ([C-11]-dLop).
Methods: Wild-type (WT) mice were injected intravenously with solutions of 5.6 MBq [C-11]-laniquidar (either no carrier added or 60 mg/kg laniquidar added) or with 5.0-7.4 MBq [C-11]-dLop (either no carrier added or 3 mg/kg desmethyl loperamide). Mice were killed, and brain and blood were collected, weighted and counted for radioactivity. Mdrla(-/-) knockout mice were incorporated as the control group.
Results: Injection of C-11-laniquidar (no carrier added) in WT mice resulted in a statistical significant lower brain uptake (0.7 +/- 0.2 %ID/g) compared to the carrier-added formulation (60 mg/kg laniquidar) (3.1 +/- 0.3 VolD/g) (P=.004), while no statistical difference could be observed between formulations of [C-11]-dLop. The [C-11]-laniquidar and [C-11]-dLop blood concentrations were not significantly different between the tested formulations in WT mice. In control animals, no effect of mass amount on brain uptake of both tracers could be demonstrated.