Serotonin receptor 1A gene (HTR1A) knockout mice show pronounced defensive behaviour and increased fear conditioning to ambiguous conditioned stimuli. Such behaviour is a hallmark of pathological human anxiety, as observed in panic disorder with agoraphobia (PD/AG). Thus, variations in HTR1A might contribute to neurophysiological differences within subgroups of PD/AG patients. Here, we tested this hypothesis by combining genetic with behavioural techniques and neuroimaging. In a clinical multicentre trial, patients with PD/AG received 12 sessions of manualized cognitive-behavioural therapy (CBT) and were genotyped for HTR1A rs6295. In four subsamples of this multicentre trial, exposure behaviour (n = 185), defensive reactivity measured using a behavioural avoidance test (BAT; before CBT: n = 245; after CBT: n = 171) and functional magnetic resonance imaging (fMRI) data during fear conditioning were acquired before and after CBT (n = 39). HTR1A risk genotype (GG) carriers more often escaped during the BAT before treatment. Exploratory fMRI results suggest increased activation of the amygdala in response to threat as well as safety cues before and after treatment in GG carriers. Furthermore, GG carriers demonstrated reduced effects of CBT on differential conditioning in regions including the bilateral insulae and the anterior cingulate cortex. Finally, risk genotype carriers demonstrated reduced self-initiated exposure behaviour to aversive situations. This study demonstrates the effect of HTR1A variation on defensive behaviour, amygdala activity, CBT-induced neural plasticity and normalization of defence behaviour in PD/AG. Our results, therefore, translate evidence from animal studies to humans and suggest a central role for HTR1A in differentiating subgroups of patients with anxiety disorders.

Background The aim of this study was to quantify the variability in spinal radiosurgery (SRS) planning practices between five international institutions, all member of the Elekta Spine Radiosurgery Research Consortium. Methods Four institutions provided one representative patient case each consisting of the medical history, CT and MR imaging. A step-wise planning approach was used where, after each planning step a consensus was generated that formed the basis for the next planning step. This allowed independent analysis of all planning steps of CT-MR image registration, GTV definition, CTV definition, PTV definition and SRS treatment planning. In addition, each institution generated one additional SRS plan for each case based on intra-institutional image registration and contouring, independent of consensus results. Results Averaged over the four cases, image registration variability ranged between translational 1.1 mm and 2.4 mm and rotational 1.1° and 2.0° in all three directions. GTV delineation variability was 1.5 mm in axial and 1.6 mm in longitudinal direction averaged for the four cases. CTV delineation variability was 0.8 mm in axial and 1.2 mm in longitudinal direction. CTV-to-PTV margins ranged between 0 mm and 2 mm according to institutional protocol. Delineation variability was 1 mm in axial directions for the spinal cord. Average PTV coverage for a single fraction18 Gy prescription was 87 ± 5 %; Dmin to the PTV was 7.5 ± 1.8 Gy averaged over all cases and institutions. Average Dmax to the PRV_SC (spinal cord + 1 mm) was 10.5 ± 1.6 Gy and the average Paddick conformity index was 0.69 ± 0.06. Conclusions Results of this study reflect the variability in current practice of spine radiosurgery in large and highly experienced academic centers. Despite close methodical agreement in the daily workflow, clinically significant variability in all steps of the treatment planning process was demonstrated. This may translate into differences in patient clinical outcome and highlights the need for consensus and established delineation and planning criteria.

Male rats were treated for 2 months with 1000 ppm nafenopin in the diet or for 4 or 7 days with a choline-devoid low-methionine diet. DNA was isolated from the livers and analyzed for the presence of cis-thymidine glycol-3'-phosphate (cis-dTGp) by 32P-postlabeling and for the Ievel of 8-hydroxy-deoxyguanosine (8-0H-dG) by electrochemical detection (ECD). In no DNA sample was the Ievel of cis-dTGp above the Iimit of detection of 1 modified thymidine per 106 nucleotides. With 8-0H-dG, a background Ievel of this modification of 20 8-0H-dG per 106 nucleosides was found in liver DNA of control rats, which was not affected by either treatment. It is postulated for thymidine glycol that a potential increase was below the Iimit of detection or was rapidly repaired in vivo and that the steady-state Ievel of endogenous 8-hydroxydeoxyguanosine appears not tobe influenced by the treatments chosen.

No abstract available

Comprehensive geochemical investigations of rnetabasites yielded constraints for a correlation of, or discrimination between the different tectonic units within the northeast Bavarian crystalline basement. The Münchberg nappe pile consists of at least five large tectonic units which exhibit differences in lithology, in part also in metamorphie grade and in metamorphie history. The metabasites in each of these nappes show their own, significant geochemical characteristics. The lowermost tectonic unit, the Bavarian lithofacies, includes the anchimetamorphie Ordovician Randschieferserie which contains alkaline basalts. In their geochemistry, they are sirnilar to the metabasites of the Fichtelgebirge crystalline complex in the autochthonous Saxo-thuringian. The next higher tectonic unit of the Münchberg nappe pile, the Prasinit-Phyllit-Serie contains metabasites which can be derived from subalkaline basalts with a clear calc-alkaline tendency. There is a striking geochemical resemblance to the metabasites of the Erbendorf Greenschist Zone (EGZ) underscorinq the similar lithology of both allochthonous units which appear to be in a similar tectonic position. The Randamphibolit-Serie higher up in the Münchberg nappe pile consists of metabasites with tholeiitic characteristics and a pronounced differentiation trend. The next higher tectonic unit, the Liegendserie of the Münchberg gneiss cornplex s. str., contains metagabbros to metagabbronorites with a high-Al basaltic composition. The amphibolites and banded hornblende gneisses of the overlying Hangendserie are of subalkaline basaltic character with calc-alkaline affinity. The Zone Erbendorf-Vohenstrauss (ZEV) is currently regarded as an allochthonous unit equivalent to the higher crystalline nappes of the Münchberg pile. However, the geochemical character of the metabasites do not encourage such a correlation. Neither the schistose and striped amphibolites nor the flaseramphibolites of the ZEV with their N-KORB and E-MORB character respectively, find convincing counterparts in the crystalline nappes of the Münchberg pile. However, an interestingly close resemblance exists between the schistose and striped amphibolites in the ZEV, on the one hand, and in the autochthonous Zone Tirschenreuth- Mähring (ZTM) and the adjacent Moldanubian sensu strictu, on the other. Owing to the absence of age criteria, our results cannot be used, so far, to reconstruct the paleogeographical position of the individual tectonic units, based on the geochemical characteristics of their respective metabasites.