Structural brain changes are associated with response of negative symptoms to prefrontal repetitive transcranial magnetic stimulation in patients with schizophrenia.

Impaired neural plasticity may be a core pathophysiological process underlying the symptomatology of schizophrenia. Plasticity-enhancing interventions, including repetitive transcranial magnetic stimulation (rTMS), may improve difficult-to-treat symptoms; however, efficacy in large clinical trials appears limited. The high variability of rTMS-related treatment response may be related to a comparably large variation in the ability to generate plastic neural changes. The aim of the present study was to determine whether negative symptom improvement in schizophrenia patients receiving rTMS to the left dorsolateral prefrontal cortex (DLPFC) was related to rTMS-related brain volume changes. A total of 73 schizophrenia patients with predominant negative symptoms were randomized to an active (n=34) or sham (n=39) 10-Hz rTMS intervention applied 5 days per week for 3 weeks to the left DLPFC. Local brain volume changes measured by deformation-based morphometry were correlated with changes in negative symptom severity using a repeated-measures analysis of covariance design. Volume gains in the left hippocampal, parahippocampal and precuneal cortices predicted negative symptom improvement in the active rTMS group (all r⩽-0.441, all P⩽0.009), but not the sham rTMS group (all r⩽0.211, all P⩾0.198). Further analyses comparing negative symptom responders (⩾20% improvement) and non-responders supported the primary analysis, again only in the active rTMS group (F(9, 207)=2.72, P=0.005, partial η 2=0.106). Heterogeneity in clinical response of negative symptoms in schizophrenia to prefrontal high-frequency rTMS may be related to variability in capacity for structural plasticity, particularly in the left hippocampal region and the precuneus.

Losses at chromosome 4q are associated with poor survival in operable ductal pancreatic adenocarcinoma.

Here we tested the prognostic impact of genomic alterations in operable localized pancreatic ductal adenocarcinoma (PDAC). Fifty-two formalin-fixed and paraffin-embedded primary PDAC were laser micro-dissected and were investigated by comparative genomic hybridization after whole genome amplification using an adapter-linker PCR. Chromosomal gains and losses were correlated to clinico-pathological parameters and clinical follow-up data. The most frequent aberration was loss on chromosome 17p (65%) while the most frequent gains were detected at 2q (41%) and 8q (41%), respectively. The concomitant occurrence of losses at 9p and 17p was found to be statistically significant. Higher rates of chromosomal losses were associated with a more advanced primary tumor stage and losses at 9p and 18q were significantly associated with presence of lymphatic metastasis (chi-square: p = 0.03, p = 0.05, respectively). Deletions on chromosome 4 were of prognostic significance for overall survival and tumor recurrence (Cox-multivariate analysis: p = 0.026 and p = 0.021, respectively). In conclusion our data suggest the common alterations at chromosome 8q, 9p, 17p and 18q as well as the prognostic relevant deletions on chromosome 4q as relevant for PDAC progression. Our comprehensive data from 52 PDAC should provide a basis for future studies with a higher resolution to discover the relevant genes located within the chromosomal aberrations identified.

Traffic exposure and subclinical cardiovascular disease: is the association modified by socioeconomic characteristics of individuals and neighbourhoods? Results from a multilevel study in an urban region.

OBJECTIVES: Traffic-related pollution is associated with cardiovascular disease in general, but previous studies suggested that low socioeconomic status (SES) groups might be more susceptible towards a negative impact. We examined whether the association between long-term exposure to high traffic and early signs of coronary artery disease is modified by SES. METHODS: Individual-level medical and social data from a population-based study were linked with census information on neighbourhood socioeconomic characteristics. Residential exposure to traffic was defined as proximity to major roads using a geographical information system. We studied associations between high traffic and coronary artery calcification (CAC) within strata of SES to examine effect modification. Data stem from an epidemiological study in Germany including 2264 women and 2037 men (45-75 years). RESULTS: High traffic and low SES were both associated with higher amounts of calcification (>or=75th age-specific percentile). More participants with low SES lived close to major roads while stratified analyses did not indicate higher susceptibility in low SES groups. Participants with low SES and simultaneous exposure to high traffic had highest levels of CAC. For example, the prevalence of high calcification was 23.9% in better-educated men with low traffic exposure but 37.7% in lower-educated men with high traffic exposure (women: 22.0% vs 28.1%). CONCLUSIONS: High traffic exposure was associated with coronary calcification in all social groups, but as low SES individuals had higher calcification in general and were also more often exposed to traffic, existing inequalities could be further shaped by traffic exposure.