Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence?

Psychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar disorder. Here we tested the hypothesis that these common variants would also influence psychotic experiences measured dimensionally in adolescents in the general population. Our aim was to test whether schizophrenia and bipolar disorder polygenic risk scores (PRS), as well as specific single nucleotide polymorphisms (SNPs) previously identified as risk variants for schizophrenia, were associated with adolescent dimension-specific psychotic experiences. Self-reported Paranoia, Hallucinations, Cognitive Disorganisation, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms, as measured by the Specific Psychotic Experiences Questionnaire (SPEQ), were assessed in a community sample of 2,152 16-year-olds. Polygenic risk scores were calculated using estimates of the log of odds ratios from the Psychiatric Genomics Consortium GWAS stage-1 mega-analysis of schizophrenia and bipolar disorder. The polygenic risk analyses yielded no significant associations between schizophrenia and bipolar disorder PRS and the SPEQ measures. The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value=2.57x10-4) and rs9960767 (p-value=6.23x10-4). Replication in an independent sample of 16-year-olds (N=3,427) assessed using the Psychotic-Like Symptoms Questionnaire (PLIKS-Q), a composite measure of multiple positive psychotic experiences, failed to yield significant results. Future research with PRS derived from larger samples, as well as larger adolescent validation samples, would improve the predictive power to test these hypotheses further. The challenges of relating adult clinical diagnostic constructs such as schizophrenia to adolescent psychotic experiences at a genetic level are discussed

Effect on human attention of exposure to the electromagnetic field emitted by mobile phones

This study examined the effect of exposure to the electromagnetic field emitted by mobile phones on human attention. Three measures of attention were administered to 72 teenagers, 37 of whom were mobile phone users. The results showed that the mobile phone users performed better on one of the three measures of attention than did the non-mobile phone users. The results suggest that exposure to the electromagnetic field emitted by mobile phones may have a mild facilitating effect on attention functions, which is consistent with previous observations that exposure to the electromagnetic field has a facilitating effect on cognitive processing. The possibility that mobile phone users may be naturally better at multiple tasking tasks was discussed. © 2001 Lippincott Williams & Wilkins.link_to_subscribed_fulltex

Effect on human attention of exposure to the electromagnetic field emitted by mobile phones

This study examined the effect of exposure to the electromagnetic field emitted by mobile phones on human attention. Three measures of attention were administered to 72 teenagers, 37 of whom were mobile phone users. The results showed that the mobile phone users performed better on one of the three measures of attention than did the non-mobile phone users. The results suggest that exposure to the electromagnetic field emitted by mobile phones may have a mild facilitating effect on attention functions, which is consistent with previous observations that exposure to the electromagnetic field has a facilitating effect on cognitive processing. The possibility that mobile phone users may be naturally better at multiple tasking tasks was discussed. © 2001 Lippincott Williams & Wilkins.link_to_subscribed_fulltex

Lower-limb sensorimotor deprivation-related brain activation in patients with chronic complete spinal cord injury

202012 bcrcVersion of RecordPublishe

Simplified Chinese translation of 13 adult item banks from the Quality of Life in Neurological Disorders (Neuro-QoL)

201901 bcrcVersion of RecordPublishe

Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics

The conjugation of proteins with ubiquitin plays numerous regulatory roles through both proteasomal-dependent and nonproteasomal-dependent functions. Alterations in ubiquitylation are observed in a wide range of pathologic conditions, including numerous malignancies. For this reason, there is great interest in targeting the ubiquitin-proteasome system in cancer. Several classes of proteasome inhibitors, which block degradation of ubiquitylated proteins, are widely used in research, and one, Bortezomib, is now in clinical use. Despite the well-defined and central role of the ubiquitin-activating enzyme (E1), no cell permeable inhibitors of El have been identified. Such inhibitors should, in principle, block all functions of ubiquitylation. We now report 4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester (PYR-41) as the first such inhibitor. Unexpectedly, in addition to blocking ubiquitylation, PYR-41 increased total sumoylation in cells. The molecular basis for this is unknown; however, increased sumoylation was also observed in cells harboring temperature-sensitive El. Functionally, PYR-41 attenuates cytokine-mediated nuclear factor-kappa B activation. This correlates with inhibition of nonproteasomal (Lys-63) ubiquitylation of TRAF6, which is essential to I kappa B kinase activation. PYR-41 also prevents the downstream ubiquitylation and proteasomal degradation of I kappa B alpha. Furthermore, PYR-41 inhibits degradation of p53 and activates the transcriptional activity of this tumor suppressor. Consistent with this, it differentially kills transformed p53-expressing cells. Thus, PYR-41 and related pyrazones provide proof of principle for the capacity to differentially kill transformed cells, suggesting the potential for E I inhibitors as therapeutics in cancer. These inhibitors can also be valuable tools for studying ubiquitylation