Effects of psychosis-associated genetic markers on brain volumetry: a systematic review of replicated findings and an independent validation.

BACKGROUND: Given psychotic illnesses' high heritability and associations with brain structure, numerous neuroimaging-genetics findings have been reported in the last two decades. However, few findings have been replicated. In the present independent sample we aimed to replicate any psychosis-implicated SNPs (single nucleotide polymorphisms), which had previously shown at least two main effects on brain volume. METHODS: A systematic review for SNPs showing a replicated effect on brain volume yielded 25 studies implicating seven SNPs in five genes. Their effect was then tested in 113 subjects with either schizophrenia, bipolar disorder, 'at risk mental state' or healthy state, for whole-brain and region-of-interest (ROI) associations with grey and white matter volume changes, using voxel-based morphometry. RESULTS: We found FWER-corrected (Family-wise error rate) (i.e. statistically significant) associations of: (1) CACNA1C-rs769087-A with larger bilateral hippocampus and thalamus white matter, across the whole brain; and (2) CACNA1C-rs769087-A with larger superior frontal gyrus, as ROI. Higher replication concordance with existing literature was found, in decreasing order, for: (1) CACNA1C-rs769087-A, with larger dorsolateral-prefrontal/superior frontal gyrus and hippocampi (both with anatomical and directional concordance); (2) ZNF804A-rs11681373-A, with smaller angular gyrus grey matter and rectus gyri white matter (both with anatomical and directional concordance); and (3) BDNF-rs6265-T with superior frontal and middle cingulate gyri volume change (with anatomical and allelic concordance). CONCLUSIONS: Most literature findings were not herein replicated. Nevertheless, high degree/likelihood of replication was found for two genome-wide association studies- and one candidate-implicated SNPs, supporting their involvement in psychosis and brain structure.

Fluoroquinolones Are Associated With Increased Risk of Aortic Aneurysm or Dissection: Systematic Review and Meta-analysis.

Fluoroquinolone use has been associated with collagen disease events, raising safety concerns. We hypothesized that the use of fluoroquinolones is associated with aortic aneurysm (AA) and aortic dissection or aortic rupture (AD/AR). We performed a systematic review with meta-analysis on studies published until March 2019. Seven observational studies were included, comprising 2,851,646 participants. The studies were evaluated regarding their risk of bias. Results on fluoroquinolone use risk comparing with nontreatment and with beta-lactam antibiotic use were extracted. The estimates were pooled through a random-effects model meta-analysis and heterogeneity assessed through the I2 statistic. Sensitivity analysis were performed, grouping studies per design and with exclusion of studies with critical risk of bias. Fluoroquinolone use was associated with a higher risk of AA/AD/AR, comparing with a nontreatment intervention (odds ratio = 2.26; 95%CI 1.93-2.65; I2 = 30%) and comparing with a beta-lactam intervention (odds ratio = 1.56; 95%CI 1.37-1.79; I2 = 0%). This harm effect remained significant when pooling the results for the AD/AR outcome only and across various study designs. Studies comparing with beta-lactam intervention were considered to have a moderate risk of bias, while the remaining ones were classified as having at least a serious risk of bias. All evaluated outcomes had very low Grading of Recommendation, Assessment, Development and Evaluation evidence. Fluoroquinolone use was associated with a significant risk of AA/AD/AR.