RESUMO
The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for â¼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.
Assuntos
Esquizofrenia/genética , Transtornos de Estresse Pós-Traumáticos/genética , Adulto , Negro ou Afro-Americano/genética , Transtorno Bipolar/genética , Estudos de Casos e Controles , Transtorno Depressivo Maior/genética , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Caracteres Sexuais , Fatores Sexuais , População Branca/genéticaRESUMO
To date, the effect of low doses of caffeine on aggression has not been systematically examined. Doses of caffeine greater than 30 mg/kg appear to reduce social interaction and aggression in all species studied. In a double blind study of the effects of low doses of caffeine on aggression, rats were housed four per cage, and aggressive behavior against an intruder was recorded during baseline and following administration of 2.5, 5, 10, and 20 mg/kg caffeine. Aggressive behavior was significantly increased following administration of the higher doses of caffeine. Doses of 5, 10, and 20 mg/kg caffeine all were effective in increasing pushing behavior, whereas doses of 5 and 10 mg/kg were most effective in increasing boxing behavior, and a dose of 10 mg/kg was significantly more effective than other doses in increasing chasing and roll-tumble-bite behaviors. Based on these results and other published reports, the inverted-U shaped dose-dependent effect of caffeine on aggression appears to apply, with aggressive behavior being most elevated following doses of 5-20 mg/kg caffeine, less elevated following 2.5 mg/kg or 30 mg/kg, and significantly reduced with doses above 40 mg/kg and at doses below 2.5 mg/kg.
