The Role of Attention-Deficit/hyperactivity Disorder in the Association between Verbal Ability and Conduct Disorder

Although there is clear evidence that low verbal ability is a risk factor for conduct disorder (CD), some researchers have questioned whether this association is due to the common comorbidity between attention-deficit/hyperactivity disorder (ADHD) and CD. The present study examined the association among verbal ability, ADHD, and CD in a genetically informative sample in order to examine the role of genes and/or environmental influences shared in common with ADHD on the covariation between verbal ability and CD. Participants were 2744 adolescents from the Center for Antisocial Drug Dependence (CADD), and included 360 monozygotic (MZ) female twin pairs, 221 dizygotic (DZ) female twin pairs, 297 MZ male twin pairs, 220 DZ male twin pairs, and 274 opposite-sex DZ twin pairs. The Diagnostic Interview Schedule for Children (DISC-IV) was used to assess lifetime symptoms of ADHD and CD. Verbal ability was assessed via the Vocabulary subtest of the Wechsler Adult Intelligence Scale III (WAIS-III) for individuals over the age of 16 and the Vocabulary subtest of the Wechsler Intelligence Scale for Children III (WISC-III) for individuals under the age of 16. There was a small but significant negative covariance between verbal ability and CD and between verbal ability and ADHD. Results also suggest that the covariation between verbal ability and CD is due to influences shared in common with ADHD

Network analysis of human glaucomatous optic nerve head astrocytes

<p>Abstract</p> <p>Background</p> <p>Astrocyte activation is a characteristic response to injury in the central nervous system, and can be either neurotoxic or neuroprotective, while the regulation of both roles remains elusive.</p> <p>Methods</p> <p>To decipher the regulatory elements controlling astrocyte-mediated neurotoxicity in glaucoma, we conducted a systems-level functional analysis of gene expression, proteomic and genetic data associated with reactive optic nerve head astrocytes (ONHAs).</p> <p>Results</p> <p>Our reconstruction of the molecular interactions affected by glaucoma revealed multi-domain biological networks controlling activation of ONHAs at the level of intercellular stimuli, intracellular signaling and core effectors. The analysis revealed that synergistic action of the transcription factors AP-1, vitamin D receptor and Nuclear Factor-kappaB in cross-activation of multiple pathways, including inflammatory cytokines, complement, clusterin, ephrins, and multiple metabolic pathways. We found that the products of over two thirds of genes linked to glaucoma by genetic analysis can be functionally interconnected into one epistatic network via experimentally-validated interactions. Finally, we built and analyzed an integrative disease pathology network from a combined set of genes revealed in genetic studies, genes differentially expressed in glaucoma and closely connected genes/proteins in the interactome.</p> <p>Conclusion</p> <p>Our results suggest several key biological network modules that are involved in regulating neurotoxicity of reactive astrocytes in glaucoma, and comprise potential targets for cell-based therapy.</p