Prader–Willi syndrome and autism spectrum disorders: an evolving story

Prader–Willi syndrome (PWS) is well-known for its genetic and phenotypic complexities. Caused by a lack of paternally derived imprinted material on chromosome 15q11–q13, individuals with PWS have mild to moderate intellectual disabilities, repetitive and compulsive behaviors, skin picking, tantrums, irritability, hyperphagia, and increased risks of obesity. Many individuals also have co-occurring autism spectrum disorders (ASDs), psychosis, and mood disorders. Although the PWS 15q11–q13 region confers risks for autism, relatively few studies have assessed autism symptoms in PWS or directly compared social, behavioral, and cognitive functioning across groups with autism or PWS. This article identifies areas of phenotypic overlap and difference between PWS and ASD in core autism symptoms and in such comorbidities as psychiatric disorders, and dysregulated sleep and eating. Though future studies are needed, PWS provides a promising alternative lens into specific symptoms and comorbidities of autism

Epigenetic polypharmacology: from combination therapy to multitargeted drugs

The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed

Kindergartners’ performance in two types of imaginary perspective-taking

This study aimed at gaining further understanding of kindergartners’ performance in imaginary perspective-taking (IPT) by examining whether they can imagine what is visible from a particular point of view (IPT type 1: visibility) and how an object or scene will look from a particular point of view (IPT type 2: appearance). The sample consisted of 4- and 5-year-old kindergartners in the Netherlands (N = 334) and in Cyprus (N = 304). IPT abilities were assessed by a paper-and-pencil test of various perspective-taking pictorial tasks. The study showed that the Dutch children performed generally better than those in Cyprus. In both countries the IPT type 1 items were on average significantly easier than the IPT type 2 items. This was confirmed by a statistical implicative analysis by which the relationships between the individual items of both IPT types were investigated and which revealed that some items are less or more difficult than other items of a particular type. Regarding the influence of children’s characteristics, in both countries it was found that mathematics ability was significantly related to IPT performance, whereas this was not the case for gender. Contrary to Cyprus, in the Netherlands the children in the second year of kindergarten had a significantly higher IPT performance than the children who were in their first year