Environmental and genetic influences on early attachment

Attachment theory predicts and subsequent empirical research has amply demonstrated that individual variations in patterns of early attachment behaviour are primarily influenced by differences in sensitive responsiveness of caregivers. However, meta-analyses have shown that parenting behaviour accounts for about one third of the variance in attachment security or disorganisation. The exclusively environmental explanation has been challenged by results demonstrating some, albeit inconclusive, evidence of the effect of infant temperament. In this paper, after reviewing briefly the well-demonstrated familial and wider environmental influences, the evidence is reviewed for genetic and gene-environment interaction effects on developing early attachment relationships. Studies investigating the interaction of genes of monoamine neurotransmission with parenting environment in the course of early relationship development suggest that children's differential susceptibility to the rearing environment depends partly on genetic differences. In addition to the overview of environmental and genetic contributions to infant attachment, and especially to disorganised attachment relevant to mental health issues, the few existing studies of gene-attachment interaction effects on development of childhood behavioural problems are also reviewed. A short account of the most important methodological problems to be overcome in molecular genetic studies of psychological and psychiatric phenotypes is also given. Finally, animal research focusing on brain-structural aspects related to early care and the new, conceptually important direction of studying environmental programming of early development through epigenetic modification of gene functioning is examined in brief

Children with Autism Understand Indirect Speech Acts: Evidence from a Semi-Structured Act-Out Task

Children with Autism Spectrum Disorder are often said to present a global pragmatic impairment. However, there is some observational evidence that context-based comprehension of indirect requests may be preserved in autism. In order to provide experimental confirmation to this hypothesis, indirect speech act comprehension was tested in a group of 15 children with autism between 7 and 12 years and a group of 20 typically developing children between 2:7 and 3:6 years. The aim of the study was to determine whether children with autism can display genuinely contextual understanding of indirect requests. The experiment consisted of a three-pronged semi-structured task involving Mr Potato Head. In the first phase a declarative sentence was uttered by one adult as an instruction to put a garment on a Mr Potato Head toy; in the second the same sentence was uttered as a comment on a picture by another speaker; in the third phase the same sentence was uttered as a comment on a picture by the first speaker. Children with autism complied with the indirect request in the first phase and demonstrated the capacity to inhibit the directive interpretation in phases 2 and 3. TD children had some difficulty in understanding the indirect instruction in phase 1. These results call for a more nuanced view of pragmatic dysfunction in autism

Macrophage apolipoprotein-E knockdown modulates caspase-3 activation without altering sensitivity to apoptosis

Apolipoprotein-E (apoE) expression may be associated with apoptosis resistance. Since macrophages constitutively synthesize apoE we speculated that this may contribute to apoptosis resistance. Using siRNA, human monocyte derived macrophage (hMDM) apoE mRNA and protein was reduced by 97% and 61%, respectively. ApoE knockdown increased staurosporine-induced caspase-3 activation by 78% without altering cell survival or apoptosis as assessed by TUNEL analysis and morphological changes. This result was confirmed using murine bone marrow derived macrophages (mBMDM) from apoE null and wild type mice. In these experiments, staurosporine-induced caspase-3 activation was increased by 49% in apoE null compared to wild type mBMDM and this was not associated with differences in TUNEL signal, annexin-V binding or DNA fragmentation. ApoE is also important for cholesterol transport and macrophage cholesterol can regulate apoptosis. Knockdown of hMDM apoE inhibited basal cholesterol efflux by 20% without altering apolipoprotein-AI mediated cholesterol efflux over 24 h. Similarly, in apoE null mBMDM a non significant trend for a 16% reduction in basal cholesterol efflux was observed as compared to wild type mBMDM. In conclusion, apoE expression modulates capase-3 activity, but this has no significant impact on sensitivity to apoptosis and only a moderate impact on basal cholesterol efflux. © 2007 Elsevier B.V. All rights reserved