Molecular biomarkers to track clinical improvement following an integrative treatment model in autistic toddlers.

OBJECTIVES: Identifying an objective, laboratory-based diagnostic tool (e.g. changes in gene expression), when used in conjunction with disease-specific clinical assessment, could increase the accuracy of the effectiveness of a therapeutic intervention. METHODS: We assessed the association between treatment outcome and blood RNA expression before the therapeutic intervention to post-treatment (after 1 year) of five autism spectrum disorder (ASD) toddlers who underwent an intensive cognitive-behavioural intervention integrated with psychomotor and speech therapy. RESULTS: We found 113 significant differentially expressed genes enriched for the nervous system, immune system, and transcription and translation-related pathways. Some of these genes, as MALAT-1, TSPO, and CFL1, appear to be promising candidates. CONCLUSIONS: Our findings show that changes in peripheral gene expression could be used in conjunction with clinical scales to monitor a rehabilitation intervention's effectiveness in toddlers affected by ASD. These results need to be validated in a larger cohort.

Intensification of maternal care by double-mothering boosts cognitive function and hippocampal morphology in the adult offspring.

Mice born from high care-giving females show, as adults, low anxiety levels, decreased responsiveness to stress, and substantial improvements in cognitive function and hippocampal plasticity. Given the relevance of this issue for preventing emotional and cognitive abnormalities in high-risk subjects, this study examines the possibility to further enhance the beneficial effects observed in the progeny by augmenting maternal care beyond the highest levels females can display in standard laboratory conditions. This was produced by placing a second female with the dam and its litter in the rearing cage from the partum until pups weaning. Maternal behavior of all females was scored during the first week postpartum, and behavioral indices of emotionality, prestress and poststress corticosterone levels, cognitive performance, and hippocampal morphology were assessed in the adult offspring. We found that pups reared by female dyads received more maternal care than pups reared by dams alone, but as adults, they did not exhibit alterations in emotionality or corticosterone response estimated in basal condition or following restraint stress. Conversely, they showed enhanced performance in hippocampal-dependent tasks including long-term object discrimination, reactivity to spatial change, and fear conditioning together with an increase in dendritic length and spine density in the CA1 region of the hippocampus. In general, the beneficial effects of dyadic maternal care were stronger when both the females were lactating. This study demonstrates that double-mothering exerts a long-term positive control on cognitive function and hippocampal neuronal connectivity. This experimental manipulation, especially if associated with increased feeding, might offer a concrete possibility to limit or reverse the consequences of negative predisposing conditions for normal cognitive development.