Roberta Fadda

Oxytocin and autism: a systematic review of randomized controlled trials.

OBJECTIVE Little is known about the effectiveness of pharmacological interventions on autism spectrum disorder (ASD). This is a systematic review of the randomized controlled trials (RCTs) of oxytocin interventions in autism, made from January 1990 to September 2013. METHOD A search of computerized databases was supplemented by manual search in the bibliographies of key publications. The methodological quality of the studies included in the review was evaluated independently by two researchers, according to a set of formal criteria. Discrepancies in scoring were resolved through discussion. RESULTS The review yielded seven RCTs, including 101 subjects with ASD (males=95) and 8 males with Fragile X syndrome. The main categories of target symptoms tested in the studies were repetitive behaviors, eye gaze, and emotion recognition. The studies had a medium to high risk of bias. Most studies had small samples (median=15). All the studies but one reported statistically significant between-group differences on at least one outcome variable. Most findings were characterized by medium effect size. Only one study had evidence that the improvement in emotion recognition was maintained after 6 weeks of treatment with intranasal oxytocin. Overall, oxytocin was well tolerated and side effects, when present, were generally rated as mild; however, restlessness, increased irritability, and increased energy occurred more often under oxytocin. CONCLUSIONS RCTs of oxytocin interventions in autism yielded potentially promising findings in measures of emotion recognition and eye gaze, which are impaired early in the course of the ASD condition and might disrupt social skills learning in developing children. There is a need for larger, more methodologically rigorous RCTs in this area. Future studies should be better powered to estimate outcomes with medium to low effect size, and should try to enroll female participants, who were rarely considered in previous studies. Risk of bias should be minimized. Human long-term administration studies are necessary before clinical recommendations can be made.

Synthesis and evaluation of anticancer activity of 2-arylamino-6-trifluoromethyl-3-(hydrazonocarbonyl)pyridines.

The synthesis and anticancer activity of 2-arylamino-6-trifluoromethyl-3-(hydrazonocarbonyl)pyridines is described. The new trifluoromethylpyridine derivatives were evaluated for their anticancer activity toward human cancer cell lines by the National Cancer Institute (NCI). Most of them had excellent growth inhibition activity, having GI(50) values in the low micromolar to nanomolar concentration range. The most potent 2,6-dichlorobenzaldehydehydrazone 29 inhibited the growth of all tested cancer cell lines with nanomolar potency, and did not show animal toxicity. Hydrazone 29 has been selected by the Biological Evaluation Committee of NCI for testing in vivo Hollow Fiber Assay.

Effects of drinking supplementary water at school on cognitive performance in children

We investigated the beneficial effects of drinking supplementary water during the school day on the cognitive performance and transitory subjective states, such as fatigue or vigor, in 168 children aged between 9 and 11years who were living in a hot climate (South Italy, Sardinia). The classes were randomly divided into an intervention group, which received water supplementation, and a control group. Dehydration was determined by urine sampling and was defined as urine osmolality greater than 800mOsm/kg H(2)O (Katz, Massry, Agomn, & Toor, 1965). The change in the scores from the morning to the afternoon of hydration levels, cognitive performance and transitory subjective states were correlated. In line with a previous observational study that evaluated the hydration status of school children living in a country with a hot climate (Bar-David, Urkin, & Kozminsky, 2005), our results showed that a remarkable proportion of children were in a state of mild, voluntary dehydration at the beginning of the school day (84%). We found a significant negative correlation between dehydration and the auditory number span, which indicates a beneficial effect of drinking supplementary water at school on short-term memory. Moreover, there was a positive correlation between dehydration and performance in the verbal analogy task. The results are discussed in the light of the complexity of the neurobiological mechanisms involved in the relationship between hydration status and cognition.

Bilingualism in Sardinia and Scotland: Exploring the cognitive benefits of speaking a ‘minority’ language

The research reports on a study investigating the cognitive benefits of bilingualism in children who speak the minority languages of Sardinian and Scottish Gaelic, in addition to their respective ‘national’ languages of Italian and English. One hundred and twenty-one children, both bilingual and monolingual, were administered a series of standardised cognitive ability tests targeted at the four areas that have been previously shown to be advantageous to bilingual children in the literature, namely, cognitive control, problem-solving ability, metalinguistic awareness and working memory. The bilingual children significantly outperformed the monolingual children in two of the four sub-tests, and the Scottish children significantly outperformed the Sardinian children in one of the sub-tests. The differences found were largely due to the superior performance of the Scottish bilingual children who receive a formal bilingual education, in contrast to the Sardinian bilingual children who mostly only speak the minority language at home. The implications of the results are discussed.

2-Acylhydrazino-5-arylpyrrole derivatives: synthesis and antifungal activity evaluation.

The synthesis and antifungal activity of 2-acylhydrazino-5-arylpyrroles 21-62 are described. Pyrrole derivatives 21-62 were evaluated for their antifungal activity towards Candida albicans ATCC 10231 and three Candida non-albicans isolated from clinical specimens. Most of them showed very good antifungal activities against Candidae, having MIC values in the 0.39-3.12 microg/mL range and enhanced inhibition potency as compared to that of fluconazole. In addition, some of the most active compounds were tested for cytotoxic activities against breast (MCF-7), lung (H-460), and central nervous system (SF-268) human cancer cell lines with the NCI anticancer drug screen. The activity of pyrroles described in this paper, along with the low toxicity, shows promise for the future development of non-toxic new antimycotic agents. The relationship between functional group variation and biological activity of the evaluated compounds is also discussed.

Mother–Infant and Extra-Dyadic Interactions with a New Social Partner: Developmental Trajectories of Early Social Abilities during Play

Mother–infant interactions during feeding and play are pivotal experiences in the development of infants’ early social abilities (Stern, 1985, 1995; Biringen, 2000). Stern indicated distinctive characteristics of mother–infant interactions, respectively, during feeding and play, suggesting to evaluate both to better describe the complexity of such early affective and social experiences (Stern, 1996). Moreover, during the first years of life, infants acquire cognitive and social skills that allow them to interact with new social partners in extra-dyadic interactions. However, the relations between mother–child interactions and infants’ social skills in extra-dyadic interactions are still unknown. We investigated longitudinally the relations between mother–child interactions during feeding and play and child’s pre-verbal communicative abilities in extra-dyadic interactions during play. 20 dyads were evaluated at T1 (infants aged between 9–22 months) and 6 months later, at T2. The interdyadic differences in mother–infant interactions during feeding and play were evaluated, respectively, with the “Feeding Scale” (Chatoor et al., 1997) and with the “Play Scale” (Chatoor, 2006) and the socio-communicative abilities of children with a new social partner during play were evaluated with the “Early Social Communication Scales” (Mundy et al., 2003). We distinguished the dyads into two categories: dyads with functional interactions (high dyadic reciprocity, low dyadic conflict) and dyads with dysfunctional interactions (lower dyadic reciprocity, higher dyadic conflict). At T1, infants belonging to dyads with dysfunctional interactions were significantly lower in “Initiating Joint Attention” and in “Responding to Joint Attention” in interaction with a new social partner compared to the infants belonging to dyads with functional interactions. At T2, infants belonging to dyads with dysfunctional interactions were significantly lower in “Initiating Social Interactions” with a new social partner compared to the infants belonging to dyads with functional interactions. There were significant correlations between the quality of mother–infant interactions during feeding and infants’ social abilities in interaction with a stranger both at T1 and at T2. This study showed a stable relation over time between mother–child interactions and child’s social communicative skills in extra-dyadic interactions.

Exploring the Role of Theory of Mind in Moral Judgment: The Case of Children with Autism Spectrum Disorder

This paper adds to the growing research on moral judgment (MJ) by considering whether theory of mind (ToM) might foster children’s autonomous MJ achievement. A group of 30 children with autism spectrum disorder (ASD) was compared in MJ and ToM with 30 typically developing (TD) children. Participants were tested for MJ with a classical Piaget’s task and for ToM with a second order False Belief task. In the moral task, children were told two versions of a story: in one version the protagonist acted according to a moral intention but the action resulted in a harmful consequence; in the other version the protagonist acted according to an immoral intention, but the action resulted in a harmless consequence. Children were asked which of the two protagonists was the “naughtier.” In line with previous studies, the results indicated that, while the majority of TD participants succeeded in the second order False Belief task, only few individuals with ASD showed intact perspective taking abilities. The analysis of the MJ in relation to ToM showed that children with ASD lacking ToM abilities judged guilty the protagonists of the two versions of the story in the moral task because both of them violated a moral rule or because they considered the consequences of the actions, ignoring any psychological information. These results indicate a heteronomous morality in individuals with ASD, based on the respect of learned moral rules and outcomes rather than others’ subjective states.

A Statistical Physics Perspective to Understand Social Visual Attention in Autism Spectrum Disorder.

This study investigated social visual attention in children with Autism Spectrum Disorder (ASD) and with typical development (TD) in the light of Brockmann and Geisel’s model of visual attention. The probability distribution of gaze movements and clustering of gaze points, registered with eye-tracking technology, was studied during a free visual exploration of a gaze stimulus. A data-driven analysis of the distribution of eye movements was chosen to overcome any possible methodological problems related to the subjective expectations of the experimenters about the informative contents of the image in addition to a computational model to simulate group differences. Analysis of the eye-tracking data indicated that the scanpaths of children with TD and ASD were characterized by eye movements geometrically equivalent to Lévy flights. Children with ASD showed a higher frequency of long saccadic amplitudes compared with controls. A clustering analysis revealed a greater dispersion of eye movements for these children. Modeling of the results indicated higher values of the model parameter modulating the dispersion of eye movements for children with ASD. Together, the experimental results and the model point to a greater dispersion of gaze points in ASD.

Impaired representational gaze following in children with autism spectrum disorder

Using eye-tracking methodology, we compared spontaneous gaze following in young children with Autism Spectrum Disorder (mean age 5.8 years) to that of typically developing children (mean age 5.7 years). Participants saw videos in which the position of a hidden object was either perceptually visible or was only represented in another persons mind. The findings indicate that children with Autism Spectrum Disorder were significantly less accurate in gaze following and observed the attended object for less time than typically developing children only in the Representational Condition. These results show that children with Autism Spectrum Disorder are responsive to gaze as a perceptual cue although they ignore its representational meaning.