Characterizing individual differences in children and adolescents with autism spectrum disorder: a descriptive study.

Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by a higher prevalence in male than in female participants. Recent studies have hypothesized the presence of different phenotypes in male and female participants with ASD. The present study aims to assess possible sex differences in cognitive and adaptive functioning, symptomatology of ASD, and psychopathological comorbidities in a large sample of children and adolescents with ASD. Methods: The study included a total of 2,146 children and adolescents diagnosed with ASD, comprising 1785 boys (mean age 7.12 ± 3.69 years) and 361 girls (mean age 6.25 ± 3.30 years). The age of the participants ranged from 1.35 to 19.05 years (mean age 9.98 ± 3.64). The study sought to include all children and adolescents diagnosed with Autism or ASD. Results: Present results showed that girls with ASD had lower IQs than boys but similar adaptive functioning. The severity of symptoms of ASD was greater in boys than in girls, as were scores on psychopathological measures. With increasing age, boys with ASD showed greater impairment in social communication skills than girls and increased psychopathological comorbidities. Older girls showed fewer restricted and repetitive behaviors. Discussion: Exploring phenotypic differences in children and adolescents with ASD fosters an understanding of subtle diagnostic facets that may go unrecognized, allowing for increasingly individualized and tailored interventions.

Celiac disease in children and adolescents with Down syndrome: behavioural, adaptive and sleep profiles.

BACKGROUND: Individuals with Down syndrome (DS) exhibit higher risk for celiac disease (CD) than general population. Although literature suggests CD could be associated with behavioural problems in both paediatric and adult age, such association has been poorly explored in children and adolescents DS. Therefore, the current study aimed to investigate differences in emotional/behavioural difficulties, adaptive skills and sleep problems between children with DS with and without CD. METHODS: Data were retrospectively collected from a database including data from 381 individuals with DS (3-18 years). The final sample included 65 participants, 27 with co-occurring CD and 38 age, IQ, sex and body mass index-matched controls without CD. Emotional/behavioural difficulties, adaptive skills and sleep problems were assessed through parent report questionnaires. RESULTS: No group differences emerged in emotional/behavioural difficulties, whereas participants in the CD group showed better adaptive skills in the practical domain than control group. Weak differences emerged in sleep problems. CONCLUSIONS: Youth with DS and co-occurring CD do not exhibit more emotional and behavioural problems than youth with DS without co-occurring CD but exhibit better adaptive skills in the practical domain.

Longitudinal data of neuropsychological profile in a cohort of Duchenne muscular dystrophy boys without cognitive impairment.

The aim of the study was to re-assess neuropsychological profile in a group of boys with Duchenne muscular dystrophy without intellectual disability and neuropsychiatric disorder three years apart from a previous evaluation, to establish possible changes over time. We were also interested in defining more in detail correlation between genotype and neuropsychological phenotype. Thirty-three of the previous 40 subjects (mean age at follow up: 10 years and 7 months) agreed to participate in the follow up study and to perform the new assessment. The results confirm a typical neuropsychological profile, with difficulty in the manipulation of stored information, poor abstract reasoning and planning capacity and impulsiveness, supporting the involvement of a cerebellar striatal cortical network for these children. The more detailed description of subgroups of subjects, according to the real expression of Dp140, let to reveal possible genotype-neuropsychological phenotype correlations, and a more general neuropsychological impairment emerged in boys without Dp140 expression.

Cognitive profile in Duchenne muscular dystrophy boys without intellectual disability: The role of executive functions.

The aim of our prospective observational study was to assess profiles of cognitive function and a possible impairment of executive functions in a cohort of boys with Duchenne muscular dystrophy without intellectual and behavior disability. Forty Duchenne boys (range of age: 6 years to 11 years and 6 months) were assessed by Wechsler Intelligence scale and battery of tests including tasks assessing working memory and executive functions (inhibition and switching, problem solving and planning). In our cohort some aspects of cognitive function were often impaired. These included multitasking, problem solving, inhibition and working memory necessary to plan and direct goal oriented behavior. Our results support the suggestion that aspects of cognitive function could be impaired even in boys without intellectual disability and support the hypothesis that executive functions may play an important role in specific aspects of cognitive impairment in Duchenne muscular dystrophy.

The influence of Generalized Anxiety Disorder on Executive Functions in children with ADHD.

The present study was aimed at verifying whether the presence of generalized anxiety disorder (GAD) affects executive functions in children with attention-deficit hyperactivity disorder (ADHD). Two groups of children with ADHD were selected for the study according to the presence or absence of GAD. The first group of 28 children with ADHD with GAD (mean age: 9 ± 1.2; males/females: 24/4) was matched for gender, age, IQ, psychiatric comorbidity with a second group of 29 children with ADHD without GAD (mean age: 8.8 ± 0.7; males/females: 26/3). The two groups with ADHD were compared to 28 typically developing children (mean age: 8.3 ± 1.3; males/females: 23/5) on different measures involving processes especially important in inhibitory control such as rule maintenance, stimulus detection, action selection and action execution. Our results indicated that, differently from children with ADHD with GAD, only the group with ADHD without GAD showed a deficit in inhibitory control. Comorbid subgroups should be differentiated, especially, to develop specific and efficient therapeutic interventions in ADHD.

The development of episodic future thinking in middle childhood.

The ability to imagine future events (episodic future thinking-EFT) emerges in preschoolers and further improves during middle childhood and adolescence. In the present study, we focused on the possible cognitive factors that affect EFT and its development. We assessed the ability to mentally project forward in time of a large cohort of 135 6- to 11-year-old children through a task with minimal narrative demands (the Picture Book Trip task adapted from Atance and Meltzoff in Cogn Dev 20(3):341-361. doi:10.1016/j.cogdev.2005.05.001, 2005) in order to avoid potential linguistic effects on children's performance. The results showed that this task can be used to assess the development of EFT at least until the age of 8. Furthermore, EFT scores correlated with measures of phonological short-term and verbal working memory. These results support the possibility that cognitive factors such as working memory play a key role in EFT.

A comparison between linguistic skills and socio-communicative abilities in Williams syndrome.

BACKGROUND: Individuals with Williams syndrome (WS) show a disharmonic linguistic profile with a clear pattern of strengths and weaknesses. Despite their sociable nature, atypical socio-communicative abilities and deficits in communication and relationship with others have been found. AIM: The aim of the present study was to investigate whether linguistic skills (LS) were in line with the pragmatic and social use of language and the cognitive development of 32 individuals with WS (18 boys and 14 girls) with a mean chronological age of 12.3 (±4.4) years. To examine the relationship between language and mental age (MA) at different ages, the issue was investigated in children and adolescents/young adults with WS. METHOD: Measures of LS, including lexical and morphosyntactic competences, and adaptive socio-communicative abilities (ASCA), pertaining to the use of language in daily living social context, were compared with the MA of participants. In a second step, participants with WS were split into two subgroups based on age, and the relationship between LS, ASCA and MA was studied. RESULTS: Although expressive and receptive LS were generally found to be in line with or better than would be expected for MA, specific deficits in receptive ASCA were documented. LS and ASCA appeared to have a different evolution during the different time windows considered. CONCLUSIONS: Our results underlined the importance of assessing linguistic abilities in the context of adaptive functioning, to guide educational and rehabilitative strategies for individuals with WS.

Adolescence is the starting point of sex-dichotomous COMT genetic effects.

The catechol-o-methyltransferase (COMT) genetic variations produce pleiotropic behavioral/neuroanatomical effects. Some of these effects may vary among sexes. However, the developmental trajectories of COMT-by-sex interactions are unclear. Here we found that extreme COMT reduction, in both humans (22q11.2 deletion syndrome COMT Met) and mice (COMT-/-), was associated to cortical thinning only after puberty and only in females. Molecular biomarkers, such as tyrosine hydroxylase, Akt and neuronal/cellular counting, confirmed that COMT-by-sex divergent effects started to appear at the cortical level during puberty. These biochemical differences were absent in infancy. Finally, developmental cognitive assessment in 22q11DS and COMT knockout mice established that COMT-by-sex-dichotomous effects in executive functions were already apparent in adolescence. These findings uncover that genetic variations severely reducing COMT result in detrimental cortical and cognitive development selectively in females after their sexual maturity. This highlights the importance of taking into account the combined effect of genetics, sex and developmental stage.

Visual perception skills: a comparison between patients with Noonan syndrome and 22q11.2 deletion syndrome.

Ventral and dorsal streams are visual pathways deputed to transmit information from the photoreceptors of the retina to the lateral geniculate nucleus and then to the primary visual cortex (V1). Several studies investigated whether one pathway is more vulnerable than the other during development, and whether these streams develop at different rates. The results are still discordant. The aim of the present study was to understand the functionality of the dorsal and the ventral streams in two populations affected by different genetic disorders, Noonan syndrome (NS) and 22q11.2 deletion syndrome (22q11.2DS), and explore the possible genotype-phenotype relationships. 'Form coherence' abilities for the ventral stream and 'motion coherence' abilities for the dorsal stream were evaluated in 19 participants with NS and 20 participants with 22q11.2DS. Collected data were compared with 55 age-matched controls. Participants with NS and 22q11.2DS did not differ in the form coherence task, and their performance was significantly lower than that of controls. However, in the motion coherence task, the group with NS and controls did not differ, and both obtained significantly higher scores than the group with 22q11.2DS. Our findings indicate that deficits in the dorsal stream are related to the specific genotype, and that in our syndromic groups the ventral stream is more vulnerable than the dorsal stream.

No evidence for the presence of genetic variants predisposing to psychotic disorders on the non-deleted 22q11.2 allele of VCFS patients.

The velo-cardio-facial syndrome (VCFS) is caused by hemizygous deletions on chromosome 22q11.2. The VCFS phenotype is complex and characterized by frequent occurrence of neuropsychiatric symptoms with up to 25-30% of cases suffering from psychotic disorders compared with only ~1% in the general population (odds ratio≈20-25). This makes the 22q11.2 deletion one of the most prominent risk factors for schizophrenia. However, its penetrance for neuropsychiatric phenotypes is incomplete suggesting that additional risk factors are required for disease development. These additional risk factors could lie anywhere on the genome, but by reducing the normal diploid to a haploid state, the 22q11.2 deletion could result in the unmasking of otherwise recessive alleles or functional variants on the non-deleted 22q11.2 allele. To test this hypothesis, we captured and sequenced the whole 22q11.2 non-deleted region in 88 VCFS patients with (n=40) and without (n=48) psychotic disorders to identify genetic variation that could increase the risk for schizophrenia. Single nucleotide variants (SNVs), small insertions/deletions (indels) and copy number variants were called and their distributions were compared between the two diagnostic groups using variant-, gene- and region-based association tests. None of these tests resulted in statistical evidence for the existence of a genetic variation in the non-deleted allele that would increase schizophrenia risk in VCFS patients. Power analysis showed that our study was able to achieve >80% statistical power to detect association of a risk variant with an odd ratio of ⩾22. However, it is certainly under-powered to detect risk variant of smaller effect sizes. Our study did not provide evidence that genetic variants of very large effect size located on the non-deleted 22q1.2 allele in VCFS patients increase the risk for developing psychotic disorders. Variants with smaller effects may be located in the remaining 22q11.2 allele and elsewhere in the genome. Therefore, whole exome or even genome sequencing for larger sample size would appear to be the next logical steps in the search for the genetic modifiers of the 22q11.2-deletion neuropsychiatric phenotype.

Brief Report: Self-Based and Mechanical-Based Future Thinking in Children with Autism Spectrum Disorder.

This brief report is a partial replication of the study by Jackson and Atance (J Dev Disabil 14:40-45, 2008) assessing nonverbal Self-based and Mechanical-based future thinking (FT) in children with Autism Spectrum Disorder (ASD). In a first step, these tasks were administered to 30 children with ASD. The two Self-based tasks were then modified as a verbal component could not be completely ruled out. Consequently, 77 children with ASD and 77 children with typical development received the modified Self-based FT tasks and the Mechanical-based FT tasks. We partially replicated the previous findings. Participants with ASD had impaired FT in both kinds of tasks and both groups performed better on tasks assessing Mechanical-based FT than Self-based FT. These results suggest that impairments of FT in ASD are not limited to Self-Projection.

Explorative function in Prader-Willi syndrome analyzed through an ecological spatial task.

This study was aimed at evaluating the spatial abilities in individuals with Prader-Willi syndrome (PWS) by using an ecological large-scale task with multiple rewards. To evaluate the extent of spatial deficit in PWS individuals, we compare their performances with those of individuals with Williams Syndrome (WS) in which the spatial deficits have been widely described. Participants had to explore an open space to search nine rewards placed in buckets arranged according to three spatial configurations: a Cross, a 3×3 Matrix and a Cluster composed by three groups of three buckets each. PWS individuals exhibited an explorative deficit in Cluster and Cross configurations, while WS participants in Matrix and Cross configurations. The findings indicate that the structural affordances of the environment influence the explorative strategies and can be related to how spatial information is processed.

Implicit learning in individuals with autism spectrum disorders: a meta-analysis.

BACKGROUND: Individuals with autism spectrum disorders (ASDs) are characterized by social communication difficulties and behavioural rigidity. Difficulties in learning from others are one of the most devastating features of this group of conditions. Nevertheless, the nature of learning difficulties in ASDs is still unclear. Given the relevance of implicit learning for social and communicative functioning, a link has been hypothesized between ASDs and implicit learning deficit. However, studies that have employed formal testing of implicit learning in ASDs provided mixed results. METHOD: We undertook a systematic search of studies that examined implicit learning in ASDs using serial reaction time (SRT), alternating serial reaction time (ASRT), pursuit rotor (PR), and contextual cueing (CC) tasks, and synthesized the data using meta-analysis. A total of 11 studies were identified, representing data from 407 individuals with ASDs and typically developing comparison participants. RESULTS: The results indicate that individuals with ASDs do not differ in any task considered [SRT and ASRT task: standardized mean difference (SMD) -0.18, 95% confidence interval (CI) -0.71 to 0.36; PR task: SMD -0.34, 95% CI -1.04 to 0.36; CC task: SMD 0.27, 95% CI -0.07 to 0.60]. CONCLUSIONS: Based on our synthesis of the existing literature, we conclude that individuals with ASDs can learn implicitly, supporting the hypothesis that implicit learning deficits do not represent a core feature in ASDs.

PTSD prevalence and associated risk factors after a fire disaster that broke out in a paediatric hospital: a cross-sectional study.

BACKGROUND: Several studies have shown a higher risk of psychological problems in health care workers exposed to serious occupational stressors. OBJECTIVES: The aim of the present study was to assess the presence of Post-traumatic Stress Disorder (PTSD) and possible risk factors in a sample of 32 workers who were at the same time rescuers and victims of a fire that broke out in the neonatal intensive care unit of a large paediatric hospital. METHODS: Immediately and six months after the event, the subjects underwent a study protocol aimed at the diagnostic assessment of PTSD, investigated via the Clinician-Administered PTSD Scale (CAPS) and the Impact of Event Scale-Revised (IES-R). RESULTS: Out of the 30 subjects examined (two were missing), six showed the diagnostic criteria for a current PTSD. Risk factors for PTSD onset were a prior psychiatric disorder, the level of involvement in the fire disaster and the presence of phobias in the days immediately after the event. Gender and level of education approached statistical significance. CONCLUSIONS: The high prevalence of PTSD found in this sample was due to the fact that the risk of death or serious injury involved infants.

Learning by observation in children with autism spectrum disorder.

BACKGROUND: Observing another person performing a complex action accelerates the observer's acquisition of the same action and limits the time-consuming process of learning by trial and error. Learning by observation requires specific skills such as attending, imitating and understanding contingencies. Individuals with autism spectrum disorder (ASD) exhibit deficits in these skills. METHOD: The performance of 20 ASD children was compared with that of a group of typically developing (TD) children matched for chronological age (CA), IQ and gender on tasks of learning of a visuomotor sequence by observation or by trial and error. Acquiring the correct sequence involved three phases: a detection phase (DP), in which participants discovered the correct sequence and learned how to perform the task; an exercise phase (EP), in which they reproduced the sequence until performance was error free; and an automatization phase (AP), in which by repeating the error-free sequence they became accurate and speedy. RESULTS: In the DP, ASD children were impaired in detecting a sequence by trial and error only when the task was proposed as first, whereas they were as efficient as TD children in detecting a sequence by observation. In the EP, ASD children were as efficient as TD children. In the AP, ASD children were impaired in automatizing the sequence. Although the positive effect of learning by observation was evident, ASD children made a high number of imitative errors, indicating marked tendencies to hyperimitate. CONCLUSIONS: These findings demonstrate the imitative abilities of ASD children although the presence of imitative errors indicates an impairment in the control of imitative behaviours.

Proactive and reactive control of movement are differently affected in Attention Deficit Hyperactivity Disorder children.

Attention-Deficit/Hyperactivity Disorder children are impaired in the ability to interrupt an ongoing action in relation to a sudden change in the environment (reactive control, measured by stop signal reaction time, SSRT). Less investigated is the ability to control the response when it is known in advance that it will be required to stop (proactive control, measured by change in Reaction time, RT). The study is aimed at exploring both the reactive and the proactive inhibitory control in a group of ADHD children compared to a group of age-matched controls. ADHD children (N=28) and Controls (N=28) performed 4 tasks: 2 tasks required to respond to the appearance of the go-signals (go task and nostop task) and 2 tasks to respond to the go signals in a context in which sometimes a restrain or suppression of the response was required (go-nogo task and stop task). ADHD children showed a longer SSRT compared to controls. Both groups showed an increment in RT by comparing the go-nogo to the go task and an increment in RT and SD by comparing the stop to the nostop task. ADHD children showed higher intra-individual variability (SD) compared to controls only in the stop and nostop task. ADHD children showed impaired reactive control but preserved proactive control, and the physical appearance of the go signal affected their reaction times intra-individual variability. A comparison between the reactive and proactive controls helps in defining neuropsychological profiles of ADHD children and can inspires therapeutic behavioral-cognitive strategies for response control.

Pancreatic large mucinous cystoadenoma with invasive ductal carcinoma in pregnancy. Case report.

BACKGROUND: Cystic tumour of the pancreas are infrequent and malignancy of the pancreas during pregnancy is extremely rare. Mucinous cystoadenomas is the most frequent cystic pancreatic neoplasm and it is seen mainly in women suggesting a sex hormone influence. Its presentation during pregnancy is extremely rare and entails difficulties in diagnosis and therapy. CASE REPORT: A 28 year old woman was referred to our service for abdominal mass. She had given birth to her second child two weeks previously. Ultrasound and CT scan showed a large cystic lesion, with sepitation and inner solid growth portions, involved mainly the left sovramesocolic space. An ultrasound-guided aspiration of the cystic fluid showed high level of CEA and CA. 19-9. The patient underwent laparotomic body-tail pancreatectomy and splenectomy. The histological examination showed mucinous cystoadenoma with associated invasive ductal carcinoma, with ovarian-like stroma and a well delimited fibrous capsule. Hystochemical study revealed a strong positivity for progesterone receptors. CONCLUSIONS: To our knowledge this is the eighth case of mucinous cystoadenoma reported in English literature and the forth with an invasive adenocarcinoma associated. This pathological entity should always be kept in mind in case of patient with an hepigastric mass during or soon after pregnancy. Aggressive approach is mandatory.

Laparoscopic splenectomy in patients under the age of eighteen. Experience in 18 cases.

BACKGROUND: Pediatric surgery is now in the forefront of minimal access procedures. Although pediatric surgeons have been skeptic about laparoscopic splenectomy, recently minimally invasive approach for spleen removal has been revaluated also in young patients. Purpose of this study was to report Authors' personal experience in patients under eighteen who underwent laparoscopic splenectomy. Results of the procedure were evaluated. PATIENTS AND METHODS: A retrospective review was undertaken in 18 splenectomised patients under the age of eighteen. Indications were hereditary spherocytosis in 10 patients, ß-thalassemia in 4, idiopathic thrombocytopenic purpura in 3 and a splenic cyst in 1 child. RESULTS: No intra-operative complications occurred. No conversion to open surgery was reported. During the follow-up one case of portal vein thrombosis, treated by medical therapy, was encountered and no other postoperative complications were observed. CONCLUSIONS: Laparoscopic approach has to be preferable for all those children undergoing spleen surgery. In experienced hands, it is of beneficial effects with a very reasonable rate of complications.

Explorative function in Williams syndrome analyzed through a large-scale task with multiple rewards.

This study aimed to evaluate spatial function in subjects with Williams syndrome (WS) by using a large-scale task with multiple rewards and comparing the spatial abilities of WS subjects with those of mental age-matched control children. In the present spatial task, WS participants had to explore an open space to search nine rewards placed in buckets arranged according to three spatial configurations: a cross, a 3 × 3 matrix and a cluster composed by three groups of three buckets each. The findings demonstrate that WS individuals were impaired in efficiently exploring the environment and in building cognitive spatial maps. In exploring the three spatial configurations, they performed worse than control subjects on all parameters analyzed. In fact, WS individuals took more time to complete the task, made more errors, performed a reduced number of error-free trials, displayed lower search efficiency, exhibited shorter spatial spans, showed a higher number of no-visits and displayed marked tendencies to perseverate and to neglect some buckets. Furthermore, WS individuals showed disorganized explorative patterns in comparison to control children. WS influenced performances differentially as a specific effect of the susceptibility of the configurations to being explored in a principled way. In the cross configuration that had strong spatial constraints, both groups exhibited their worst performances. In the matrix configuration, the altered explorative strategies of the WS subjects primarily affected their central exploration. The performances in the cluster configuration indicated that chunking was a strategy of strength in both TD and WS groups. In conclusion, WS individuals' deficits exhibited in the present explorative test may be considered an index of their difficulties in spatial orientation and motion perception displayed in the real world. The marked impairment in spatial information processing is discussed in neuro-anatomical alterations reported in WS.