Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.

Abstract

Background

Little is known about the Quality of Life (QOL) in parents of children with developmental diseases as compared to other severe neurological or psychiatric disorders. Aims of the present study were: to evaluate QOL in parents of children affected by Pervasive Development Disorder (PDDs), Cerebral Palsy (CP) or Mental Retardation (MR) as compared to a control group (CG); to evaluate QOL of parents of patients with different types of PDDs, namely Autistic Disorder (AD), High Function Autism/Asperger Syndromes (HFA/AS) and Pervasive Developmental Disorder Not Otherwise Specified (PPD-NOS); and to compare the level of impairment in QOL of mothers and fathers within PDDs, CP, MR groups and between AD, HFA/AS, PDD-NOS sub-groups.

Methods

The sample consisted of 212 parents (115 mothers and 97 fathers) of 135 children or adolescents affected by PDDs, MR or CP. An additional sample of 77 parents (42 mothers and 35 fathers) of 48 healthy children was also included and used as a control group. QOL was assessed by the WHOQOL-BREF questionnaire.

Results

Compared with parents of healthy children, parents in the PDDs group reported impairment in physical activity (p = 0.0001) and social relationships (p = 0.0001) and worse overall perception of their QOL (p = 0.0001) and health (p = 0.005). Scores in the physical (p = 0.0001), psychological (p = 0.0001) and social relationships domains (p = 0.0001) and in the physical (p = 0.0001) and social relationships (p = 0.0001) domains were lower compared to the MR group CP group respectively. Little differences were observed between MR, CP and control groups. The level of impairment of physical (p = 0.001) and psychological (p = 0.03) well-being were higher in mothers than in fathers in the PDDs and CP groups respectively; in the other groups, and across all the other domains of QQL impairment was similar. There were no statistically significant differences in the scores between the AD, HFA/AS and PDD-NOS sub-groups, but parents in the HFA/AS sub-group seemed to display a lower QOL compared to the AD sub-group.

Conclusion

Parents of children with PDDs seem to display a higher burden, probably for a combination of environmental and genetic factors. Within this group of parents also those of HFA or AS people have higher stress. These finding must be taken into account in policy making to provide better and more specific supports and interventions for this group of diseases.

Several psychiatric conditions, both internalizing and externalizing, have been documented in comorbidity with Asperger Syndrome (AS) and High Functioning Autism (HFA). In this review we examine the interplay between psychiatric comorbidities and AS/HFA. In particular, we will focus our attention on three main issues. First, we examine which psychiatric disorders are more frequently associated with AS/HFA. Second, we review which diagnostic tools are currently available for clinicians to investigate and diagnose the associated psychiatric disorders in individuals with AS/HFA. Third, we discuss the challenges that clinicians and researchers face in trying to determine whether the psychiatric symptoms are phenotypic manifestations of AS/HFA or rather they are the expression of a distinct, though comorbid, disorder. We will also consider the role played by the environment in the manifestation and interpretation of these symptoms. Finally, we will propose some strategies to try to address these issues, and we will discuss therapeutic implications.

The Autism Spectrum Quotient (AQ) has been used to define the 'broader' (BAP), 'medium' (MAP) and 'narrow' autism phenotypes (NAP). We used a new Italian version of the AQ to test if difference on AQ scores and the distribution of BAP, MAP and NAP in autism parents (n = 245) versus control parents (n = 300) were replicated in a Sicilian sample. Parents of children with autism spectrum conditions scored higher than the control parents on total AQ, social skills and communication subscales, and exhibited higher rates of BAP, MAP and NAP. We conclude that the Italian AQ is a cross-culturally reliable measure of these different phenotypes, and can be used to identify a phenotypic gradient of severity of autistic traits in families. To understand the molecular basis of these phenotypes will require its use in genetic association studies.

To examine indices of behavioural and emotional problems and temperamental traits in clinically referred children and adolescents suffering from tension headache or migraine. Headache in childhood and adolescence (<18 years) has been associated with the presence of behavioural and emotional difficulties, but limited data are available on the relationship between these problems and different types of headache. Clinically referred children and adolescents (N=114), 6-16 years of age, suffering from primary headache according to the diagnostic criteria of the International Headache Society, 47 with tension-type headache (TH) and 67 with migraine (M), and 36 normal controls without headache (NC) were assessed using the Parent Child Behaviour Checklist (CBCL), Children's Depression Inventory (CDI), Multidimensional Anxiety Scale for Children (MASC), Conner's Parent Rating Scale (CPRS), and Emotionality-Activity-Sociability-Shyness Scale (EAS). Psychological and personality self-rating assessments were obtained also on the children's parents and siblings. Although most headache patients had scores within the normative non-pathological range, both TH and M patients had higher CBCL total, internalizing, and externalizing scores than NC (P<0.001), and TH patients had higher scores than M patients. TH and M had higher CDI and MASC scores than NC (P<0.05), with no difference between the headache groups. TH patients had higher Emotionality and Shyness scores, and lower Sociability scores than M patients. Clinically referred children and adolescents with TH and M had higher scores of behavioural and emotional symptoms, both of internalizing and externalizing type, than normal peers. The TH group had greater psychological and temperamental difficulties than the M group.

Background: Anxiety symptoms are relatively common among children and adolescents and can interfere with functioning. The prevalence of anxiety and the relationship between anxiety and school performance were examined among elementary, middle, and high school students.

Children with Autism Spectrum Disorder (ASD) are at an increased risk for sleep disturbances, and studies indicate that between 50 and 80% of children with ASD experience sleep problems. These problems increase parental stress and adversely affect family quality of life. Studies have also suggested that sleep disturbances may increase behavioral problems in this clinical population. Although understanding the causes of sleep disorders in ASD is a clinical priority, the causal relationship between these two conditions remains unclear. Given the complex nature of ASD, the etiology of sleep problems in this clinical population is probably multi-factorial. In this overview, we discuss in detail three possible etiological explanations of sleep problems in ASD that can all contribute to the high rate of these symptoms in ASD. Specifically, we examine how neurobiological alterations, genetic mutations, and disrupted sleep architecture can cause sleep problems in individuals with ASD. We also discuss how sleep problems may be a direct result of core symptoms of ASD. Finally, a detailed examination of the relationship between sleep problems and associated clinical features and psychiatric comorbidities in individuals with ASD is described.

Parents of children with autism spectrum disorder (ASD) were shown to experience more stress than parents of typically developing peers, although little is known about risk factors predicting stress in this population. The aim of this study was to evaluate parental stress levels and behavioral and emotional problems in a sample of preschool children with ASD as compared to typically developing (TD) peers and to investigate the role of several factors, including the severity of autistic symptoms, adaptive skills, cognitive abilities and behavioral and emotional problems, on parental stress. Results confirmed that parents of children with ASD experience higher stress levels than parents of TD and that children with ASD show more behavioral and emotional problems than controls. Moreover, our results showed that behavioral and emotional problems are strong predictors of parental stress, while stress related to a parent-child dysfunctional relationship was associated with daily living and communication skills as well as cognitive abilities. Findings revealed different behavioral and emotional problems affecting parental stress in ASD and TD samples. No association between the severity of autism symptoms and parental stress was detected. These results suggest that dysfunctional behaviors in preschool children with ASD have a strong impact on parental stress, profoundly affecting the well-being of the entire family. Therefore, strategies aimed at the early detection and management of these behavioral and emotional problems are crucial in order to prevent parental stress and to develop the most appropriate treatment interventions.