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. Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While mutations in several genes have been identified in patients with ASD, little is known about their effects on neuronal function and their interaction with other genetic variations. Using a combination of genetic and functional approaches, we identified novel SHANK2 mutations including a de novo loss of one copy of the SHANK2 gene in a patient with autism and several mutations observed in patients that reduced neuronal cell contacts in vitro. Further genomic analysis of three patients carrying de novo SHANK2 deletions identified additional rare genomic imbalances previously associated with neuropsychiatric disorders. Taken together, 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.

Objective: To compare the long-term self-esteem and social function outcomes of individuals with untreated and treated ADHD across childhood, adolescence, and adulthood. Method: A systematic search of 12 databases was performed to identify peer-reviewed, primary research articles, published January 1980 to December 2011, reporting long-term self-esteem and/or social function outcomes (≥2 years; life consequences distinct from symptoms) of individuals with untreated or treated ADHD. Results: Overall, 127 studies reported 150 outcomes. Most outcomes were poorer in individuals with untreated ADHD versus non-ADHD controls (57% [13/23] for self-esteem; 73% [52/71] for social function). A beneficial response to treatment (pharmacological, nonpharmacological, and multimodal treatments) was reported for the majority of self-esteem (89% [8/9]) and social function (77% [17/22]) outcomes. Conclusion: Untreated ADHD was associated with poorer long-term self-esteem and social function outcomes compared with non-ADHD controls. Treatment for ADHD was associated with improvement in outcomes; however, further long-term outcome studies are needed.

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.

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.

Objectives: Attention deficit/hyperactivity disorder (ADHD) and anxiety disorders are among the most common psychiatric disorders with a 25% comorbidity rate with each other. In this study, we overview the comorbidity between ADHD and anxiety disorders in a longitudinal perspective across the lifespan and we discuss possible therapeutic strategies. Methods: A literature search was performed using PubMed to identify clinical studies assessing comorbidity between ADHD and anxiety disorders from childhood to adulthood. Results: Anxiety disorders may substantially change the presentation, the prognosis, and the treatment of ADHD itself. In childhood, the presence of generalised anxiety disorder, could prevent the typical inhibitory dysfunction present in ADHD, in adolescence may increase the deficit of working memory, and in adulthood may enhance the presence of sleep problems. Individuals with comorbid ADHD and anxiety disorders would benefit from adjunctive psychosocial or adjunctive pharmacotherapy interventions to cognitive behavioural treatment. Conclusions: The management of individuals with comorbid ADHD and anxiety disorders could be challenging for clinicians, and assessing the developmental course is crucial in order to shed light on individualised treatment.