High-resolution chromosomal microarray analysis for copy-number variations in high-functioning autism reveals large aberration typical for intellectual disability.

Copy-number variants (CNVs), in particular rare, small and large ones (< 1% frequency) and those encompassing brain-related genes, have been shown to be associated with neurodevelopmental disorders like autism spectrum disorders (ASDs), attention deficit hyperactivity disorder (ADHD), and intellectual disability (ID). However, the vast majority of CNV findings lack specificity with respect to autistic or developmental-delay phenotypes. Therefore, the aim of the study was to investigate the size and frequency of CNVs in high-functioning ASD (HFA) without ID compared with a random population sample and with published findings in ASD and ID. To investigate the role of CNVs for the "core symptoms" of high-functioning autism, we included in the present exploratory study only patients with HFA without ID. The aim was to test whether HFA have similar large rare (> 1 Mb) CNVs as reported in ASD and ID. We performed high-resolution chromosomal microarray analysis in 108 children and adolescents with HFA without ID. There was no significant difference in the overall number of rare CNVs compared to 124 random population samples. However, patients with HFA carried significantly more frequently CNVs containing brain-related genes. Surprisingly, six HFA patients carried very large CNVs known to be typically present in ID. Our findings provide new evidence that not only small, but also large CNVs affecting several key genes contribute to the genetic etiology/risk of HFA without affecting their intellectual ability.

Implementation of early intensive behavioural intervention for children with autism in Switzerland.

BACKGROUND: There is a major gap between the US and most European countries regarding the implementation of early intensive behavioural intervention (EIBI) for children with autism. The present paper reports on the current status of EIBI in Switzerland and on the effectiveness of EIBI under clinical conditions in a Swiss pilot project. METHODS: The paper combines a narrative report of the care system for children with autism in Switzerland and an initial evaluation of EIBI as implemented in the Department of Child and Adolescent Psychiatry, University of Zurich. RESULTS: The current situation of the implementation of EIBI for children with autism in Switzerland is characterized by marked deficits in its acceptance. Major reasons include insufficient governmental approval and lacking legal and financial support. In addition, ignorance among health care providers and educational professionals has contributed to this situation precluding that children with autism receive the most beneficial assistance. The authors have initiated and been working in an intervention centre offering EIBI for a decade and report on their experience with the implementation of EIBI. Based on their clinical practice, they document that EIBI also works efficiently under ordinary mental health service conditions. CONCLUSIONS: EIBI needs to be implemented more intensively in Switzerland. Although the effects of EIBI as implemented in Zurich are promising, the results are not as pronounced as under controlled research conditions.

CNTNAP2 gene in high functioning autism: no association according to family and meta-analysis approaches.

The Contactin Associated Protein-like 2 (CNTNAP2) gene has been discussed to be associated with different symptoms of autism spectrum disorders (ASDs) and other neurodevelopmental disorders. We aimed to elucidate the genetic association of CNTNAP2 within high functioning ASD (HFA), focusing on autism specific symptoms and reducing intelligence related factors. Furthermore, we compared our findings conducting a meta-analysis in patients with ASD and HFA only. A case-control association study was performed for HFA (HFA, n = 105; controls, n = 133). Moreover, we performed a family-based association study (DFAM) analysis (HFA, n = 44; siblings, n = 57). Individuals were genotyped for the two most frequently reported single nucleotide polymorphisms (SNPs) in the CNTNAP2 gene (rs2710102, rs7794745). Furthermore, a meta-analysis using the MIX2 software integrated our results with previously published data. A significant association for the carriers of the T-allele of the rs7794745 with HFA was found in the case-control sample [OR = 1.547; (95 % CI 1.056-2.266); p = 0.025]. No association could be found by DFAM with any of the CNTNAP2 SNPs with HFA. The meta-analysis of both SNPs did not show a significant association with either ASD or with HFA. Overall, including case-control, sibs, and meta-analysis, we could not detect any significant association with the CNTNAP2 gene and HFA. Our results point in the direction that CNTNAP2 may not play a major role in HFA, but rather seems to have a significance in neurodevelopmental disorders or in individuals displaying intellectual delays.

[Outpatient treatment of selective mutism: long-standing selective mutism in a 17-year-old male]. / Die ambulante Behandlung des elektiven Mutismus am Beispiel eines langjährig bestehenden elektiven Mutismus bei einem 17-Jährigen.

The present case report describes the successful treatment of a 17 year old male adolescent suffering for 10 years from selective mutism. Following a summary review of recent publications on therapy approaches, the report describes the treatment concept in the present case, including detailed assessment of co-morbid disorders, motivation for change, behaviour therapy with supporting drug intervention, and intensive co-operation with parents and other caretakers.

First Alarm and Time of Diagnosis in Autism Spectrum Disorders.

Early diagnosis of autism spectrum disorder (ASD) is of paramount importance as it opens the road to early intervention, which is associated with better prognosis. However, early diagnosis is often delayed until preschool or school age. The purpose of the current retrospective study was to explore the age of recognition of first alarming symptoms in boys and girls as well as the age at diagnosis of different subtypes of ASD in a small sample. A total of 128 parents' of children with ASDs were participated in the survey by completing a self-report questionnaire about early signs and symptoms that raised their concern. Parents of children with autism voiced concerns earlier and obtained diagnosis significantly earlier compared to parents of children with Asperger syndrome (p value <0.000). No significant difference (p value<0.05) has been detected between males and females in early manifestation of first signs and symptoms of ASD. The mean age at diagnosis was 3.8 years for autistic disorder, 6.2 years for children with Asperger syndrome and 6.4 years for other, e.g., PDD-NOS. The most commonly reported symptoms were speech and language problems (p value = 0.001) for children who were later diagnosed with autism, while behavior problems (p value = 0.046) as well as difficulties in education at school (p value = 0.013) for children with Asperger syndrome. The gap between early identification and diagnosis pinpoints the urgent need for national systematic early screening, the development of reliable and sensitive diagnostic instruments for infants and toddlers and heightened awareness of early signs of ASD among parents, teachers, and healthcare professionals and providers as well.

Association study in siblings and case-controls of serotonin- and oxytocin-related genes with high functioning autism.

BACKGROUND: Autism spectrum disorder (ASD) is heritable and neurodevelopmental with unknown causes. The serotonergic and oxytocinergic systems are of interest in autism for several reasons: (i) Both systems are implicated in social behavior, and abnormal levels of serotonin and oxytocin have been found in people with ASD; (ii) treatment with selective serotonin reuptake inhibitors and oxytocin can yield improvements; and (iii) previous association studies have linked the serotonin transporter (SERT; SLC6A4), serotonin receptor 2A (HTR2A), and oxytocin receptor (OXTR) genes with ASD. We examined their association with high functioning autism (HFA) including siblings and their interaction. METHODS: In this association study with HFA children (IQ > 80), siblings, and controls, participants were genotyped for four single nucleotide polymorphisms (SNPs) in OXTR (rs2301261, rs53576, rs2254298, rs2268494) and one in HTR2A (rs6311) as well as the triallelic HTTLPR (SERT polymorphism). RESULTS: We identified a nominal significant association with HFA for the HTTLPR s allele (consisting of S and LG alleles) (p = .040; odds ratio (OR) = 1.697, 95% CI 1.191-2.204)). Four polymorphisms (HTTLPR, HTR2A rs6311, OXTR rs2254298 and rs53576) in combination conferred nominal significant risk for HFA with a genetic score of ≥4 (OR = 2.09, 95% CI 1.05-4.18, p = .037). The resulting area under the receiver operating characteristic curve was 0.595 (p = .033). CONCLUSIONS: Our findings, combined with those of previous reports, indicate that ASD, in particular HFA, is polygenetic rather than monogenetic and involves the serotonergic and oxytocin pathways, probably in combination with other factors.

Prevalence of self-reported seasonal affective disorders and the validity of the seasonal pattern assessment questionnaire in young adults Findings from a Swiss community study.

BACKGROUND: The objective of this study was to expand the knowledge on the prevalence of self-reported Seasonal Affective Disorder (SAD) and to further study the validity of the Seasonal Pattern Assessment Questionnaire (SPAQ). METHODS: A total of N=844 young adults were assessed in a Swiss community study by use of the SPAQ, a Seasonal Affective Disorders Questionnaire (SADQ), the Young Adult Self Report (YASR), the Centre for Epidemiologic Depression Scale (CES-D), and scales for measuring self-esteem, self-awareness and life events. At a second stage, a total of N=534 screen positives and controls were subjected to the Composite International Diagnostic Interview (M-CIDI) for the assessment of mental disorders. According to the SPAQ classification a group of SAD subjects and a group of subsyndromal SAD subjects (S-SAD) were defined. In addition, a third group of high-scoring depressives (HSD) subjects scoring above the 75th percentile of the CES-D was defined. Comparisons included these three groups and the rest of the sample serving as controls. RESULTS: The weighted prevalence for SAD in this sample was 7.84% based on the SPAQ alone. With the addition of the SADQ, weighted prevalence rates dropped to 2.22%. Weighted subsyndromal SAD was 33.04%. Across the vast majority of scales, the SAD group was indistinguishable from the HSD group. These two groups scored highest, whereas the S-SAD group had an intermediate position and the controls had the lowest scores. SAD was best predicted by the CES-D total score. CONCLUSIONS: The SPAQ as a single measure leads to an overestimation of SAD which, nevertheless, is a rather common phenomenon also in this central European population. The findings on the validity of the SPAQ are extended by showing that predominantly general aspects of depression are measured.

Comorbidity of Asperger syndrome and gender identity disorder.

The case of a 35-year-old biological woman with Asperger syndrome (AS) and gender identity disorder (GID) fulfilling DSM-IV criteria is reported. Against the background of recently emerging theories of cognitive male pattern underlying autism we present additional psychological assessments in order to discuss any possible interaction or discrimination between AS and GID. Whilst we explain GID as a secondary feature of AS, we examine the assumption of the necessity of treating GID in AS as a primary GID in accordance with international standards. We consider the treatment of GID as compelling, particularly because curative therapy for AS is lacking and with GID treatment in this vein, the patient gains psychosocial improvement.