Genetics of autistic disorders : review and clinical implications

Twin and family studies in autistic disorders (AD) have elucidated a high heritability of AD. In this literature review, we will present an overview on molecular genetic studies in AD and highlight the most recent findings of an increased rate of copy number variations in AD. An extensive literature search in the PubMed database was performed to obtain English published articles on genetic findings in autism. Results of linkage, (genome wide) association and cytogenetic studies are presented, and putative aetiopathological pathways are discussed. Implications of the different genetic findings for genetic counselling and genetic testing at present will be described. The article ends with a prospectus on future directions. Keywords: Autistic disorder , Linkage , Whole genome association , Copy number variation , Mutatio

Can Task-Switching Training Enhance Executive Control Functioning in Children with Attention Deficit/-Hyperactivity Disorder?

The key cognitive impairments of children with attention deficit/-hyperactivity disorder (ADHD) include executive control functions such as inhibitory control, task-switching, and working memory (WM). In this training study we examined whether task-switching training leads to improvements in these functions. Twenty children with combined type ADHD and stable methylphenidate medication performed a single-task and a task-switching training in a crossover training design. The children were randomly assigned to one of two groups. One group started with the single-task training and then performed the task-switching training and the other group vice versa. The effectiveness of the task-switching training was measured as performance improvements (relative to the single-task training) on a structurally similar but new switching task and on other executive control tasks measuring inhibitory control and verbal WM as well as on fluid intelligence (reasoning). The children in both groups showed improvements in task-switching, that is, a reduction of switching costs, but not in performing the single-tasks across four training sessions. Moreover, the task-switching training lead to selective enhancements in task-switching performance, that is, the reduction of task-switching costs was found to be larger after task-switching than after single-task training. Similar selective improvements were observed for inhibitory control and verbal WM, but not for reasoning. Results of this study suggest that task-switching training is an effective cognitive intervention that helps to enhance executive control functioning in children with ADHD

Phenotypic and measurement influences on heritability estimates in childhood ADHD

Twin studies described a strongly heritable component of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. However, findings varied considerably between studies. In addition, ADHD presents with a high rate of comorbid disorders and associated psychopathology. Therefore, this literature review reports findings from population-based twin studies regarding the influence of subtypes, assessment instruments, rater effects, sex differences, and comorbidity rates on ADHD heritability estimates. In addition, genetic effects on the persistence of ADHD are discussed. By reviewing relevant factors influencing heritability estimates more homogeneous subtypes relevant for molecular genetic studies can be elicited. A systematic search of population-based twin studies in ADHD was performed, using the databases PubMed and PsycInfo. Results of family studies were added in case insufficient or contradictory findings were obtained in twin studies. Heritability estimates were strongly influenced by rater effects and assessment instruments. Inattentive and hyperactive–impulsive symptoms were likely influenced by common as well as specific genetic risk factors. Besides persistent ADHD, ADHD accompanied by symptoms of conduct or antisocial personality disorder might be another strongly genetically determined subtype, however, family environmental risk factors have also been established for this pattern of comorbidity

Osteoporosis in Canadian adult cystic fibrosis patients: A descriptive study

BACKGROUND: Cystic fibrosis is the most common fatal autosomal recessive genetic disease in the Caucasian population. Osteoporosis is increasingly being recognised as an important complication in people with cystic fibrosis. METHODS: A descriptive study of adult cystic fibrosis patients receiving care at a Canadian tertiary care hospital was conducted to evaluate the prevalence of osteoporosis, the prevalence of non-vertebral fractures, and the change in bone mineral density during the course of a year. Data on bone mineral density were obtained for 40 adult cystic fibrosis patients by reviewing dual x-ray absorptiometry scans taken at baseline (when annual scans became standard clinical practice) and one year prior to baseline. Data on prevalent fractures were obtained by reviewing all available patient charts. Clinical and laboratory data were collected from an existing clinic database. RESULTS: Over half of the 40 patients had reduced T- and Z-scores at baseline. For the 27 patients who had data available one year prior to baseline, total hip and lumbar spine bone mineral density had decreased by 3.04% and 0.86% after one year while total body bone mineral density had not changed significantly. Four prior non-vertebral fractures were reported in three patients (1,146 patient-years). CONCLUSION: This study confirms that osteoporosis is a significant problem in adult cystic fibrosis patients, and constitutes the first published evidence of cystic fibrosis bone disease in Canadians

Validation of the network of relationship inventory in female and male adolescents

Friendships and their different qualities have been shown to be important for adolescents\u27 socio-emotional development and psychological adjustment. In empirical research on such friendship qualities, the Network of Relationship Inventory-Relationship Quality Version (NRI-RQV) is a widely used questionnaire. Here, we conduct an extensive validation of a German version of the NRI-RQV, investigating its factor structure, reliability, and concurrent validity, in a sample of N= 679 adolescents aged 13-18 years. Applying multigroup confirmatory factor analysis, we further test whether the factor structure of the friendship quality construct holds across groups of males and females. Results showed that a structure with nine correlated first-order factors fit the data well, indicating nine distinct friendship qualities in males and females. Measurement invariance testing suggested the same underlying friendship quality construct, albeit differences in mean scores per gender. As evidence for concurrent validity, closeness and discordant friendship qualities showed expected correlations with empathy and social problems, respectively, but not with aggressive behavior. Overall, results indicate good psychometric properties for the German version of the NRI-RQV as a measure of friendship qualities in both males and females. (DIPF/Orig.

Adenosine A2A receptor gene (ADORA2A) variants may increase autistic symptoms and anxiety in autism spectrum disorder

Autism spectrum disorders (ASDs) are heterogeneous disorders presenting with increased rates of anxiety. The adenosine A2A receptor gene (ADORA2A) is associated with panic disorder and is located on chromosome 22q11.23. Its gene product, the adenosine A2A receptor, is strongly expressed in the caudate nucleus, which also is involved in ASD. As autistic symptoms are increased in individuals with 22q11.2 deletion syndrome, and large 22q11.2 deletions and duplications have been observed in ASD individuals, in this study, 98 individuals with ASD and 234 control individuals were genotyped for eight single-nucleotide polymorphisms in ADORA2A. Nominal association with the disorder was observed for rs2236624-CC, and phenotypic variability in ASD symptoms was influenced by rs3761422, rs5751876 and rs35320474. In addition, association of ADORA2A variants with anxiety was replicated for individuals with ASD. Findings point toward a possible mediating role of ADORA2A variants on phenotypic expression in ASD that need to be replicated in a larger sample

Migration background and juvenile mental health: a descriptive retrospective analysis of diagnostic rates of psychiatric disorders in young people

Introduction: This article presents diagnostic rates for specific mental disorders in a German pediatric inpatient population over a period of 20 years with respect to migration background and socioeconomic status (SES).Methods: Diagnostic data were obtained over a period of 20 years from 8,904 patients who visited a child and adolescent psychiatry mental health service in Germany. Data from 5,985 diagnosed patients (ICD-9 and ICD-10 criteria) were included with respect to gender, migration background, and SES.Results: Migration- and gender-specific effects were found for both periods of assessment. The group of boys with a migration background showed significantly higher rates of reactions to severe stress, adjustment disorders, and posttraumatic stress disorder compared to their male, non-migrant counterparts. Conversely, boys without a migration background showed a significantly higher percentage rate of hyperkinetic disorders than male migrants. Similar results were found for female migrants in the latter assessment period (ICD-10). In addition, female migrants showed lower rates of emotional disorders whose onset occurs in childhood compared to their non-migrant counterparts.Conclusions: Data from this investigation provide preliminary evidence that the prevalence of various psychiatric disorders in children and adolescents is influenced by migration background and SES