Genetic analysis of reelin gene (RELN) SNPs: No association with autism spectrum disorder in the Indian population

Involvement of reelin with Autism spectrum disorder (ASD) has been implicated through several biochemical as well as genetic studies. Reelin is an extracellular signaling protein, which plays a significant role in cytoarchitectonic pattern formation of different brain areas during development. Reelin gene (RELN) is located on chromosome 7q22; an important autism critical region identified through several genome-wide scans. A number of genetic studies have been carried out to investigate the association of reelin with autism. Recently we reported possible paternal effect in the transmission of CGG repeat alleles of RELN in the susceptibility towards autism. Further analysis on other polymorphisms is warranted to validate the status of RELN as a candidate for autism. Therefore in the present study, we have investigated six more SNPs (rs727531, rs2072403, rs2072402, rs362691, rs362719, rs736707) in 102 patients, 182 parents and 101 healthy controls. We have followed DSM-IV criteria and the screening for autism was carried out using CARS. Genomic DNA isolated from blood was used for PCR and subsequent RFLP analysis. Finally, case-control and family-based association studies were carried out to examine the genetic association of these SNP markers with ASD in the Indian population. But, we failed to detect either preferential parental transmission of any alleles of the markers to affected offspring or any biased allelic or genotypic distribution between the cases and controls. Thus the present study suggests that these SNPs of RELN are unlikely to be associated with ASD in the Indian population.     

Stereotypies and repetitive/restrictive behaviours in infants with autism and pervasive developmental disorder

Purpose: Autism Spectrum Disorders (ASD) are characterized by severe and debilitating symptoms including stereotyped and repetitive behaviours. Stereotypies and repetitive behaviours constitute core features of ASD and markedly impede attempts to remediate the disorder. Little previous research has examined characteristics of the core features of ASD in infants.

Method: In the present study, 760 infants with autism, PDD-NOS or no diagnosis of ASD but at risk for other developmental delays or physical disabilities were evaluated with respect to the nature and extent of their stereotyped and ritualistic behaviour using the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT). A Kruskal-Wallis test with follow-up Mann-Whitney tests were employed to test for significant differences.

Results: Infants with autism evinced the highest amount of stereotypic behaviour, followed by those with PDD-NOS and atypical development. A sub-set of BISCUIT items could accurately predict diagnostic group membership.

Conclusions: These data suggest that many core features of ASD are distinct and can be reliably identified early in life. The potential early identification of these behavioural challenges could lead to earlier intervention practices and symptom alleviation for children in this population.     

Neonatal factors among subjects diagnosed with a pervasive developmental disorder in the US

Purpose: Contradictory studies suggest that some neonatal factors may be associated with a pervasive developmental disorder (PDD) diagnosis, but limited data is available from longitudinal, prospective medical record assessments.

Materials and methods: The present hypothesis-testing longitudinal, case-control study evaluated birth characteristics among cases diagnosed with a PDD in comparison to controls by examining prospectively collected automated medical records within the Vaccine Safety Datalink (VSD) database.

Results: Cases were Health Maintenance Organization (HMO)-enrolled from birth until diagnosed with International Classification of Disease, 9th revision (ICD-9) PDD (299.xx) and controls were HMO-enrolled from birth for at least 4.75?years without a PDD diagnosis. The birth characteristics examined included: gender, gestational age in weeks at birth, mean birth weight in grams, Appearance-Pulse-Grimace-Activity-Respiration (APGAR) scores at 1?minute and 5?minutes, and maternal age in years at birth. Cases had a significantly increased male/female ratio relative to controls. By contrast, mean gestational age at birth, mean birth weight, mean maternal age at birth, and mean APGAR scores at 1?minute and 5?minutes were not statistically different among cases compared to controls.

Conclusions: This study indicates that cases diagnosed with a PDD as compared to controls do not have significant differences in neonatal factors.     

The Interrelationships of Psychopathology Symptoms on Social Skills in Adults with Autism or PDD-NOS and Intellectual Disability

Autism Spectrum Disorders (ASD) are debilitating, life long conditions which are known to co-occur with intellectual disability (ID) and comorbid psychopathology. All of these are risk factors, yet little has been done to explore the degree that these variables alone and in combination impact the well being of such persons. Three-hundred and two adults with severe or profound ID were studied. From the total sample, 137 evinced ASD (either autism or PDD-NOS). The Diagnostic Assessment for the Severely Handicapped-II (DASH-II) was used to assess psychopathology symptoms. Social behaviors were assessed using the Matson Evaluation of Social Skills for Individuals with sEvere Retardation (MESSIER). For participants with ASD, psychopathology symptoms, particularly impulse and mania, were associated with negative social behaviors (i.e., nonverbal, verbal, and general) as well as positive verbal and nonverbal social skills. For participants with ID only, impulse symptoms, as well as symptoms of mania, PDD/autism, anxiety, organic, and stereotypy were associated with negative social behaviors, but not positive social skills as was found for participants with ASD.     

Brief Report: Autistic Traits in Twins Vs. Non-Twins—A Preliminary Study

Previous studies have suggested that among affected sib pairs with autism there is an increase in the frequency of twins over what would be expected in comparison to the prevalence of twins in the general population. In this study we sought to determine whether sub-threshold autistic traits were more pronounced in twins than in non-twins. The Social Responsiveness Scale (SRS) was administered in an epidemiologic twin sample (n=802) and in a separate population-based sample of non-twins ascertained from a local school district (n=255). For males (but not females), the mean SRS score was significantly higher among twins than among non-twins. As has been suggested for autism, twin status may incur increased liability to sub-threshold autistic symptomatology, particularly in males.     

Can a Diagnosis of Asperger Syndrome be Made in Very Young Children with Suspected Autism Spectrum Disorder?

Of a cohort of 104 children with Autism, PDD-NOS or specific language disorder, recruited at age 2–3 years of age, only three appeared to meet diagnostic assessment criteria for Asperger syndrome (AS). The children were followed up at 4–5 years, and assessments at both time points included the Autism Diagnostic Interview (ADI-R), the Autism Diagnostic Observation Schedule (ADOS) and the Mullen Scales of Early Learning. The paper explores the reasons why so few children with possible AS were identified early, including problems inherent in the assessment tools and the range of normal variation within characteristics required for a diagnosis. Only 10 children altogether had first words by 24 months, and abilities in the average range, and 9 were followed up. All of these able children had varied repetitive behaviours, and these increased in terms of ADI-R algorithm score over a 13 month interval. However, items concerning resistance to change and liking of routines tended to decrease in terms of reported impact on the child and family. Repetitive behaviours seem significant in the early referral of able children for a PDD diagnosis, but identification of children with AS is more likely to occur reliably once children are older and enter school.     

A systematic review of off-label uses of memantine for psychiatric disorders

Recent data points to glutamatergic dysfunction in mood disorders, anxiety disorders, obsessive-compulsive disorder, and schizophrenia. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease that acts at the N-methyl-d-aspartate receptor, has been used off-label for various psychiatric disorders. Although promising, the available data for the use of memantine in these disorders is limited. Given this data, the routine use of memantine for depression, schizophrenia, obsessive-compulsive disorder, substance abuse, pervasive developmental disorders, bipolar disorder, and binge eating disorder cannot be recommended at this time.