Siblings are a critical part of lifelong support for individuals with autism spectrum disorder (ASD). But siblings face their own social-emotional adjustment needs. These needs may be addressed through programs that include support groups specifically for the siblings. This study examined the effects of a community program on typical siblings' depression, anxiety, ASD knowledge, and peer network as well as reciprocal interactions between the typical sibling and sibling with ASD. The program provided a sibling support group, a skills intervention for children with ASD, and an inclusive recreation time. Siblings reported significant decreases in depression and physiological anxiety and improvements in their peer network. Autism knowledge increased but only approached significance. Direct observations revealed improvement in reciprocal interactions by most children that did not reach statistical significance. Parents, typical siblings, and interventionists indicated positive reactions to the program and its goals and outcomes. Findings are discussed in terms of the need to continue to explore interventions for siblings of children with ASD.

The results support previous evidence for the IS factor, its familiality, and the identification of IP as an additional strong candidate trait for genetic studies of autism.

The present study taught typically developing (TD) siblings of children with autism spectrum disorders (ASD) social-communicative and self-management skills. The authors' hypothesized that the acquisition of self-management skills would support generalization of targeted social-communicative responses. A multiple baseline probe design across sibling dyads was used to decrease exposure to unnecessary sessions in the absence of intervention. Four TD siblings were taught self-management of a social skills curriculum using behavioral skills training, which consisted of instructions, modeling, practice, and subsequent feedback. Results indicated that TD siblings learned to self-manage the social skills curriculum with some generalization across novel settings and over time. Comparisons of social-communicative responses to their typical peers provided some support for the social validity of the intervention outcomes. These results support the use of self-management, when explicitly programming for generalization, which continues to be a key consideration when including TD siblings in interventions with their siblings with ASD.

Evidence for a genetic association between autism and two single nucleotide polymorphisms (SNPs), rs2056202 and rs2292813, in the mitochondrial aspartate/glutamate carrier (SLC25A12) gene led us to ask whether any of the four previously identified familial traits in autism spectrum disorders (ASD) varied by these SNPs. In 355 ASD cases from 170 sibships we examined levels of the four traits in these SNPs using ANCOVA models. The primary models selected unrelated affected cases and used age and sex as covariates. An ancillary set of models used all affected siblings and included "sibship" as a random effects independent variable. We found significantly lower levels of routines and rituals associated with the presence of the less frequent A allele in rs2056206. No other significant differences were observed. The rs2056202 polymorphism may be associated with levels of routines and rituals in autism and related disorders.

Overtransmission of particular haplotypes of NrCAM, that may relate to the expression level of NrCAM in the brain, appeared to be associated with autism in the severe obsessive-compulsive behavior subset.

brium (LD) and located in the 3 0 region of the second LD block within the ACE gene, identified as described in Baghai and co-workers, which spans the promoter region as well as all coding regions for ACE isoforms 1 and 2. 2,7 Only for rs4311, the P-value was still significant after Bonferroni correction for multiple testing (Table 1). All five SNPs entered the replication and significant P-values after Bonferroni correction were found for rs4311 and rs4333 (Table 1); rs4329 (P = 0.04), rs4344 (P = 0.01), rs4353 (P = 0.04) were nominally associated in sample 2.Although the association replicated in both samples, the direction of this association was different. The T allele of rs4311 and 4333 was the risk allele in sample 1, while we observed a heterozygous disadvantage for both SNPs in sample 2. The reason for true but diverse, in extreme reversed associations, known as the flip-flop phenomenon, are discussed in a recent publication by Lin et al. 8 Flip-flop associations may indicate heterogeneous effects of the same true variant due to differences in the LD structure between the genotyped SNPs and the disease susceptibility locus in two investigated samples. 8 Following this idea, the reported SNPs could be non-causal but in LD with a genuine causal variant and/or multilocus effects that we are not able to account for, and this may lead to different associations. Interestingly, these SNPs are located in the same LD block as the promoter variant associated with unipolar depression, but are clustered at the 3 0 end of this block. While the variant rs4291 associated with unipolar depression was not significantly associated with panic disorders, all of the five SNPs associated with panic disorder were also nominally associated with unipolar depression. 2 The ACE gene may thus be an example for a genetic or locus overlap between anxiety and depression.Taken together, we have identified an association of two SNPs (rs4311 and rs4333) in the ACE gene with syndromal panic attacks, which could be replicated in an independent case/control sample, although in a different direction. Further studies have to be performed to elucidate the functional correlates of this association, especially regarding ACE activity in vivo in patients with panic attacks.

This study was conducted to examine the relationship between whole blood serotonin level and behavioral symptoms in 78 subjects with autism. No significant associations were found between serotonin level and the primary behavioral outcome measures. However, a significant inverse relationship between serotonin level and self-injury was demonstrated. Keywordsautism; serotonin; repetitive behavior; self-injury; aggression INTRODUCTIONAutism is a severe neurodevelopmental disorder. Its etiology most probably resides primarily in complex genetics and genetic heterogeneity likely accounts for the historic difficulty in reliably identifying susceptibility genes. Autistic symptoms are also well recognized in many other genetic disorders with disparate etiologies, and it is possible that these symptoms represent a phenotype with a common neurochemical substrate (Chugani, 2002). Genetic analysis would greatly benefit from the identification of specific quantitative characteristics, such as biochemical measures. Quantitative measures such as whole blood serotonin may help identify a subgroup of patients with a homogeneous phenotype and provide a complementary strategy for genetic studies beyond relying on qualitative criteria such as those elicited from the widely used Autism Diagnostic Interview-Revised (ADI-R). Biochemical investigation in autism may also potentially identify subgroups that are pathophysiologically related and the Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Kuperman et al., 1985) and sibling recurrence (Piven et al., 1991). NIH Public AccessBeginning with a study by Schain and Freedman in 1961, most investigators have found that serotonin levels measured in whole blood are significantly higher in autistic subjects as compared to normal controls, and approximately one-third of autistic individuals are considered to have hyperserotonemia. There is also a significant body of evidence to support the notion that serotonin plays an important role in brain development and affects a range of social behavior, affect regulation, aggression, and anxiety. Recent neuroimaging studies are noteworthy in their ability to demonstrate developmental changes in brain serotonin synthesis capacity and using positron emission tomography (PET), Chugani et al. (1999) found significant differences between autistic and nonautistic children in serotonin synthesis capacity. These results must be interpreted with caution because of the methodology employed, but may suggest that there is a disruption in the mechanisms that regulate serotonin synthesis during development in autism....

The male-to-female (M:F) ratio for autism spectrum disorders (ASD), typically about 4:1, appears to decrease with increasing paternal age, but this relationship has not been systematically tested. With 393 ASD cases from families with two or more ASD cases, we categorized paternal age into five age groups (<30, 30–34, 35–39, 40–44, 45+) and found that the M:F ratio was significantly decreased with increasing paternal age groups and remained so after also adjusting for maternal age. No significant relationship between maternal age group and the M:F ratio was observed. This study suggests that the M:F ratio is reduced with increasing paternal age consistent with de novo genetic or genomic anomalies arising more frequently as men age and then conceive children.