Anna M. Abbacchi

Sibling Recurrence and the Genetic Epidemiology of Autism

OBJECTIVE Although the symptoms of autism exhibit quantitative distributions in nature, estimates of recurrence risk in families have never previously considered or incorporated quantitative characterization of the autistic phenotype among siblings. METHOD The authors report the results of quantitative characterization of 2,920 children from 1,235 families participating in a national volunteer register, with at least one child clinically affected by an autism spectrum disorder and at least one full biological sibling. RESULTS A traditionally defined autism spectrum disorder in an additional child occurred in 10.9% of the families. An additional 20% of nonautism-affected siblings had a history of language delay, one-half of whom exhibited autistic qualities of speech. Quantitative characterization using the Social Responsiveness Scale supported previously reported aggregation of a wide range of subclinical (quantitative) autistic traits among otherwise unaffected children in multiple-incidence families and a relative absence of quantitative autistic traits among siblings in single-incidence families. Girls whose standardized severity ratings fell above a first percentile severity threshold (relative to the general population distribution) were significantly less likely to have elicited community diagnoses than their male counterparts. CONCLUSIONS These data suggest that, depending on how it is defined, sibling recurrence in autism spectrum disorder may exceed previously published estimates and varies as a function of family type. The results support differences in mechanisms of genetic transmission between simplex and multiplex autism and advance current understanding of the genetic epidemiology of autism spectrum conditions.

Familial Aggregation of Quantitative Autistic Traits in Multiplex versus Simplex Autism

Recent research has suggested that the mode of inheritance for simplex autism (SA, one individual in the family affected) may be distinct from that for multiplex autism (MA, two or more individuals affected). Since sub clinical autistic traits have been observed in “unaffected” relatives of children with autism, we explored whether the distributions of such traits in families supported differential modes of genetic transmission for SA and MA autism. We measured patterns of familial aggregation of quantitative autistic traits (QAT) in children and parents in 80 SA families and 210 MA families, using the Social Responsiveness Scale. When considering all SA and MA siblings who scored below a uniform quantitative (clinical‐level) severity threshold, MA brothers exhibited a distinct pathological shift in the distribution, compared to SA brothers (P < 0.0001). Such aggregation of QAT was also observed in fathers but not among females in MA families. Significant spousal correlations for QAT—suggestive of assortative mating—were observed in both SA and MA families, but neither group was characterized by a greater‐than‐chance level of concordant elevation among spousal pairs in this volunteer sample. Among male first degree relatives, there exist distinct patterns of QAT manifestation for simplex versus multiplex autism. These findings are consistent with the results of molecular genetic studies that have suggested differential modes of intergenerational transmission for SA and MA. Characterization of QAT and other endophenotypes among close relatives may be useful for reducing sample heterogeneity in future genetic and neurobiologic studies of autism.

Developmental course of autistic social impairment in males

Recent research has suggested that autistic social impairment (ASI) is continuously distributed in nature and that subtle autistic-like social impairments aggregate in the family members of children with pervasive developmental disorders (PDDs). This study examined the longitudinal course of quantitatively characterized ASI in 3- to 18-year-old boys with and without PDD. We obtained assessments of 95 epidemiologically ascertained male-male twin pairs and a clinical sample of 95 affected children using the Social Responsiveness Scale (SRS), at two time points, spaced 1-5 years apart. Longitudinal course was examined as a function of age, familial loading for PDD, and autistic severity at baseline. Interindividual variation in SRS scores was highly preserved over time, with test-retest correlation of 0.90 for the entire sample. SRS scores exhibited modest general improvement over the study period; individual trajectories varied as a function of severity at baseline and were highly familial. Quantitative measurements of ASI reflect heritable traitlike characteristics. Such measurements can serve as reliable indices of phenotypic severity for genetic and neurobiologic studies, and have potential utility for ascertaining incremental response to intervention.

Quantitative assessment of autistic symptomatology in preschoolers

Given a growing emphasis on early intervention for children with autism, valid quantitative tools for measuring treatment response are needed. The Social Responsiveness Scale (SRS) is a brief (15–20 minute) quantitative measure of autistic traits in 4-to 18-year-olds, for which a version for 3-year-olds was recently developed. We obtained serial SRS measurements on 73 preschool children with (n = 51) and without (n = 22) autism spectrum conditions. Inter-rater reliability (mothers and teachers) and test–retest reliability were of the order of 0.75 (Pearsons r). There was substantial agreement between SRS scores and (1) the Vineland Adaptive Behavior Composite (Pearsons r = –0.86) and (2) scores for social impairment on the Autism Diagnostic Interview–Revised (r = 0.63). Overall, quantitative autistic trait scores tended to improve over time in preschoolers, irrespective of treatment conditions. We conclude that it is possible to obtain reliable quantitative measurements of autistic social impairment in preschoolers, suitable for assessing treatment response.

Lack of evidence for increased genetic loading for autism among families of affected females: A replication from family history data in two large samples

Both the broad and narrow phenotypes of autism have been consistently observed in family members of affected individuals. Additionally, autism spectrum disorders (ASDs) present four times more often in males than in females, for reasons that are currently unknown. In this study, we examined whether there were differences in familial loading of ASD among families of male versus female probands. Analyses were conducted with existing data from two distinct samples. The first sample contained 417 individuals with autism and Aspergers disorder and included information on the ASD diagnoses of their first- and second-degree relatives. The second sample consisted of 405 sibships participating in the Autism Genetic Resource Exchange, of which one or more siblings had an ASD diagnosis. Results from both samples did not suggest significant differences in the prevalence of ASD among relatives of affected males versus females.

Personality and posttraumatic stress disorder among directly exposed survivors of the Oklahoma City bombing

BACKGROUND Few disaster studies have specifically examined personality in association with exposure to disaster and development of posttraumatic stress disorder (PTSD). A study of survivors of the Oklahoma City bombing examined PTSD and personality measured after the disaster. METHODS In a random sample of 255 survivors from a bombing survivor registry, 151 (59%) completed both full PTSD and personality assessments using the Diagnostic Interview Schedule and the Temperament and Character Inventory, respectively. RESULTS Postbombing PTSD was associated with low self-directedness and low cooperativeness, and also with high self-transcendence and harm avoidance in most configurations. Disorganized (schizotypal) character and explosive (borderline) temperament configurations were associated with PTSD; creative and autocratic character configurations were negatively associated with PTSD. CONCLUSIONS Clinicians should be vigilant for PTSD among individuals with personality disorders and also be aware that personality disorders are likely to be overrepresented among people with PTSD. Treatment of PTSD may need to take into account comorbid personality disorders and personality features.

Quantitative autistic trait measurements index background genetic risk for ASD in Hispanic families

BackgroundRecent studies have indicated that quantitative autistic traits (QATs) of parents reflect inherited liabilities that may index background genetic risk for clinical autism spectrum disorder (ASD) in their offspring. Moreover, preferential mating for QATs has been observed as a potential factor in concentrating autistic liabilities in some families across generations. Heretofore, intergenerational studies of QATs have focused almost exclusively on Caucasian populations—the present study explored these phenomena in a well-characterized Hispanic population.MethodsThe present study examined QAT scores in siblings and parents of 83 Hispanic probands meeting research diagnostic criteria for ASD, and 64 non-ASD controls, using the Social Responsiveness Scale-2 (SRS-2). Ancestry of the probands was characterized by genotype, using information from 541,929 single nucleotide polymorphic markers.ResultsIn families of Hispanic children with an ASD diagnosis, the pattern of quantitative trait correlations observed between ASD-affected children and their first-degree relatives (ICCs on the order of 0.20), between unaffected first-degree relatives in ASD-affected families (sibling/mother ICC = 0.36; sibling/father ICC = 0.53), and between spouses (mother/father ICC = 0.48) were in keeping with the influence of transmitted background genetic risk and strong preferential mating for variation in quantitative autistic trait burden. Results from analysis of ancestry-informative genetic markers among probands in this sample were consistent with that from other Hispanic populations.ConclusionsQuantitative autistic traits represent measurable indices of inherited liability to ASD in Hispanic families. The accumulation of autistic traits occurs within generations, between spouses, and across generations, among Hispanic families affected by ASD. The occurrence of preferential mating for QATs—the magnitude of which may vary across cultures—constitutes a mechanism by which background genetic liability for ASD can accumulate in a given family in successive generations.

Autism-Related Variation in Reciprocal Social Behavior: A Longitudinal Study

Deficits in reciprocal social behavior are a characterizing feature of autism spectrum disorder (ASD). Autism‐related variation in reciprocal social behavior (AVR) in the general population is continuously distributed and highly heritable—a function of additive genetic influences that overlap substantially with those which engender clinical autistic syndromes. This is the first long‐term prospective study of the stability of AVR from childhood through early adulthood, conducted via serial ratings using the Social Responsiveness Scale, in a cohort‐sequential study involving children with ASD, other psychiatric conditions, and their siblings (N = 602, ages = 2.5–29). AVR exhibits marked stability throughout childhood in individuals with and without ASD.