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Younger siblings of children with autism spectrum disorder (ASD; high-risk siblings) are at elevated risk for developing the broader autism phenotype (BAP), which consists of subclinical features of ASD. We examined conversational skills in a naturalistic context and standardized assessments of pragmatic language and communication skills in high-risk and low-risk school-age children with BAP (n = 22) and ASD (n = 18) outcomes, as well as comparison children without ASD or BAP (n = 135). Children with BAP characteristics exhibited lower conversational skills than comparison children, but did not differ on any of three standardized measures. Only the conversational ratings significantly predicted membership in the BAP versus Comparison group. This suggests that naturalistic tasks are crucial when assessing social-communication difficulties in children with a family history of ASD. LAY SUMMARY: The broader autism phenotype (BAP) consists of subclinical features of autism spectrum disorder (ASD) and is more common among family members of those with ASD. School-age children with BAP characteristics exhibited lower conversational skills than comparison children, but did not differ on standardized language measures tapping similar abilities. This suggests that naturalistic tasks may be more sensitive to the social-communication difficulties seen in some children with a family history of ASD than the standardized language tests used in most evaluations.

OBJECTIVE: We evaluated trajectories of attention-deficit/hyperactivity (ADHD)-relevant behaviors in a sample of infants at high and low familial risk for ADHD who were prospectively evaluated at 12, 18, and 24 months of age. METHOD: Participants included 43 infants at risk for ADHD based on family history (i.e., diagnosed first-degree relative) and 40 low-risk infants (i.e., no family history of ADHD). Instances of inattention, out-of-seat, and grabbing behavior were coded from video; analogous constructs were rated by examiners unaware of familial risk status after completing structured standardized assessments with the infants/toddlers. At the end of each study visit, examiners solicited parents’ concerns about their child’s behavior. Differences in ADHD-related behaviors and parent concerns were examined between 12 to 24 months of age. RESULTS: Infants with an older sibling or parent diagnosed with ADHD were distinguishable from infants with no family history of ADHD as early as 12 months of age based on directly-observed and examiner reports of behavior, particularly with respect to hyperactive-impulsive behavior. Parents of infants at familial risk for ADHD also reported significantly more behavior/temperament concerns as early as 12 months of age compared to parents of infants at low risk for ADHD. CONCLUSIONS: These findings highlight the ability to detect genetic liability for ADHD by the end of the first year of life, suggesting that well-designed family risk studies of ADHD are feasible and may be clinically valuable. They also suggest the potential for earlier detection of risk for ADHD than has previously been possible.

Author(s): Young, Gregory S; Constantino, John N; Dvorak, Simon; Belding, Ashleigh; Gangi, Devon; Hill, Alesha; Hill, Monique; Miller, Meghan; Parikh, Chandni; Schwichtenberg, AJ; Solis, Erika; Ozonoff, Sally | Abstract: BackgroundSigns of autism are present in the first 2nyears of life, but the average age of diagnosis lags far behind. Instruments that improve detection of autism risk in infancy are needed. This study developed and tested the psychometric properties of a novel video-based approach to detecting ASD in infancy.MethodsA prospective longitudinal study of children at elevated or lower risk for autism spectrum disorder was conducted. Participants were 76 infants with an older sibling with ASD and 37 infants with no known family history of autism. The Video-referenced Infant Rating System for Autism (VIRSA) is a web-based application that presents pairs of videos of parents and infants playing together and requires forced-choice judgments of which video is most similar to the child being rated. Parents rated participants on the VIRSA at 6, 9, 12, and 18nmonths of age. We examined split-half and test-retest reliability; convergent and discriminant validity; and sensitivity, specificity, and negative and positive predictive value for concurrent and 36-month ASD diagnoses.ResultsThe VIRSA demonstrated satisfactory reliability and convergent and discriminant validity. VIRSA ratings were significantly lower for children ultimately diagnosed with ASD than children with typical development by 12nmonths of age. VIRSA scores at 18nmonths identified all children diagnosed with ASD at that age, as well as 78% of children diagnosed at 36nmonths.ConclusionsThis study represents an initial step in the development of a novel video-based approach to detection of ASD in infancy. The VIRSA's psychometric properties were promising when used by parents with an older affected child, but still must be tested in community samples with no family history of ASD. If results are replicated, then the VIRSA's low-burden, web-based format has the potential to reduce disparities in communities with limited access to screening.

We examined the relationship between video-based media viewing (screen time), behavioral outcomes, and language development in 120 36-month-old children with a family history of Autism Spectrum Disorder (ASD) or Attention-Deficit/Hyperactivity Disorder (ADHD) or no family history of either condition. Participants were classified into one of three diagnostic groups: ASD (n = 20), ADHD Concerns (children with elevated ADHD symptoms; n = 14), or Comparison (n = 86). Children in the ADHD Concerns group spent more time viewing screen media than Comparison children. Increased screen time was associated with lower receptive and expressive language scores across groups. Future longitudinal studies are needed to determine the direction of effects and causality.

Author(s): Ozonoff, Sally; Gangi, Devon; Hanzel, Elise P; Hill, Alesha; Hill, Monique M; Miller, Meghan; Schwichtenberg, AJ; Steinfeld, Mary Beth; Parikh, Chandni; Iosif, Ana-Maria | Abstract: While previous studies suggested that regressive forms of onset were not common in autism spectrum disorder (ASD), more recent investigations suggest that the rates are quite high and may be under-reported using certain methods. The current study undertook a systematic investigation of how rates of regression differed by measurement method. Infants with (n = 147) and without a family history of ASD (n = 83) were seen prospectively for up to 7 visits in the first three years of life. Reports of symptom onset were collected using four measures that systematically varied the informant (examiner vs. parent), the decision type (categorical [regression absent or present] vs. dimensional [frequency of social behaviors]), and the timing of the assessment (retrospective vs. prospective). Latent class growth models were used to classify individual trajectories to see whether regressive onset patterns were infrequent or widespread within the ASD group. A majority of the sample was classified as having a regressive onset using either examiner (88%) or parent (69%) prospective dimensional ratings. Rates of regression were much lower using retrospective or categorical measures (from 29 to 47%). Agreement among different measurement methods was low. Declining trajectories of development, consistent with a regressive onset pattern, are common in children with ASD and may be more the rule than the exception. The accuracy of widely used methods of measuring onset is questionable and the present findings argue against their widespread use. Autism Res 2018, 11: 788-797. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY:This study examines different ways of measuring the onset of symptoms in autism spectrum disorder (ASD). The present findings suggest that declining developmental skills, consistent with a regressive onset pattern, are common in children with ASD and may be more the rule than the exception. The results question the accuracy of widely used methods of measuring symptom onset and argue against their widespread use.

Converging evidence suggests shared genetic underpinnings of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Studies of infants at risk for ASD have proliferated over the past decade; the few studies that have followed these infants beyond age 3 report a range of difficulties facing a subset of these infants as they reach school age, including elevated levels of attention problems and externalizing behavior. Given this, we aimed to identify early predictors of school-age ADHD outcomes in a sample of infant siblings at risk for ASD. This study reports on a sample of 59 infants at high and low risk for ASD who had been followed for more than a decade, collecting data at regular intervals from 3 to 36months and then determining diagnostic outcome at 8-10years of age. Seventeen participants were diagnosed with Diagnostic and Statistical Manual of Mental Disorders (5th ed.) ADHD at school age (n=14 high risk, 3 low risk). As infants, the ADHD outcome group demonstrated atypical longitudinal patterns of sustained visual attention. A significantly larger proportion of their parents reported behavior/temperament problems at 36months of age, and examiners noted the presence of inattentive, hyperactive, and/or impulsive behaviors in this group by 18months of age. These data suggest that behavioral indicators of risk for later ADHD may be present early in development, which may improve earlier detection and treatment of the disorder.

Studies of infants at risk for autism spectrum disorder (ASD) have proliferated, but few of these samples have been followed longer-term. We conducted a follow-up study, at age 5.5-9 years, of younger siblings of children with ASD (high-risk group, n = 79) or typical development (low-risk group, n = 60), originally recruited as infants. Children with ASD were excluded because of the focus on understanding the range of non-ASD outcomes among high-risk siblings. Using examiner ratings, parent ratings, and standardized assessments, we evaluated differences in clinical outcomes, psychopathology symptoms, autism symptoms, language skills, and nonverbal cognitive abilities. After adjusting for covariates, the high-risk group had increased odds of any clinically elevated/impaired score across measures relative to the low-risk group (43% vs. 12%, respectively). The high-risk group also had increased odds of examiner-rated Clinical Concerns (CC) outcomes (e.g., ADHD concerns, broader autism phenotype, speech-language difficulties, anxiety/mood problems, learning problems) relative to the low-risk group (38% vs. 13%, respectively). The high-risk group with CC outcomes had higher parent-reported psychopathology and autism symptoms, and lower directly-assessed language skills, than the Low-Risk Typically Developing (TD) and High-Risk TD groups, which did not differ. There were no differences in nonverbal cognitive skills. For some in the high-risk group, clinical concerns persisted from early childhood, whereas for others clinical concerns were first evident at school-age. Results suggest continued vulnerability in at least a subgroup of school-age children with a family history of ASD and suggest that this population may benefit from continued screening and monitoring into the school-age years. Autism Res 2016, 9: 632-642. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Objective To examine longitudinal patterns of response to name from 6-24 months of age in infants at high and low risk for autism spectrum disorder (ASD). Study design A response to name task was tested at 6, 9, 12, 15, 18, and 24 months of age in 156 infant siblings of children with ASD (high-risk) or typical development (low-risk). At 36 months of age, participants were classified into 1 of 3 outcome groups: group with ASD (n = 20), high-risk group without ASD (n = 76), or low-risk group without ASD (n = 60). Differences in longitudinal performance were assessed using generalized estimating equations, and sensitivity and specificity for identifying ASD were calculated. Differences in age 36-month functioning were examined between infants who developed ASD and repeatedly vs infrequently failed to respond to name. Results At 9 months of age, infants developing ASD were more likely to fail to orient to their names, persisting through 24 months. Sensitivity/specificity for identifying ASD based on at least 1 failure between 12 and 24 months were estimated at .70 in this sample. One-half of the infants who developed ASD had repeated failures in this timeframe, and demonstrated lower age 36-month receptive language, and earlier diagnosis of ASD than infants with ASD who had infrequent failures. Conclusions In addition to recommended routine broad-based and ASD-specific screening, response to name should be regularly monitored in infants at risk for ASD. Infants who consistently fail to respond to their names in the second year of life may be at risk not only for ASD but also for greater impairment by age 3 years.

PURPOSE Studies suggest peer-led self-management training improves chronic illness outcomes by enhancing illness management self-efficacy. Limitations of most studies, however, include use of multiple outcome measures without predesignated primary outcomes and lack of randomized follow-up beyond 6 months. We conducted a 1-year randomized controlled trial of Homing in on Health (HIOH), a Chronic Disease Self-Management Program variant, addressing these limitations. METHODS We randomized outpatients (N = 415) aged 40 years and older and who had 1 or more of 6 common chronic illnesses, plus functional impairment, to HIOH delivered in homes or by telephone for 6 weeks or to usual care. Primary outcomes were the Medical Outcomes Study 36-ltem short-form health survey‘s physical component (PCS-36) and mental component (MCS-36) summary scores. Secondary outcomes included the EuroQol EQ-5D and visual analog scale (EQ VAS), hospitalizations, and health care expenditures. RESULTS Compared with usual care, HIOH delivered in the home led to significantly higher illness management self-efficacy at 6 weeks (effect size = 0.27; 95% CI, 0.10–0.43) and at 6 months (0.17; 95% CI, 0.01–0.33), but not at 1 year. In-home HIOH had no significant effects on PCS-36 or MCS-36 scores and led to improvement in only 1 secondary outcome, the EQ VAS (1-year effect size = 0.40; CI, 0.14–0.66). HIOH delivered by telephone had no significant effects on any outcomes. CONCLUSIONS Despite leading to improvements in self-efficacy comparable to those in other CDSMP studies, in-home HIOH had a limited sustained effect on only 1 secondary health status measure and no effect on utilization. These findings question the cost-effectiveness of peer-led illness self-management training from the health system perspective.

Objective This study had 3 goals, which were to examine the following: the frequency of atypical development, consistent with the broader autism phenotype, in high-risk infant siblings of children with autism spectrum disorder (ASD); the age at which atypical development is first evident; and which developmental domains are affected. Method A prospective longitudinal design was used to compare 294 high-risk infants and 116 low-risk infants. Participants were tested at 6, 12, 18, 24, and 36 months of age. At the final visit, outcome was classified as ASD, Typical Development (TD), or Non-TD (defined as elevated Autism Diagnostic Observation Schedule [ADOS] score, low Mullen Scale scores, or both). Results Of the high-risk group, 28% were classified as Non-TD at 36 months of age. Growth curve models demonstrated that the Non-TD group could not be distinguished from the other groups at 6 months of age, but differed significantly from the Low-Risk TD group by 12 months on multiple measures. The Non-TD group demonstrated atypical development in cognitive, motor, language, and social domains, with differences particularly prominent in the social-communication domain. Conclusions These results demonstrate that features of atypical development, consistent with the broader autism phenotype, are detectable by the first birthday and affect development in multiple domains. This highlights the necessity for close developmental surveillance of infant siblings of children with ASD, along with implementation of appropriate interventions as needed.

A fundamental component of pediatric practice is parent appraisal of child development.1 Developmental history taking, including elicitation of parental concerns, is standard in most routine pediatric visits and is used to alert physicians to the possibility of conditions requiring further evaluation. As the incidence of and media attention to autism spectrum disorders (ASD) increase, concerns about the possibility of these conditions are increasingly being raised by parents.2 Recently published guidelines from the American Academy of Pediatrics recommend that pediatricians ask parents about developmental concerns at each well-child visit and screen all children for autism twice by the second birthday.3 If concerns are identified by parents, the American Academy of Pediatrics' surveillance and screening algorithm3 recommends that an autism-specific screener should be administered and/or the child should be referred for a diagnostic evaluation, depending on the level of concern. Thus, parent report alone can trigger a referral for further evaluation. Retrospective studies indicate that parents recognize signs of autism far earlier than it is diagnosed. Although symptoms are typically present by the second birthday and one third of parents cite concerns before the first birthday,4 diagnoses are often not made until the fourth year of life or later.5 Early concerns are sometimes dismissed,2 resulting in a several month to several year delay of diagnosis.6–8 Thus, early detection methods need improvement, in the hope that earlier diagnosis will lead to earlier initiation of treatment and reduced disability. As reviewed below, there is a robust literature on the accuracy of parent reports in general and for predicting developmental delays specifically; little, however, is known about their utility in predicting later autism diagnoses. Several studies have examined how well parent information corresponds with developmental tests and/or expert clinical judgment. Correlations are moderately high (0.45– 0.65) between parent report of vocabulary and concurrent expressive language scores9 and very strong (0.80) between parent estimation of their child's developmental age and actual developmental quotients obtained through standardized testing.10 Parent concerns in high-risk infants were confirmed by formal assessment 95% of the time.11 Glascoe and colleagues12 have standardized the measurement of parent concerns through an instrument, the Parents' Evaluation of Developmental Status (PEDS). It is designed for children birth to 8 years and asks both general questions about concerns (please list any concerns about your child's learning, behavior, or development) and specific questions about concerns in 10 individuals domains (i.e., cognitive, language, motor, self-help). The Parents' Evaluation of Developmental Status demonstrates high accuracy in predicting disability (sensitivity 0.79 and specificity 0.72 in a sample aged 21 to 84 months).13 Although the Parents' Evaluation of Developmental Status was developed as a broadband screening instrument, a recent investigation found that parent concerns recorded between 18 and 59 months were correlated with concurrent scores on the Modified Checklist for Autism in Toddlers,14 suggesting that it might be useful to screen for ASD as well. This finding was not replicated in a study screening 18- to 30-month old infants in primary care settings,15 however, leading these authors to suggest that ASD-specific tools will be needed in the universal screening process. However, the importance of assessing the accuracy of parent reports of early development and their predictive validity for identifying autism is complicated in several ways. Several studies suggest that signs of autism emerge gradually over time and that the earliest symptoms are subtle and not easy to detect, particularly by untrained observers.16 A few retrospective studies suggest that symptoms can be detected before the first birthday in some children,17,18 but these early differences appear to be nonspecific (e.g., sleeping, eating, temperament patterns) and do not differentiate children with developmental delays from those with autism.19 Group differences are more reliably present and consistently found across studies in the second year of life.20 Several prospective investigations of infants at higher risk for autism (because of family history) have failed to find differences at 6 months between children who are later diagnosed with autism and those who develop typically.21–24 Bryson et al,25 in a consecutive case series of infant siblings who developed autism, followed prospectively from 6 months, describe several children whose symptoms are not present at their 6- and 12-month visits but emerge slowly during the second year of life. Not a single child who developed autism (n = 9) displayed marked limitations in social reciprocity at 6 months. All 9 infants were described as interested in social interactions, responsive to others, demonstrating sustained eye contact and social smiles. This pattern of slow emergence of symptoms during the first year and a half of life may complicate efforts to use parent reports to identify autism symptoms earlier. A second complication is the influence of risk status on parent reporting. Several studies have demonstrated that parents' perceptions of child development are impacted by their child's health status. For example, low birth weight children were rated as in poor health significantly more commonly by parents than by professionals.26 In prospective studies that follow high-risk families who already have a child with autism, as in this investigation, it is possible that parents may have heightened vigilance to developmental variations and over-report concerns. Conversely, it is equally possible that such parents will be more astute observers of child development who notice subtle manifestations of early developmental problems that may not yet be apparent on standardized assessments. Studies have shown that typically developing children whose parents reported concerns but who passed developmental screens (apparent false positives) performed significantly lower on tests of cognitive functioning and had significantly more behavioral problems than children whose parents raised no concerns.27 It was concluded that parents who appeared to be excessively worried were in fact “… vigilant observers who noticed behavioral and developmental problems that fall in the gray zone between disabled and average.”27(p. 6) Parent concerns have also been found to correlate with developmental test scores in toddlers at risk for autism.28 This study collected parent concerns about development for infants at high and low risk for autism, using a prospective, longitudinal design. Parents were asked about developmental concerns at study intake and when their infant was 6, 12, and 18 months. Infants were then followed up until 36 months, when diagnostic status was determined. We examined whether the number and type of parent concerns differed over time as a function of outcome status. Although previous studies have examined the ability of parent concerns to predict concurrent test scores in children at risk for autism,14,28 this study is the first to examine the relationship between longitudinal parent report and later diagnostic outcome.

Patient self-report is a practical method for measuring adherence, but little is known about its optimal use.To examine the retest reliability and predictive validity of 3 different types of self-report adherence measures among patients with common chronic illnesses.Correlation and regression analyses of data from an ongoing randomized controlled trial.Patients (N = 415) agedor=40 years recruited from a primary care network with arthritis, asthma, chronic lung disease, congestive heart failure, depression, and/or diabetes mellitus, plus impairment inor=1 basic activity and/or a score ofor=4 on the 10-item Center for Epidemiologic Studies Depression Scale.: Self-report adherence (administered variously at baseline, 2, 4, and 6 weeks, and 6 months): number of pills taken/number of pills prescribed (PT/PP), using 1-7 days recall, and global reports of medication adherence and overall adherence tendencies. Six-month functional outcomes: Health Assessment Questionnaire (HAQ) and Short Form-36 (SF-36).Correlation coefficients among contemporaneously administered 1-7 days PT/PP measures wereor=0.78. Correlations among PT/PP measures and global adherence measures, and among PT/PP measures at 2 and 4 weeks, ranged from 0.11 to 0.54. PT/PP measures usingor=3-4 days recall significantly predicted adjusted 6-month HAQ but not SF-36 score.Self-report PT/PP and general medication adherence measures tap different behavioral constructs. Self-reported PT/PP at a given point in time is not necessarily representative of medication adherence over time. Among chronically ill patients, 3-4 days recall of PT/PP yield adherence estimates, which are practically as reliable and valid as longer intervals and which predict functional outcomes.

Identifying moderators of the effects of self-efficacy enhancing interventions could facilitate their refinement and more targeted, cost-effective delivery. Current theories and data concerning the potential moderating effect of depressive symptoms on interventions to enhance patient chronic illness self-management self-efficacy are conflicting.To explore the moderating effect of depressive symptoms on the effect of an intervention to enhance patient self-efficacy for self-managing chronic illness.Regression analyses using baseline and postintervention (6 weeks) data from an ongoing randomized controlled trial.Patients (N = 415) agedor=40 years recruited from a primary care network in Northern California with arthritis, asthma, chronic obstructive pulmonary disease, congestive heart failure, depression, and/or diabetes mellitus, plus impairment inor=1 basic activity, and/or a score ofor=4 on the 10-item Center for Epidemiologic Studies Depression Scale (CES-D).Stanford self-efficacy scale, self-reported depression, CES-D, and Medical Outcomes Study Short Form health status questionnaire (SF-36) Mental Component Summary score.Regression analyses revealed the intervention was effective primarily in those with self-reported depression (interaction effect F = 8.24, P = 0.0003), highest CES-D score category (F = 5.68, P = 0.0037), and lowest (most depressed) Mental Component Summary-36 tercile (F = 4.36, P = 0.0135).Individuals with more depressive symptoms seem more likely to experience self-efficacy gains from chronic illness self-management training than individuals with less depressive symptoms. Future self-management training studies should stratify subjects within study groups by depressive symptom level to further explore its potential moderating effect.

Objective To examine prospectively the emergence of behavioral signs of autism in the first years of life in infants at low and high risk for autism. Method A prospective longitudinal design was used to compare 25 infants later diagnosed with an autism spectrum disorder (ASD) with 25 gender-matched low-risk children later determined to have typical development. Participants were evaluated at 6, 12, 18, 24, and 36 months of age. Frequencies of gaze to faces, social smiles, and directed vocalizations were coded from video and rated by examiners. Results The frequency of gaze to faces, shared smiles, and vocalizations to others were highly comparable between groups at 6 months of age, but significantly declining trajectories over time were apparent in the group later diagnosed with ASD. Group differences were significant by 12 months of age on most variables. Although repeated evaluation documented loss of skills in most infants with ASD, most parents did not report a regression in their child's development. Conclusions These results suggest that behavioral signs of autism are not present at birth, as once suggested by Kanner, but emerge over time through a process of diminishment of key social communication behaviors. More children may present with a regressive course than previously thought, but parent report methods do not capture this phenomenon well. Implications for onset classification systems and clinical screening are also discussed.