Pre-treatment clinical and gene expression patterns predict developmental change in early intervention in autism.

Funder: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)Early detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on the outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and provided a blood sample, here we find that very early treatment engagement (i.e., <24 months) leads to greater gains while controlling for time in treatment. Pre-treatment clinical behavioral measures predict 21% of the variance in the rate of skill growth during early intervention. Pre-treatment blood leukocyte gene expression patterns also predict the rate of skill growth, accounting for 13% of the variance in treatment slopes. Results indicated that 295 genes can be prioritized as driving this effect. These treatment-relevant genes highly interact at the protein level, are enriched for differentially histone acetylated genes in autism postmortem cortical tissue, and are normatively highly expressed in a variety of subcortical and cortical areas important for social communication and language development. This work suggests that pre-treatment biological and clinical behavioral characteristics are important for predicting developmental change in the context of early intervention and that individualized pre-treatment biology related to histone acetylation may be key

Use of a Differential Observing Response to Expand Restricted Stimulus Control

This study extends previous work on the use of differential observing responses (DOR) to remediate atypically restricted stimulus control. A participant with autism had high matching-to-sample accuracy scores with printed words that had no letters in common (e.g., cat, lid, bug) but poor accuracy with words that had two letters in common (e.g., cat, can, car). In the DOR intervention, she matched the distinguishing letters of the overlapping words (e.g., t, n, r) immediately prior to matching the whole words. Accuracy scores improved, and accuracy remained high when DOR requirements were withdrawn

Reduction of stimulus overselectivity with nonverbal differential observing responses.

Three individuals with mental retardation exhibited stimulus overselectivity in a delayed matching-to-sample task in which two sample stimuli were displayed on each trial. Intermediate accuracy scores indicated that participants could match one of the samples but not both of them. Accuracy in a baseline condition was compared to accuracy with a differential observing response procedure. This procedure prompted participants to make simultaneous identity-matching responses that required observation and discrimination of both sample stimuli. These observing responses were never followed by differential consequences. When observing responses were prompted, participants' accuracy scores improved. In a return to the baseline condition, when differential observing responses were no longer prompted, accuracy returned to intermediate levels. The results show that stimulus overselectivity can be greatly reduced by a behavioral intervention that controls observing behavior and verifies discrimination, but that exposure to such procedures alone may be insufficient for lasting benefits

Reinforcer frequency and restricted stimulus control.

Stimulus control was evaluated in 3 individuals with moderate to severe mental retardation by delayed identity matching-to-sample procedures that presented either one or two discrete forms as sample stimuli on each trial. On pretests, accuracy scores on one-sample trials were uniformly high. On two-sample trials, the correct stimulus (i.e., the one that subsequently appeared in the comparison array) varied unpredictably, and accuracy scores were substantially lower, suggesting that both sample stimuli did not exert stimulus control on every trial. Subjects were then given training sessions with the one-sample task and with a new set of four stimuli. For two of the stimuli, correct matching responses were followed by reinforcers on a variable-ratio schedule that led to a high reinforcer rate. For the other two stimuli, correct responses were followed by reinforcers on a variable-ratio schedule that led to a substantially lower reinforcer rate. Results on two-sample tests that followed showed that (a) on trials in which comparison arrays consisted of one high reinforcer-rate and one low reinforcer-rate stimulus, subjects most often selected the high-rate stimulus; and (b) on trials in which the comparison arrays were either two high reinforcer-rate stimuli or two low reinforcer-rate stimuli and the samples were one high reinforcer- and one low reinforcer-rate stimulus, accuracy was higher on trials with the high-rate comparisons. These results indicate that the frequency of stimulus control by high reinforcer-rate samples was greater than that by low reinforcer-rate samples. Following more training with the one-sample task and reversed reinforcement schedules for all stimuli, the differences in stimulus control frequencies on two-sample tests also reversed. These results demonstrate experimental control by reinforcement contingencies of which of two sample stimuli controlled selections in the two-sample task. The procedures and results may prove to be relevant for understanding restricted stimulus control and stimulus overselectivity

Observing Behavior and Atypically Restricted Stimulus Control

Restricted stimulus control refers to discrimination learning with atypical limitations in the range of controlling stimuli or stimulus features. In the study reported here, 4 normally capable individuals and 10 individuals with intellectual disabilities (ID) performed two-sample delayed matching to sample. Sample-stimulus observing was recorded with an eye-tracking apparatus. High accuracy scores indicated stimulus control by both sample stimuli for the 4 nondisabled participants and 4 participants with ID, and eye tracking data showed reliable observing of all stimuli. Intermediate accuracy scores indicated restricted stimulus control for the remaining 6 participants. Their eye-tracking data showed that errors were related to failures to observe sample stimuli and relatively brief observing durations. Five of these participants were then given interventions designed to improve observing behavior. For 4 participants, the interventions resulted initially in elimination of observing failures, increased observing durations, and increased accuracy. For 2 of these participants, contingencies sufficient to maintain adequate observing were not always sufficient to maintain high accuracy; subsequent procedure modifications restored it, however. For the 5th participant, initial improvements in observing were not accompanied by improved accuracy, an apparent instance of observing without attending; accuracy improved only after an additional intervention that imposed contingencies on observing behavior. Thus, interventions that control observing behavior seem necessary but may not always be sufficient for the remediation of restricted stimulus control

Impact of COVID-19 on adolescent HIV prevention and treatment research in the AHISA Network

Members of the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA) network conduct research aiming to close gaps between what is known to be impactful across the HIV prevention and treatment cascade, and services delivered to optimize outcomes for adolescents/young adults (AYA) in high HIV-prevalence settings. The COVID-19 pandemic introduced new challenges which threaten to exacerbate care and access disparities. We report results of a survey among AHISA teams with active AYA HIV research programs in African countries to determine how the pandemic has impacted their efforts. Results highlighted the detrimental impact of the pandemic on research efforts and the expanded need for implementation research to help provide evidence-based, context-specific pandemic recovery support. Key lessons learned included the viability of remote service delivery strategies and other innovations, the need for adaptive systems that respond to evolving contextual needs, and the need for organized documentation plans, within empathic and flexible environments

Pre-treatment clinical and gene expression patterns predict developmental change in early intervention in autism.

Early detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on the outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and provided a blood sample, here we find that very early treatment engagement (i.e., &lt;24 months) leads to greater gains while controlling for time in treatment. Pre-treatment clinical behavioral measures predict 21% of the variance in the rate of skill growth during early intervention. Pre-treatment blood leukocyte gene expression patterns also predict the rate of skill growth, accounting for 13% of the variance in treatment slopes. Results indicated that 295 genes can be prioritized as driving this effect. These treatment-relevant genes highly interact at the protein level, are enriched for differentially histone&nbsp;acetylated genes in autism postmortem cortical tissue, and are normatively highly expressed in a variety of subcortical and cortical areas important for social communication and language development. This work suggests that pre-treatment biological and clinical behavioral characteristics are important for predicting developmental change in the context of early intervention and that individualized pre-treatment biology&nbsp;related to&nbsp;histone acetylation may be key

Infantile Autism

Autism is a severe form of psychopathology in childhood and is characterized, in general, by severe withdrawal and lack of social behavior, severe language and attentional deficits, and the presence of bizarre, repetitive behaviors (J. K. Wing, 1966). The severity of the behavioral deficits and excesses in such children frequently causes great turmoil in the family, affecting not only the lives of the child and immediate family, but the community as well. Autism occurs approximately in one out of every 2,500 children and is often not diagnosed until the child is between 1 and 5 years of age. Although there are currently many theories relating to the etiology of the disorder, there is no consistent evidence in support of any one of them (Egel, Koegel, & Schreibman, 1980; Schreibman, 1988). Most professionals, however, now take the position that autism is of organic etiology and that the disorder is probably present from birth. The nature and range of deficits associated with the disorder make it resistant to most forms of treatment intervention