Difficulties in reciprocal social interaction are hallmark features of several neuropsychiatric disorders, most notably autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SSD). Recent behavioral studies of adults with SSD and ASD have highlighted not only the similarities but also some divergent patterns of social impairments in the two disorders - with ASD characterized by lower social motivation, poorer social reciprocity, and undermentalizing, and SSD characterized by greater reciprocity but poor expressiveness. Given the public health significance of social disability and social isolation, it is crucial to explore the neurobiological mechanisms underlying these social skill deficits across both groups, as well as to understand how these relate to real-world behaviors. Although antipsychotics have been shown to be effective in reducing positive symptoms in SSD, they are not effective in addressing the devastating social disability associated with the disorder, which contributes to chronic functional impairment. It is thus imperative to identify behavioral interventions for children and adolescents that have already shown promise in other clinical groups such as ASD. By enhancing our understanding of the neurobiological underpinnings of social impairments in adolescent-onset SSD and how they compare to those observed in ASD, we will be able to refine treatment targets and better predict outcomes for each group. To this effect, the proposed study will examine biomarkers that are likely related to positive outcomes from targeted social skills intervention in adolescents with SSD and ASD. Building upon an established evidence-based treatment - the Program for the Education and Enrichment of Relational Skills (PEERS), we will collect resting state functional imaging (rs-fcMRI), task-paradigm functional BOLD activation (fMRI), and magnetic resonance spectroscopy (MRS) before and after 30 SSD and 30 ASD adolescents, 12-18 years of age, undergo the 16-week evidence-based PEERS behavioral intervention. These data will then be compared to a matched sample of 30 typically developing (TD) adolescents who are not enrolled in the PEERS program but will undergo two MRI scans 16-weeks apart. The overarching goal of the study will be to create a novel multimodal neuroimaging design to examine the neural underpinning of social difficulties in SSD and ASD, explore neuroplasticity in both groups in response to a brief targeted social-skills intervention, and predict treatment response and its contribution to long-term maintenance of skills after treatment completion.
The following are the study's specific aims:
Aim 1: Assess treatment related changes in 'social brain' regions following evidence-based social skills training in ASD and SSD group, compared to neural patterns observed in TD adolescents.
Hypothesis 1a: rs-fcMRI indices within social brain networks will look more improved (similar to TD adolescents) post-treatment compared to pre-treatment for the both ASD and SSD groups (e.g., greater connectivity in social brain networks in ASD group, lower connectivity of extraneous regions in SSD group).
Hypothesis 1b: fMRI brain activation in social brain regions in response to the social task-paradigm will look more improved (similar to TD adolescents) post-treatment compared to pre-treatment for both ASD and SSD group (e.g., greater activation in social brain networks in ASD group, lower activation of extraneous regions in SSD group). Hypothesis 1c: There will be significant improvement (similar to TD adolescents) in MRS indices of GABA (inhibitory) and glutamate (excitatory) neurometabolite concentrations within social brain networks in ASD and SSD post- treatment compared to pre-treatment (e.g., lower glutamate/higher GABA in social brain regions in ASD group, higher glutamate/higher GABA in social brain regions in SSD group).
Aim 2: To test whether pre- and post-treatment neural changes are meaningfully related to behavioral measures of treatment outcome.
Hypothesis 2: Neural responses post-intervention will correlate with gains in social motivation and reciprocity behavioral outcomes measures in the ASD group, and gains in social expressivity outcome measures in the SSD group.
Exploratory Aim 3: Given that both ASD and SSD are characterized as spectrum disorders of varying severity, heterogeneous etiologies, and comorbidities, we aim to explore how individual differences in patterns of brain connectivity and activation might predict treatment response and treatment maintenance dimensionally in addition to the category-based diagnostic systems proposed above. Given the exploratory nature of the proposed aim, specific hypotheses are not projected regarding the precise changes in neural activity on an individual basis. However, accomplishing this goal will us understand underlying neural mechanisms of treatment-related change across groups, and serve to better target interventions to address the heterogeneity of social cognition deficits observed in both ASD and SSD.
