Daily Living Skills in Adolescent and Young Adult Males With Fragile X Syndrome

By adulthood, most males with fragile X syndrome (FXS) require support to navigate day-to-day settings. The present study cross-sectionally: (1) characterized the profile of daily living skills in males with FXS and (2) examined associated participant characteristics (i.e., fragile X mental retardation protein [FMRP] expression, nonverbal cognition, language, autism symptomatology, and anxiety symptomatology) using the Waisman-Activities of Daily Living questionnaire. Males with FXS (n = 57, ages 15–23 years) needed more help/support in the areas of domestic and community daily livings skills, than in the area of personal daily living skills. Significant associations were observed between reduced daily living skills and lower nonverbal cognition, receptive language, expressive language, and increased autism symptomatology. Receptive language emerged as the strongest unique predictor of daily living skill performance.

Narrative Analysis in Adolescents With Fragile X Syndrome

This study analyzed narratives of male and female adolescents with fragile X syndrome (FXS). The impact of structural language, cognition and autism symptomatology on narrative skills and the association between narratives and literacy were examined. Narratives from 32 adolescents with FXS (24 males, 8 females) were analyzed for macrostructure. Relationships between narrative macrostructure, language scores, cognitive scores, Childhood Autism Rating Scale-Second Edition scores and literacy skills were examined. Males produced more simplistic narratives, whereas the females' narratives were more complex. Language scores predicted narrative scores above and beyond nonverbal cognitive skills and autism symptomatology. Narrative scores correlated with literacy scores. Narrative skills in FXS are predicted by language skills and are correlated with literacy skills. Investigation into narrative interventions in FXS is needed.

Excitatory/inhibitory imbalance in autism: the role of glutamate and GABA gene-sets in symptoms and cortical brain structure

Background: The excitatory/inhibitory (E/I) imbalance hypothesis posits that an imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism spectrum disorder (autism). However, how E/I imbalance arises and how it may differ across autism symptomatology and brain regions is not well understood. Methods: We used innovative analysis methods - combining competitive gene-set analysis and gene-expression profiles in relation to cortical thickness (CT)- to investigate the relationship between genetic variance, brain structure and autism symptomatology of participants from the EU-AIMS LEAP cohort (autism=360, male/female=259/101; neurotypical control participants=279, male/female=178/101) aged 6 to 30 years. Competitive gene-set analysis investigated associations between glutamatergic and GABAergic signaling pathway gene-sets and clinical measures, and CT. Additionally, we investigated expression profiles of the genes within those sets throughout the brain and how those profiles relate to differences in CT between autistic and neurotypical control participants in the same regions. Results: The glutamate gene-set was associated with all autism symptom severity scores on the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) within the autistic group, while the GABA set was associated with sensory processing measures (using the SSP subscales) across all participants. Brain regions with greater gene expression of both glutamate and GABA genes showed greater differences in CT between autistic and neurotypical control participants. Conclusions: Our results suggest crucial roles for glutamate and GABA genes in autism symptomatology as well as CT, where GABA is more strongly associated with sensory processing and glutamate more with autism symptom severity.

Maternal Mental Health and Parenting Stress and Their Relationships to Characteristics of the Child With Fragile X Syndrome

Although previous research supports the notion that characteristics of both the child and the mother impact maternal well-being and parenting stress in mothers of children with FXS, more work is needed in which self-report measures are supplemented by physiological measures of stress and well-being. The inclusion of physiological measures, such as heart rate variability (HRV), may provide a window into the biological origins and consequences of maternal perceptions of their experiences, including the challenges of raising a child with developmental challenges. The proposed project, therefore, involved the collection of multimodal assessment data from mothers and their school-aged children with FXS. Further, given the importance of understanding how mothers of youth with FXS are faring in their everyday environment, the present study collected all data using telehealth procedures and wearable technology. Participants were 20 biological mothers and their children with FXS between the ages of 6 and 11 years. We measured maternal mental health and parenting stress through self-report as well as through HRV as a more objective measure of psychological well-being. We also examined the associations between these variables and child characteristics such as externalizing and internalizing behaviors as well as autism symptomatology. We found significant support for an elevated rate of depressive symptoms in the sample of mothers (35%) and some potential indicators for heightened rates of anxiety (15%) when compared to normed samples and rates in the general population. We also found that the mothers presented with an atypical HRV profile akin to those experiencing depression or chronic stress, although limitations of the present measure suggest the need for additional confirmatory research. Further, we found that child externalizing behaviors were the primary correlates of maternal well-being. These findings contribute to the growing body of literature regarding the unique challenges faced by these mother-child dyads and supports the importance of increasing the availability of services available to these mothers, not only for meeting the needs of their children's development and behavior, but in supporting their own well-being as well.

Measurement of Sleep Behaviors in Chromosome 15q11.2-13.1 Duplication (Dup15q Syndrome)

Duplication of chromosome 15q11.2-q13.1 (dup15q syndrome) results in hypotonia, intellectual disability (ID), and autism symptomatology. Clinical electroencephalography has shown abnormal sleep physiology, but no studies have characterized sleep behaviors. The present study used the Children's Sleep Habits Questionnaire (CSHQ) in 42 people with dup15q syndrome to examine the clinical utility of this questionnaire and quantify behavioral sleep patterns in dup15q syndrome. Individuals with fully completed forms (56%) had higher cognitive abilities than those with partially completed forms. Overall, caregivers indicated a high rate of sleep disturbance, though ratings differed by epilepsy status. Results suggest that clinicians should use caution when using standardized questionnaires and consider epilepsy status when screening for sleep problems in dup15q syndrome.

Identifying and Describing Subtypes of Spontaneous Empathic Facial Expression Production in Autistic Adults

Background: It is unclear whether atypical patterns of facial expression production metrics in autism reflect the dynamic and nuanced nature of facial expressions or a true diagnostic difference. Further, the heterogeneity observed across autism symptomatology suggests a need for more adaptive and personalized social skills programs. For example, it would be useful to have a better understanding of the different expressiveness profiles within the autistic population and how they differ from neurotypicals to help develop systems that train facial expression production and reception. Methods:We used automated facial coding and an unsupervised clustering approach to limit inter-individual variability in facial expression production that may have otherwise obscured group differences in previous studies, allowing an "apples-to-apples" comparison between autistic and neurotypical adults. Specifically, we applied k-means clustering to identify subtypes of facial expressiveness in an autism group (N=27) and a neurotypical control group (N=57) separately. The two most stable clusters from these analyses were then further characterized and compared on the basis of their expressiveness and emotive congruence to emotionally charged stimuli. Results: Our main finding was that autistic adults show heightened spontaneous facial expressions in response to negative emotional images. The group effect did not extend to positive emotional images, and we did not find evidence for greater incongruous (i.e., inappropriate) facial expressions in autism. Conclusion: These findings build on previous work suggesting valence-specific effects of autism on emotional empathy and suggest the need for intervention programs to focus on social skills in the context of both negative and positive emotions.

Capturing cognitive and behavioral variability among individuals with Down syndrome: a latent profile analysis

Background There is a high degree of inter- and intra-individual variability observed within the phenotype of Down syndrome. The Down Syndrome Cognition Project was formed to capture this variability by developing a large nationwide database of cognitive, behavioral, health, and genetic information on individuals with Down syndrome, ages 6–25 years. The current study used the Down Syndrome Cognition Project database to characterize cognitive and behavioral variability among individuals with Down syndrome. Methods Latent profile analysis was used to identify classes across a sample of 314 participants based on their cognition (IQ and executive functioning), adaptive and maladaptive behavior, and autism spectrum disorder symptomatology. A multivariate multinomial regression model simultaneously examined demographic correlates of class. Results Results supported a 3-class model. Each class demonstrated a unique profile across the subdomains of cognition and behavior. The “normative” class was the largest (n = 153, 48%) and displayed a relatively consistent profile of cognition and adaptive behavior, with low rates of maladaptive behavior and autism symptomatology. The “cognitive” class (n = 109, 35%) displayed low cognitive scores and adaptive behavior and more autism symptomatology, but with low rates of maladaptive behavior. The “behavioral” class, the smallest group (n = 52, 17%), demonstrated higher rates of maladaptive behavior and autism symptomatology, but with cognition levels similar to the “normative” class; their adaptive behavior scores fell in between the other two classes. Household income and sex were the only demographic variables to differ among classes. Conclusions These findings highlight the importance of subtyping the cognitive and behavioral phenotype among individuals with Down syndrome to identify more homogeneous classes for future intervention and etiologic studies. Results also demonstrate the feasibility of using latent profile analysis to distinguish subtypes in this population. Limitations and future directions are discussed.

Fostering Socio-Emotional Competencies in Children with Autism using a Parent-Assisted Serious Game: A Multicenter Randomized Controlled Trial (Preprint)

Objective: Serious games (SGs) are a promising means of fostering socio-emotional skills in children with autism spectrum conditions (ASC). However, alexithymia and emotional empathy have not yet been addressed adequately, and there is a lack of randomized controlled trials (RCT) to investigate skill maintenance and the transfer to functional behavior. Method: The manualized, parent-assisted SG Zirkus Empathico (ZE) was tested against an active control group, in a six-week multicenter RCT. Eighty-two children aged 5-10 years with ASC were assessed at baseline, post-treatment, and three-month follow-up. Parent-rated empathy and emotion recognition skills were defined as the primary outcomes. The secondary outcomes included measures of emotional awareness, emotion regulation, autism social symptomatology (Social Responsiveness Scale), and subjective therapy goals. Results: Training effects were observed after the intervention for empathy (d = 0.71) and emotion recognition (d = 0.50), but not at follow-up. Moderate effects on emotional awareness, emotion regulation, and autism social symptomatology were indicated by the short and mid-term assessments. Parents reported treatment goal attainment and positive training transfer. Conclusion: While a six-week training with ZE failed to induce lasting changes in empathy and emotion recognition, it may be effective for improving emotion regulation and mitigate alexithymia and general autism symptomatology.

The trend of association between autism traits in mothers and severity of autism symptomatology in children

Purpose Autism spectrum disorders (ASD) are heterogeneous disorders, and heterogeneity lies both at genetic and phenotypic levels. To better understand the etiology and pathway that may contribute to autism symptomatology, it is important to study milder expressions of autism characteristics – autistic traits or milder expressions of autism phenotype, especially in intergenerational context. This study aims to see the trend of association, if any, between child autism symptom and mothers’ autism phenotype as well as mothers’ theory of mind and to see if mothers’ theory of mind was associated with their own autistic traits. Design/methodology/approach Data were collected from 96 mothers of children with varying symptom severity of autism (mild, moderate and severe) using Autism Spectrum Quotient and faux pas recognition test. Analysis of variance, trend analysis and t-test were done. Findings Results showed a linear trend of relationship between mothers’ autism phenotype and child symptom severity. However, the groups did not have significant differences in theory of mind. Only a few components of theory of mind were found to be associated with autistic traits. These findings question the prevailing idea that theory of mind can be a reliable endophenotype of autism. Research limitations/implications There has been a lack of research assessing the possible link between parents’ autism phenotype and symptom severity of ASD children. This study is a preliminary step towards that direction. This study indicates a probability of shared genetic liability between mothers and offspring, which would have important consequences for understanding the mechanisms that lead to autism. Practical implications This study offers implications for treatment planning of those with clinical ASD. An awareness of parental factors is critical for any holistic intervention plan when a family seeks treatment for their child. This study suggests that while individualising interventions, clinicians may consider possible presence of high levels of autistic traits and related cognitive features present in the probands’ parents. Originality/value There has been lack of research assessing the possible link between parents’ autism phenotype and symptom severity of ASD children. This study, even though preliminary, is a step towards that direction. This study suggests that autism traits might be influenced by common genetic variation and indicates a probability of shared genetic liability between mothers and offspring, which would have important consequences for understanding the mechanisms that lead to autism.

Genetic modifiers in rare disorders: the case of fragile X syndrome

Methods employed in genome-wide association studies are not feasible ways to explore genotype–phenotype associations in rare disorders due to limited statistical power. An alternative approach is to examine relationships among specific single nucleotide polymorphisms (SNPs), selected a priori, and behavioural characteristics. Here, we adopt this strategy to examine relationships between three SNPs (5-HTTLPR, MAOA, COMT) and specific clinically-relevant behaviours that are phenotypic of fragile X syndrome (FXS) but vary in severity and frequency across individuals. Sixty-four males with FXS participated in the current study. Data from standardised informant measures of challenging behaviour (defined as physical aggression, property destruction, stereotyped behaviour, and self-injury), autism symptomatology, attention-deficit-hyperactivity-disorder characteristics, repetitive behaviour and mood/interest and pleasure were compared between each SNP genotype. No association was observed between behavioural characteristics and either 5-HTTLPR (serotonin) or MAOA (monoamine oxidase) genotypes. However, compared to the COMT (dopamine) AG and GG genotypes, the AA genotype was associated with greater interest and pleasure in the environment, and with reduced risk for property destruction, stereotyped behaviour and compulsive behaviour. The results suggest that common genetic variation in the COMT genotype affecting dopamine levels in the brain may contribute to the variability of challenging and repetitive behaviours and interest and pleasure in this population. This study identifies a role for additional genetic risk in understanding the neural and genetic mechanisms contributing to phenotypic variability in neurodevelopmental disorders, and highlights the merit of investigating SNPs that are selected a priori on a theoretical basis in rare populations.