Typically-developing Siblings Research Articles

Bioenergetic signatures of neurodevelopmental regression.

Background: Studies have linked autism spectrum disorder (ASD) to physiological abnormalities including mitochondrial dysfunction. Mitochondrial dysfunction may be linked to a subset of children with ASD who have neurodevelopmental regression (NDR). We have developed a cell model of ASD which demonstrates a unique mitochondrial profile with mitochondrial respiration higher than normal and sensitive to physiological stress. We have previously shown similar mitochondrial profiles in individuals with ASD and NDR. Methods: Twenty-six ASD individuals without a history of NDR (ASD-NoNDR) and 15 ASD individuals with a history of NDR (ASD-NDR) were recruited from 34 families. From these families, 30 mothers, 17 fathers and 5 typically developing (TD) siblings participated. Mitochondrial respiration was measured in peripheral blood mononuclear cells (PBMCs) with the Seahorse 96 XF Analyzer. PBMCs were exposed to various levels of physiological stress for 1h prior to the assay using 2,3-dimethoxy-1,4-napthoquinone. Results: ASD-NDR children were found to have higher respiratory rates with mitochondria that were more sensitive to physiological stress as compared to ASD-NoNDR children, similar to our cellular model of NDR. Differences in mitochondrial respiration between ASD-NDR and TD siblings were similar to the differences between ASD-NDR and ASD-NoNDR children. Interesting, parents of children with ASD and NDR demonstrated patterns of mitochondrial respiration similar to their children such that parents of children with ASD and NDR demonstrated elevated respiratory rates with mitochondria that were more sensitive to physiological stress. In addition, sex differences were seen in ASD children and parents. Age effects in parents suggested that mitochondria of older parents were more sensitive to physiological stress. Conclusion: This study provides further evidence that children with ASD and NDR may have a unique type of mitochondrial physiology that may make them susceptible to physiological stressors. Identifying these children early in life before NDR occurs and providing treatment to protect mitochondrial physiology may protect children from experiencing NDR. The fact that parents also demonstrate mitochondrial respiration patterns similar to their children implies that this unique change in mitochondrial physiology may be a heritable factor (genetic or epigenetic), a result of shared environment, or both.

Exploring Genetic and Neural Risk of Specific Reading Disability within a Nuclear Twin Family Case Study: A Translational Clinical Application.

Imaging and genetic studies have characterized biological risk factors contributing to specific reading disability (SRD). The current study aimed to apply this literature to a family of twins discordant for SRD and an older sibling with reading difficulty. Intraclass correlations were used to understand the similarity of imaging phenotypes between pairs. Reading-related genes and brain region phenotypes, including asymmetry indices representing the relative size of left compared to right hemispheric structures, were descriptively examined. SNPs that corresponded between the SRD siblings and not the typically developing (TD) siblings were in genes ZNF385D, LPHN3, CNTNAP2, FGF18, NOP9, CMIP, MYO18B, and RBFOX2. Imaging phenotypes were similar among all sibling pairs for grey matter volume and surface area, but cortical thickness in reading-related regions of interest (ROIs) was more similar among the siblings with SRD, followed by the twins, and then the TD twin and older siblings, suggesting cortical thickness may differentiate risk for this family. The siblings with SRD had more symmetry of cortical thickness in the transverse temporal and superior temporal gyri, while the TD sibling had greater rightward asymmetry. The TD sibling had a greater leftward asymmetry of grey matter volume and cortical surface area in the fusiform, supramarginal, and transverse temporal gyrus. This exploratory study demonstrated that reading-related risk factors appeared to correspond with SRD within this family, suggesting that early examination of biological factors may benefit early identification. Future studies may benefit from the use of polygenic risk scores or machine learning to better understand SRD risk.

Perceived Social Support, Normalization, and Subjective Well-Being Among Family Members of a Child with Autism Spectrum Disorder.

The experience of family members of children with autism spectrum disorder (ASD) is not uniform. This study focused on mothers of a child with ASD (Study 1) and typically developing siblings (TDSs) during their emerging adulthood (Study 2). Similarities and differences were explored regarding a proposed model examining the paths of perceived social support (PSS) and normalization (a coping strategy) with subjective well-being: satisfaction with life (SWL) and positive affect (PA). Similarities were found in the paths between PSS, normalization, and SWL, in mothers and TDSs, but differences emerged regarding PA. These findings highlight the importance of PSS as a resource that contributes to normalization and SWL. Professional awareness of family members' PSS and their engagement in normalization is needed.

What If You Can't Ask Them? Psychometric Properties of a Behavioral Assessment of Sibling Relationship Quality.

Building on studies of preferences for social interaction in children with autism spectrum disorder (ASD) we sought to provide a way for siblings with ASD to express their perspective about the quality of their sibling relationships. We developed a behavioral assessment of sibling relationship preference (Sibling Relationship Assessment [SRA]) and examined the psychometric properties of test-retest reliability, inter-rater reliability, and convergent validity. The SRA was feasible to administer and revealed expected differences between sibling dyads with one sibling with ASD compared to typically-developing sibling dyads. We found strong positive correlations for inter-rater reliability and test-retest reliability and convergent validity. The SRA provides a way to assess the perspective of the sibling with ASD that taps one characteristic, preference for spending time with one's sibling, of the quality of sibling relationships.

Predicting typically-developing siblings’ acceptance of their sibling with ASD during emerging adulthood

BackgroundTypically-developing siblings’ (TDS) acceptance of a brother or sister with AutismSpectrum Disorder (ASD) has been minimally explored, despite the life-long nature ofthese relationships and the potential impact on future involvement with and care of thesibling. This study focused on TDS during the complicated time of emerging adulthood, which is characterized by increasing independence and identity formation. AimsGrounded in Siblings Embedded Systems Framework, the study examined emergingadult TDS’ acceptance of their sibling with ASD, and variables predicting acceptance. Specifically, demographic variables, including those relating to emerging adulthood (marital status, occupation), internal resources (emotions towards siblings, optimism, sense of coherence) and social support were examined. Methods & proceduresThe study included 237 TDS (Mage=22) of children with ASD (Mage=17), andsome with ASD and intellectual developmental disorder (IDD). Participants completedsix self-report questionnaires. ResultsTD sisters were more accepting than brothers, and employed siblings, married siblings, and those affiliating with more religious streams reported higher levels of acceptance. Differences in acceptance, and in how internal resources and social support predictedacceptance, were found based on the presence/absence of IDD. Conclusions & implicationsThe study provides insight into TDS’ acceptance, and indicates that emergingadult TDS are an important group for their sibling’s future care. Developing programs toincrease the support for emerging adult TDS is needed.

The Relation of Parental Expressed Emotion, Parental Affiliate Stigma, and Typically-developing Sibling Internalizing Behavior in Families with a Child with ASD.

Caregivers of children with autism spectrum disorder (ASD) experience greater stress, expressed emotion (EE), and affiliate stigma than caregivers of children without ASD. Siblings of children with ASD often experience greater negative functioning than siblings of individuals without ASD. The current study found significant interrelations among symptom severity and externalizing behavior in children with ASD; parental stress, affiliate stigma, and EE; and TD sibling internalizing behavior. In addition, certain subcomponents of affiliate stigma predicted unique variance in EE and TD sibling internalizing behavior. Findings may increase understanding of psychosocial functioning in families with children with ASD and allow clinicians to improve outcomes for all family members. Limitations of the study included self-report data, limited sample diversity, and a cross-sectional design.

Urinary Untargeted Metabolic Profile Differentiates Children with Autism from Their Unaffected Siblings.

Autism Spectrum Disorder (ASD) encompasses a clinical spectrum of neurodevelopmental conditions that display significant heterogeneity in etiology, symptomatology, and severity. We previously compared 30 young children with idiopathic ASD and 30 unrelated typically-developing controls, detecting an imbalance in several compounds belonging mainly to the metabolism of purines, tryptophan and other amino acids, as well as compounds derived from the intestinal flora, and reduced levels of vitamins B6, B12 and folic acid. The present study describes significant urinary metabolomic differences within 14 pairs, including one child with idiopathic ASD and his/her typically-developing sibling, tightly matched by sex and age to minimize confounding factors, allowing a more reliable identification of the metabolic fingerprint related to ASD. By using a highly sensitive, accurate and unbiased approach, suitable for ensuring broad metabolite detection coverage on human urine, and by applying multivariate statistical analysis, we largely replicate our previous results, demonstrating a significant perturbation of the purine and tryptophan pathways, and further highlight abnormalities in the “phenylalanine, tyrosine and tryptophan” pathway, essentially involving increased phenylalanine and decreased tyrosine levels, as well as enhanced concentrations of bacterial degradation products, including phenylpyruvic acid, phenylacetic acid and 4-ethylphenyl-sulfate. The outcome of these within-family contrasts consolidates and extends our previous results obtained from unrelated individuals, adding further evidence that these metabolic imbalances may be linked to ASD rather than to environmental differences between cases and controls. It further underscores the excess of some gut microbiota-derived compounds in ASD, which could have diagnostic value in a network model differentiating the metabolome of autistic and unaffected siblings. Finally, it points toward the existence of a “metabolic autism spectrum” distributed as an endophenotype, with unaffected siblings possibly displaying a metabolic profile intermediate between their autistic siblings and unrelated typically-developing controls.

Affiliated stigma and contact frequency in sibling relationships of adults with intellectual disabilities: The mediation of relational motivations

Background: Typically developing (TD) siblings play a crucial role in promoting the health and well-being of adults with intellectual disabilities. Their involvement in the sibling relationship during adulthood may predict their likelihood of providing care to the sibling with intellectual disabilities (ID). However, different types of motivations (discretionary and obligatory) related to the contact frequency of TD siblings have not been fully explored. Little is known about how their negative experiences, such as affiliated stigma, influences relational motivations, which consequently affect contact frequency. This study examined these links in a Chinese context. Method: In total, 1,298 Chinese siblings were surveyed using questionnaires, and structural equation modelling was used to test the mediation effect. Results: Contact frequencies of TD siblings were significantly affected by discretionary motivation, obligatory motivation, and stigma experiences. The findings supported the mediating effect of obligatory motivation in the relationship between affiliated stigma and contact frequency. Conclusion: This study is among the first to examine whether the relational motivation of TD siblings predicts their contact frequency within their relationships with adult siblings with ID. We found that both types of relational motivations of TD siblings positively predicted contact behavior.

Analysis of gait synchrony and balance in neurodevelopmental disorders using computer vision techniques.

Gait tasks are commonly administered during motor assessments of children with neurodevelopmental disorders (NDDs). Gait analyses are often conducted in laboratory settings using costly and cumbersome experiments. In this paper, we propose a computational pipeline using computer vision techniques as an ecological and precise method to quantify gait in children with NDDs with challenging behaviors. We analyzed videos of 15 probands (PB) and 12 typically developing (TD) siblings, engaged in a preferred-pace walking task, using pose estimation software to track points of interest on their bodies over time. Analyzing the extracted information revealed that PB children had significantly less whole-body gait synchrony and poorer balance compared to their TD siblings. Our work offers a cost-effective method while preserving the validity of its results. This remote approach increases access to more diverse and distant cohorts and thus lowers barriers to research participation, further enriching our understanding of motor outcomes in NDDs.

The Impact of COVID-19 on Anxiety and Worries for Families of Individuals with Special Education Needs and Disabilities in the UK

COVID-19 has affected people across the world. The current study examined anxiety and worries during the first UK national lockdown in March 2020. Parents (n = 402) reported on their own anxiety and worries as well as that of their son/daughter with Special Education Needs and Disabilities (SEND) and typically developing (TD) child (n = 186) at three time points. Although both groups showed increased anxiety across the three time points, levels of anxiety in the SEND group, but not the TD siblings, were predicted by awareness about COVID-19. In addition, worries differed between the groups showing that COVID-19 impacts the wellbeing of those with SEND differently to that of their TD siblings.

Seeing the siblings: Gender differences in emerging-adult siblings of individuals with autism spectrum disorder

BackgroundThe present study focused on typically developing siblings (TDS) in emerging adulthood of individuals with autism spectrum disorder (ASD) and sought insight into how gender may interact with positive and negative affects in this population. In addition, we aimed to explore the gender differences as a moderator in the link between personal resources (i.e., family cohesion and flexibility coping strategy) and positive and negative affects among such TDS. An understanding of gender differences in this population should prove relevant to the development of potential interventions. MethodA total of 116 emerging adult (age 18–29) TDS of younger siblings with ASD (the latter were under the age of 18 at the time of data collection), 80 females and 36 males, participated in the study. All participants completed self-report measures. ResultsFemale TDS reported higher negative affect than male TDS, while no differences emerged regarding positive affect. Female siblings reported higher family cohesion and higher flexibility in the forward-focused subscale of flexibility coping strategy, but not in its trauma-focused subscale, compared to male siblings. Additionally, gender moderates the links between family cohesion and positive affect but not negative affect. Gender also moderates the association between flexibility and negative affect, but not positive affect. ConclusionsThis study highlights the gender differences among TDS in emerging adulthood of individuals with ASD in relation to negative affect, family cohesion, and flexibility coping strategy.Understanding the gender-specific internal and external experiences of TDS as interplaying with their resources, at the unique developmental stage of emerging adulthood, may afford to identify TDS in need and to suggest potential interventions.

The Moderating Role of Self-Disclosure Among Typically Developing Siblings of Individuals with Autism Spectrum Disorder

Typically developing siblings (TDS) of individuals with Autism Spectrum Disorder (ASD) often have high caregiving responsibilities for parents (parent-focused parentification; PFP) or siblings (sibling-focused parentification; SFP). Prior research demonstrates that PFP is associated with TDS’ adjustment risk whereas SFP is associated with positive sibling relationships and social support moderates these associations. The purpose of the present study (N = 108) was to extended prior work by examining self-disclosure of worries about siblings with ASD to parents as a moderator between both parentification roles and TDS’ relational and adjustment outcomes. TDS college students ages 18 to 24 (M = 20.37, SD = 1.55) completed online surveys assessing parentification, disclosure, negative sibling interactions, depressive symptoms, well-being, and self-esteem. High disclosure to parents was protective against risk to well-being at high levels of PFP, which suggests a family pattern in which TDS’ caregiving is reciprocated by parents to underscore the importance of parents as a critical source of social support for TDS during the transition to adulthood. The impact of disclosure was more nuanced in the context of sibling-focused parentification; high disclosure to parents was associated with risk to sibling relationships at high levels of SFP and enhanced well-being at low levels of SFP, suggesting that the benefit of self-disclosure is not maintained when TDS’ responsibilities for siblings are too great.

Influences of parentification and benefit finding on prosocial behavior among typically developing siblings of individuals with autism spectrum disorder

BackgroundPrior research examining typically developing siblings (TDS) of individuals with Autism Spectrum Disorder (ASD) reports both higher and lower levels of prosocial behavior among TDS. TDS’ experiences (parent-focused parentification, sibling-focused parentification) and perceptions of experiences (ASD benefit finding, role benefit finding) may interact to influence TDS prosocial behavior. Aims1) Examine influences of TDS’ experiences and perceptions of TDS experiences on prosocial behavior and 2) examine interactions between TDS’ experiences of parentification and perceptions of experiences influencing prosocial behavior while controlling for the Broad Autism Phenotype (BAP). Methods and proceduresTDS [N = 108; M(SD) age = 20.37(1.55)] were college students who reported having a sibling with ASD, defined as “Autism Spectrum Disorder”, “Autism”, “Asperger’s”, and “Pervasive Developmental Disability”. TDS completed an online survey about their experiences and perceptions of experiences. Outcomes and resultsControlling for gender and BAP, there was a significant interaction between ASD benefit finding and sibling-focused parentification such that at low levels of ASD benefit finding, sibling-focused parentification negatively predicted prosocial behavior. Lower BAP scores and female gender were associated with greater levels of prosocial behavior. Conclusions and implicationsTDS experiences and perceptions of experiences are important for understanding TDS prosocial behavior.

Adult siblings of people with and without intellectual and developmental disabilities: Sibling relationship attitudes and psychosocial outcomes

There is still little research on the relationships between adults with intellectual and developmental disabilities and their typically-developing siblings, despite the importance of these ties for siblings’ psychological well-being, especially in terms of depression, anxiety, and life satisfaction. In this study, the sibling relationship attitudes of adult siblings of people with (N = 133) and without (N = 140) intellectual and developmental disabilities were explored. Feelings, behaviors, and thoughts related to sibling relationships were measured using the Lifespan Sibling Relationship Scale; depression was measured using the Beck Depression Inventory-II; anxiety was measured using the Beck Anxiety Inventory; and life satisfaction was measured using the Satisfaction With Life Scale. Results indicate that higher levels of positive sibling relationship attitudes are negatively related to levels of depression and anxiety, and positively related to levels of life satisfaction. Furthermore, adult siblings of people with intellectual and developmental disabilities show less positive sibling relationship attitudes, higher levels of depression and anxiety, and lower levels of life satisfaction. Finally, group membership, indirectly through sibling relationship attitudes, was related to depressive and anxious symptoms, as well as to life satisfaction. Implications for future research and policies are discussed.

The quality of the relationship between typically developing children and their siblings with and without intellectual disability: Insights from children's drawings

The current study examined the relationships of typically developing (TD) children with siblings with and without intellectual disabilities (ID), as expressed in TD children's drawings and questionnaires answered by TD children and their mothers. It also examined group differences in the sibling relationships, as well as the associations between having a sibling with or without ID and sibling relationships, and TD children's social-emotional adjustment. Participants were mothers and their TD children (8–13 years). Some had ID siblings ID (N=28); others had TD siblings (N=31). Sibling relationships were examined via mothers' and target children's completion of questionnaires, and objective visual indicators (location, size, distance) and observed content-based indicators (support, investment, presence of parents) of children's drawings were assessed following the art-based phenomenological analytic approach. Mothers reported on children's social-emotional adjustment. Findings indicated differences in sibling relationships, including higher levels of positive relationships for children with ID siblings. Children's drawings also showed positive relationship aspects for these children. Sibling relationship qualities were significantly associated with children's adjustment. Children's drawings may be a useful data gathering tool to deepen our understanding of unique aspects of sibling relationships.

Augmenting Sibling Support with Parent-Sibling Training in Families of Children with Autism

ABSTRACT Background: Typically developing (TD) siblings are an important part of the family system, but may show strained relationships in families of children with ASD. Objective: We augmented a sibling support group with parent-sibling training in which parents learned (through instructions, modeling, rehearsal, and feedback) how to prompt and reinforce prosocial behaviors in their TD children. Method: We examined the effects of parent-sibling training on parent and TD sibling behaviors in a multiple baseline across families design. Results: Parent prompting and reinforcement of TD sibling prosocial behaviors increase. TD sibling prosocial behaviors such as sharing with and talking to their sibling with ASD also increased. Broader measures of the sibling relationship showed some improvements. Conclusion: Findings suggest ways to support families of children with ASD with future investigations of parent-sibling training examining longer intervention, all family members’ adjustment and relationships, and sibling characteristics that influence response to parent-sibling training.

Cortical surface architecture endophenotype and correlates of clinical diagnosis of autism spectrum disorder.

Prior structural magnetic resonance imaging studies demonstrated atypical gray matter characteristics in siblings of individuals with autism spectrum disorder (ASD). However, they did not clarify which aspect of gray matter is related to the endophenotype (i.e., genetic vulnerability) of ASD. Further, because they did not enroll siblings of typically developing (TD) people, they may have underestimated the difference between individuals with ASD and their unaffected siblings. The current study aimed to address these gaps. We recruited 30 pairs of adult male siblings (15 pairs with an ASD endophenotype and 15 pairs without) and focused on four gray matter parameters: cortical volume and three surface-based parameters (cortical thickness, fractal dimension, and sulcal depth [SD]). First, we sought to identify a pattern of an ASD endophenotype, comparing the four parameters. Then, we compared individuals with ASD and their unaffected siblings in the cortical parameters to identify neural correlates for the clinical diagnosis accounting for the difference between TD siblings. A sparse logistic regression with a leave-one-pair-out cross-validation showed the SD as having the highest accuracy for the identification of an ASD endophenotype (73.3%) compared with the other three parameters. A bootstrapping analysis accounting for the difference in the SD between TD siblings showed a significantly large difference between individuals with ASD and their unaffected siblings in six out of 68 regions of interest. This proof-of-concept study suggests that an ASD endophenotype emerges in the SD and that neural bases for ASD diagnosis can be discerned from the endophenotype when accounting for the difference between TD siblings.

When One Sibling has Autism: Adjustment and Sibling Relationship

The presence of autism spectrum disorder (ASD) in one sibling can impact typically developing (TD) siblings’ adjustment and quality of the sibling relationship. The present study examined the impact of sibling characteristics on both the sibling relationship and adjustment in TD siblings using self, parent, and clinician reports. Fifty-two TD siblings and parents completed questionnaires about TD sibling adjustment and sibling relationship quality. Greater behavior difficulties in siblings with ASD related to poorer TD sibling adjustment and quality of the sibling relationship. A more positive TD sibling perception of the sibling relationship was associated with greater TD sibling coping and support. Findings are discussed in terms of how these risk factors can inform interventions.

Machine learning approach to identify a resting-state functional connectivity pattern serving as an endophenotype of autism spectrum disorder.

Endophenotype refers to a measurable and heritable component between genetics and diagnosis, and the same endophenotype is present in both individuals with a diagnosis and their unaffected siblings. Determination of the neural correlates of an endophenotype and diagnosis is important in autism spectrum disorder (ASD). However, prior studies enrolling individuals with ASD and their unaffected siblings have generally included only one group of typically developing (TD) subjects; they have not accounted for differences between TD siblings. Thus, they could not differentiate the neural correlates for endophenotype from the clinical diagnosis. In this context, we enrolled pairs of siblings with an ASD endophenotype (individuals with ASD and their unaffected siblings) and pairs of siblings without this endophenotype (pairs of TD siblings). Using resting-state functional MRI, we first aimed to identify an endophenotype pattern consisting of multiple functional connections (FCs) then examined the neural correlates of FCs for ASD diagnosis, controlling for differences between TD siblings. Sparse logistic regression successfully classified subjects as to the endophenotype (area under the curve = 0.78, classification accuracy = 75%). Then, a bootstrapping approach controlling for differences between TD siblings revealed that an FC between the right middle temporal gyrus and right anterior cingulate cortex was substantially different between individuals with ASD and their unaffected siblings, suggesting that this FC may be a neural correlate for the diagnosis, while the other FCs represent the endophenotype. The current findings suggest that an ASD endophenotype pattern exists in FCs, and a neural correlate for ASD diagnosis is dissociable from this endophenotype. (250 words).

Siblings’ experiences of growing up with children with autism in Taiwan and the United Kingdom

BackgroundA child’s diagnosis of autism impacts their whole family, in both positive and negative ways, that may be influenced by cultural beliefs. AimsWe aimed to describe the experiences of mothers and typically-developing siblings of children with autism in two cultural contexts. MethodsFourteen mother-sibling dyads from Taiwan and the UK participated in semi-structured interviews. ResultsWhilst there were similarities in sibling experiences, a negative tone regarding the influence of autism was more evident in Taiwan, where families also cited societal judgement and cultural-specific expectations. In the UK, a more balanced tone was apparent: mothers emphasised educating and involving the siblings. It is speculated that UK siblings had a greater understanding of their parents’ stress, leading to more adaptive family dynamics. Various types of support service were mentioned in the UK, whereas the availability of social services and support appeared to be relatively limited in Taiwan. ImplicationsOur data suggest that cultural context may have a significant impact on the responses of the family members. This is mediated by both differences in attitudes and traditions, and availability of resources. Support for family members needs to be sensitive to such cultural differences, as well as recognising positive experiences.