Trajectories of Competitive Employment of Autistic Adults through Late Midlife.

Autistic adults experience challenges in maintaining employment; however, little is known about patterns of competitive employment through late midlife. This longitudinal study examined the change in hours of competitive employment for a cohort of autistic adults over a 22-year period. The study's aims were to provide a fine-grained analysis of competitive employment patterns, to determine whether there was age-related change, and to test whether trajectories differed between those with and without intellectual disability (ID). Using an accelerated longitudinal design, trajectories of hours of competitive employment were estimated from young adulthood through late midlife in a community-based cohort (n = 341; 1327 observations). Results indicated a significant curvilinear trajectory of age-related change in hours of competitive employment, with differences between those with and without ID. For those without ID, the number of competitive employment hours increased from young adulthood until early midlife, then leveled off and decreased into late midlife. For those with ID, engagement in competitive employment was low throughout. Although competitive employment is just one option for vocational engagement, it is a goal often articulated by autistic adults who seek entry into the general workforce. The present research reveals their degree of engagement in the competitive workforce across the decades of adulthood.

Impact of the Great Recession on Adults With Autism and Their Mothers.

Autistic individuals and their families are at risk for poor outcomes in employment and mental health and may be vulnerable to long-term effects of broader societal conditions. The aim of the current longitudinal study was to understand the impact of the Great Recession of 2007-2009 on autistic individuals and their mothers (N = 392). Hierarchical linear modeling (HLM) results indicated that problem behavior of autistic adults increased in the years following the recession. The rate at which autistic individuals moved away and lived separately from their mothers also slowed during the recession. Mothers experienced significantly higher levels of depressive symptoms postrecession, compared to prerecession. In many other respects, the autistic individuals and their mothers did not experience negative outcomes, suggesting resilience and a strong safety net. These included the physical health and vocational/employment status of the autistic adults and their mothers. Results point to specific areas of vulnerability of autistic individuals and their mothers during the economic downturn, as well as a broad pattern of resilience in these families.

Autism through midlife: trajectories of symptoms, behavioral functioning, and health.

BACKGROUND: This study describes change in autism symptoms, behavioral functioning, and health measured prospectively over 22 years. Most studies tracking developmental trajectories have focused on autism during childhood, although adulthood is the longest stage of the life course. A robust understanding of how autistic people change through midlife and into older age has yet to be obtained. METHODS: Using an accelerated longitudinal design with 9 waves of data, developmental trajectories were estimated from adolescence through midlife and into early old age in a community-based cohort (n = 406). The overall aim was to determine whether there were age-related increases or decreases, whether the change was linear or curvilinear, and whether these trajectories differed between those who have ID and those who have average or above-average intellectual functioning. Subsequently, the slopes of the trajectories were evaluated to determine if they differed depending on age when the study began, with the goal of identifying possible cohort effects. RESULTS: There were significant trajectories of age-related change for all but one of the measures, although different measures manifested different patterns. Most autism symptoms improved through adulthood, while health worsened. An inverted U-shaped curve best described change for repetitive behavior symptoms, activities of daily living, maladaptive behaviors, and social interaction. For these measures, improved functioning was evident from adolescence until midlife. Then change leveled off, with worsening functioning from later midlife into early older age. Additionally, differences between autistic individuals with and without ID were evident. Although those who have ID had poorer levels of functioning, there were some indications that those without ID had accelerating challenges in their aging years that were not evident in those with ID - increases in medications for physical health problems and worsening repetitive behaviors. CONCLUSIONS: Meeting the needs of the increasingly large population of autistic adults in midlife and old age requires a nuanced understanding of life course trajectories across the long stretch of adulthood and across multiple domains. Given the heterogeneity of autism, it will be important not to generalize across sub-groups, for example those who are minimally verbal and those who have above-average intellectual functioning.

Mortality in Women across the FMR1 CGG Repeat Range: The Neuroprotective Effect of Higher Education.

Higher education has been shown to have neuroprotective effects, reducing the risk of Alzheimer's and Parkinson's diseases, slowing the rate of age-related cognitive decline, and is associated with lower rates of early mortality. In the present study, the association between higher education, fragile X messenger ribonucleoprotein 1 (FMR1) cytosine-guanine-guanine (CGG) repeat number, and mortality before life expectancy was investigated in a population cohort of women born in 1939. The findings revealed a significant interaction between years of higher education and CGG repeat number. Counter to the study's hypothesis, the effects of higher education became more pronounced as the number of CGG repeats increased. There was no effect of years of higher education on early mortality for women who had 25 repeats, while each year of higher education decreased the hazard of early mortality by 8% for women who had 30 repeats. For women with 41 repeats, the hazard was decreased by 14% for each additional year of higher education. The interaction remained significant after controlling for IQ and family socioeconomic status (SES) measured during high school, as well as factors measured during adulthood (family, psychosocial, health, and financial factors). The results are interpreted in the context of differential sensitivity to the environment, a conceptualization that posits that some people are more reactive to both negative and positive environmental conditions. Expansions in CGG repeats have been shown in previous FMR1 research to manifest such a differential sensitivity pattern.

Insight and Recommendations for Fragile X-Premutation-Associated Conditions from the Fifth International Conference on FMR1 Premutation.

The premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene is characterized by an expansion of the CGG trinucleotide repeats (55 to 200 CGGs) in the 5' untranslated region and increased levels of FMR1 mRNA. Molecular mechanisms leading to fragile X-premutation-associated conditions (FXPAC) include cotranscriptional R-loop formations, FMR1 mRNA toxicity through both RNA gelation into nuclear foci and sequestration of various CGG-repeat-binding proteins, and the repeat-associated non-AUG (RAN)-initiated translation of potentially toxic proteins. Such molecular mechanisms contribute to subsequent consequences, including mitochondrial dysfunction and neuronal death. Clinically, premutation carriers may exhibit a wide range of symptoms and phenotypes. Any of the problems associated with the premutation can appropriately be called FXPAC. Fragile X-associated tremor/ataxia syndrome (FXTAS), fragile X-associated primary ovarian insufficiency (FXPOI), and fragile X-associated neuropsychiatric disorders (FXAND) can fall under FXPAC. Understanding the molecular and clinical aspects of the premutation of the FMR1 gene is crucial for the accurate diagnosis, genetic counseling, and appropriate management of affected individuals and families. This paper summarizes all the known problems associated with the premutation and documents the presentations and discussions that occurred at the International Premutation Conference, which took place in New Zealand in 2023.

Health Effects of Sleep Quality in Premutation Carrier Mothers of Individuals With Fragile X Syndrome.

Sleep plays an integral role in supporting well-being, and sleep difficulties are common in mothers of individuals with developmental disabilities, including fragile X syndrome (FXS). This study assessed whether the effects of sleep quality on physical health and depression are exacerbated by genetic risk factors (CGG repeats) in FMR1 premutation carrier mothers of individuals with FXS. Poor sleep quality predicted a greater number of physical health conditions for mothers with CGG repeats in the mid-premutation range (90-110 repeats), but not for those in the lower (< 90 repeats) or higher (> 110 repeats) ends of the range. A significant association between poor sleep quality and maternal depressive symptoms was also observed, but there was no evidence that this effect varied by level of genetic vulnerability. This research extends our understanding of individual differences in the effects of sleep quality among mothers of individuals with FXS.

Improving Retention of Diverse Samples in Longitudinal Research on Developmental Disabilities.

Developmental disabilities (DD) research has depended on volunteer and clinical samples, with limited racial/ethnic diversity. This study focused on improving diversity and retention in DD research. The sample included 225 parents with a child with DD and 4,002 parents without children with DD from diverse racial/ethnic groups, drawn from Midlife in the United States, a national longitudinal study. Unexpectedly, parents of children with DD from diverse racial/ethnic groups were more likely to participate longitudinally than other groups. Relative participant payment was a factor that enhanced their likelihood of retention. This research illustrates how large national studies can be leveraged to increase representativeness and ongoing participation of diverse racial/ethnic groups, especially in combination with other factors, such as parenting a child with DD.

Social Network Diversity and Mental Health Among Mothers of Individuals With Autism.

The present study examined the associations between networks of social relationships and psychological well-being among mothers of adolescents and adults with autism (n = 352) over a 12-year period of time. A structural equation modeling approach was used to delineate the relative impacts of network size and relationship diversity on maternal mental health, and to assess whether such effects are bidirectional. Mothers with more diverse relationships experienced reductions in depression and anxiety symptoms over time, and the psychological benefits of diversity remained after adjusting for network size. Results also suggest bidirectional links between network size, diversity, and maternal mental health. Research and clinical implications are discussed.

FMR1 CGG Repeats and Stress Influence Self-Reported Cognitive Functioning in Mothers.

Variation in the FMR1 gene may affect aspects of cognition, such as executive function and memory. Environmental factors, such as stress, may also negatively impact cognitive functioning. Participants included 1,053 mothers of children with and without developmental disabilities. Participants completed self-report measures of executive function, memory, and stress (i.e., life events, parenting status), and provided DNA to determine CGG repeat length (ranging from 7 to 192 CGGs). Stress exposure significantly predicted greater self-reported difficulties in executive function and the likelihood of memory problems. Cubic CGG effects independently predicted executive function and memory difficulties, suggesting effects of both genetic variation and environmental stress exposure on cognitive functioning.

The effect of college degree attainment on neurodegenerative symptoms in genetically at-risk women.

Using longitudinal data, the present study examined the association between college degree attainment and the manifestation of neurodegenerative symptoms among women (n = 93) at elevated genetic risk. The neurodegenerative symptoms investigated in this study are due to FXTAS (Fragile X-associated Tremor/Ataxia Syndrome), a condition with onset after age 50. Those at risk for FXTAS have a mutation of a single gene found on the X chromosome. FXTAS is characterized by intention tremor, gait ataxia, executive function deficits, memory issues, and neuropathy. College degree attainment has been shown to provide neuroprotective effects in the general population, delaying the development of neurodegenerative conditions such as Alzheimer's disease. For this reason, college degree attainment is a potentially salient resource for those at risk of FXTAS. The results of the present research indicated significantly more severe FXTAS symptoms in women who did not attain a college degree as compared with those who were college graduates, although the two groups were similar in age, genetic risk, household income, health behaviors, and general health problems. Furthermore, symptoms in those who did not attain a college degree worsened over the 9-year study period at a significantly faster rate than the college graduates. The association between college degree attainment and FXTAS symptoms was significantly mediated by depression, which was lower among the graduates than those who did not attain a college degree. Thus, the present research is an example of how a sociodemographic factor can mitigate neurodegenerative conditions in genetically at-risk adults.

Advancing artificial intelligence-assisted pre-screening for fragile X syndrome.

BACKGROUND: Fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism, is significantly underdiagnosed in the general population. Diagnosing FXS is challenging due to the heterogeneity of the condition, subtle physical characteristics at the time of birth and similarity of phenotypes to other conditions. The medical complexity of FXS underscores an urgent need to develop more efficient and effective screening methods to identify individuals with FXS. In this study, we evaluate the effectiveness of using artificial intelligence (AI) and electronic health records (EHRs) to accelerate FXS diagnosis. METHODS: The EHRs of 2.1 million patients served by the University of Wisconsin Health System (UW Health) were the main data source for this retrospective study. UW Health includes patients from south central Wisconsin, with approximately 33 years (1988-2021) of digitized health data. We identified all participants who received a code for FXS in the form of International Classification of Diseases (ICD), Ninth or Tenth Revision (ICD9 = 759.83, ICD10 = Q99.2). Only individuals who received the FXS code on at least two occasions ("Rule of 2") were classified as clinically diagnosed cases. To ensure the availability of sufficient data prior to clinical diagnosis to test the model, only individuals who were diagnosed after age 10 were included in the analysis. A supervised random forest classifier was used to create an AI-assisted pre-screening tool to identify cases with FXS, 5 years earlier than the time of clinical diagnosis based on their medical records. The area under receiver operating characteristic curve (AUROC) was reported. The AUROC shows the level of success in identification of cases and controls (AUROC = 1 represents perfect classification). RESULTS: 52 individuals were identified as target cases and matched with 5200 controls. AI-assisted pre-screening tool successfully identified cases with FXS, 5 years earlier than the time of clinical diagnosis with an AUROC of 0.717. A separate model trained and tested on UW Health cases achieved the AUROC of 0.798. CONCLUSIONS: This result shows the potential utility of our tool in accelerating FXS diagnosis in real clinical settings. Earlier diagnosis can lead to more timely intervention and access to services with the goal of improving patients' health outcomes.

Change in Maladaptive Behavior Affects Intergenerational Relationships in Fragile X Syndrome.

This study investigated the bidirectional effects of change in maladaptive behaviors among adolescents and adults with fragile X syndrome (FXS) and change in their intergenerational family relationships over a 7.5-year period. Indicators of the intergenerational family relationship between premutation carrier mothers and their adolescent or adult son/daughter with FXS included a measure of the quality of the relationship, as well as descriptions provided by mothers of their relationship with their son/daughter (positive remarks, critical remarks). Maladaptive behaviors decreased, maternal positive remarks increased, and maternal critical remarks and relationship quality remained stable over time. Bidirectional effects of change were observed in predicting maladaptive behaviors and maternal positive remarks, although maladaptive behaviors more strongly predicted positive remarks than the reciprocal association. This research suggests prioritizing maladaptive behaviors in the context of family interventions.

Verbal inhibition declines among older women with high FMR1 premutation expansions: A prospective study.

The FMR1 premutation has been associated with difficulties in executive functioning, including verbal inhibition. However, little is known about the longitudinal profiles of verbal inhibition among FMR1 premutation carriers, particularly in women, and how individual factors such as aging and CGG repeat length may contribute to changes in verbal inhibition over time. The present study examined verbal inhibition performance (i.e., inhibition errors) on the Hayling Sentence Completion Task in a cohort of 92 women with the FMR1 premutation across two timepoints approximately three years apart. We examined the effects of age, CGG repeat length, and their interactions on verbal inhibition over time. We also evaluated whether response latency affected verbal inhibition errors. We found no significant change in verbal inhibition in the full cohort during the three-year study period. However, a subset of FMR1 premutation carriers, namely older participants with higher CGG repeats, evidenced greater declines in verbal inhibition over time. Longer response latencies did not compensate for verbal inhibition errors. The findings suggest that a subset of women with the FMR1 premutation may be at earlier, increased risk for changes in executive functioning, which if confirmed, should be considered as part of the clinical profile associated with the premutation.

Family history of FXTAS is associated with age-related cognitive-linguistic decline among mothers with the FMR1 premutation.

BACKGROUND: Women who carry a premutation allele of the FMR1 gene are at increased vulnerability to an array of age-related symptoms and disorders, including age-related decline in select cognitive skills. However, the risk factors for age-related decline are poorly understood, including the potential role of family history and genetic factors. In other forms of pathological aging, early decline in syntactic complexity is observed and predicts the later onset of neurodegenerative disease. To shed light on the earliest signs of degeneration, the present study characterized longitudinal changes in the syntactic complexity of women with the FMR1 premutation across midlife, and associations with family history of fragile X-associated tremor/ataxia syndrome (FXTAS) and CGG repeat length. METHODS: Forty-five women with the FMR1 premutation aged 35-64 years at study entry participated in 1-5 longitudinal assessments spaced approximately a year apart (130 observations total). All participants were mothers of children with confirmed fragile X syndrome. Language samples were analyzed for syntactic complexity and participants provided information on family history of FXTAS. CGG repeat length was determined via molecular genetic testing. RESULTS: Hierarchical linear models indicated that women who reported a family history of FXTAS exhibited faster age-related decline in syntactic complexity than those without a family history, with that difference emerging as the women reached their mid-50 s. CGG repeat length was not a significant predictor of age-related change. CONCLUSIONS: Results suggest that women with the FMR1 premutation who have a family history of FXTAS may be at increased risk for neurodegenerative disease, as indicated by age-related loss of syntactic complexity. Thus, family history of FXTAS may represent a personalized risk factor for age-related disease. Follow-up study is needed to determine whether syntactic decline is an early indicator of FXTAS specifically, as opposed to being a more general age-related cognitive decline associated with the FMR1 premutation.

Verbal Ability, Behavior Problems, and Mother-Child Relationship Quality in Autism Spectrum Disorder.

This study examined differences in mother-child relationship quality and parent-rated child behavior problems based on child verbal status (i.e., minimally verbal versus verbal) in mothers and their adolescent and adult children with autism spectrum disorder (n = 219 dyads; child Mage = 25.38 years, SD = 10.22). Relationship quality was assessed via parent-reported maternal burden and mother-child closeness, and coded speech samples ascertaining maternal critical and positive remarks regarding the child. Groups did not differ in relationship quality. The verbal group was more likely to display disruptive and socially inappropriate behaviors, but otherwise the groups did not differ in behavior problems. Verbal status moderated the relationship between behavior problems and negative (maternal burden, critical remarks) but not positive (mother-child closeness, positive remarks) aspects of relationship quality.

Social network typology and health among parents of children with developmental disabilities: Results from a national study of midlife adults.

OBJECTIVE: There is increasing interest in the role of contextual factors in promoting well-being among parents of children with developmental disabilities. This study aimed to examine whether social network types moderate the impacts of having a child with a developmental disability on parents' health. METHODS: Using cross-sectional data from the Midlife in the United States survey (MIDUS 2 and Refresher cohorts), we analyzed a sample of 363 parents of children with developmental disabilities and 4,919 parents of children without developmental disabilities. K-means cluster analysis was implemented to identify a social network typology. Modified Poisson and negative binomial regression models estimated the effect of having a child with a developmental disability and the typology on parents' physical health (self-rated health, number of chronic conditions) and mental health (self-rated mental health, major depression). RESULTS: The cluster analysis revealed two social network types. Parents of children with developmental disabilities were more likely to have "restricted/unsupported" networks, whereas parents in the comparison group were more likely to have "diverse/supported" networks. Social support was more important for differentiating the network types of parents of children with developmental disabilities, while social integration was more salient for the comparison group. Parents of children with developmental disabilities fared worse on all outcomes relative to parents of children without disabilities. However, the typology had a compensatory psychological effect; the diverse/supported network type conferred greater mental health benefits to parents of children with developmental disabilities than to those in the comparison group. The diverse/supported network type was also associated with better physical health, but the associations did not differ between the two parent groups. CONCLUSIONS: The results of this study emphasize the importance of social determinants of well-being for those with exceptional parenting responsibilities. Strengthening social networks may have a particularly positive impact on such parents' mental health.

Impact of Working Together for adults with autism spectrum disorder: a multifamily group intervention.

BACKGROUND: Adults with autism spectrum disorder (ASD) have lower engagement in their communities, higher rates of unemployment/underemployment, and continued difficulties with challenging behavior compared to their neurotypical peers. Multi-family psychoeducation emphasizes education and problem-solving with the goal of improving these outcomes for the individual with the disability. METHODS: Using a randomized waitlist control design, the present study evaluated a multi-family group psychoeducation intervention, Working Together, for adults on the autism spectrum without intellectual disability (n = 40). Five waves of data were collected at 3-month intervals. In this design, families in the intervention condition participated in intervention during the 6 months between baseline and time 3 data collection; the waitlist control condition received the intervention immediately after the time 3 data collection. We compared these two conditions, intervention group (n = 20) vs waitlist control group (n = 20), on key outcomes for the adults with ASD: engagement in work-related activities, engagement in meaningful activities, and behavior problems. RESULTS: Results indicated medium to large effect sizes associated with the Working Together intervention across key outcomes, including adults on the spectrum experiencing significant increases in meaningful activities and decreases in internalizing problems. Although increases in work-related activities were not statistically significant, an observed one-half of a standard deviation difference from before to after the intervention indicated clinically significant change. We also found maintenance of the treatment effect through 6 months post-treatment for the intervention group and replication of the treatment effect within the control group after they received the intervention. CONCLUSION: Working Together is a promising multi-family group psychoeducation intervention designed to improve functioning during adulthood. These findings highlight the need for more intervention services research during adulthood and specifically the need for family-centered supports.

Is FMR1 CGG Repeat Number Polymorphism Associated With Phenotypic Variation in the General Population? Report From a Cohort of 5,499 Adults.

FMR1 CGG repeat length was assayed in 5499 research participants (2637 men and 2862 women) in the Wisconsin Longitudinal Study (WLS), a population-based cohort. Most past research has focused on clinically-ascertained individuals with expansions in CGG repeats, either those with fragile X syndrome (> 200 CGG repeats), the FMR1 premutation (55-200 repeats), or in the gray zone (variously defined as 45-54 or 41-54 repeats). In contrast, the WLS is a unique source of data that was obtained from an unselected cohort of individuals from the general population for whom FMR1 CGG repeat length was assayed. The WLS is a random sample of one-third of all high school seniors in the state of Wisconsin in 1957. The most recent round of data collection was in 2011; thus, the study spanned over 50 years. Saliva samples were obtained from 69% of surviving members of the cohort in 2008 and 2011, from which CGG repeats were assayed. With one exception, the CGG repeat length of all members of this cohort was below 100 (ranging from 7 to 84). The present study evaluated the genotype-phenotype associations of CGG repeat number and IQ, college graduation, age at menopause, number of biological children, having a child with intellectual or developmental disabilities, and the likelihood of experiencing an episode of depression during adulthood. Linear and curvilinear effects were probed. Although effect sizes were small, significant associations were found between CGG repeat length and high school IQ score, college graduation, number of biological children, age at menopause, and the likelihood of having an episode of depression. However, there was no significant association between repeat length and having a child diagnosed with an IDD condition. This study demonstrates a continuum of phenotype effects with FMR1 repeat lengths and illustrates how research inspired by a rare genetic condition (such as fragile X syndrome) can be used to probe genotype-phenotype associations in the general population.