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BACKGROUND: Mindfulness-based stress reduction (MBSR) alleviates depression and anxiety in adults with autism spectrum disorder (ASD); however, underlying therapeutic neural mechanisms and mindfulness-specific effects have yet to be elucidated. METHODS: We randomly assigned adults with ASD to MBSR or social support/education (SE). They completed questionnaires that assessed depression, anxiety, mindfulness traits, autistic traits and executive functioning abilities as well as a self-reflection functional MRI task. We used repeated-measures analysis of covariance (ANCOVA) to evaluate behavioural changes. To identify task-specific connectivity changes, we performed a generalized psychophysiological interactions (gPPI) functional connectivity (FC) analysis on regions of interest (ROIs; insula, amygdala, cingulum and prefrontal cortex [PFC]). We used Pearson correlations to explore brain-behaviour relationships. RESULTS: Our final sample included 78 adults with ASD - 39 who received MBSR and 39 who received SE. Mindfulness-based stress reduction uniquely improved executive functioning abilities and increased mindfulness traits, whereas both MBSR and SE groups showed reductions in depression, anxiety and autistic traits. Decreases specific to MBSR in insula-thalamus FC were associated with anxiety reduction and increased mindfulness traits, including the trait "nonjudgment;" MBSR-specific decreases in PFC-posterior cingulate connectivity correlated with improved working memory. Both groups showed decreased amygdala-sensorimotor and medial-lateral PFC connectivity, which corresponded with reduced depression. LIMITATIONS: Larger sample sizes and neuropsychological evaluations are needed to replicate and extend these findings. CONCLUSION: Together, our findings suggest that MBSR and SE are similarly efficacious for depression, anxiety and autistic traits, whereas MBSR produced additional salutary effects related to executive functioning and mindfulness traits. Findings from gPPI identified shared and distinct therapeutic neural mechanisms, implicating the default mode and salience networks. Our results mark an early step toward the development of personalized medicine for psychiatric symptoms in ASD and offer novel neural targets for future neurostimulation research. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04017793.
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Transtorno do Espectro Autista , Atenção Plena , Humanos , Adulto , Atenção Plena/métodos , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/terapia , Ansiedade/psicologia , Transtornos de Ansiedade , Estresse Psicológico/diagnóstico por imagem , Estresse Psicológico/terapia , Apoio SocialRESUMO
The male preponderance in autism spectrum disorder (ASD) led to the hypothesis that aspects of female biology are protective against ASD. Females with ASD (ASD-F) report more compensatory behaviors (i.e. "camouflaging") to overcome ASD-related social differences, which may be a mechanism of protection. No studies have examined sex-related brain pathways supporting camouflaging in ASD-F, despite its potential to inform mechanisms underlying the ASD sex bias. We used functional connectivity (FC) to investigate "sex-atypical" and "sex-typical" FC patterns linked to camouflaging in adults with ASD and examined multimodal coherence of findings via structural connectometry. Exploratory associations with cognitive/emotional functioning examined the adaptive nature of FC patterns. We found (i) "sex-atypical" FC patterns linked to camouflaging in the hypothalamus and precuneus and (ii) "sex-typical" patterns in the right anterior cingulate and anterior parahippocampus. Higher hypothalamic FC with a limbic reward cluster also correlated with better cognitive control/emotion recognition. Structural connectometry validated FC results with consistent brain pathways/effect patterns implicated in ASD-F. In summary, "male-typical" and "female-typical" brain connectivity patterns support camouflaging in ASD-F in circuits implicated in reward, emotion, and memory retrieval. "Sex-atypical" results are consistent with fetal steroidogenic/neuroinflammatory hypotheses. However, female genetics/biology may contribute to "female-typical" patterns implicated in camouflaging.
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Transtorno do Espectro Autista , Transtorno Autístico , Masculino , Adulto , Humanos , Feminino , Transtorno do Espectro Autista/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Vias Neurais/diagnóstico por imagemRESUMO
Autism spectrum disorder (ASD) is a neurodevelopmental disability and recent evidence suggests that autistic adults are more likely to develop Alzheimer's disease (Alz) and other dementias compared to neurotypical (NT) adults. The ε4-allele of the Apolipoprotein E (APOE) gene is the strongest genetic risk factor for Alz and negatively impacts cognition in middle-aged and older (MA+) adults. This study aimed to determine the impact of the APOE ε4-allele on verbal learning and memory in MA+ autistic adults (ages 40-71 years) compared to matched NT adults. Using the Auditory Verbal Learning Test (AVLT), we found that ε4 carriers performed worse on short-term memory and verbal learning across diagnosis groups, but there was no interaction with diagnosis. In exploratory analyses within sex and diagnosis groups, only autistic men carrying APOE ε4 showed worse verbal learning (p = 0.02), compared to autistic men who were not carriers. Finally, the APOE ε4-allele did not significantly affect long-term memory in this sample. These findings replicate previous work indicating that the APOE ε4-allele negatively impacts short-term memory and verbal learning in MA+ adults and presents new preliminary findings that MA+ autistic men may be vulnerable to the effects of APOE ε4 on verbal learning. Future work with a larger sample is needed to determine if autistic women may also be vulnerable.
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Doença de Alzheimer , Transtorno do Espectro Autista , Transtorno Autístico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alelos , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Transtorno do Espectro Autista/genética , Transtorno Autístico/genética , Genótipo , Testes Neuropsicológicos , Aprendizagem VerbalRESUMO
PURPOSE: Adults with autism spectrum disorder (ASD) consistently report worse functional health and well-being, compared to neurotypical (NT) peers. In a series of studies, we aimed to elucidated the effects of sex, age, and their interaction on health-related quality of life (HRQoL) and evaluated the effectiveness of mindfulness-based stress reduction (MBSR) for improving health-, disability-, and autism-related QoL, with possible sex and age outcome moderators, in adults with ASD. METHODS: Study 1 used the 36-Item Short Form Survey to compare mental and physical HRQoL composite scores in adults with ASD (n = 67) and matched NT adults (n = 66). Study 2 was a randomized pilot evaluation of the effect of MBSR, compared to an active control intervention with social support and relaxation education (support/education; n = 56), on the World Health Organization QoL BREF, Disability, and Autism-Specific scales in adults with ASD. RESULTS: In Study 1, we replicated findings that mental HRQoL is worse in both men and women with ASD, compared to NT counterparts, but physical HRQoL is only worse in women with ASD. We present novel findings that older age is associated with better mental HRQoL in women with ASD only. In Study 2, MBSR improved disability-related QoL in adults with ASD over and above the support/education intervention, but both interventions improved mental HRQoL. Lastly, both interventions were more effective for HRQoL improvements in women with ASD. CONCLUSION: Findings encourage precision medicine approaches tailored to age and sex groups for best HRQoL outcomes in adults with ASD. CLINICALTRIALS: gov Identifier: NCT04017793.
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Transtorno do Espectro Autista , Atenção Plena , Adulto , Transtorno do Espectro Autista/terapia , Feminino , Humanos , Masculino , Projetos Piloto , Qualidade de Vida/psicologia , Apoio SocialRESUMO
Adults with autism spectrum disorder (ASD) experience high rates of depression and anxiety, and some evidence suggests mindfulness-based stress reduction (MBSR) is effective in reducing these symptoms. However, the neural mechanisms of symptom alleviation, and benefit of MBSR beyond education/support groups are unknown. Maladaptive forms of self-reflection are linked to ASD, depression, and anxiety. In this pilot study, we hypothesized (a) MBSR would reduce depression and anxiety in adults with ASD and (b) a mechanism of symptom alleviation would be increased blood oxygen level-dependent signal in neural self-reflection hubs. Twenty-eight adults were randomly assigned to an 8-week MBSR group (n = 15) or a support group (n = 13) that met for the same amount of time with relaxation education materials. Based on previous self-reflection literature in ASD, regions of interest (ROIs) were middle cingulate cortex (MCC) and ventromedial prefrontal cortex (vmPFC). Only the MBSR group demonstrated significant reductions in depression, and neither group significantly changed in anxiety. Only the MBSR group increased activity of right MCC during self-reflection, and the increase correlated with depression alleviation. There were no changes in vmPFC for the MBSR group or either ROI for the support/education group. Seed-to-voxel connectivity analysis revealed that only the MBSR group increased functional connectivity between right MCC and pre/postcentral gyrus, suggesting MBSR may increase primary sensorimotor input to higher order cognitive brain regions. Taken together, MBSR may be effective for reducing depression in adults with ASD, and the neural mechanism may be increasing frontal circuit involvement during self-directed thought.
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Transtorno do Espectro Autista/complicações , Encéfalo/diagnóstico por imagem , Transtorno Depressivo/terapia , Atenção Plena/métodos , Adolescente , Adulto , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/psicologia , Transtorno Depressivo/complicações , Transtorno Depressivo/diagnóstico por imagem , Transtorno Depressivo/psicologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Despite changes to brain integrity with aging, some functions like basic language processes remain remarkably preserved. One theory for the maintenance of function in light of age-related brain atrophy is the engagement of compensatory brain networks. This study examined age-related changes in the neural networks recruited for simple language comprehension. METHODS: Sixty-five adults (native English-speaking, right-handed, and cognitively normal) aged 17-85 years underwent a functional magnetic resonance imaging (fMRI) reading paradigm and structural scanning. The fMRI data were analyzed using independent component analysis to derive brain networks associated with reading comprehension. RESULTS: Two typical frontotemporal language networks were identified, and these networks remained relatively stable across the wide age range. In contrast, three attention-related networks showed increased activation with increasing age. Furthermore, the increased recruitment of a dorsal attention network was negatively correlated to gray matter thickness in temporal regions, whereas an anterior frontoparietal network was positively correlated to gray matter thickness in insular regions. CONCLUSIONS: We found evidence that older adults can exert increased effort and recruit additional attentional resources to maintain their reading abilities in light of increased cortical atrophy.
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Envelhecimento , Atenção/fisiologia , Córtex Cerebral , Compreensão/fisiologia , Idioma , Rede Nervosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Envelhecimento/fisiologia , Atrofia/patologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/patologia , Rede Nervosa/fisiologia , Leitura , Adulto JovemRESUMO
Increased risks associated with Coronavirus disease 2019 (COVID-19) among individuals with autism spectrum disorder (ASD) combined with previous reports of heightened vaccine hesitancy among parents of children with ASD indicate the need for a better understanding of attitudes and behaviors related to COVID-19 vaccines among the ASD community. This study is the first to our knowledge to use a mixed-methods approach to understand attitudes toward COVID-19 vaccines among parents of children with ASD and autistic adults. Participants were 135 members of the ASD community residing in the state of Arizona (99 parents of children with ASD and 36 autistic adults) who responded to the third (Spring 2021) and fourth (Summer 2021) time points of a larger longitudinal online survey. Quantitative findings indicated that autistic adults had slightly more favorable attitudes toward COVID-19 vaccines than parents, and attitudes in both subsamples became more positive over time. However, both parents and autistic adults reported COVID-19 vaccine uptake that was consistent with or better than the general population at both time points. Thematic analysis of responses to open-ended questions identified five themes that characterized factors that contributed to participants' decisions about COVID-19 vaccinations, including: (1) Desiring a Return to Normalcy, (2) Protection of Self and Others, (3) Previous Experience with COVID-19 (4) Science and Medical Professionals,and (5) Skepticism Regarding Safety, Effectiveness, and Need. Current findings combined with emerging literature paint a relatively optimistic picture about COVID-19 vaccine acceptance in the ASD community.
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Transtorno do Espectro Autista , Transtorno Autístico , COVID-19 , Criança , Adulto , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , PaisRESUMO
Epigenetic processes, including DNA methylation, are emerging as key areas of interest for their potential roles as biomarkers and contributors to the risk of neurodevelopmental, psychiatric, and other brain-based disorders. Despite this growing focus, there remains a notable gap in our understanding of how DNA methylation correlates with individual variations in brain function and structure. Additionally, the dynamics of these relationships during developmental periods, which are critical windows during which many disorders first appear, are still largely unexplored. The current study extends the field by examining if peripheral DNA methylation of myelination-related genes predicts white matter volume in a healthy pediatric population [N = 250; females = 113; age range 2 months-14 years; Mage = 5.14, SDage = 3.60]. We assessed if DNA methylation of 17 myelin-related genes predict white matter volume and if age moderates these relationships. Results highlight low variability in myelin-related epigenetic variance at birth, which rapidly increases non-linearly with age, and that DNA methylation, measured at both the level of a CpG site or gene, is highly predictive of white matter volume, in early childhood but not late childhood. These novel findings propel the field forward by establishing that DNA methylation of myelin-related genes from a peripheral tissue is a predictive marker of white matter volume in children and is influenced by developmental stage. The research underscores the significance of peripheral epigenetic patterns as a proxy for investigating the effects of environmental factors, behaviors, and disorders associated with white matter.
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LAY ABSTRACT: Existing research has identified an increased risk of depression among autistic adults, which can negatively impact their adaptive functioning abilities and socioeconomic outcomes. Mobile app-based meditation is a feasible, accessible, and effective self-care solution for depression among neurotypical adults, but there is limited evidence for the long-term benefits of app-based meditation among autistic adults. Habits are a key behavioral strategy for maintaining behavior change, and anchoring is one effective habit formation intervention that has yet to be tested among autistic adults. This study demonstrates that it is both feasible and effective to integrate the anchoring habit formation strategy into an app-based meditation intervention for establishing meditation habits among autistic adults. In addition, the study shows that app-based meditation habits were successful at maintaining reductions in depressive symptoms over 6 months. These results demonstrate the power of anchoring-based habit formation interventions for establishing healthy habits among autistic adults, which offers a promising behavioral intervention technique for establishing other healthy habits among autistic adults. The study also shows that app-based meditation habits are an effective long-term self-care solution for managing depressive symptoms among autistic adults that should be used by mental health providers and policymakers. Future research should test this combined anchoring and app-based meditation intervention technique among larger samples of autistic adults and over longer durations to better understand the mechanisms underlying the success of this intervention.
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PURPOSE: Precision medicine is an emerging intervention paradigm that leverages knowledge of risk factors such as genotypes, lifestyle, and environment toward proactive and personalized interventions. Regarding genetic risk factors, examples of interventions informed by the field of medical genomics are pharmacological interventions tailored to an individual's genotype and anticipatory guidance for children whose hearing impairment is predicted to be progressive. Here, we show how principles of precision medicine and insights from behavior genomics have relevance for novel management strategies of behaviorally expressed disorders, especially disorders of spoken language. METHOD: This tutorial presents an overview of precision medicine, medical genomics, and behavior genomics; case examples of improved outcomes; and strategic goals toward enhancing clinical practice. RESULTS: Speech-language pathologists (SLPs) see individuals with various communication disorders due to genetic variants. Ways of using insights from behavior genomics and implementing principles of precision medicine include recognizing early signs of undiagnosed genetic disorders in an individual's communication patterns, making appropriate referrals to genetics professionals, and incorporating genetic findings into management plans. Patients benefit from a genetics diagnosis by gaining a deeper and more prognostic understanding of their condition, obtaining more precisely targeted interventions, and learning about their recurrence risks. CONCLUSIONS: SLPs can achieve improved outcomes by expanding their purview to include genetics. To drive this new interdisciplinary framework forward, goals should include systematic training in clinical genetics for SLPs, enhanced understanding of genotype-phenotype associations, leveraging insights from animal models, optimizing interprofessional team efforts, and developing novel proactive and personalized interventions.
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Transtornos da Comunicação , Patologia da Fala e Linguagem , Humanos , Fala , Medicina de Precisão , Transtornos da Comunicação/genética , Genômica , Comunicação , Patologia da Fala e Linguagem/educaçãoRESUMO
CEE (conjugated equine estrogens) is the most widely prescribed estrogen-only menopausal hormone therapy in the United States, and is comprised of over 50% estrone (E1) sulfate. Following CEE administration, E1 is the principal circulating estrogen. However, the cognitive and neurobiological effects of E1 in a middle-aged rodent model have not yet been evaluated. We assessed cognitive effects of continuous E1 treatment in middle-aged surgically menopausal rats using a maze battery. We also quantified number of choline acetyltransferase-immunoreactive (ChAT-IR) neurons in distinct basal forebrain regions known in earlier studies in to be impacted by the most potent naturally-circulating estrogen in rodents and women, 17ß-estradiol (17ß-E2), as well as CEE. On the spatial working memory delayed-match-to-sample water maze, the highest E1 dose impaired memory performance during acquisition and after delay challenge. E1 did not impact ChAT-IR neuron number in the medial septum (MS) or horizontal/vertical diagonal bands. In a comparison study, 17ß-E2 increased MS ChAT-IR neuron number. Findings indicate that E1 negatively impacts spatial working memory and memory retention, and does not increase ChAT-IR neuron number in basal forebrain, as does 17ß-E2. Thus, data from prior studies suggest that 17ß-E2 and CEE can enhance cognition and increase number of ChAT-IR basal forebrain neurons, while here we show that E1 does not induce these effects. Findings from preclinical basic science studies can inform the design of specific combinations of estrogens that could be beneficial to the brain and cognition. Accumulating data suggest that E1 is not likely to be among these key beneficial estrogens.
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Neurônios Colinérgicos/efeitos dos fármacos , Estrogênios Conjugados (USP)/efeitos adversos , Estrona/efeitos adversos , Memória/efeitos dos fármacos , Prosencéfalo/efeitos dos fármacos , Animais , Estradiol/farmacologia , Terapia de Reposição de Estrogênios/efeitos adversos , Estrogênios/administração & dosagem , Estrogênios/efeitos adversos , Estrogênios Conjugados (USP)/administração & dosagem , Estrona/administração & dosagem , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Menopausa/efeitos dos fármacos , Ovariectomia , Ratos , Ratos Endogâmicos F344RESUMO
BACKGROUND: The unprecedented challenges introduced by the Coronavirus disease 2019 (COVID-19) pandemic may be amplified for children with autism spectrum disorder (ASD) and their families. AIMS: The current study aimed to describe the experiences of children with ASD and their families during the pandemic and to identify the needs of this community during emergency situations. METHODS AND PROCEDURES: Participants were 122 parents of 122 children and adolescents (aged 3-18 years; one parent per family participated) with ASD living in Arizona, USA who participated in the first time point (July/August 2020) of a larger longitudinal survey study. A qualitative approach based in grounded theory methodology was used to analyze six open-ended survey questions. OUTCOMES AND RESULTS: The resulting conceptual model included a core category, Longing for Stability, and four main categories: Public Health Measures Yielding New Challenges and Unexpected Gains, Experiencing Abrupt Changes across Developmental Domains, Changing Family Dynamics, and Protective Factors. CONCLUSIONS: Findings add to limited research examining whether, and how, emergency events uniquely impact the ASD community, identifying potential methods by which services can be proactively adapted to best support the needs of children with ASD.
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Transtorno do Espectro Autista , Transtorno Autístico , COVID-19 , Adolescente , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , COVID-19/epidemiologia , Criança , Humanos , Pandemias , PaisRESUMO
Research aimed at understanding cognitive and brain aging in adults with autism spectrum disorder (ASD) is growing, but critical longitudinal work is scant. Adults with ASD struggle with tasks involving visual memory compared with neurotypical adults (NT). This may be related to differences in size or integrity of the hippocampus and its' primary structural connectivity pathway, the fornix. The aim of this study was to describe preliminary findings of longitudinal aging trajectories in short- and long-term visual memory abilities in middle-age and older adults with ASD, compared with matched NT adults. We then evaluated baseline multi-modal imaging metrics of the hippocampal system, including the relatively novel metric of free-water, as potential correlates of longitudinal memory change in the ASD group. Middle-age and older adults with ASD (n = 25) and matched NT adults (n = 25) between the ages of 40 and 70 years were followed longitudinally at ~2-year intervals (range 2-5 years). Participants completed the Wechsler Memory Scale III Visual Reproduction task. Longitudinal mixed models were utilized to detect group differences in memory change with baseline age and sex as covariates. Hippocampal volume was measured via T1-weighted MRI images with FreeSurfer. Fornix fractional anisotropy and hippocampal and fornix free-water were measured from diffusion tensor imaging scans. Exploratory correlations were run between individual hippocampal system metrics and longitudinal slopes of visual memory change. There was a significant group by time interaction for long-term visual memory, such that middle-age and older adults with ASD declined faster than matched NT adults. There was no group by time interaction for short-term visual memory. Baseline hippocampal free-water was the only hippocampal system metric that correlated with long-term visual memory change in the ASD group. As one of the first longitudinal cognitive and brain aging studies in middle-age and older adults with ASD, our findings suggest vulnerabilities for accelerated long-term visual memory decline, compared to matched NT adults. Further, baseline hippocampal free-water may be a predictor of visual memory change in middle-age and older adults with ASD. These preliminary findings lay the groundwork for future prognostic applications of MRI for cognitive aging in middle-age and older adults with ASD.
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Uncovering the complex network of the brain is of great interest to the field of neuroimaging. Mining from these rich datasets, scientists try to unveil the fundamental biological mechanisms in the human brain. However, neuroimaging data collected for constructing brain networks is generally costly, and thus extracting useful information from a limited sample size of brain networks is demanding. Currently, there are two common trends in neuroimaging data collection that could be exploited to gain more information: 1) multimodal data, and 2) longitudinal data. It has been shown that these two types of data provide complementary information. Nonetheless, it is challenging to learn brain network representations that can simultaneously capture network properties from multimodal as well as longitudinal datasets. Here we propose a general fusion framework for multi-source learning of brain networks - multimodal brain network fusion with longitudinal coupling (MMLC). In our framework, three layers of information are considered, including cross-sectional similarity, multimodal coupling, and longitudinal consistency. Specifically, we jointly factorize multimodal networks and construct a rotation-based constraint to couple network variance across time. We also adopt the consensus factorization as the group consistent pattern. Using two publicly available brain imaging datasets, we demonstrate that MMLC may better predict psychometric scores than some other state-of-the-art brain network representation learning algorithms. Additionally, the discovered significant brain regions are synergistic with previous literature. Our new approach may boost statistical power and sheds new light on neuroimaging network biomarkers for future psychometric prediction research by integrating longitudinal and multimodal neuroimaging data.
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Algoritmos , Neuroimagem , Biomarcadores , Encéfalo/diagnóstico por imagem , Estudos Transversais , Humanos , Imageamento por Ressonância Magnética , Neuroimagem/métodosRESUMO
We used functional magnetic resonance imaging (fMRI) to investigate cross-sectional differences in functional connectivity across cognitive networks at rest among age and sex matched college students with very low food security [food insecurity (FI); n = 20] and with high food security (n = 20). The participants completed the Behavior Rating Inventory of Executive Function-2 (BRIEF-2) and Adverse Childhood Experiences (ACEs) questionnaires. Seven-minute resting-state fMRI scans were collected. Independent Component Analysis assessed group connectivity differences in three large-scale networks: the default-mode network (DMN), the frontoparietal network (FPN), and the salience network (SN). FI was associated with poorer Global BRIEF scores (adjusted ß = 8.36; 95% CI: 2.32, 14.40) and five BRIEF subscales: Inhibit, Initiate, Working Memory, Plan, and Organize (p-values < 0.05). The students with FI had greater functional connectivity between the FPN and left middle temporal gyrus (cluster size p-FWE = 0.029), the SN and precuneus (cluster size p-FWE < 0.001), and the SN and right middle frontal gyrus (cluster size p-FWE = 0.016) compared to the students with high food security. Exploratory correlations revealed that greater connectivity between the SN and right middle frontal gyrus was associated with poorer BRIEF Inhibit scores (p = 0.038), and greater connectivity between the FPN and left middle temporal gyrus was associated with poorer BRIEF Organize scores (p = 0.024) for the students with FI. Greater functional connectivity between the FPN, DMN, and SN at rest may contribute to executive function difficulties for college students with FI.
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Mapeamento Encefálico , Encéfalo , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Estudos Transversais , Insegurança Alimentar , Humanos , EstudantesRESUMO
Research studying aging in adults with autism spectrum disorder (ASD) is growing, but longitudinal work is needed. Autistic adults have increased risk of dementia, altered hippocampal volumes and fornix integrity, and verbal memory difficulties compared with neurotypical (NT) adults. This study examined longitudinal aging in middle-age adults with ASD versus a matched NT group, and compared findings with cross-sectional age effects across a broad adult age range. Participants were 194 adults with (n = 106; 74 male) and without (n = 88; 52 male) ASD, ages 18-71. Participants (n = 45; 40-70 age range) with two visits (2-3 years apart) were included in a longitudinal analysis. Hippocampal volume, fornix fractional anisotropy (FA), and verbal memory were measured via T1-weighted MRI, diffusion tensor imaging, and the Rey Auditory Verbal Learning Test, respectively. Longitudinal mixed models were used for hippocampal system variables and reliable change index categories were used for Auditory Verbal Learning Test analyses. Multivariate regression was used for cross-sectional analyses. Middle-age adults with ASD had greater longitudinal hippocampal volume loss and were more likely to show clinically meaningful decline in short-term memory, compared with NT. In contrast, cross-sectional associations between increasing age and worsening short-term memory were identified in NT, but not autistic adults. Reduced fornix FA and long-term memory in ASD were found across the broad cross-sectional age range. These preliminary longitudinal findings suggest accelerated hippocampal volume loss in ASD and slightly higher rates of clinically-meaningful decline in verbal short-term memory. Contradictory cross-sectional and longitudinal results underscore the importance of longitudinal aging research in autistic adults. LAY SUMMARY: Autistic adults have increased risk of dementia, differences in brain memory structures, and difficulty with memory compared with neurotypical (NT) adults. However, there are no publications that follow the same middle-age autistic adults over time to see how their brain and memory change. Our preliminary findings in a small middle-age autism sample suggest a key memory brain structure, the hippocampus, may shrink faster over 2-3 years compared with NT, and short-term memory may become more challenging for some. Across a broad adult range, autistic adults also had reduced integrity of connections to the hippocampus and greater challenges with long-term memory. In our larger sample across a broad age range, the results did not hint at this aforementioned pattern of accelerated aging. This underscores the importance of more aging research in autism, and especially research where people are followed over time.
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Transtorno do Espectro Autista , Demência , Adolescente , Adulto , Idoso , Transtorno do Espectro Autista/complicações , Pré-Escolar , Estudos Transversais , Imagem de Tensor de Difusão , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Adulto JovemRESUMO
Emerging research suggests mindfulness-based therapies positively impact adults with autism spectrum disorder (ASD). However, questions concerning intervention active ingredients, the breadth and duration of impact, and psychological and neural mechanisms of change remain. Here we discuss what is known about mindfulness-based therapies in adults with ASD and offer suggestions for future research.
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Females with autism spectrum disorder (ASD) have been long overlooked in neuroscience research, but emerging evidence suggests they show distinct phenotypic trajectories and age-related brain differences. Sex-related biological factors (e.g., hormones, genes) may play a role in ASD etiology and have been shown to influence neurodevelopmental trajectories. Thus, a lifespan approach is warranted to understand brain-based sex differences in ASD. This systematic review on MRI-based sex differences in ASD was conducted to elucidate variations across the lifespan and inform biomarker discovery of ASD in females We identified articles through two database searches. Fifty studies met criteria and underwent integrative review. We found that regions expressing replicable sex-by-diagnosis differences across studies overlapped with regions showing sex differences in neurotypical cohorts. Furthermore, studies investigating age-related brain differences across a broad age-span suggest distinct neurodevelopmental patterns in females with ASD. Qualitative comparison across youth and adult studies also supported this hypothesis. However, many studies collapsed across age, which may mask differences. Furthermore, accumulating evidence supports the female protective effect in ASD, although only one study examined brain circuits implicated in "protection." When synthesized with the broader literature, brain-based sex differences in ASD may come from various sources, including genetic and endocrine processes involved in brain "masculinization" and "feminization" across early development, puberty, and other lifespan windows of hormonal transition. Furthermore, sex-related biology may interact with peripheral processes, in particular the stress axis and brain arousal system, to produce distinct neurodevelopmental patterns in males and females with ASD. Future research on neuroimaging-based sex differences in ASD would benefit from a lifespan approach in well-controlled and multivariate studies. Possible relationships between behavior, sex hormones, and brain development in ASD remain largely unexamined.
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Transtorno do Espectro Autista , Imageamento por Ressonância Magnética , Adolescente , Adulto , Transtorno do Espectro Autista/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Longevidade , Masculino , Caracteres SexuaisRESUMO
In women, medroxyprogesterone acetate (MPA) is the most commonly used progestin component of hormone therapy (HT). In vitro, MPA negatively impacts markers of neuronal health and exacerbates experimentally-induced neurotoxicity. There is in vitro evidence that these factors are driven by GABAergic and neurotrophic systems. Whether these effects translate to a negative impact on brain function has not been tested in vivo, clinically or preclinically. Here we evaluate the mnemonic and neurobiological effects of MPA in the surgically menopausal rat. Aged ovariectomized (OVX) rats were given subcutaneous vehicle, natural progesterone, low-dose MPA or high-dose MPA. Multiple cognitive domains were analyzed via the water radial-arm maze (WRAM) and Morris maze (MM). Cognitive brain regions were assayed for changes in the GABAergic system by evaluating GAD protein, the synthesizing enzyme for GABA, and neurotrophins. On the WRAM, both progestin types impaired learning. Further, high-dose MPA impaired delayed memory retention on the WRAM, and exacerbated overnight forgetting on the MM. While neurotrophins were not affected by progesterone or MPA treatment, both progestin types altered GAD levels. MPA significantly and progesterone marginally decreased GAD levels in the hippocampus, and both MPA and progesterone significantly increased GAD levels in the entorhinal cortex. These findings suggest that MPA, the most commonly used progestin in HT, is detrimental to learning and two types of memory, and modulates the GABAergic system in cognitive brain regions, in aged surgically menopausal rats. These findings, combined with in vitro evidence that MPA is detrimental to neuronal health, indicates that MPA has negative effects for brain health and function.
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Anticoncepcionais Femininos/efeitos adversos , Acetato de Medroxiprogesterona/efeitos adversos , Transtornos da Memória/induzido quimicamente , Ácido gama-Aminobutírico/metabolismo , Animais , Feminino , Hipocampo/efeitos dos fármacos , Transtornos da Memória/diagnóstico , Menopausa , Ovariectomia , Ratos , Ratos Endogâmicos F344RESUMO
Background: Approximately 50,000 U.S. teens with autism spectrum disorder (ASD) become adults every year, however little is known regarding how age influences social cognition and if men and women with ASD are differentially impacted across the adult lifespan. Social cognition declines non-linearly with age in neurotypical (NT) adults. Moreover, sex differences have been observed on RME tasks in NT adults but not adults with ASD, although aging effects have been largely ignored. Objective: This cross-sectional study examined the influence of age and sex on social cognition in adults with ASD compared to NT adults. Methods: The Reading the Mind in the Eyes (RME) task was administered to evaluate the theory of mind abilities in 95 adults with ASD and 82 NT adults ages 18-71 years. The main effects of diagnosis, age, and sex, as well as two-way and three-way interaction were modeled using linear and quadratic aging terms in a multiple regression analysis. Results: A main effect of diagnosis was observed, indicating poorer performance in adults with ASD relative to NT adults. Age and sex interactions were nonsignificant. Discussion: We replicated previous findings of reduced theory of mind (ToM) abilities in adults with ASD, compared to NT adults. While interactions were nonsignificant, visual inspection of quadratic age curves indicated the possibility of unique ToM trajectories in men and women with and without ASD that should be investigated in larger longitudinal studies.