A pilot, single-arm feasibility study of an integrated cognitive-behavioral treatment for anxiety in young autistic children.

OBJECTIVE: Anxiety is prevalent in young autistic children under 7 years of age. Yet there is a paucity of empirically based interventions for this age group. DINO Strategies for Anxiety and Uncertainty Reduction (DINOSAUR) is an innovative cognitive behavioral intervention that seeks to optimize treatment response in young autistic children by targeting anxiety and the contributing mechanisms of intolerance of uncertainty and parental accommodation using a telehealth delivery model. This pilot, single-arm study examines the preliminary feasibility of DINOSAUR. METHODS: Fourteen autistic children ages 4-6 years with average language and cognitive skills and their parents received the intervention. Quantitative and qualitative data pertaining to parent satisfaction and treatment outcomes were collected. RESULTS: Attendance, retention, and parent satisfaction ratings offer preliminary support for the feasibility of the treatment model. Change in clinical severity ratings on a semi-structured parent interview of anxiety and parents' qualitative report suggests the potential to benefit young autistic children. CONCLUSIONS: Results support future study of the DINOSAUR model in a larger, randomized controlled trial.

Genetic liability for gastrointestinal inflammation disorders and association with gastrointestinal symptoms in children with and without autism.

Children with autism spectrum disorder (ASD) have a greater prevalence of gastrointestinal (GI) symptoms than children without ASD. We tested whether polygenic scores for each of three GI disorders (ulcerative colitis, inflammatory bowel disease, and Crohn's disease) were related to GI symptoms in children with and without ASD. Using genotyping data (564 ASD cases and 715 controls) and external genome-wide association study summary statistics, we computed GI polygenic scores for ulcerative colitis (UC-PGS), inflammatory bowel disease (IDB-PGS), and Crohn's disease (CD-PGS). Multivariable logistic regression models, adjusted for genetic ancestry, were used to estimate associations between each GI-PGS and (1) ASD case-control status, and (2) specific GI symptoms in neurotypical children and separately in ASD children. In children without ASD, polygenic scores for ulcerative colitis were significantly associated with experiencing any GI symptom (adjusted odds ratio (aOR) = 1.36, 95% confidence interval (CI) = 1.03-1.81, p = 0.03) and diarrhea specifically (aOR = 5.35, 95% CI = 1.77-26.20, p = 0.01). Among children without ASD, IBD-PGS, and Crohn's PGS were significantly associated with diarrhea (aOR = 3.55, 95% CI = 1.25-12.34, p = 0.02) and loose stools alternating with constipation (aOR = 2.57, 95% CI = 1.13-6.55, p = 0.03), respectively. However, the three PGS were not associated with GI symptoms in the ASD case group. Furthermore, polygenic scores for ulcerative colitis significantly interacted with ASD status on presentation of any GI symptom within a European ancestry subset (aOR = 0.42, 95% CI = 0.19-0.88, p = 0.02). Genetic risk factors for some GI symptoms differ between children with and without ASD. Furthermore, our finding that increased genetic risks for GI inflammatory disorders are associated with GI symptoms in children without ASD informs future work on the early detection of GI disorders.

Gastrointestinal Dysfunction in Genetically Defined Neurodevelopmental Disorders.

Gastrointestinal symptoms are common in most forms of neurodevelopment disorders (NDDs) such as in autism spectrum disorders (ASD). The current patient-reported outcome measures with validated questionnaires used in the general population of children without NDDS cannot be used in the autistic individuals. We explore here the multifactorial pathophysiology of ASD and the role of genetics and the environment in this disease spectrum and focus instead on possible diagnostics that could provide future objective insight into the connection of the gut-brain-microbiome in this disease entity. We provide our own data from both humans and a zebrafish model of ASD called Phelan-McDermid Syndrome. We hope that this review highlights the gaps in our current knowledge on many of these profound NDDs and that it provides a future framework upon which clinicians and researchers can build and network with other interested multidisciplinary specialties.

Association of common infections with cognitive performance in the Baltimore Epidemiologic Catchment Area study follow-up.

INTRODUCTION: Growing evidence suggests that some common infections are causally associated with cognitive impairment; however, less is known about the burden of multiple infections. METHODS: We investigated the cross-sectional association of positive antibody tests for herpes simplex virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV), and Toxoplasma gondii (TOX) with Mini-Mental State Examination (MMSE) and delayed verbal recall performance in 575 adults aged 41-97 from the Baltimore Epidemiologic Catchment Area Study. RESULTS: In multivariable-adjusted zero-inflated Poisson (ZIP) regression models, positive antibody tests for CMV (p = .011) and herpes simplex virus (p = .018) were individually associated with poorer MMSE performance (p = .011). A greater number of positive antibody tests among the five tested was associated with worse MMSE performance (p = .001). DISCUSSION: CMV, herpes simplex virus, and the global burden of multiple common infections were independently associated with poorer cognitive performance. Additional research that investigates whether the global burden of infection predicts cognitive decline and Alzheimer's disease biomarker changes is needed to confirm these findings.

Psychiatric Presentations and Medication Use in Older Adults With Intellectual and Developmental Disabilities.

OBJECTIVE: Adults with intellectual and developmental disabilities (IDD) are living longer, yet research about the medical and psychiatric needs of older adults still lags behind that of younger individuals with IDD. The aim of this study was to assess age-related differences in the mental health presentations of adults with IDD. METHODS: Fully deidentified data for adults 30 years and older were extracted from the START (Systemic, Therapeutic, Assessment, Resources, and Treatment) Information Reporting System, a deidentified database housed at the Center for START Services. Caregivers and START team documents reported psychiatric diagnoses, service use, recent stressors, and challenging behaviors. t Tests, Mann Whitney U tests, χ2 tests, and multinominal logistic regression models were used to compare the two age groups, 30-49 years (n = 1,188) versus 50 years and older (n = 464). RESULTS: Older adults had more medical conditions, fewer reported psychiatric conditions, and were more likely to be taking more psychiatric medications compared to younger adults, after adjusting for demographic variables, disability level, and number of recent stressors. CONCLUSION: Although older individuals reported fewer psychiatric diagnoses, they were more likely to take higher numbers of psychiatric medications and have more medical conditions. Clinicians and researchers ought to devote more attention to the healthcare needs of older adults with IDD, a vulnerable group exposed to polypharmacy and at risk of adverse events.

Sluggish cognitive tempo profiles in survivors of childhood cancer as compared to children with attention-deficit/hyperactivity disorder.

PURPOSE: Neurocognitive late effects including problems with attention have been reported in pediatric oncology survivors. While some researchers have characterized these late effects as similar to symptoms of attention-deficit/hyperactivity disorder, inattentive presentation (ADHD-I), there remains some controversy as to whether these concerns in oncology patients are best conceptualized according to an ADHD-I or sluggish cognitive tempo (SCT) framework. The aim of this study was to describe SCT symptoms in children with ADHD-I or oncology diagnoses; identify groups of SCT symptoms among children with brain tumors (BT), acute lymphoblastic leukemia (ALL), or ADHD-I; and identify whether specific SCT profiles are associated with these diagnoses. METHODS: The sample was comprised of 364 youth (146 BT, 149 ADHD-I, 69 ALL) referred for a neuropsychological evaluation at an academic medical center. Caregivers completed the SCT scale as part of the clinical evaluation. RESULTS: Groups differed on mean scores for the SCT scales (Total, Sleepy/sluggish, Low initiation, and Daydreamy) by diagnosis (all p < 0.05), with the ADHD-I group having higher SCT symptoms on all scales. Latent profile analysis showed significant differences between latent SCT classes according to ADHD-I versus cancer diagnosis. The ADHD-I group was significantly more likely to be in the high SCT class compared to the oncology groups. CONCLUSION: Findings add to the understanding of SCT symptoms in pediatric oncology survivors. There is utility in applying the SCT framework to the oncology population; however, pediatric survivors are likely to be rated differently than youth with ADHD-I. Implications and future directions are discussed.

Key stakeholder perspectives on obstacles to an autism-specific Medicaid waiver service delivery model.

BACKGROUND: Children and youth with autism spectrum disorder have significant, multi-system needs that require supports, such as the autism waiver (AW) service delivery model. This study aimed to identify and describe characteristics of the AW, define obstacles and strengths in the provision of adequate services and provide recommendations for improving overall effectiveness. METHODS: This mixed-methods exploratory study used an electronic survey to gain information and perceptions of AW provider agency directors (n = 27) and service coordinators (n = 30). RESULTS: The key barriers reported were the shortage of qualified staff, inadequate staff training, complexity of cases or symptom severity of clients and lack of communication at multiple levels throughout the agency as well as with parents. CONCLUSIONS: Recommendations include reinforcing the workforce through higher salaries, greater training and communication interventions. These strategies may reduce staff turnover and shortage, lighten the caseload, reduce the waitlist period and improve the effectiveness and responsiveness of AW services.

Trajectories of Mental Distress Among U.S. Adults During the COVID-19 Pandemic.

BACKGROUND: Cross-sectional studies have found that the coronavirus disease 2019 (COVID-19) pandemic has negatively affected population-level mental health. Longitudinal studies are necessary to examine trajectories of change in mental health over time and identify sociodemographic groups at risk for persistent distress. PURPOSE: To examine the trajectories of mental distress between March 10 and August 4, 2020, a key period during the COVID-19 pandemic. METHODS: Participants included 6,901 adults from the nationally representative Understanding America Study, surveyed at baseline between March 10 and 31, 2020, with nine follow-up assessments between April 1 and August 4, 2020. Mixed-effects logistic regression was used to examine the association between date and self-reported mental distress (measured with the four-item Patient Health Questionnaire) among U.S. adults overall and among sociodemographic subgroups defined by sex, age, race/ethnicity, household structure, federal poverty line, and census region. RESULTS: Compared to March 11, the odds of mental distress among U.S. adults overall were 1.84 (95% confidence interval [CI] = 1.65-2.07) times higher on April 1 and 1.92 (95% CI = 1.62-2.28) times higher on May 1; by August 1, the odds of mental distress had returned to levels comparable to March 11 (odds ratio [OR] = 0.80, 95% CI = 0.66-0.96). Females experienced a sharper increase in mental distress between March and May compared to males (females: OR = 2.29, 95% CI = 1.85-2.82; males: OR = 1.53, 95% CI = 1.15-2.02). CONCLUSIONS: These findings highlight the trajectory of mental health symptoms during an unprecedented pandemic, including the identification of populations at risk for sustained mental distress.

Long-term physical health outcomes of obsessive-compulsive personality disorder traits.

BACKGROUND: Obsessive-compulsive personality disorder (OCPD) is characterized by pervasive and persistent traits including preoccupation with orderliness, perfectionism, and control. Relatively little is known about the potential relationship between OCPD traits and physical health. METHODS: We investigated the association between OCPD traits and several self-reported medical conditions in 249 individuals followed prospectively from 1981 until 2004/2005 as part of the Epidemiological Catchment Area. RESULTS: The OCPD trait score was inversely related to hypertension in males, in models unadjusted (OR = 0.66; 95% CI, 0.45-0.90) and adjusted (OR = 0.70; 95% CI, 0.47-0.95) for sociodemographic variables. Perfectionism was inversely related to hypertension in the unadjusted models for men (OR = 0.34; 95% CI, 0.12-0.89). Indecisiveness was positively associated with heart conditions in adjusted models for women (OR = 3.46; 95% CI, 1.11-10.52). CONCLUSION: OCPD traits are associated with cardiovascular health in both sexes. Further studies are needed to understand the specificity of these relationships, as well as to determine the underlying mechanism.

Mental Distress in the United States at the Beginning of the COVID-19 Pandemic.

Objectives. To assess the impact of the COVID-19 pandemic on mental distress in US adults.Methods. Participants were 5065 adults from the Understanding America Study, a probability-based Internet panel representative of the US adult population. The main exposure was survey completion date (March 10-16, 2020). The outcome was mental distress measured via the 4-item version of the Patient Health Questionnaire.Results. Among states with 50 or more COVID-19 cases as of March 10, each additional day was significantly associated with an 11% increase in the odds of moving up a category of distress (odds ratio = 1.11; 95% confidence interval = 1.01, 1.21; P = .02). Perceptions about the likelihood of getting infected, death from the virus, and steps taken to avoid infecting others were associated with increased mental distress in the model that included all states. Individuals with higher consumption of alcohol or cannabis or with history of depressive symptoms were at significantly higher risk for mental distress.Conclusions. These data suggest that as the COVID-19 pandemic continues, mental distress may continue to increase and should be regularly monitored. Specific populations are at high risk for mental distress, particularly those with preexisting depressive symptoms.

Mental distress during the COVID-19 pandemic among US adults without a pre-existing mental health condition: Findings from American trend panel survey.

Most individuals in the United States have no history of a mental health condition yet are at risk for psychological distress due to the COVID-19 pandemic. The objective of this study was to assess the frequency and risk and protective factors of psychological distress, during the beginning of the COVID-19 pandemic, in this group. Data comes from the Pew Research Center's American Trends Panel (ATP), a probability-based online survey panel representative of the US adult population. The analytic sample consisted of 9687 individuals with no prior history of a mental health condition who completed the survey between March 19-24, 2020. Explanatory variables included sociodemographic factors and items related to behavior, perceptions, and experiences surrounding the pandemic. The outcome was psychological distress, measured by five items on symptoms of anxiety, depression, loneliness, sleep difficulties, and hyperarousal. A multivariable linear regression model was used to identify risk and protective factors for psychological distress. Fifteen percent of the sample experienced 2 psychological distress symptoms for at least 3 days over the past week; 13% had three or more symptoms. Risk factors for higher distress included searching online or using social media to post about coronavirus, reporting that the outbreak caused major changes to personal life, and perception that the virus was a threat to the US economy, the individual's personal health or finances. This has important implications for mental health service delivery.

Sex Differences in the Gut-Brain Axis: Implications for Mental Health.

PURPOSE OF REVIEW: The purpose of this article is to highlight how sex differences in the gut-brain axis may contribute to the discrepancies in incidence of neurodevelopmental, psychiatric, and neurodegenerative disorders between females and males. We focus on autism spectrum disorder, psychotic disorders, stress and anxiety disorders, depression, Alzheimer's disease, and Parkinson's disease and additionally discuss the comorbidity between inflammatory bowel disorder and mental health disorders. RECENT FINDINGS: Human and animal studies show that sex may modify the relationship between the gut or immune system and brain and behavior. Sex also appears to modify the effect of microbial treatments such as probiotics and antibiotics on brain and behavior. There is emerging evidence that assessing the role of sex in the gut-brain axis may help elucidate the etiology of and identify effective treatments for neurodevelopmental, psychiatric, and neurodegenerative disorders.

Napping characteristics and cognitive performance in older adults.

OBJECTIVES: To determine the association of napping intention, frequency, and duration with cognition in a nationally-representative sample of US older adults. METHODS: We performed a cross-sectional analysis of community-dwelling Medicare beneficiaries aged ≥65 years from Rounds 3 or 4 (2013-2014) of the National Health and Aging Trends Study (N = 2549). Participants reported past-month napping intention (intentional/unintentional), napping frequency (rarely/never [non-nappers], some days [infrequent nappers], most days/every day [frequent nappers]), and average nap duration (we categorized as ≤30 minutes [short]; 31-60 minutes [moderate]; and > 60 minutes [long]). Cognitive outcomes were performance on immediate and delayed word recall tests (IWR and DWR, respectively), the Clock Drawing Test (CDT), and self-rated memory (score: 1[excellent]-5[very poor]). RESULTS: After adjustment for potential confounders, unintentional nappers had poorer immediate word recall test performance than non-nappers (B = -0.23, P < 0.01) and intentional nappers (B = -0.26, P < 0.01). After further adjustment for daytime sleepiness, frequent nappers reported poorer self-rated memory than non-nappers (B = 0.14, P < 0.05). Compared with short nappers, long nappers had poorer IWR (B = -0.26, P < 0.05) and CDT scores (B = -0.17, P < 0.05). Except for the association of nap duration with IWR and CDT, these associations remained after excluding participants with dementia and/or proxy respondents. Among participants undiagnosed with dementia or proxies, moderate-duration naps were associated with better DWR than short naps (B = 0.24, P < 0.05). Neither napping intentionality nor frequency was associated with CDT performance. CONCLUSIONS: Among older adults, distinct aspects of napping are associated with cognitive performance. Prospective research, with objective measures of napping, is needed to elucidate the link between napping and cognitive trajectories.

Enduring mental health in the Baltimore epidemiologic catchment area follow-up study.

PURPOSE: To estimate the prevalence of enduring mental health (EMH) and examine important correlates of EMH 23 years later in the Baltimore Epidemiologic Catchment Area Follow-Up study. METHODS: We estimated the prevalence of EMH among 964 adults with diagnostic data at all four study waves (1981-2004). Those with EMH were compared to those with any mental or behavioral disorder by demographic, psychosocial, and health characteristics. We used forward selection models to identify the most important predictors of EMH. RESULTS: Twenty-six percent of participants met criteria for enduring mental health across the four waves. Neuroticism, GHQ-20 score, childhood conduct problems, female sex, maternal depression, and poor self-rated health were negatively associated with EMH. CONCLUSIONS: We identified several malleable factors associated with a decreased likelihood of enduring mental health. Interventions that target high neuroticism, childhood conduct problems, or maternal depression may increase the likelihood that children achieve EMH later in life. Identifying and treating other factors such as poor self-reported health and greater psychological distress may also keep sub-clinical symptoms from developing into a full mental or behavioral disorder.

Association of Time in Bed, Social Jetlag, and Sleep Disturbances With Cognitive Performance in Children With ADHD.

OBJECTIVES: Children with ADHD commonly exhibit sleep disturbances, but there is limited knowledge about how sleep and sleep timing are associated with cognitive dysfunction in children with ADHD. METHODS: Participants were 350 children aged 5 to 12 years diagnosed with ADHD. Three sleep-related constructs-time in bed, social jetlag (i.e., discrepancy in sleep timing pattern between school nights and weekend nights), and sleep disturbances were measured using a caregiver-report questionnaire. Linear regression models assessed the associations between sleep-related constructs and cognitive performance. RESULTS: After adjustment for sociodemographic variables, there were few associations between time in bed or sleep disturbances and cognitive performance, however, greater social jetlag was negatively associated with processing speed (ß = -.20, 95% CI [-0.35, -0.06]), visually-based reasoning (ß = -.13, 95% CI [-0.27, 0.00]), and language-based reasoning (ß = -.22, 95% CI [-0.36, -0.08]); all p < .05). CONCLUSION: Social jetlag, but not time in bed or disturbances, was associated with lower cognitive performance among children with ADHD.

Accelerometer-assessed sleep and decline in physical function in older men.

OBJECTIVES: Assess the prospective association of actigraphically measured sleep with self-report and objective measures of physical function among community-dwelling older men. METHODS: Participants were (n = 1496) men aged ≥65 years from the Osteoporotic Fractures in Men Study and ancillary sleep study who were followed up at 4 years for physical function outcomes. Sleep predictors included baseline total sleep time (<6, 6-8 hours [reference], >8 hours), sleep efficiency (<80% or ≥80% [reference]), wake after sleep onset (<90 [reference] or ≥90 minutes), and sleep onset latency (<30 [reference] or ≥30 minutes), measured by wrist actigraphy. Outcomes included self-reported difficulties in mobility and instrumental activities of daily living and objective measures of physical performance (time to complete chair stands, gait speed, grip strength, best narrow walk pace). Multivariable regression models estimated associations between the sleep predictors and change in physical function at follow-up, adjusting for demographic and health-related variables. RESULTS: Participants with short average baseline total sleep time (<6 hours) had significantly greater slowing in their walking speed from baseline to follow-up. Participants with long baseline sleep onset latency (≥30 minutes) had significant increases in mobility difficulties and time to complete chair stands. Sleep efficiency and wake after sleep onset were not significantly associated with any outcomes. No sleep predictors were associated with change in instrumental activities of daily living. CONCLUSIONS: These findings add to the body of evidence showing links between poor sleep and subsequent declines in physical function. Further experimental research is needed to understand the mechanisms at play.

Diagnostic certainty during in-person and telehealth autism evaluations.

Background: Many diagnostic evaluations abruptly shifted to telehealth during the COVID-19 pandemic; however, little is known about the impact on diagnosis patterns for children evaluated for autism spectrum disorder (ASD). The purpose of this clinical research study was to examine (1) the frequency of diagnoses evaluated beyond ASD; (2) the frequency of diagnoses made, including ASD; and (3) clinician diagnostic certainty for all diagnoses evaluated for children who received an evaluation due to primary concerns about ASD via telehealth during the pandemic compared to those evaluated in person before the pandemic at an ASD specialty clinic. Methods: The sample included 2192 children, 1-17 years (M = 6.5 years; SD = 3.9), evaluated by a physician/psychologist at an ASD specialty center. A total of 649 children were evaluated in-person September 1, 2019-March 13, 2020 (pre-pandemic) and 1543 were evaluated via telehealth March 14, 2020-July 26, 2021 (during pandemic). Upon completion of each evaluation, clinicians provided a final diagnostic determination (i.e., "Yes," "No," "Possible," or "Not Assessed") for the following DSM-5 conditions: ASD, attention-deficit/hyperactivity disorder (ADHD), intellectual developmental disorder (IDD), anxiety (ANX), depression (DEP), and behavioral disorder (BD). "Possible" indicated lower certainty and the diagnosis was not provided. "Not Assessed" indicated the disorder was not evaluated. Results: Diagnostic certainty for ASD and ADHD was lower and clinicians evaluated for and made diagnoses of IDD less often during evaluations that occurred via telehealth during the pandemic versus in person before the pandemic. DEP and BD were diagnosed more frequently, diagnostic certainty of DEP was lower, and no differences in the frequency of ANX diagnoses emerged during evaluations conducted via telehealth during the pandemic compared to those conducted in person before the pandemic. Conclusions: Differences emerged in the frequency of diagnoses evaluated and made and diagnostic certainty for evaluations conducted via telehealth during the pandemic compared to in person before the pandemic, which likely impacted patients and reflect real-word challenges. Future work should examine whether these patterns are generalizable and the mechanisms that contribute to these differences.

Food, nutrition, and autism: from soil to fork.

Food and nutrition-related factors have the potential to impact development of autism spectrum disorder (ASD) and quality of life for people with ASD, but gaps in evidence exist. On 10 November 2022, Tufts University's Friedman School of Nutrition Science and Policy and Food and Nutrition Innovation Institute hosted a 1-d meeting to explore the evidence and evidence gaps regarding the relationships of food and nutrition with ASD. This meeting report summarizes the presentations and deliberations from the meeting. Topics addressed included prenatal and child dietary intake, the microbiome, obesity, food-related environmental exposures, mechanisms and biological processes linking these factors and ASD, food-related social factors, and data sources for future research. Presentations highlighted evidence for protective associations with prenatal folic acid supplementation and ASD development, increases in risk of ASD with maternal gestational obesity, and the potential for exposure to environmental contaminants in foods and food packaging to influence ASD development. The importance of the maternal and child microbiome in ASD development or ASD-related behaviors in the child was reviewed, as was the role of discrimination in leading to disparities in environmental exposures and psychosocial factors that may influence ASD. The role of child diet and high prevalence of food selectivity in children with ASD and its association with adverse outcomes were also discussed. Priority evidence gaps identified by participants include further clarifying ASD development, including biomarkers and key mechanisms; interactions among psychosocial, social, and biological determinants; interventions addressing diet, supplementation, and the microbiome to prevent and improve quality of life for people with ASD; and mechanisms of action of diet-related factors associated with ASD. Participants developed research proposals to address the priority evidence gaps. The workshop findings serve as a foundation for future prioritization of scientific research to address evidence gaps related to food, nutrition, and ASD.

Influences of the Immune System and Microbiome on the Etiology of ASD and GI Symptomology of Autistic Individuals.

Autism Spectrum Disorder is a developmental condition associated with impairments in communication and social interactions, and repetitive and restricted behavior or interests. Autistic individuals are more likely to experience gastrointestinal (GI) symptoms than neurotypical individuals. This may be partially due to dysbiosis of the gut microbiome. In this article, we describe the interaction of the microbiome and immune system on autism etiology. We also summarize the links between the microbiome and gastrointestinal and related symptoms among autistic individuals. We report that microbial interventions, including diet, probiotics, antibiotics, and fecal transplants, and immune-modulating therapies such as cytokine blockade during the preconception, pregnancy, and postnatal period may impact the neurodevelopment, behavior, and gastrointestinal health of autistic individuals.