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Hyperactivity is a key symptom and the most observable manifestation of attention-deficit/hyperactivity disorder (ADHD). The over-activity associated with ADHD can cause specific challenges in academic settings, extracurricular activities and social relationships. Cognitive control challenges are also well established in ADHD. The current study included 44 children between the ages of 10 and 17 diagnosed with ADHD or who were typically developing (TD), all of whom had no psychiatric co-morbidity or significant learning disorders. Participants wore an actometer on their ankle while performing a flanker paradigm in order to objectively measure their rates of activity in association with cognitive control. Analyses assessed the relationship between frequency and intensity of activity to task accuracy on a trial-by-trial basis. A significant interaction effect between group and performance revealed that more intense movement was associated with better performance in the ADHD group but not in the TD group. The ADHD group demonstrated more intense activity than the TD group during correct (but not error) trials. Within-group, children with ADHD generated higher intensity movements in their correct trials compared to their error trials, whereas the TD group did not demonstrate any within-group differences. These findings suggest that excessive motoric activity associated with clinically significant ADHD symptoms may reflect compensatory efforts to modulate attention and alertness. Future research should systematically explore the relationship between motion in ADHD and how it might be used to improve cognitive performance.

Despite the prevalence and significant concern of COVID-19 in maternal and offspring health, little is known about the impact of COVID-19 during pregnancy on newborn immunity and neurodevelopment. This study aimed to examine 1) the relationship between maternal COVID-19 during pregnancy and newborn immune profiles and investigate the 2) associations between specific newborn immune profiles and the risk of subsequent diagnosis of a neurodevelopmental disorder (NDD) among children with prenatal exposure to COVID-19. Newborn dried bloodspots (NBS) from 545 children born at Kaiser Permanente Northern California between January 2020 and September 2021 (460 [223 males, 237 females] to COVID-19-infected [COVID+] mothers; 85 [45 males, 40 females] to COVID-19-uninfected [COVID-] mothers) were used to profile newborn immune molecules via a 42-plex cytokine/chemokine assay. Among the 460 children born to COVID+ mothers, 73 (47 males, 27 females) were later diagnosed with an NDD. In the first set of analyses examining the association between maternal COVID-19 infection during pregnancy and newborn immune profile, the results adjusted for covariates but uncorrected for multiple comparisons showed that newborns of COVID+ mothers had significantly higher levels of IL-22 (estimate [est.] = 0.16, 95 % Cl 0.01, 0.3, p = 0.04) and GM-CSF (est. = 0.27, 95 % Cl 0.09, 0.46, p = 0.004) compared to newborns of COVID- mothers. These differences were no longer statistically significant after multiple comparison adjustments. In the second analysis exploring the association between newborn profile and later diagnosis of NDD among newborns born to COVID+ mothers, the results adjusted for covariates revealed an association between higher neonatal levels of IL-22 (hazard ratio [HR] = 0.49, 95 % Cl 0.33, 0.75, p = 0.001) and lower risk of a later diagnosis of an NDD, which remained significant after multiple comparison adjustments (p = 0.04). Other neonatal cytokines/chemokines/growth factors such as sCD40L (HR = 0.7, 95 % Cl 0.57, 0.9, p = 0.009), IP-10 (HR = 0.46, 95 % Cl 0.25, 0.83, p = 0.009), MIG (HR = 0.52, 95 % Cl 0.3, 0.9, p = 0.02), FLT-3L (HR = 0.45, 95 % Cl 0.24, 0.83, p = 0.01), PDGF AB/BB (HR = 0.56, 95 % Cl 0.36, 0.99, p = 0.046), VEGF (HR = 0.57, 95 % Cl 0.34, 0.98, p = 0.04), and IL-4 (HR = 0.48, 95 % Cl 0.26, 0.93, p = 0.03) were no longer statistically significant after multiple comparison adjustments. Despite the imbalance between the number of COVID-19 exposed and unexposed newborns in this study cohort, our novel findings enhance our understanding of the potential impact of maternal COVID-19 infection during pregnancy on the developing neonatal immune system. Our findings highlight the role of immune molecules, beyond those considered to be pro-inflammatory, that may be crucial in maternal and newborn immunity against COVID-19 infection during pregnancy. Furthermore, our results suggest that reduced levels of neonatal immune molecules in newborns of COVID + mothers may be linked to an increased risk of a subsequent diagnosis of an NDD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Self-regulation abilities in childhood are predictive of a range of challenges later in life, making it important to identify difficulties in this area as early as possible. Autistic children and those with attention-deficit/hyperactivity disorder (ADHD) often have difficulties with self-regulation, but little is known about the similarities and differences in such abilities across neurodevelopmental conditions., Method: We examined self-regulation using a delay of gratification task in 36-month-old autistic children ( n  = 20), those showing clinically relevant concerns for ADHD (i.e. ADHD Concerns; n  = 24), and Comparison children without these conditions ( n  = 130); early predictors of self-regulation were also assessed., Results: Both the Autism and ADHD Concerns groups had greater difficulty waiting for a desired snack than the Comparison group. At the longest delay trial (30 seconds), a substantial percentage of autistic children (50%) and those with ADHD Concerns (35%) consumed the snack prematurely, in contrast to only 16% of the Comparison group. Parent-reported temperament-based impulsivity at 18 months and examiner-observed ADHD-like traits at 24 months were associated with increased self-regulation challenges at 36 months, regardless of group. Adjusting for verbal abilities attenuated some of these differences and associations, suggesting that language may be an important mechanism undergirding early self-regulatory abilities., Conclusion: Given possible links between preschool self-regulation and a range of critical functional outcomes, future studies may explore the efficacy of early interventions targeting impulsivity and regulatory behaviors in infants and toddlers at elevated likelihood for developing self-regulation challenges to potentially reduce the impact of these difficulties later in life.

Converging data show that exposure to maternal immune activation (MIA) in utero alters brain development in animals and increases the risk of neurodevelopmental disorders in humans. A recently developed non-human primate MIA model affords opportunities for studies with uniquely strong translational relevance to human neurodevelopment. The current longitudinal study used 1H-MRS to investigate the developmental trajectory of prefrontal cortex metabolites in male rhesus monkey offspring of dams (n = 14) exposed to a modified form of the inflammatory viral mimic, polyinosinic:polycytidylic acid (Poly IC), in the late first trimester. Brain metabolites in these animals were compared to offspring of dams that received saline (n = 10) or no injection (n = 4). N-acetylaspartate (NAA), glutamate, creatine, choline, myo-inositol, taurine, and glutathione were estimated from PRESS and MEGA-PRESS acquisitions obtained at 6, 12, 24, 36, and 45 months of age. Prior investigations of this cohort reported reduced frontal cortical gray and white matter and subtle cognitive impairments in MIA offspring. We hypothesized that the MIA-induced neurodevelopmental changes would extend to abnormal brain metabolite levels, which would be associated with the observed cognitive impairments. Prefrontal NAA was significantly higher in the MIA offspring across all ages (p < 0.001) and was associated with better performance on the two cognitive measures most sensitive to impairment in the MIA animals (both p < 0.05). Myo-inositol was significantly lower across all ages in MIA offspring but was not associated with cognitive performance. Taurine was elevated in MIA offspring at 36 and 45 months. Glutathione did not differ between groups. MIA exposure in male non-human primates is associated with altered prefrontal cortex metabolites during childhood and adolescence. A positive association between elevated NAA and cognitive performance suggests the hypothesis that elevated NAA throughout these developmental stages reflects a protective or resilience-related process in MIA-exposed offspring. The potential relevance of these findings to human neurodevelopmental disorders is discussed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The rising number of children identified with autism has led to exponential growth in for-profit applied behavior analysis (ABA) agencies and the use of highly structured approaches that may not be developmentally appropriate for young children. Multiple clinical trials support naturalistic developmental behavior interventions (NDBIs) that integrate ABA and developmental science and are considered best practices for young autistic children. The Early Start Denver Model (ESDM) is a comprehensive NDBI shown to improve social communication outcomes for young autistic children in several controlled efficacy studies. However, effectiveness data regarding NDBI use in community-based agencies are limited., Methods: This study uses a community-partnered approach to test the effectiveness of ESDM compared to usual early behavioral intervention (EBI) for improving social communication and language in autistic children served by community agencies. This is a hybrid type 1 cluster-randomized controlled trial with 2 conditions: ESDM and EBI. In the intervention group, supervising providers will receive training in ESDM; in the control group, they will continue EBI as usual. We will enroll and randomize 100 supervisors (50 ESDM, 50 EBI) by region. Each supervisor enrolls 3 families of autistic children under age 5 (n = 300) and accompanying behavior technicians (n = 200). The primary outcome is child language and social communication at 6 and 12 months. Secondary outcomes include child adaptive behavior, caregiver use of ESDM strategies, and provider intervention fidelity. Child social motivation and caregiver fidelity will be tested as mediating variables. ESDM implementation determinants will be explored using mixed methods., Discussion: This study will contribute novel knowledge on ESDM effectiveness, the variables that mediate and moderate child outcomes, and engagement of its mechanisms in community use. We expect results from this trial to increase community availability of this model and access to high-quality intervention for young autistic children, especially those who depend on publicly funded intervention services. Understanding implementation determinants will aid scale-up of effective models within communities., Trail Registration: Clinicaltrials.gov identifier number NCT06005285. Registered on August 21, 2023., Protocol Version: Issue date 6 August 2024; Protocol amendment number: 02., (© 2024. The Author(s).)

Clinical and academic research continues to become more complex as our knowledge and technology advance. A substantial and growing number of specialists in biostatistics, data science, and library sciences are needed to support these research systems and promote high-caliber research. However, that support is often marginalized as optional rather than a fundamental component of research infrastructure. By building research infrastructure, an institution harnesses access to tools and support/service centers that host skilled experts who approach research with best practices in mind and domain-specific knowledge at hand. We outline the potential roles of data scientists and statisticians in research infrastructure and recommend guidelines for advocating for the institutional resources needed to support these roles in a sustainable and efficient manner for the long-term success of the institution. We provide these guidelines in terms of resource efficiency, monetary efficiency, and long-term sustainability. We hope this work contributes to-and provides shared language for-a conversation on a broader framework beyond metrics that can be used to advocate for needed resources., Competing Interests: Conflict of interest: The authors declare no conflicts of interest with the publication of this work.

Maternal autoimmunity, and more specifically, the production of specific maternal autoantibodies, has been associated with altered offspring neurodevelopment. Maternal autoantibody-related (MAR) autism is a subtype of autism that is linked to gestational exposure to certain combinations of autoantibodies to proteins known to be important for fetal neurodevelopment. We wanted to address whether mothers with autism-specific patterns of autoantibodies have a skewed cytokine and chemokine profile during an immune response to infection. To do so, we examined a subset of mothers from the Early Markers for Autism (EMA) study who either produced known patterns of MAR autoantibodies (MAR+) or did not (MAR-). We compared the cytokine/chemokine profiles of MAR+ and MAR- mothers in the context of positive immunoglobulin G (IgG) reactivity to several viral and parasitic agents. We observed that MAR+ mothers have a higher level of proinflammatory cytokine interferon-gamma regardless of IgG status. Additionally, when comparing MAR+ and MAR- mothers in the context of the different pathogens, MAR+ mothers consistently had increases in multiple proinflammatory cytokines and chemokines., Competing Interests: Author JW has patents issued for the ELISA technology used to screen for MAR ABs and has founded a UC Davis startup company to develop the technology for commercial use. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 McLellan, Croen, Iosif, Yoshida, Ashwood, Yolken and Van de Water.)

Adolescence has been characterized as a period of risky and possibly suboptimal decision-making, yet the development of decision-making in autistic adolescents is not well understood. To investigate decision-making in autism, we evaluated performance on 2 computerized tasks capturing decision-making under explicit risk and uncertainty in autistic and non-autistic adolescents/young adults ages 12-22 years. Participants completed the Game of Dice Task (32 IQ-matched participant pairs) to assess decision-making under explicit risk and the modified Iowa Gambling Task (35 IQ-matched pairs) to assess decision-making under uncertainty. Autistic participants overall made riskier decisions than non-autistic participants on the Game of Dice Task, and the odds of making riskier decisions varied by age and IQ. In contrast, the autistic group showed comparable levels of learning over trial blocks to the non-autistic group on the modified Iowa Gambling Task. For both tasks, younger autistic participants performed poorer than their non-autistic counterparts, while group differences diminished in older ages. This age-related pattern suggests positive development during adolescence on risk assessment and decision-making in autism but also implies differential developmental trajectories between groups. These findings also suggest differential performance by the risk type, with additional complex influences of IQ and fluid cognition, which warrants further investigations., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Associations between maternal immune dysregulation (including autoimmunity and skewed cytokine/chemokine profiles) and offspring neurodevelopmental disorders such as autism have been reported. In maternal autoantibody-related autism, specific maternally derived autoantibodies can access the fetal compartment to target eight proteins critical for neurodevelopment. We examined the relationship between maternal autoantibodies to the eight maternal autoantibody-related autism proteins and cytokine/chemokine profiles in the second trimester of pregnancy in mothers of children later diagnosed with autism and their neonates' cytokine/chemokine profiles. Using banked maternal serum samples from 15 to 19 weeks of gestation from the Early Markers for Autism Study and corresponding banked newborn bloodspots, we identified three maternal/offspring groups based on maternal autoantibody status: (1) mothers with autoantibodies to one or more of the eight maternal autoantibody-related autismassociated proteins but not a maternal autoantibody-related autism-specific pattern, (2) mothers with a known maternal autoantibody-related autism pattern, and (3) mothers without autoantibodies to any of the eight maternal autoantibody-related autism proteins. Using a multiplex platform, we measured maternal second trimester and neonatal cytokine/chemokine levels. This combined analysis aimed to determine potential associations between maternal autoantibodies and the maternal and neonatal cytokine/chemokine profiles, each of which has been shown to have implications on offspring neurodevelopment independently., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Multiple pathway models propose that attention deficit hyperactivity disorder (ADHD) arises from dysfunction in separate systems comprised of a "cool" or cognitive pathway versus a "hot" or emotional/reward pathway. Interactions between these pathways and the degree of maturation may further determine functional outcomes for adolescents ranging from those diagnosed with ADHD to typical development (TD). We used a latent profile analysis on rating scales and behavioral task performance assessing emotion, irritability, impulsivity, risk-taking, future orientation, and processing speed (PS) to identify subgroups of TD adolescents and adolescents with ADHD (N = 152) based on the hot and cool pathway model. We identified four classes: 1) High-Complex Challenges; 2) Moderate-Mixed Challenges; 3) Non-Emotive Impulsivity; and 4) High Regulation and Control. A multiple pathway model of ADHD is supported with classes differing in degree of emotional lability and irritability, types of impulsivity, and ability to use future consequences to modulate impulsivity and PS. The classes differed regarding functional behavior, with the High-Complex class demonstrating the most severe functional challenges in academic-related functioning. The Moderate-Mixed class also displayed significant functional challenges but with moderate emotional lability and irritability ratings. The Non-Emotive Impulsivity class exhibited low emotionality and low irritability, yet high impulsivity with limited negative functional consequences, and was composed of a mix of ADHD and TD adolescents. Differences between classes suggest ADHD symptomatology may represent both categorical and dimensional differences. Precision health interventions may be more effective in addressing the specific challenges associated with the classes rather than a one-size-fits-all approach to treating ADHD., (© 2023. The Author(s).)

Background: Asynchronous telepsychiatry (ATP) consultations are a novel form of psychiatric consultation. Studies comparing patient and provider satisfaction for ATP with that for synchronous telepsychiatry (STP) do not exist. Methods: This mixed-methods study is a secondary analysis of patients' and primary care providers' (PCPs) satisfaction from a randomized clinical trial of ATP compared with STP. Patients and their PCPs completed satisfaction surveys, and provided unstructured feedback about their experiences with either ATP or STP. Differences in patient satisfaction were assessed using mixed-effects logistic regression models, and the qualitative data were analyzed using thematic analysis with an inductive coding framework. Results: Patient satisfaction overall was high with 84% and 97% of respondents at 6 months reported being somewhat or completely satisfied with ATP and STP, respectively. Patients in the STP group were more likely to report being completely satisfied, to recommend the program to a friend, and to report being comfortable with their care compared with ATP (all p < 0.05). However, there was no difference between the patients in ATP and STP in perceived change in clinical outcomes ( p  = 0.51). The PCP quantitative data were small, and thus only summarized descriptively. Conclusions: Patients expressed their overall satisfaction with both STP and ATP. Patients in ATP reported more concerns about the process, likely because feedback after ATP was slower than that after STP consultations. PCPs had no apparent preference for STP or ATP, and reported implementing the psychiatrists' recommendations for both groups when such recommendations were made, which supports our previous findings. Trial Registration: ClinicalTrials.gov NCT02084979; https://clinicaltrials.gov/ct2/show/NCT02084979.

Maternal infection has emerged as an important environmental risk factor for neurodevelopmental disorders, including schizophrenia and autism spectrum disorders. Animal model systems of maternal immune activation (MIA) suggest that the maternal immune response plays a significant role in the offspring's neurodevelopment and behavioral outcomes. Extracellular free water is a measure of freely diffusing water in the brain that may be associated with neuroinflammation and impacted by MIA. The present study evaluates the brain diffusion characteristics of male rhesus monkeys (Macaca mulatta) born to MIA-exposed dams (n = 14) treated with a modified form of the viral mimic polyinosinic:polycytidylic acid at the end of the first trimester. Control dams received saline injections at the end of the first trimester (n = 10) or were untreated (n = 4). Offspring underwent diffusion MRI scans at 6, 12, 24, 36, and 45 months. Offspring born to MIA-exposed dams showed significantly increased extracellular free water in cingulate cortex gray matter starting as early as 6 months of age and persisting through 45 months. In addition, offspring gray matter free water in this region was significantly correlated with the magnitude of the maternal IL-6 response in the MIA-exposed dams. Significant correlations between brain volume and extracellular free water in the MIA-exposed offspring also indicate converging, multimodal evidence of the impact of MIA on brain development. These findings provide strong evidence for the construct validity of the nonhuman primate MIA model as a system of relevance for investigating the pathophysiology of human neurodevelopmental psychiatric disorders. Elevated free water in individuals exposed to immune activation in utero could represent an early marker of a perturbed or vulnerable neurodevelopmental trajectory., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

We used parent report data to investigate video game playing, aggression, and social impairment in adolescents with autism spectrum disorder. Parents of autistic adolescents were more likely to report that their child plays video games as a hobby compared to parents of adolescents with typical development and also reported that their children spent more time playing video games. For autistic participants, we found no differences in aggression levels or social impairment when comparing players versus non-players. However, playing video games "more than average," as compared to "average" was associated with greater aggression and greater social impairment on "awareness" and "mannerisms" subscales. Future studies should focus on how type of video game(s) played is associated with these clinically important variables., (© 2022. The Author(s).)

Introduction: Recent work challenged past findings that documented relational memory impairments in autism. Previous studies often relied solely on explicit behavioral responses to assess relational memory integrity, but successful performance on behavioral tasks may rely on other cognitive abilities (e.g., executive functioning) that are impacted in some autistic individuals. Eye-tracking tasks do not require explicit behavioral responses, and, further, eye movements provide an indirect measure of memory. The current study examined whether memory-specific viewing patterns toward scenes differ between autistic and non-autistic individuals., Methods: Using a long-term memory paradigm that equated for complexity between item and relational memory tasks, participants studied a series of scenes. Following the initial study phase, scenes were re-presented, accompanied by an orienting question that directed participants to attend to either features of an item (i.e., in the item condition) or spatial relationships between items (i.e., in the relational condition) that might be subsequently modified during test. At test, participants viewed scenes that were unchanged (i.e., repeated from study), scenes that underwent an "item" modification (an exemplar switch) or a "relational" modification (a location switch), and scenes that had not been presented before. Eye movements were recorded throughout., Results: During study, there were no significant group differences in viewing directed to regions of scenes that might be manipulated at test, suggesting comparable processing of scene details during encoding. However, there was a group difference in explicit recognition accuracy for scenes that underwent a relational change. Marginal group differences in the expression of memory-based viewing effects during test for relational scenes were consistent with this behavioral outcome, particularly when analyses were limited to scenes recognized correctly with high confidence. Group differences were also evident in correlational analyses that examined the association between study phase viewing and recognition accuracy and between performance on the Picture Sequence Memory Test and recognition accuracy., Discussion: Together, our findings suggest differences in the integrity of relational memory representations and/or in the relationships between subcomponents of memory in autism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Minor, Hannula, Gordon, Ragland, Iosif and Solomon.)

Immune dysregulation, including aberrant peripheral cytokine/chemokine levels, is implicated in neurodevelopmental disorders (NDD) such as autism spectrum disorder (ASD). While the diagnosis of ASD is more common in males compared to females, sex effects in immune dysregulation related to neurodevelopment remain understudied. The aim of this exploratory study was to determine whether there are sex-specific effects in neonatal immune dysregulation with respect to an ASD or delayed development (DD) diagnosis. We utilized the data from the Early Markers for Autism study, a population based case-control study of prenatal and neonatal biomarkers of ASD. The immune profile of newborns later diagnosed with ASD (n = 482, 91 females), DD (n = 140, 61 females) and sex-matched general population controls (GP; n = 378, 67 females) were analyzed using neonatal bloodspots (NBS) via 42-plex multiplex assay. Multiple linear regression analysis was performed to identify whether sex was associated with differences in cytokine/chemokine levels of children with ASD, DD, and GP. A sex by diagnosis interaction effect was observed only for the chemokine macrophage migration inhibitory factor (MIF), with males displaying higher levels of NBS MIF than females in the GP control group (p = 0.02), but not in ASD (p = 0.52) or DD (p = 0.29) groups. We found that regardless of child diagnosis, newborn bloodspot eluates from females had a significantly higher concentration than males with the same diagnosis of the chemokines granulocyte chemotactic protein 2 (GCP-2; p < 0.0001), macrophage inflammatory protein 2-alpha (GROβ; p = 0.002), interferon-inducible t-cell alpha chemoattractant (I-TAC; p < 0.0001), stromal cell-derived factor 1 alpha and beta (SDF-1α-β; p = 0.03), innate inflammatory chemokines interferon-gamma induced protein 10 (IP-10; p = 0.02), macrophage inflammatory protein 1-alpha (MIP-1α; p = 0.02), and Th1-related pro-inflammatory cytokine interleukin-12 active heterodimer (IL-12p70; p = 0.002). In contrast, males had a higher concentration than females of secondary lymphoid-tissue chemokine (6CKINE; p = 0.02), monocyte chemotactic protein 1 (MCP-1; p = 0.005) and myeloid progenitor inhibitory factor 1 (MPIF-1; p = 0.03). Results were similar when analyses were restricted to NBS from DD and ASD further classified as ASD with intellectual disability (ID), ASD without ID, and DD (GCP-2, p = 0.007; I-TAC, p = 0.001; IP-10, p = 0.005; IL-12p70, p = 0.03 higher in females; MPIF-1, p = 0.03 higher in male). This study is the first to examine sex differences in neonatal cytokine/chemokine concentrations, and whether these differences are associated with neurodevelopmental outcomes. Results highlight the importance of considering sex as a critical factor in understanding the immune system as it relates to child development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Epidemiological studies suggest that maternal immune activation (MIA) is a significant risk factor for future neurodevelopmental disorders, including schizophrenia (SZ), in offspring. Consistent with findings in SZ research and work in rodent systems, preliminary cross-sectional findings in nonhuman primates suggest that MIA is associated with dopaminergic hyperfunction in young adult offspring., Methods: In this unique prospective longitudinal study, we used [ 18 F]fluoro-l-m-tyrosine positron emission tomography to examine the developmental time course of striatal presynaptic dopamine synthesis in male rhesus monkeys born to dams (n = 13) injected with a modified form of the inflammatory viral mimic, polyinosinic:polycytidylic acid [poly(I:C)], in the late first trimester. Striatal (caudate, putamen, and nucleus accumbens) dopamine from these animals was compared with that of control offspring born to dams that received saline (n = 10) or no injection (n = 4). Dopamine was measured at 15, 26, 38, and 48 months of age. Prior work with this cohort found decreased prefrontal gray matter volume in MIA offspring versus controls between 6 and 45 months of age. Based on theories of the etiology and development of SZ-related pathology, we hypothesized that there would be a delayed (relative to the gray matter decrease) increase in striatal fluoro-l-m-tyrosine signal in the MIA group versus controls., Results: [ 18 F]fluoro-l-m-tyrosine signal showed developmental increases in both groups in the caudate and putamen. Group comparisons revealed significantly greater caudate dopaminergic signal in the MIA group at 26 months., Conclusions: These findings are highly relevant to the known pathophysiology of SZ and highlight the translational relevance of the MIA model in understanding mechanisms by which MIA during pregnancy increases risk for later illness in offspring., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Lay Abstract: Research has found differences in responding to various sensory stimuli among autistic individuals, which are associated with social and adaptive skills. However, our understanding of sensory profiles in autism has been complicated due to the variable presentation of sensory symptoms. One way to better understand variability in sensory symptoms is to use advanced statistical approaches, such as latent profile analysis, that allow for the identification of more similar sensory classes in otherwise variable groups. We used the Short Sensory Profile to identify homogeneous classes of sensory reactivity in autistic children based on both severity and modality and examined whether sensory classes differed in terms of autism characteristics, adaptive skills, and attention-deficit/hyperactivity disorder symptoms. Based on the pattern of both severity and modality, four sensory classes emerged and were named Moderate/Mixed (35.5%; probable-to-definite differences in all modalities except in movement sensitivity and low energy/weakness), Severe/Mixed (8.5%; definite sensory differences in all modalities except in low energy/weakness), Moderate/Broad (14.6%; probable-to-definite differences in all modalities), and Low/Mixed (41.1%; typical scores in most modalities with probable differences in taste/smell sensitivity, under-responsive/seeks sensation, and auditory filtering). The Severe/Mixed class exhibited greater problems in a variety of areas such as social, adaptive, and attention-deficit/hyperactivity disorder symptoms, whereas the Low/Mixed class showed overall fewer problems. This may provide insight for clinicians and researchers aiming to understand whether autistic children who exhibit distinct sensory patterns are more or less likely to also experience social, adaptive, and/or attention/behavior-related difficulties.

Background: There are a few ecologically valid measurements of Daily Living Skills (DLS)-a critical component of adaptive functioning (AF)-for autistic adolescents and young adults. This is particularly important given that DLS predict outcomes as autistic adolescents transition to adulthood., Methods: We pilot-tested the assessment section of two modules of the Computerized Functional Skills Assessment and Training program (CFSAT) in 25 autistic ( n  = 4 female) and 25 non-autistic ( n  = 6 female) adolescents and young adults to evaluate preliminary feasibility in an autistic sample. Tasks involved using an ATM and ticket-buying machine. We also assessed AF and DLS with a well-validated self-report questionnaire. We examined group differences in performance and relationships between performance on CFSAT and an existing measure of AF and DLS. We also conducted regression analyses to investigate the associations between age, IQ, executive functioning (EF), and CFSAT task performance., Results: All but one autistic participant were able to complete the CFSAT tasks. Autistic participants made more errors, but did not take longer to complete the task, than non-autistic participants. Performance correlated strongly with self-reported AF generally and DLS specifically. The regression analyses revealed that task performance was associated with EF in the autistic group, but not the non-autistic group., Conclusions: These results provide preliminary support for the use of a new performance-based ecologically valid assessment of DLS in an autistic population. Two CFSAT modules were well-tolerated and detected differences in DLS ability. Strong correlations with an existing measure of AF suggest evidence of construct validity. The EF was associated with CFSAT task performance in autistic individuals. Such a tool could help identify individuals who would benefit from a DLS intervention., Competing Interests: Dr. Harvey has received consulting fees or travel reimbursements from Alkermes, Bio Excel, Boehringer Ingelheim, Karuna Pharma, Minerva Pharma, and Sunovion Pharma during the past year. He receives royalties from the Brief Assessment of Cognition in Schizophrenia (Owned by Verasci, Inc.). He is chief scientific officer of iFunction, Inc., the owner of the CFSAT software. The remaining authors have no conflicts of interest relevant to the content of this article to declare., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

Background: We extended our study of trajectories of intellectual development of autistic individuals in early (mean age 3 years; T1), and middle childhood (mean age 5 years, 7 months; T2) into later middle childhood/preadolescence (mean age 11 years, 6 months; T3) in the longitudinal Autism Phenome Project cohort. Participants included 373 autistic children (115 females)., Methods: Multivariate latent class growth analysis was used to identify distinct IQ trajectory subgroups. Baseline and developmental course group differences and predictors of trajectory membership were assessed using linear mixed effects models with repeated measures with pairwise testing, multinomial logistic regression models, and sensitivity analyses., Results: We isolated three IQ trajectories between T1 and T3 for autistic youth that were similar to those found in our prior work. These included a group with persistent intellectual disability (ID; 45%), a group with substantial increases in IQ (CHG; 39%), and a group with persistently average or above IQs (P-High; 16%). By T3, the groups did not differ in ADOS-2 calibrated severity scores (CSS), and there were no group differences between Vineland (VABS) communication scores in CHG and P-High. T1-T3 externalizing behaviors declined significantly for CHG, however, there were no significant T3 group differences between internalizing or externalizing symptoms. T1 correlates for CHG and P-High versus ID group membership included higher VABS communication and lower ADOS-2 CSS. A T1 to T2 increase in VABS communication scores and a decline in externalizing predicted CHG versus ID group membership at T3, while T1 to T2 improvement in VABS communication and reduction in ADOS-2 CSS predicted P-High versus ID group membership., Conclusions: Autistic youth exhibit consistent IQ developmental trajectories from early childhood through preadolescence. Factors associated with trajectory group membership may provide clues about prognosis, and the need for treatments that improve adaptive communication and externalizing symptoms., Competing Interests: Conflicts of Interest Drs. Solomon, Iosif, Nordahl, Cho, Heath, and Ferrer and Mr. Srivastav report no biomedical financial interests or potential conflicts of interest. Dr. Amaral is on the Scientific Advisory Board of Stemina Biomaker Discovery and Axial Biotherapeutics.

Women who contract a viral or bacterial infection during pregnancy have an increased risk of giving birth to a child with a neurodevelopmental or psychiatric disorder. The effects of maternal infection are likely mediated by the maternal immune response, as preclinical animal models have confirmed that maternal immune activation (MIA) leads to long lasting changes in offspring brain and behavior development. The present study sought to determine the impact of MIA-exposure during the first or second trimester on neuronal morphology in dorsolateral prefrontal cortex (DLPFC) and hippocampus from brain tissue obtained from MIA-exposed and control male rhesus monkey (Macaca mulatta) during late adolescence. MIA-exposed offspring display increased neuronal dendritic branching in pyramidal cells in DLPFC infra- and supragranular layers relative to controls, with no significant differences observed between offspring exposed to maternal infection in the first and second trimester. In addition, the diameter of apical dendrites in DLPFC infragranular layer is significantly decreased in MIA-exposed offspring relative to controls, irrespective of trimester exposure. In contrast, alterations in hippocampal neuronal morphology of MIA-exposed offspring were not evident. These findings demonstrate that a maternal immune challenge during pregnancy has long-term consequences for primate offspring dendritic structure, selectively in a brain region vital for socioemotional and cognitive development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Maternal hormonal risk factors for autism spectrum disorder (ASD) in offspring could intersect genetic and environmental risk factors., Objectives: This analysis explored ASD risk in association with maternal testosterone, androstenedione, and dehydroepiandrosterone (DHEA) measured in first, second, and third trimesters of pregnancy., Methods: MARBLES is a prospective pregnancy cohort study based at the MIND Institute in Northern California that enrolls mothers who have at least one child previously diagnosed with ASD and are expecting, or planning to have another child. At 36 months the younger sibling is clinically classified as having ASD, or as non-typically developing (Non-TD), or typically developing (TD). Maternal androgens during pregnancy were measured in serum samples from 196 mothers. Multivariable logistic regression models estimated risk of ASD and Non-TD in offspring compared to TD, in relation to the log-transformed maternal androgen concentrations, at each trimester., Results: Non-significant associations were observed, and borderline significant associations were only observed in some stratified unadjusted models. Second trimester maternal testosterone was non-significantly associated with ASD in female offspring, although not after adjustment, aRR 1.54 (95% CI 0.71, 3.33), and second trimester maternal DHEA was non-significantly associated with non-TD in male offspring, again not after adjustment, aRR 0.50 (95% CI 0.21, 1.21). Secondary analysis suggested that third trimester androgen concentrations in mothers with male offspring had significant or near significant associations with their child's Social Responsiveness Scale score., Conclusion: No significant associations were found between maternal androgen concentrations and risk of ASD or Non-TD in the child., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RJ Schmidt receives research funding from the Simons Foundation, was a paid consultant for a research study at Drexel University, and has received honoraria from NIH for grant reviews. A-M Iosif has received honoraria for reviewing activities from Elsevier, NIH and Department of Defense. L Granillo and NW Snyder declare no competing financial interests.

This pilot study sought to identify potential markers of improvement from pre-post treatment in response to computerized working memory (WM) training for youth (ages 8-18) with autism spectrum disorder (ASD) and comorbid intellectual disability (ID) in a single arm, pre-post design. Participants included 26 children with ASD and 18 with comorbid ASD and fragile X syndrome (ASD+FXS). Analyses were adjusted for age and IQ. The ASD group demonstrated greater improvement on WM training relative to the ASD+FXS group. Participants improved on WM and far transfer outcomes, however, there were no significant group differences in improvement except for repetitive behavior. Higher hyperactivity/impulsivity ratings predicted lower performance on visuospatial WM. Findings suggest cognitive training may be beneficial for youth with ASD and ID, warranting further exploration., (©AAIDD.)

Background: Heightened motor activity is a hallmark of attention-deficit/hyperactivity disorder (ADHD), yet high activity levels are also often reported in young children with autism spectrum disorder (ASD). It is currently unclear whether increased motor activity represents a distinct versus shared early predictor of ASD and ADHD; no prior studies have directly examined this prospectively. We investigated differences in longitudinal patterns of objectively measured motor activity during early development., Methods: Participants included 113 infants at high and low risk for ASD or ADHD. Continuous motion-based activity was recorded using tri-axial accelerometers at 12, 18, 24, and 36 months of age. At 36 months, participants were categorized into one of three outcome groups: ASD (n = 19), ADHD Concerns (n = 17), and Typically Developing (TD; n = 77). Group differences in trajectories of motor activity were examined in structured and semistructured contexts. Associations with behaviors relevant to ASD, ADHD, and general development were also examined., Results: In both structured and semistructured contexts, both the ASD and ADHD Concerns groups exhibited heightened activity relative to the TD group by 18 months; the ASD group exhibited higher activity than the ADHD Concerns group at 24-36 months in the structured context only. Attention/behavior regulation, nonverbal, and verbal development-but not social engagement-were differentially associated with objectively measured activity by outcome group across contexts., Conclusions: Overactivity may be a shared, rather than distinct, precursor of atypical development in infants/toddlers developing ASD and concerns for ADHD, emerging as early as 18 months. Group differences in overactivity may be context-specific and associated with different underlying mechanisms., (© 2021 Association for Child and Adolescent Mental Health.)

Anxiety and depression are common non-motor symptoms of Parkinson's disease (PD). Caregivers of people with PD may experience severe caregiver burden. This study explored the feasibility and potential benefits of an online mindfulness-based cognitive therapy (MBCT) intervention for improving anxiety and depressive symptoms in people with PD and their caregivers (ClinicalTrials.gov NCT04469049, 7/8/2020). People with PD or parkinsonism and anxiety and/or depressive symptoms and caregivers of people with PD participated in one of three online MBCT groups. Demographic variables, pre- and post-MBCT behavioral measures (GAD-7, PHQ-9, Five Facet Mindfulness Questionnaire - FFMQ-15, Caregiver Self-Assessment Questionnaire - CSAQ), and satisfaction surveys were collected. Descriptive statistics were used to summarize data. Pre- and post-MBCT behavioral scores were compared using mixed-effect models. Fifty-six potential participants were assessed for eligibility. Twenty-eight entered MBCT groups; all but one completed the intervention. The overall sample analyzed (22 people with PD, 4 caregivers) showed significant GAD-7 and PHQ-9 score reductions and FFMQ-15 total and observing and non-reactivity subscale score increases (all p 's < 0.05). Participants with PD and anxiety symptoms ( n  = 14) had a significant GAD-7 score reduction; those with PD and depressive symptoms ( n  = 12) had a significant PHQ-9 score reduction (both p 's < 0.05). Participants with PD also had a significant FFMQ-15 observing subscale score increase ( p  < 0.05). The caregiver sample was too small to be analyzed separately. Online MBCT is feasible (as measured by high attendance, completion rate, and participant satisfaction) and may be effective in improving anxiety and depressive symptoms in people with PD., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022.)

Human epidemiological studies implicate exposure to infection during gestation in the etiology of neurodevelopmental disorders. Animal models of maternal immune activation (MIA) have identified the maternal immune response as the critical link between maternal infection and aberrant offspring brain and behavior development. Here we evaluate neurodevelopment of male rhesus monkeys ( Macaca mulatta ) born to MIA-treated dams ( n = 14) injected with a modified form of the viral mimic polyinosinic:polycytidylic acid at the end of the first trimester. Control dams received saline injections at the same gestational time points ( n = 10) or were untreated ( n = 4). MIA-treated dams exhibited a strong immune response as indexed by transient increases in sickness behavior, temperature, and inflammatory cytokines. Although offspring born to control or MIA-treated dams did not differ on measures of physical growth and early developmental milestones, the MIA-treated animals exhibited subtle changes in cognitive development and deviated from species-typical brain growth trajectories. Longitudinal MRI revealed significant gray matter volume reductions in the prefrontal and frontal cortices of MIA-treated offspring at 6 months that persisted through the final time point at 45 months along with smaller frontal white matter volumes in MIA-treated animals at 36 and 45 months. These findings provide the first evidence of early postnatal changes in brain development in MIA-exposed nonhuman primates and establish a translationally relevant model system to explore the neurodevelopmental trajectory of risk associated with prenatal immune challenge from birth through late adolescence. SIGNIFICANCE STATEMENT Women exposed to infection during pregnancy have an increased risk of giving birth to a child who will later be diagnosed with a neurodevelopmental disorder. Preclinical maternal immune activation (MIA) models have demonstrated that the effects of maternal infection on fetal brain development are mediated by maternal immune response. Since the majority of MIA models are conducted in rodents, the nonhuman primate provides a unique system to evaluate the MIA hypothesis in a species closely related to humans. Here we report the first longitudinal study conducted in a nonhuman primate MIA model. MIA-exposed offspring demonstrate subtle changes in cognitive development paired with marked reductions in frontal gray and white matter, further supporting the association between prenatal immune challenge and alterations in offspring neurodevelopment., (Copyright © 2021 the authors.)

Objective : To evaluate how distinct presentations of anxiety symptoms and intellectual impairment influence the measurement and estimated rate of clinically significant anxiety in autism spectrum disorder (ASD). Method : The sample included 75 children (ages 9-13 years) with ASD and varied IQ and 52 typically developing (TD) controls and parents. Parents completed anxiety symptom scales and a diagnostic interview, designed to (1) differentiate anxiety and ASD and (2) examine DSM-specified and unspecified ("distinct") anxiety presentations in each child, including fears of change, special interests, idiosyncratic stimuli and social confusion rather than evaluation. Children completed standard intellectual and ASD diagnostic assessments. Results : 69% of those with ASD had clinically-significant anxiety, including 21% DSM-specified anxiety disorders, 17% distinct anxiety, and 31% both. Only 8% of TD children had clinically-significant anxiety, all DSM-specified. DSM-specified anxiety disorders in children with ASD and intellectual impairment (IQ<70) were predominantly specific phobias. DSM-specified anxiety other than specific phobia was significantly less common in children with, versus without, intellectual impairment; this was not the case for distinct anxiety. The sensitivities of anxiety scales were moderate to poor, particularly in cases with intellectual impairment. Conclusions : ASD is associated with more frequent and varied presentations of clinical anxiety, which may align with and differ from the specified anxiety disorders of the DSM. Standard parent report anxiety scales have reduced sensitivity to detect clinical anxiety in ASD, particularly in children with intellectual impairment.

Objective: Alarming rates of anxiety and burnout in pre-clinical health profession trainees are now challenged by additional COVID-19 stressors. This study explored COVID-related stressors among first-year medical, physician assistant, nurse practitioner, and veterinary medical students. The authors examined associations between resilience, news monitoring, and COVID stress., Methods: Students completed an online questionnaire that included the Brief Resilience Scale at their matriculation in August 2019. Survey results were linked to demographic information collected by all schools. A follow-up survey in May 2020 included original questions on COVID-19 stressors and news monitoring. Statistical analyses included descriptive statistics and multivariable linear regression models., Results: Across schools, 74% (266/360) provided consent for the 2019 survey, and 76% (201/264) responded to COVID-19 questions in the follow-up 2020 survey. Students were "extremely" or "very" concerned about family members getting infected (n = 71, 76% School of Medicine (SOM); n = 31, 76% School of Nursing (SON); n = 50, 75% School of Veterinary Medicine (SVM)) and curriculum schedule changes (n = 72, 78%, SOM; n = 28, 68% SON; n = 52, 79% SVM). Greater frequency of COVID news monitoring was associated with greater COVID-related stress (p = 0.02). Higher resilience at matriculation was associated with lower COVID-related stress ten months later (p < 0.001)., Conclusions: Amid COVID-19 uncertainty, health science schools should address the immense student stress regarding curriculum disruptions. The results of this study underscore the powerful role of resilience in protecting against stress not only during the known academic rigor of health professions training but also during unprecedented crises., (© 2021. The Author(s).)

Objective : We evaluated trajectories of attention-deficit/hyperactivity (ADHD)-relevant behaviors in a sample of infants at high and low familial risk for ADHD who were prospectively evaluated at 12, 18, and 24 months of age. Method : Participants included 43 infants at risk for ADHD based on family history (i.e., diagnosed first-degree relative) and 40 low-risk infants (i.e., no family history of ADHD). Instances of inattention, out-of-seat, and grabbing behavior were coded from video; analogous constructs were rated by examiners unaware of familial risk status after completing structured standardized assessments with the infants/toddlers. At the end of each study visit, examiners solicited parents' concerns about their child's behavior. Differences in ADHD-related behaviors and parent concerns were examined between 12 and 24 months of age. Results : Infants with an older sibling or parent diagnosed with ADHD were distinguishable from infants with no family history of ADHD as early as 12 months of age based on directly observed and examiner reports of behavior, particularly with respect to hyperactive-impulsive behavior. Parents of infants at familial risk for ADHD also reported significantly more behavior/temperament concerns as early as 12 months of age compared to parents of infants at low risk for ADHD. Conclusions : These findings highlight the ability to detect genetic liability for ADHD by the end of the first year of life, suggesting that well-designed family risk studies of ADHD are feasible and may be clinically valuable. They also suggest the potential for earlier detection of risk for ADHD than has previously been possible.

Objective: Asynchronous telepsychiatry (ATP) is an integrative model of behavioral health service delivery that is applicable in a variety of settings and populations, particularly consultation in primary care. This article outlines the development of a training model for ATP clinician skills. Methods: Clinical and procedural training for ATP clinicians (n = 5) was provided by master's-level, clinical mental health providers developed by three experienced telepsychiatrists (P.Y. D.H., and J.S) and supervised by a tele-psychiatrist (PY, GX, DL) through seminar, case supervision, and case discussions. A training manual and one-on-one sessions were employed for initial training. Unstructured expert discussion and feedback sessions were conducted in the training phase of the study in year 1 and annually thereafter over the remaining 4 years of the study. The notes gathered during those sessions were synthesized into themes to gain a summary of the study telepsychiatrist training recommendations for ATP interviewers. Results: Expert feedback and discussion revealed three overarching themes of recommended skill sets for ATP interviewers: (1) comprehensive skills in brief psychiatric interviewing, (2) adequate knowledge base of behavioral health conditions and therapeutic techniques, and (3) clinical documentation, integrated care/consultation practices, and e-competency skill sets. The model of training and skill requirements from expert feedback sessions included these three skill sets. Technology training recommendations were also identified and included: (1) awareness of privacy/confidentiality for electronic data gathering, storage, management, and sharing; (2) technology troubleshooting; and (3) video filming/retrieval. Conclusions: We describe and provide a suggested training model for the use of ATP integrated behavioral health. The training needs for ATP clinicians were assessed on a limited convenience sample of experts and clinicians, and more rigorous studies of training for ATP and other technology-focused, behavioral health services are needed. Clinical Trials number: NCT03538860.

We evaluated repetitive behavior with objects in infants at risk for autism spectrum disorder (ASD) from 9 to 36 months of age, and associations between early repetitive behavior and social engagement. Infant siblings of children with ASD (high-risk) or typical development (low-risk) were administered a task eliciting repetitive object use at 9, 12, 15, 18, 24, and 36 months of age. Infants (n = 147) were classified into 1 of 3 outcome groups at 36 months: Low-Risk Non-ASD (n = 58), High-Risk Non-ASD (n = 72), and ASD (n = 17). Behavior was coded from video for frequencies of unusual visual inspection, spinning, and rotating behaviors. Differences in unusual visual inspection were most prominent, consistent, and present earliest: At 9 months, the ASD group engaged in this behavior more frequently than both other groups, persisting through 36 months. Differences in frequencies of spinning and rotating were later-appearing, more time-limited, and/or related to familial ASD risk rather than ultimate diagnosis. Sensitivity and specificity estimates for the presence of unusual visual inspection at 9 months of age were in the moderate range (.60 and .68, respectively) for ASD versus Low-Risk Non-ASD comparisons, generally increasing over time. Unusual visual inspection at 9 months predicted 12-month social behavior controlling for 9-month social behavior, but not vice versa, with no evidence of moderation by ASD diagnosis. In summary, unusual visual inspection of objects is present and stable by 9 months of age in infants developing ASD and predicts reduced social engagement three-months later. Close monitoring of this behavior may aid early detection. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background: Asynchronous telepsychiatry (ATP; delayed-time) consultations are a novel form of psychiatric consultation in primary care settings. Longitudinal studies comparing clinical outcomes for ATP with synchronous telepsychiatry (STP) are lacking., Objective: This study aims to determine the effectiveness of ATP in improving clinical outcomes in English- and Spanish-speaking primary care patients compared with STP, the telepsychiatry usual care method., Methods: Overall, 36 primary care physicians from 3 primary care clinics referred a heterogeneous sample of 401 treatment-seeking adult patients with nonurgent psychiatric disorders. A total of 184 (94 ATP and 90 STP) English- and Spanish-speaking participants (36/184, 19.6% Hispanic) were enrolled and randomized, and 160 (80 ATP and 80 STP) of them completed baseline evaluations. Patients were treated by their primary care physicians using a collaborative care model in consultation with the University of California Davis Health telepsychiatrists, who consulted with patients every 6 months for up to 2 years using ATP or STP. Primary outcomes (the clinician-rated Clinical Global Impressions [CGI] scale and the Global Assessment of Functioning [GAF]) and secondary outcomes (patients' self-reported physical and mental health and depression) outcomes were assessed every 6 months., Results: For clinician-rated primary outcomes, ATP did not promote greater improvement than STP at 6-month follow-up (ATP vs STP, adjusted difference in follow-up at 6 months vs baseline differences for CGI: 0.2, 95% CI -0.2 to 0.6; P=.28; and GAF: -0.6, 95% CI -3.1 to 1.9; P=.66) or 12-month follow-up (ATP vs STP, adjusted difference in follow-up at 12 months vs baseline differences for CGI: 0.4, 95% CI -0.04 to 0.8; P=.07; and GAF: -0.5, 95% CI -3.3 to 2.2; P=.70), but patients in both arms had statistically and clinically significant improvements in both outcomes. There were no significant differences in improvement from baseline between ATP and STP on any patient self-reported ratings at any follow-up (all P values were between .17 and .96). Dropout rates were higher than predicted but similar between the 2 arms. Of those with baseline visits, 46.8% (75/160) did not have a follow-up at 1 year, and 72.7% (107/147) did not have a follow-up at 2 years. No serious adverse events were associated with the intervention., Conclusions: This is the first longitudinal study to demonstrate that ATP can improve clinical outcomes in English- and Spanish-speaking primary care patients. Although we did not find evidence that ATP is superior to STP in improving clinical outcomes, it is potentially a key part of stepped mental health interventions available in primary care. ATP presents a possible solution to the workforce shortage of psychiatrists and a strategy for improving existing systems of care., Trial Registration: ClinicalTrials.gov NCT02084979; https://clinicaltrials.gov/ct2/show/NCT02084979., (©Peter M Yellowlees, Michelle Burke Parish, Alvaro D Gonzalez, Steven R Chan, Donald M Hilty, Byung-Kwang Yoo, J Paul Leigh, Robert M McCarron, Lorin M Scher, Andres F Sciolla, Jay Shore, Glen Xiong, Katherine M Soltero, Alice Fisher, Jeffrey R Fine, Jennifer Bannister, Ana-Maria Iosif. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 20.07.2021.)

Background: Narrative communication is often more persuasive for promoting health behaviour change than communication using facts and figures; the extent to which narrative persuasiveness is due to patients' identification with the storyteller vs engagement with the story is unclear., Objective: To examine the relative impacts of patient engagement, age concordance and gender concordance on perceived persuasiveness of video-recorded narrative clips about opioid tapering., Methods: Patient raters watched and rated 48 brief video-recorded clips featuring 1 of 7 different storytellers describing their experiences with opioid tapering. The dependent variable was clips' perceived persuasiveness for encouraging patients to consider opioid tapering. Independent variables were rater engagement with the clip, rater-storyteller gender concordance and rater-storyteller age concordance (<60 vs ≥60). Covariates were rater beliefs about opioids and opioid tapering, clip duration and clip theme. Mixed-effects models accounted for raters viewing multiple clips and clips nested within storytellers., Results: In multivariable models, higher rater engagement with the clip was associated with higher perceived persuasiveness (coefficient = 0.46, 95% CI 0.39-0.53, P < .001). Neither age concordance nor gender concordance significantly predicted perceived persuasiveness. The theme Problems with opioids also predicted perceived persuasiveness., Conclusion: Highly engaging, clinically relevant stories are likely persuasive to patients regardless of the match between patient and storyteller age and gender. When using patient stories in tools to promote health behaviour change, stories that are clinically relevant and engaging are likely to be persuasive regardless of storytellers' demographics., Patient or Public Contribution: Patients were involved as storytellers (in each clip) and assessed the key study variables., (© 2021 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Two independent cohorts (N = 155, N = 126) of infants at high and low risk for autism spectrum disorder (ASD) were followed prospectively between 6 and 36 months of age, when n = 46 were diagnosed with ASD. Gaze to adult faces was coded-during a developmental assessment (Cohort 1) or a play interaction (Cohort 2). Across both cohorts, most children developing ASD showed sharp declines in gaze to faces over time, relative to children without ASD. These findings suggest that declining developmental trajectories may be more common than previously recognized by retrospective methods. Trajectory-based screening methods could potentially identify children in the early stages of symptom onset and allow for early intervention before the full disorder has developed., (© 2020 Society for Research in Child Development.)

Despite the clinically significant impact of executive dysfunction on the outcomes of adolescents and young adults with autism spectrum disorders (ASD), we lack a clear understanding of its prevalence, profile, and development. To address this gap, we administered the NIH Toolbox Cognition Battery to a cross-sectional Intelligence Quotient (IQ) case-matched cohort with ASD (n = 66) and typical development (TD; n = 66) ages 12-22. We used a general linear model framework to examine group differences in task performance and their associations with age. Latent profile analysis (LPA) was used to identify subgroups of individuals with similar cognitive profiles. Compared to IQ case-matched controls, ASD demonstrated poorer performance on inhibitory control (P < 0.001), cognitive flexibility (P < 0.001), episodic memory (P < 0.02), and processing speed (P < 0.001) (components of Fluid Cognition), but not on vocabulary or word reading (components of Crystallized Cognition). There was a significant positive association between age and Crystallized and Fluid Cognition in both groups. For Fluid (but not Crystallized) Cognition, ASD performed more poorly than TD at all ages. A four-group LPA model based on subtest scores best fit the data. Eighty percent of ASD belonged to two groups that exhibited relatively stronger Crystallized versus Fluid Cognition. Attention deficits were not associated with Toolbox subtest scores, but were lowest in the group with the lowest proportion of autistic participants. Adaptive functioning was poorer in the groups with the greatest proportion of autistic participants. Autistic persons are especially impaired on Fluid Cognition, and this more flexible form of thinking remains poorer in the ASD group through adolescence. LAY SUMMARY: A set of brief tests of cognitive functioning called the NIH Toolbox Cognition Battery was administered to adolescents and young adults with autism spectrum disorders (ASD; n = 66) and typical development (TD; n = 66) ages 12-22 years. Compared to TD, ASD showed poorer performance in inhibiting responses, acting flexibly, memorizing events, and processing information quickly (Fluid Cognition). Groups did not differ on vocabulary or word reading (Crystallized Cognition). Crystallized and Fluid Cognition increased with age in both groups, but the ASD group showed lower Fluid, but not Crystallized, Cognition than TD at all ages. A categorization analysis including all participants showed that most participants with ASD fell into one of two categories: a group characterized by poor performance across all tasks, or a group characterized by relatively stronger Crystallized compared to Fluid Cognition. Adaptive functioning was poorer for participants in these groups, which consisted of mostly individuals with ASD, while ADHD symptoms were lowest in the group with the greatest proportion of TD participants., (© 2020 International Society for Autism Research and Wiley Periodicals LLC.)

Few studies have explored autism spectrum disorder (ASD) screening in the first year of life. The current investigation examines the psychometric properties of the Infant-Toddler Checklist starting in the first year of life in a sample at elevated and average risk for ASD based on family history. 283 participants were followed from 6 to 36 months, when diagnostic outcome was determined. The results indicated low to moderate sensitivity, specificity, and positive predictive value across ages for broadly distinguishing any delays from typical development, as well as for more narrowly discriminating children with ASD from those who were typically developing. Implications for utilizing ASD screening tools in the first year of life with high risk samples are discussed.

Diminished response to name, a potential early marker of autism spectrum disorder (ASD), may also indicate risk for other disorders characterized by attention problems, including attention-deficit/hyperactivity disorder (ADHD). Using a familial risk design, we examined whether response to name ability at 6, 12, 18, 24, and 36 months of age differed between three 36-month outcome groups: ASD, ADHD Concerns, or a Comparison group. Persistent differences between the ASD and Comparison groups were evident beginning at 12 months; differences between the ADHD Concerns and Comparison groups were evident between 12 and 18 months only. Results suggest that response to name may be a general marker for ASD and ADHD risk in infancy but a specific indicator of ASD by 24-months.

Objective: To compare effectiveness of a narrative-based educational video versus an informational pamphlet for increasing patients' self-efficacy and intention to taper their opioid use., Methods: Five thousand participants recruited from MTurk were screened to identify eligible patients. Eligible participants (n = 365, 49.9 % female, mean age = 37 years) were randomized to either watch the narrative video or read the pamphlet. Linear regression models were used for the main analysis., Results: Participants' perceptions of tapering effectiveness were higher in the video group (mean = 4.06) than the pamphlet group (mean = 3.67), adjusted mean difference = 0.34, 95 %CI 0.13 - 0.54,P < 0.001. Participants' perceptions of tapering self-efficacy were also higher in the video group (mean = 3.97) than the pamphlet group (mean = 3.60), adjusted mean difference = 0.32, 95 %CI 0.09 - 0.55, P < 0.001. Perceived tapering effectiveness and self-efficacy were both positively associated with post-intervention tapering intention (Spearman rank correlation coefficient = 0.38 and 0.53, respectively, both P < 0.001)., Conclusion: A narrative-based video about opioid tapering enhanced patients' perceptions of the effectiveness of tapering and their tapering self-efficacy., Practice Implications: Narrative-based videos may be effective for changing patient attitudes about opioid tapering., (Published by Elsevier B.V.)

Working memory (WM) deficits are key in attention deficit hyperactivity disorder (ADHD). Nevertheless, WM is not universally impaired in ADHD. Additionally, the neural basis for WM deficits in ADHD has not been conclusively established, with regions including the prefrontal cortex, cerebellum, and caudate being implicated. These contradictions may be related to conceptualizations of WM capacity, such as load (amount of information) versus operational-complexity (maintenance-recall or manipulation). For instance, relative to neurotypical (NT) individuals, complex WM operations could be impaired in ADHD, while simpler operations are spared. Alternatively, all operations may be impaired at higher loads. Here, we compared the impact of these two components of WM capacity: load and operational-complexity, between ADHD and NT, behaviorally and neurally. We hypothesized that the impact of WM load would be greater in ADHD, and the neural activation would be altered. Participants (age-range 12-23 years; 50 ADHD (18 females); 82 NT (41 females)) recalled three or four objects (load) in forward or backward order (operational-complexity) during functional magnetic resonance imaging scanning. The effects of diagnosis and task were compared on performance and neural engagement. Behaviorally, we found significant interactions between diagnosis and load, and between diagnosis, load, and complexity. Neurally, we found an interaction between diagnosis and load in the right striatum, and between diagnosis and complexity in the right cerebellum and left occipital gyrus. The ADHD group displayed hypo-activation compared to NT group during higher load and greater complexity. This informs mechanisms of functional problems related to WM in adolescents and young adults with ADHD (e.g., academic performance) and remedial interventions (e.g., WM-training)., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aims of this study were to identify a subset of children with autism spectrum disorder (ASD) and co-occurring symptoms of psychopathology, and to evaluate associations between this subgroup and biological sex and amygdala volume., Method: Participants included 420 children (ASD: 91 girls, 209 boys; typically developing controls: 57 girls, 63 boys). Latent profile analysis was used to identify ASD subgroups based on symptoms of psychopathology, adaptive functioning, cognitive development, and autism severity. Differences in the proportions of girls and boys across subgroups were evaluated. Magnetic resonance imaging scans were acquired (346 children); amygdala volumes were evaluated in relation to subgroups and problem behavior scores., Results: Three ASD subgroups were identified. One group was characterized by high levels of psychopathology and moderate impairment on other measures (High Psychopathology Moderate Impairments [HPMI], comprising 27% of the sample). The other two subgroups had lower symptoms of psychopathology but were differentiated by high and low levels of impairment on other measures. A higher proportion of girls were classified into the HPMI subgroup (40% of girls versus 22% of boys). Relative to controls, amygdala volumes were enlarged only in the HPMI subgroup. There was a positive association between right amygdala volume and internalizing behaviors in girls but not in boys with ASD., Conclusion: A higher proportion of girls with ASD faced greater challenges with psychopathology, suggesting a need for closer evaluation and potentially earlier intervention to help improve outcomes. Amygdala enlargement was associated with co-occurring symptoms of psychopathology, and sex-specific correlations with symptoms were observed., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are believed to share partially overlapping causal mechanisms suggesting that early risk markers may also overlap. Using latent profile analysis (LPA) in a sample of infants enriched for ASD and ADHD, we first examined the number of distinct groups of 3-year-old children, based on ADHD and ASD symptomatology. To investigate early predictors of ASD and ADHD symptom profiles, we next examined differences in trajectories of infant behaviors among the LPA classes spanning general development, negative affect, attention, activity level, impulsivity, and social behavior. Participants included 166 infants at familial risk for ASD (n = 89), ADHD (n = 38), or low-risk for both (n = 39) evaluated at 12, 18, 24, and 36 months of age. A three-class solution was selected reflecting a Typically Developing (TD) class (low symptoms; n = 108), an ADHD class (high ADHD/low ASD symptoms; n = 39), and an ASD class (high ASD/ADHD symptoms; n = 19). Trajectories of infant behaviors were generally suggestive of a gradient pattern of differences, with the greatest impairment within the ASD class followed by the ADHD class. These findings indicate a mixture of overlapping and distinct early markers of preschool ASD- and ADHD-like profiles that can be difficult to disentangle early in life.

Objective: We examined growth trajectories of hippocampal volume (HV) in early childhood in a longitudinal cohort of male and female participants with autism spectrum disorder (ASD) and typically developing (TD) individuals, and investigated HV in those with large brains. Relations between factors potentially associated with hippocampal size and growth were investigated., Method: Participants received 1 to 3 structural magnetic resonance imaging scans between ages 25 and 80 months (unique participants: ASD, n =200; TD, n =110; total longitudinal scans, n = 593). HV growth during this period was examined using mixed-effects linear models. Associations between early HV and growth rates, and IQ and adaptive functioning, were evaluated., Results: After accounting for cerebral hemisphere volume, male participants exhibited larger left and right HV than female participants. Hippocampal growth rates did not differ by sex. In children with larger hemisphere volumes, male and female participants with ASD had relatively larger HV than TD participants of similar hemisphere volume. This effect was present in a broader group than only those with disproportionate megalencephaly (male participants with large cerebral volumes relative to body size). Right hippocampi were larger than left hippocampi in both groups and sexes. Right versus left volume differences were greater for ASD. After adjusting for hemisphere volume, male participants with ASD showed a significant positive association between right hippocampal growth and adaptive behavior., Conclusion: HV was relatively greater in ASD in analyses adjusting for hemisphere volume, whereas only subtle differences were observed in HV and growth between participants with ASD and TD participants in unadjusted analyses, suggesting that ASD involves atypical coupling between HV and brain size., (Copyright © 2019 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Lay Abstract: Prior studies suggest that maternal polyunsaturated fatty acids intake during pregnancy may have protective effects on autism spectrum disorder in their children. However, they did not examine detailed timing of maternal polyunsaturated fatty acid intake during pregnancy, nor did they evaluate plasma concentrations. This study investigates whether maternal polyunsaturated fatty acids in defined time windows of pregnancy, assessed by both questionnaires and biomarkers, are associated with risk of autism spectrum disorder and other non-typical development in the children. Food frequency questionnaires were used to estimate maternal polyunsaturated fatty acid intake during the first and second half of pregnancy. Gas chromatography measured maternal plasma polyunsaturated fatty acid concentrations in the third trimester. In all, 258 mother-child pairs from a prospective cohort were included. All mothers already had a child with autism spectrum disorder and were planning a pregnancy or pregnant with another child. Children were clinically assessed longitudinally and diagnosed at 36 months. For polyunsaturated fatty acid intake from questionnaires, we only found mothers consuming more omega-3 in the second half of pregnancy were 40% less likely to have children with autism spectrum disorder. For polyunsaturated fatty acid concentrations in the third-trimester plasma, we did not observe any statistical significance in relation to the risk of autism spectrum disorder. However, our study confirmed associations from previous studies between higher maternal docosahexaenoic acid and eicosapentaenoic acid plasma concentrations in the late pregnancy and reduced risk for non-typical development. This study markedly advanced understandings of whether and when maternal polyunsaturated fatty acid intake influences risk for autism spectrum disorder and sets the stage for prevention at the behavioral and educational level.

Although meta-analyses suggest that schizophrenia (SZ) is associated with a more severe neurocognitive phenotype than mood disorders such as bipolar disorder, considerable between-subject heterogeneity exists in the phenotypic presentation of these deficits across mental illnesses. Indeed, it is unclear whether the processes that underlie cognitive dysfunction in these disorders are unique to each disease or represent a common neurobiological process that varies in severity. Here we used latent profile analysis (LPA) across 3 distinct cognitive domains (cognitive control, episodic memory, and visual integration; using data from the CNTRACS consortium) to identify distinct profiles of patients across psychotic illnesses. LPA was performed on a sample of 223 psychosis patients (59 with Type I bipolar disorder, 88 with SZ, and 76 with schizoaffective disorder). Seventy-three healthy control participants were included for comparison but were not included in sample LPA. Three latent profiles ("Low," "Moderate," and "High" ability) were identified as the underlying covariance across the 3 domains. The 3-profile solution provided highly similar fit to a single continuous factor extracted by confirmatory factor analysis, supporting a unidimensional structure. Diagnostic ratios did not significantly differ between profiles, suggesting that these profiles cross diagnostic boundaries (an exception being the Low ability profile, which had only one bipolar patient). Profile membership predicted Brief Psychiatric Rating Scale and Young Mania Rating Scale symptom severity as well as everyday communication skills independent of diagnosis. Biological, clinical and methodological implications of these findings are discussed., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Telemedicine is a convenient health service delivery modality for patients with movement disorders, including Parkinson's disease (PD), but is currently underutilized in the management of associated psychiatric symptoms. This study explored the feasibility of and patient satisfaction with telepsychiatry services at an academic movement disorders center., Methods: All patients seen by telepsychiatry between January and December 2017 at the UCSF Movement Disorders and Neuromodulation Center were invited to participate. Participation was voluntary. Patients received an initial survey after the first telepsychiatry visit and satisfaction surveys after each visit. Survey responses were collected online via Research Electronic Data Capture (REDCap). Frequencies were calculated for categorical variables, and means and standard deviations were generated for continuous variables., Results: Thirty-three patients (79% with PD; 72% Medicare recipients; 64% men; mean age, 61.1 ± 10.5 years; mean distance to clinic, 79.9 ± 81.3 miles) completed a total of 119 telepsychiatry and 62 in-person visits. Twenty-two initial surveys and 50 satisfaction surveys (from 21 patients) were collected. Patients were very satisfied with the care (95%), convenience (100%), comfort (95%), and overall visit (95%). Technical quality was somewhat lower rated, with 76% patients reporting they were very satisfied, while 19% were satisfied. All patients would recommend telemedicine to friends or family members., Conclusions: Telepsychiatry is a feasible option for patients with movement disorders, leading to high patient satisfaction and improved access to care. Technical aspects still need optimization. Whenever available, telepsychiatry can be considered in addition to in-person visits. Future studies with larger samples should explore its impact on patient care outcomes and caregiver burden., Competing Interests: Competing interestsThe authors declare that they have no competing interests.