1. Belmonte MK. Motor symptoms in the ASD diagnostic criteria: A conservative perspective. Autism Res;2022 (Sep);15(9):1582-1584.

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2. Bishop JC, Nichols C, Kranz S, Lukacs JK, Block ME. Determinants of physical activity of transitioning adult children with Autism Spectrum Disorder. Heliyon;2022 (Aug);8(8):e10150.

Many young adults on the autism spectrum do not attain the recommended minimum weekly amount of moderate to vigorous physical activity (MVPA) to prevent significant health risks. Autism symptoms as well as environmental factors may play a key role in the physical activity (PA) behaviors of young adults on the autism spectrum. The socioecological model (SEM) has been previously used to identify determinants of PA among people within many disability categories. AIMS: Explore the overall relationship between determinants of PA of MVPA among parents and their young adult child with ASD as well as MVPA determinants segmented by caregiver level of support. METHODS: 336 parents of adult children with ASD completed the Determinants of Physical Activity and Eating Behaviors for Young Adults with ASD Scale. RESULTS: Children’s weekly time spent in MVPA was predicted by parent self-reported MVPA, exercise competency, video game use, social skills, and neighborhood qualities. Parent weekly time spent in MVPA was predicted by their child’s weekly MVPA, parent exercise competency, parent discretionary time, available home exercise equipment, and parent attitude towards physical activity. CONCLUSION: These results support the administration of quality community-based motor development, motor skills, and exercise skills programs focused on increasing physical activity and parent’s influential role in their children’s weekly MVPA.

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3. Burrows CA, Grzadzinski RL, Donovan K, Stallworthy IC, Rutsohn J, St John T, Marrus N, Parish-Morris J, MacIntyre L, Hampton J, Pandey J, Shen MD, Botteron KN, Estes AM, Dager SR, Hazlett HC, Pruett JR, Jr., Schultz RT, Zwaigenbaum L, Truong KN, Piven J, Elison JT. A Data-Driven Approach in an Unbiased Sample Reveals Equivalent Sex Ratio of Autism Spectrum Disorder-Associated Impairment in Early Childhood. Biol Psychiatry;2022 (Jun 7)

BACKGROUND: Sex differences in the prevalence of neurodevelopmental disorders are particularly evident in autism spectrum disorder (ASD). Heterogeneous symptom presentation and the potential of measurement bias hinder early ASD detection in females and may contribute to discrepant prevalence estimates. We examined trajectories of social communication (SC) and restricted and repetitive behaviors (RRBs) in a sample of infant siblings of children with ASD, adjusting for age- and sex-based measurement bias. We hypothesized that leveraging a prospective elevated familial likelihood sample, deriving data-driven behavioral constructs, and accounting for measurement bias would reveal less discrepant sex ratios than are typically seen in ASD. METHODS: We conducted direct assessments of ASD symptoms at 6 to 9, 12 to 15, 24, and 36 to 60 months of age (total n(observations) = 1254) with infant siblings of children with ASD (n = 377) and a lower ASD-familial-likelihood comparison group (n = 168; n(observations) = 527). We established measurement invariance across age and sex for separate models of SC and RRB. We then conducted latent class growth mixture modeling with the longitudinal data and evaluated for sex differences in trajectory membership. RESULTS: We identified 2 latent classes in the SC and RRB models with equal sex ratios in the high-concern cluster for both SC and RRB. Sex differences were also observed in the SC high-concern cluster, indicating that girls classified as having elevated social concerns demonstrated milder symptoms than boys in this group. CONCLUSIONS: This novel approach for characterizing ASD symptom progression highlights the utility of assessing and adjusting for sex-related measurement bias and identifying sex-specific patterns of symptom emergence.

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4. Chavers TN, Schlosser RW, Cheng C, Koul R. Effects of Interventions Involving Speech Output Technologies on Communication Outcomes for Individuals With Developmental Disabilities: A Scoping Review. Am J Speech Lang Pathol;2022 (Sep 7);31(5):2248-2267.

PURPOSE: This scoping review aimed to map the literature on the effects of interventions involving speech output technologies on communication outcomes for individuals with developmental disabilities other than autism spectrum disorder. METHOD: A scoping review methodology was used to limit bias in searching, selecting, coding, and synthesizing relevant intervention studies. This involved a multifaceted search for studies conducted between 1991 and March 2021 using various electronic databases, ancestry searches, and forward citation searches from selected articles. Studies had to meet stringent inclusion criteria. Each study was summarized in terms of authors, purpose, participants, design, speech output, outcomes, effectiveness, and quality appraisal. RESULTS: Twenty-five single-case experimental design studies (88 participants) and one group design studies (62 participants) qualified for inclusion. Most of the participants had multiple diagnoses followed by a diagnosis of cerebral palsy and Down syndrome. Most studies focused on requesting behaviors and to a much lesser extent on syntactic structure and word identification. A dearth of high-quality studies was identified. CONCLUSIONS: Overall, there is a paucity of high-quality research investigating the effects of speech output technologies for children with developmental disabilities. Additionally, several directions for future research are posited. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.20468928.

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5. Choi B, Yi E. The Impact of Income and Social Capital on the Health of People with Developmental Disabilities. Healthcare (Basel);2022 (Aug 15);10(8)

This study examines the impact of income and social capital on the health of people with developmental disabilities, focusing on the moderating effects of income and social capital on health. Hierarchical regression analysis was conducted using data from 235 people with developmental disabilities who participated in the second wave of the Disability and Life Dynamics Panel. The findings show that people with developmental disabilities who were female, employed, and did not have multiple disabilities and chronic diseases were more likely to display higher levels of self-rated health. Furthermore, self-rated health was higher in those earning a higher income. The social network had a significantly positive effect on health, but its moderating effect on the impact of income did not carry statistical significance. Trust was found to have a moderating effect on the impact of income on health, where the group with greater trust and lower income was healthier than the group with lower trust. The findings suggest the need to provide income support and establish social capital for people with developmental disabilities to improve their health, and this study offers related policy implications.

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6. Crowley N, O’Connell H, Gervin M. Autistic spectrum disorder without intellectual impairment in adult mental health services – fostering new perspectives and enhancing existing services. Ir J Psychol Med;2022 (Sep);39(3):312-318.

Autistic spectrum disorder (ASD) is a neuro-developmental disability with multi-systemic impacts. Individuals with ASD without intellectual impairment (DSM-V) or Aspergers (DSM-IV) are often particularly vulnerable to mental health problems such as anxiety disorders including social phobia and generalised anxiety disorder, depressive disorders and psychosis. Adults with ASD without intellectual impairment suffer higher rates of physical and psychiatric morbidity, display a poorer ability to engage with treatment and have a lower chance of recovery compared with the general population. It is widely acknowledged that adults with suspected ASD without intellectual impairment and co-morbid mental health problems are often not best supported through adult mental health services and often require more tailored supports. This review seeks to (a) increase awareness in the area of undiagnosed cases of ASD without intellectual impairment in adult mental health settings and (b) highlights the importance of identifying this population more efficiently by referring to best practice guidelines. The value of future research to examine the benefit of having a team of specialist staff within adult mental health teams who have received ASD training and who are supported to work with the ‘core difficulties’ of ASD is discussed and a model for the same is proposed. It is proposed that a specialist team could form a ‘hub’ for the development of expertise in ASD, which when adequately resourced and funded could reach across an entire region, offering consultancy and diagnostic assessments and interventions.

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7. Deniz E, Francis G, Torgerson C, Toseeb U. Parent-mediated play-based interventions to improve social communication and language skills of preschool autistic children: A systematic review and meta-analysis protocol. PLoS One;2022;17(8):e0270153.

Early years interventions have shown to be effective in improving the social communication and language skills of autistic children. Therefore, various play-based interventions have been developed to support those developmental areas of autistic children. Although researchers have previously reported the overall effectiveness of different types of play-based interventions on the social communication and language skills of autistic children, no previous systematic reviews have yet evaluated the effectiveness of parent-mediated play-based interventions in preschool autistic children. The overarching aims of the study will be to (i) report the key characteristics and (ii) synthesise the results of studies evaluating parent-mediated play-based interventions targeting the social communication and language skills of preschool autistic children using experimental designs. A comprehensive search for and screening of the relevant studies published between 2000 and 2021 will be undertaken. To be included, studies will have to (i) use either a randomised control trial or quasi-experimental design, (ii) focus on preschool autistic children aged six years old or younger, (iii) deliver a play-based intervention in non-educational settings, and (iv) include at least one parent as the mediator of the intervention. Data extraction of all included studies will be undertaken using a specially devised template and they will also be assessed for risk of bias using an adapted form from the Cochrane Risk of Bias tool. The overall characteristics of the included studies will be reported and a narrative synthesis of the results of the included studies will be undertaken. A meta-analysis may be performed (if justified) to report the pooled effect size of the parent-mediated play-based interventions on the social communication and language skills of preschool autistic children. Trial registration: The current study protocol was pre-registered with the international prospective register of systematic reviews (PROSPERO: CRD42022302220).

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8. Du Y, He X, Kochunov P, Pearlson G, Hong LE, van Erp TGM, Belger A, Calhoun VD. A new multimodality fusion classification approach to explore the uniqueness of schizophrenia and autism spectrum disorder. Hum Brain Mapp;2022 (Aug 15);43(12):3887-3903.

Schizophrenia (SZ) and autism spectrum disorder (ASD) sharing overlapping symptoms have a long history of diagnostic confusion. It is unclear what their differences at a brain level are. Here, we propose a multimodality fusion classification approach to investigate their divergence in brain function and structure. Using brain functional network connectivity (FNC) calculated from resting-state fMRI data and gray matter volume (GMV) estimated from sMRI data, we classify the two disorders using the main data (335 SZ and 380 ASD patients) via an unbiased 10-fold cross-validation pipeline, and also validate the classification generalization ability on an independent cohort (120 SZ and 349 ASD patients). The classification accuracy reached up to 83.08% for the testing data and 72.10% for the independent data, significantly better than the results from using the single-modality features. The discriminative FNCs that were automatically selected primarily involved the sub-cortical, default mode, and visual domains. Interestingly, all discriminative FNCs relating to the default mode network showed an intermediate strength in healthy controls (HCs) between SZ and ASD patients. Their GMV differences were mainly driven by the frontal gyrus, temporal gyrus, and insula. Regarding these regions, the mean GMV of HC fell intermediate between that of SZ and ASD, and ASD showed the highest GMV. The middle frontal gyrus was associated with both functional and structural differences. In summary, our work reveals the unique neuroimaging characteristics of SZ and ASD that can achieve high and generalizable classification accuracy, supporting their potential as disorder-specific neural substrates of the two entwined disorders.

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9. Fredskild MU, Engell R, Kessing LV. [Bipolar affective disorder in autism spectrum disorder]. Ugeskr Laeger;2022 (Aug 15);184(33)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a global prevalence of approximately 1%. This review summarises new evidence of association between bipolar disorder (BD) and ASD. The mood episodes of BD can present atypically in people with ASD, potentially leading to misdiagnosis. Anamnesis regarding family history of affective disorders as well as previous mood episode is important among people with ASD to capture the BD diagnosis. Precaution with SSRI-treatment among people with ASD is crucial as the treatment can potentially trigger a mood episode of an underlying BD.

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10. Gallagher L, McGrath J. Autism spectrum disorders: current issues and future directions. Ir J Psychol Med;2022 (Sep);39(3):237-239.

This edition of Irish Journal of Psychological Medicine is a Special Themed Issue on Autism Spectrum Disorders (ASD). Mental health services are not currently meeting the needs of autistic people across the lifespan. We have limited evidence based treatments for core symptoms and comorbidities and there is lack of awareness and under-recognition of ASD, particularly in adults and certain groups of individuals. The key themes in this edition focus on challenges with recognition and diagnosis and address these from both clinical and research perspectives. Co-occurring conditions also feature, which are also under-recognised and can contribute to less optimal outcomes. New and existing research developments in stratification for clinical trials and neuroimaging are also discussed. We hope this Issue highlights relevant current issues in ASD, and provides insights which can help address the challenges in providing evidence based pathways to better meet the needs of autistic people into the future.

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11. Gilmore D, Longo A, Krantz M, Radford D, Hand BN. Five Ways Providers Can Improve Mental Healthcare for Autistic Adults: A Review of Mental Healthcare Use, Barriers to Care, and Evidence-Based Recommendations. Curr Psychiatry Rep;2022 (Aug 15):1-7.

PURPOSE OF REVIEW: We reviewed the literature from 2017 to 2022 on autistic adults’ use of mental healthcare and barriers to care. To encourage immediate improvement in mental healthcare, we provide five strategies mental health providers can use to better care for autistic adults. RECENT FINDINGS: Most autistic adults use mental healthcare and use it more often than non-autistic adults. Autistic adults’ experiences with mental healthcare are characterized by (1) lack of providers knowledgeable about autism, (2) use of treatments that may not be accommodating to individual needs, and (3) difficulty navigating the complex healthcare system. These barriers contribute to prevalent unmet needs for mental healthcare. Autistic adults use mental healthcare frequently but have unmet mental health needs. As necessary systemic changes develop, providers can begin immediately to better care for autistic adults by learning about their needs and taking personalized care approaches to meet those needs.

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12. Karaminis T, Stavrakaki S. The psychometric properties of the Greek version of the Social Communication Questionnaire. Autism Res;2022 (Sep);15(9):1768-1780.

There is a scarcity of diagnostic assessments and screening tools for autism spectrum disorders (ASD) in Greek. In this study, we examined the psychometric properties of the recently developed Greek version of the Social Communication Questionnaire (SCQ). We used parental responses for 311 children (mean age: 7.54 years old, SD = 1.92), 122 with a diagnosis of ASD (93 boys, 29 girls) and 189 neurotypical children (104 boys, 85 girls), with 167 responses referring to the Lifetime and 144 to the Current form of the SCQ. Both forms presented adequate construct validity based on the four-factor model, while in both forms, autistic children presented higher SCQ total and subscale scores (four factors) than typical children. The forms had excellent internal reliability. An item-response-theory analysis suggested that over 80% of test items fitted adequately a Rasch model, while a preliminary analysis of gender biases suggested that a small number of items (Lifetime: five; Current: six out of 39) were differentially sensitive to autistic symptomatology in boys and girls. A receiver-operating-characteristic analysis showed excellent diagnostic performance based on the SCQ total score (Lifetime: area-under-the-curve/AUC = 0.937, Current: AUC = 0.963), and acceptable to excellent discrimination for the four subscales (AUCs between 0.737 and 0.955). Our preliminary results suggest that the Greek SCQ presents satisfactory psychometric properties and can be used for differentiating children with ASD from typical children in initial assessments within clinical and research settings. LAY SUMMARY: Autism spectrum disorder (ASD or autism) is a lifelong neurodevelopmental condition with a prevalence of ~1.5%-2% and characterized by difficulties in social interaction and communication and repetitive and restricted behaviors. There is increasing concern that research in ASD has focused on a small number of languages and cultural settings and that this bias challenges the identification and diagnosis of the condition in other languages and cultures, which are underrepresented in autism research. One such language is Greek (spoken by ~13.5 million), for which there is a scarcity of standardized instruments for the diagnosis of autism. This study examines the psychometric properties of the recently published Greek version of the Social Communication Questionnaire (SCQ), a widely used screening tool for ASD. We conduct an in-depth psychometric analysis of the Greek SCQ, including both forms in which the instrument is available (Lifetime and Current). This analysis shows that the Greek SCQ can be used for differentiating children with ASD from typical children in initial assessments within clinical and research settings. The findings of this study have implications for clinicians, special educators and researchers working with Greek-speaking individuals with ASD and, more broadly, for cross-cultural autism research.

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13. Li B, Xu Y, Pang D, Zhao Q, Zhang L, Li M, Li W, Duan G, Zhu C. Interrelation between homocysteine metabolism and the development of autism spectrum disorder in children. Front Mol Neurosci;2022;15:947513.

Evidence is emerging that dysregulation of circulating concentrations of homocysteine, an important intermediate in folate and vitamin B12 metabolism, is associated with autism spectrum disorder (ASD), but comprehensive assessments and correlations with disease characteristics have not been reported. Multivariate ordinal regression and restricted cubic spline (RCS) models were used to estimate independent correlations between serum homocysteine, folate, and vitamin B12 levels and clinical outcomes and severity of children with ASD. After adjusting for confounding factors, serum homocysteine levels were significantly higher in children with ASD than in healthy controls (β: 0.370; 95% CI: 0.299~0.441, p < 0.001). Moreover, homocysteine had a good diagnostic ability for distinguishing children with ASD from healthy subjects (AUC: 0.899, p < 0.001). The RCS model indicated a positive and linear association between serum homocysteine and the risk of ASD. The lowest quartile of folate was positively associated with ASD severity (OR: 4.227, 95% CI: 1.022~17.488, p = 0.041) compared to the highest quartile, and serum folate showed a negative and linear association with ASD severity. In addition, decreased concentrations of folate and vitamin B12 were associated with poor adaptive behavior developmental quotients of the Gesell Developmental Schedules (p < 0.05). Overall, an increased homocysteine level was associated with ASD in a linear manner and is thus a novel diagnostic biomarker for ASD. Decreased concentrations of folate and vitamin B12 were associated with poor clinical profiles of children with ASD. These findings suggest that homocysteine-lowering interventions or folate and vitamin B12 supplementation might be a viable treatment strategy for ASD.

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14. Li LS, Zhang Q, Liu H, Wu QH, Yang T, Chen J, Li TY. Involvement of retinoic acid receptor α in the autistic-like behavior of rats with vitamin A deficiency by regulating neurexin 1 in the visual cortex: a mechanism study. Zhongguo Dang Dai Er Ke Za Zhi;2022 (Aug 15);24(8):928-935.

OBJECTIVES: To study the mechanism of retinoic acid receptor α (RARα) signal change to regulate neurexin 1 (NRXN1) in the visual cortex and participate in the autistic-like behavior in rats with vitamin A deficiency (VAD). METHODS: The models of vitamin A normal (VAN) and VAD pregnant rats were established, and some VAD maternal and offspring rats were given vitamin A supplement (VAS) in the early postnatal period. Behavioral tests were performed on 20 offspring rats in each group at the age of 6 weeks. The three-chamber test and the open-field test were used to observe social behavior and repetitive stereotyped behavior. High-performance liquid chromatography was used to measure the serum level of retinol in the offspring rats in each group. Electrophysiological experiments were used to measure the long-term potentiation (LTP) level of the visual cortex in the offspring rats. Quantitative real-time PCR and Western blot were used to measure the expression levels of RARα, NRXN1, and N-methyl-D-aspartate receptor 1 (NMDAR1). Chromatin co-immunoprecipitation was used to measure the enrichment of RARα transcription factor in the promoter region of the NRXN1 gene. RESULTS: The offspring rats in the VAD group had autistic-like behaviors such as impaired social interactions and repetitive stereotypical behaviors, and VAS started immediately after birth improved most of the behavioral deficits in offspring rats. The offspring rats in the VAD group had a significantly lower serum level of retinol than those in the VAN and VAS groups (P<0.05). Compared with the offspring rats in the VAN and VAS groups, the offspring rats in the VAD group had significant reductions in the mRNA and protein expression levels of NMDAR1, RARα, and NRXN1 and the LTP level of the visual cortex (P<0.05). The offspring rats in the VAD group had a significant reduction in the enrichment of RARα transcription factor in the promoter region of the NRXN1 gene in the visual cortex compared with those in the VAN and VAS groups (P<0.05). CONCLUSIONS: RARα affects the synaptic plasticity of the visual cortex in VAD rats by regulating NRXN1, thereby participating in the formation of autistic-like behaviors in VAD rats.

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15. Lindenmaier Z, Ellegood J, Stuive M, Easson K, Yee Y, Fernandes D, Foster J, Anagnostou E, Lerch JP. Examining the effect of chronic intranasal oxytocin administration on the neuroanatomy and behavior of three autism-related mouse models. Neuroimage;2022 (Aug 15);257:119243.

Although initially showing great potential, oxytocin treatment has encountered a translational hurdle in its promise of treating the social deficits of autism. Some debate surrounds the ability of oxytocin to successfully enter the brain, and therefore modify neuroanatomy. Moreover, given the heterogeneous nature of autism, treatment will only amerliorate symptoms in a subset of patients. Therefore, to determine whether oxytocin changes brain circuitry, and whether it does so variably, depending on genotype, we implemented a large randomized, blinded, placebo-controlled, preclinical study on chronic intranasal oxytocin treatment in three different mouse models related to autism with a focus on using neuroanatomical phenotypes to assess and subset treatment response. Intranasal oxytocin (0.6IU) was administered daily, for 28 days, starting at 5 weeks of age to the 16p11.2 deletion, Shank3 (exon 4-9) knockout, and Fmr1 knockout mouse models. Given the sensitivity of structural magnetic resonance imaging (MRI) to the neurological effects of interventions like drugs, along with many other advantages, the mice underwent in vivo longitudinal and high-resolution ex vivo imaging with MRI. The scans included three in vivo T1weighted, 90 um isotropic resolution scans and a T2-weighted, 3D fast spin echo with 40um isotropic resolution ex vivo scan to assess the changes in neuroanatomy using established automated image registration and deformation based morphometry approaches in response to oxytocin treatment. The behavior of the mice was assessed in multiple domains, including social behaviours and repetitive behaviours, among others. Treatment effect on the neuroanatomy did not reach significance, although the pattern of trending effects was promising. No significant effect of treatment was found on social behavior in any of the strains, although a significant effect of treatment was found in the Fmr1 mouse, with treatment normalizing a grooming deficit. No other treatment effect on behavior was observed that survived multiple comparisons correction. Overall, chronic treatment with oxytocin had limited effects on the three mouse models related to autism, and no promising pattern of response susceptibility emerged.

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16. Meisner OC, Nair A, Chang SWC. Amygdala connectivity and implications for social cognition and disorders. Handb Clin Neurol;2022;187:381-403.

The amygdala is a hub of subcortical region that is crucial in a wide array of affective and motivation-related behaviors. While early research contributed significantly to our understanding of this region’s extensive connections to other subcortical and cortical regions, recent methodological advances have enabled researchers to better understand the details of these circuits and their behavioral contributions. Much of this work has focused specifically on investigating the role of amygdala circuits in social cognition. In this chapter, we review both long-standing knowledge and novel research on the amygdala’s structure, function, and involvement in social cognition. We focus specifically on the amygdala’s circuits with the medial prefrontal cortex, the orbitofrontal cortex, and the hippocampus, as these regions share extensive anatomic and functional connections with the amygdala. Furthermore, we discuss how dysfunction in the amygdala may contribute to social deficits in clinical disorders including autism spectrum disorder, social anxiety disorder, and Williams syndrome. We conclude that social functions mediated by the amygdala are orchestrated through multiple intricate interactions between the amygdala and its interconnected brain regions, endorsing the importance of understanding the amygdala from network perspectives.

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17. Nebel MB, Lidstone DE, Wang L, Benkeser D, Mostofsky SH, Risk BB. Accounting for motion in resting-state fMRI: What part of the spectrum are we characterizing in autism spectrum disorder?. Neuroimage;2022 (Aug 15);257:119296.

The exclusion of high-motion participants can reduce the impact of motion in functional Magnetic Resonance Imaging (fMRI) data. However, the exclusion of high-motion participants may change the distribution of clinically relevant variables in the study sample, and the resulting sample may not be representative of the population. Our goals are two-fold: 1) to document the biases introduced by common motion exclusion practices in functional connectivity research and 2) to introduce a framework to address these biases by treating excluded scans as a missing data problem. We use a study of autism spectrum disorder in children without an intellectual disability to illustrate the problem and the potential solution. We aggregated data from 545 children (8-13 years old) who participated in resting-state fMRI studies at Kennedy Krieger Institute (173 autistic and 372 typically developing) between 2007 and 2020. We found that autistic children were more likely to be excluded than typically developing children, with 28.5% and 16.1% of autistic and typically developing children excluded, respectively, using a lenient criterion and 81.0% and 60.1% with a stricter criterion. The resulting sample of autistic children with usable data tended to be older, have milder social deficits, better motor control, and higher intellectual ability than the original sample. These measures were also related to functional connectivity strength among children with usable data. This suggests that the generalizability of previous studies reporting naïve analyses (i.e., based only on participants with usable data) may be limited by the selection of older children with less severe clinical profiles because these children are better able to remain still during an rs-fMRI scan. We adapt doubly robust targeted minimum loss based estimation with an ensemble of machine learning algorithms to address these data losses and the resulting biases. The proposed approach selects more edges that differ in functional connectivity between autistic and typically developing children than the naïve approach, supporting this as a promising solution to improve the study of heterogeneous populations in which motion is common.

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18. Palumbi R. Editorial: Metabolic profiles of autistic and typically developing children. Front Psychiatry;2022;13:1005521.

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19. Pan N, Lin LZ, Wang X, Guo CH, Jing J, Li XH. Association between paternal age at childbirth and autism spectrum disorder in offspring. Zhongguo Dang Dai Er Ke Za Zhi;2022 (Aug 15);24(8):863-868.

OBJECTIVES: To study the association between paternal age at childbirth and the risk of autism spectrum disorder (ASD) in offspring. METHODS: In this cross-sectional study, 71 children with ASD who were diagnosed in the Department of Child Healthcare in six hospitals in Guangzhou, Foshan, Beijing, Wuhan, Hangzhou, and Chongqing of China from August 2016 to March 2017 were enrolled as subjects, and 284 typically developing children matched for age, sex, and maternal age at childbirth with the ASD children served as controls. A self-design questionnaire was used to collect the data on social demography, maternal pregnancy, and delivery. The association between paternal age at childbirth and the development of ASD in offspring was evaluated by the logistic regression analysis. RESULTS: After control for demographic factors and pregnancy- and delivery-related factors, the logistic regression analysis showed that a relatively high paternal age at childbirth was significantly associated with the increased risk of ASD in offspring (OR=1.12, 95%CI: 1.02-1.23, P<0.05). After grouping based on the paternal age, the logistic regression analysis showed that paternal age at childbirth of ≥40 years was significantly associated with the risk of ASD in offspring (before adjustment: OR=7.08, 95%CI: 1.77-28.32, P<0.05; after adjustment: OR=8.50, 95%CI: 1.71-42.25, P<0.05). CONCLUSIONS: High paternal age at childbirth is significantly associated with the increased risk of ASD in offspring, and paternal age at childbirth ≥40 years may be the high-risk age group for ASD in offspring.

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20. Patel Y, Shin J, Abé C, Agartz I, Alloza C, Alnæs D, Ambrogi S, Antonucci LA, Arango C, Arolt V, Auzias G, Ayesa-Arriola R, Banaj N, Banaschewski T, Bandeira C, Başgöze Z, Cupertino RB, Bau CHD, Bauer J, Baumeister S, Bernardoni F, Bertolino A, Bonnin CDM, Brandeis D, Brem S, Bruggemann J, Bülow R, Bustillo JR, Calderoni S, Calvo R, Canales-Rodríguez EJ, Cannon DM, Carmona S, Carr VJ, Catts SV, Chenji S, Chew QH, Coghill D, Connolly CG, Conzelmann A, Craven AR, Crespo-Facorro B, Cullen K, Dahl A, Dannlowski U, Davey CG, Deruelle C, Díaz-Caneja CM, Dohm K, Ehrlich S, Epstein J, Erwin-Grabner T, Eyler LT, Fedor J, Fitzgerald J, Foran W, Ford JM, Fortea L, Fuentes-Claramonte P, Fullerton J, Furlong L, Gallagher L, Gao B, Gao S, Goikolea JM, Gotlib I, Goya-Maldonado R, Grabe HJ, Green M, Grevet EH, Groenewold NA, Grotegerd D, Gruber O, Haavik J, Hahn T, Harrison BJ, Heindel W, Henskens F, Heslenfeld DJ, Hilland E, Hoekstra PJ, Hohmann S, Holz N, Howells FM, Ipser JC, Jahanshad N, Jakobi B, Jansen A, Janssen J, Jonassen R, Kaiser A, Kaleda V, Karantonis J, King JA, Kircher T, Kochunov P, Koopowitz SM, Landén M, Landrø NI, Lawrie S, Lebedeva I, Luna B, Lundervold AJ, MacMaster FP, Maglanoc LA, Mathalon DH, McDonald C, McIntosh A, Meinert S, Michie PT, Mitchell P, Moreno-Alcázar A, Mowry B, Muratori F, Nabulsi L, Nenadić I, O’Gorman Tuura R, Oosterlaan J, Overs B, Pantelis C, Parellada M, Pariente JC, Pauli P, Pergola G, Piarulli FM, Picon F, Piras F, Pomarol-Clotet E, Pretus C, Quidé Y, Radua J, Ramos-Quiroga JA, Rasser PE, Reif A, Retico A, Roberts G, Rossell S, Rovaris DL, Rubia K, Sacchet M, Salavert J, Salvador R, Sarró S, Sawa A, Schall U, Scott R, Selvaggi P, Silk T, Sim K, Skoch A, Spalletta G, Spaniel F, Stein DJ, Steinsträter O, Stolicyn A, Takayanagi Y, Tamm L, Tavares M, Teumer A, Thiel K, Thomopoulos SI, Tomecek D, Tomyshev AS, Tordesillas-Gutiérrez D, Tosetti M, Uhlmann A, Van Rheenen T, Vazquez-Bourgón J, Vernooij MW, Vieta E, Vilarroya O, Weickert C, Weickert T, Westlye LT, Whalley H, Willinger D, Winter A, Wittfeld K, Yang TT, Yoncheva Y, Zijlmans JL, Hoogman M, Franke B, van Rooij D, Buitelaar J, Ching CRK, Andreassen OA, Pozzi E, Veltman D, Schmaal L, van Erp TGM, Turner J, Castellanos FX, Pausova Z, Thompson P, Paus T. Virtual Ontogeny of Cortical Growth Preceding Mental Illness. Biol Psychiatry;2022 (Aug 15);92(4):299-313.

BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.

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21. Shah NV, Kim DJ, Patel N, Beyer GA, Hollern DA, Wolfert AJ, Kim N, Suarez DE, Monessa D, Zhou PL, Eldib HM, Passias PG, Schwab FJ, Lafage V, Paulino CB, Diebo BG. The 5-factor modified frailty index (mFI-5) is predictive of 30-day postoperative complications and readmission in patients with adult spinal deformity (ASD). J Clin Neurosci;2022 (Aug 15);104:69-73.

BACKGROUND: There is limited research regarding the association between the mFI-5 and postoperative complications among adult spinal deformity (ASD) patients. METHODS: Using the National Surgical Quality Improvement Project (NSQIP) database, patients with Current Procedural Terminology (CPT) codes for > 7-level fusion or < 7-level fusion with International Classification of Diseases, Ninth Revision (ICD-9) codes for ASD were identified between 2008 and 2016. Univariate analyses with post-hoc Bonferroni correction for demographics and preoperative factors were performed. Logistic regression assessed associations between mFI-5 scores and 30-day post-operative outcomes. RESULTS: 2,120 patients met criteria. Patients with an mFI-5 score of 4 or 5 were excluded, given there were<20 patients with those scores. Patients with mFI-5 scores of 1 and 2 had increased 30-day rates of pneumonia (3.5 % and 4.3 % vs 1.6 %), unplanned postoperative ventilation for > 48 h (3.1 % and 4.3 % vs 0.9 %), and UTIs (4.4 % and 7.4 % vs 2.0 %) than patients with a score of 0 (all, p < 0.05). Logistic regression revealed that compared to an mFI-5 of 0, a score of 1 was an independent predictor of 30-day reoperations (OR = 1.4; 95 % CI 1.1-18). A score of 2 was an independent predictor of overall (OR = 2.4; 95 % CI 1.4-4.1) and related (OR = 2.2; 95 % CI 1.2-4.1) 30-day readmissions. A score of 3 was not predictive of any adverse outcome. CONCLUSION: The mFI-5 score predicted complications and postoperative events in the ASD population. The mFI-5 may effectively predict 30-day readmissions. Further research is needed to identify the benefits and predictive value of mFI-5 as a risk assessment tool.

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22. Zielinski BA, Andrews DS, Lee JK, Solomon M, Rogers SJ, Heath B, Nordahl CW, Amaral DG. Sex-dependent structure of socioemotional salience, executive control, and default mode networks in preschool-aged children with autism. Neuroimage;2022 (Aug 15);257:119252.

The structure of large-scale intrinsic connectivity networks is atypical in adolescents diagnosed with autism spectrum disorder (ASD or autism). However, the degree to which alterations occur in younger children, and whether these differences vary by sex, is unknown. We utilized structural magnetic resonance imaging (MRI) data from a sex- and age- matched sample of 122 autistic and 122 typically developing (TD) children (2-4 years old) to investigate differences in underlying network structure in preschool-aged autistic children within three large scale intrinsic connectivity networks implicated in ASD: the Socioemotional Salience, Executive Control, and Default Mode Networks. Utilizing structural covariance MRI (scMRI), we report network-level differences in autistic versus TD children, and further report preliminary findings of sex-dependent differences within network topology.

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