1. Appleby R, Wright S, Williams L, Stanley M. Australian parents’ experiences of owning an autism assistance dog. Health & social care in the community. 2022.

Autism assistance dogs (AADs) increase safety for children with autism and their families. Autism assistance dogs can also decrease familial stress and the isolation which families may experience due to fear for their child’s safety and judgement from others within the community. Currently there is a paucity of literature on parents’ experiences of AADs. Therefore, this study aimed to develop a rich understanding of parents’ experiences of owning an AAD. A mixed methods design was utilised, with a qualitative descriptive design and the use of occupational mapping. Eight families were recruited through an Australian AAD programme and participated in semi-structured in-depth interviews throughout 2017. The interviews were analysed thematically. Mobility in the community before and after introduction of the dog was measured using occupational mapping. Families plotted on Google Map printouts the places they frequented before and after placement of their dog. Five major themes emerged from the analysis of the interviews: freedom through restraint; expanding our world; a calming/sensory tool (AAD); « at the end of the day they’re dogs »; and, friendship and personal growth. The occupational maps demonstrated a median increase of 8.5 more places and 20.50 km further travelled from home after having the dog for over a year. Families with an AAD experienced an expanded world for the child and their family. Families experienced freedom in the places they could go, decreased isolation due to the safety which the dog provides. Occupational mapping supported the qualitative data, showing increased mobility and decreased isolation of the family. The paradox of freedom through restraint is a new and key finding which requires further exploration. The results provide support for funding and increased awareness of AAD programmes. Future longitudinal comparative studies are needed to explore the long-term impact of AADs on the child and family.

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2. Bafna A, Deokate V. Percutaneous atrial septal defect closure in a case of Poland syndrome with dextrocardia: ASD closure in Poland syndrome with dextrocardia. AsiaIntervention. 2022; 8(1): 56-7.

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3. Davies J, Glinn L, Osborne LA, Reed P. Exploratory Study of Parenting Differences for Autism Spectrum Disorder and Attachment Disorder. Journal of autism and developmental disorders. 2022.

The current study explored similarities and differences in parenting stress (PSI) and behaviours in parent reports of autism spectrum disorder (ASD) and attachment disorder (AD). 155 parents whose children had developmental delays and disorders completed the social communication questionnaire, Randolph attachment questionnaire, strengths and difficulties questionnaire, PSI, and parent-child relationship inventory. Parents of children with AD reported greater levels of PSI than parents of children with ASD. Parents of children reaching criteria for both disorders reported the greatest levels of PSI. Limit setting was poorest in parents of children with both classifications, followed by parents of children with AD, and then ASD. Limit setting mediated the relationship between PSI and child behaviour problems for parents of children with ASD < but not for parents of children with AD. These findings suggest different areas of difficulty for parents of children with these conditions, which may be of help in designing interventions.

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4. Durbin A, Balogh R, Lin E, Palma L, Plumptre L, Lunsky Y. Changes in community and hospital-based health care use during the COVID-19 pandemic for adults with and without intellectual and developmental disabilities. Journal of intellectual disability research : JIDR. 2022; 66(5): 399-412.

BACKGROUND: Due to the functional, cognitive and communication impairments associated with intellectual and/or developmental disabilities (IDD), adaptations to service delivery during the COVID-19 pandemic may impact people with IDD differently than others. For community and hospital-based services, this study describes the proportion of adults with and without IDD who used health care in the year pre-COVID-19 and the first year of the pandemic. METHODS: This retrospective cohort study used linked health administrative databases to identify adults aged 18-105 years with and without IDD using unique encoded identifiers. Counts and proportions of adults who used health care services were reported for the pre-COVID-19 year (16 March 2019 to 14 March 2020) and the first COVID-19 year (15 March 2020 to 15 March 2021). RESULTS: Across services, the proportion of adults who used services was lower during the first COVID-19 year compared with the year prior, except for virtual physician visits that increased markedly for people with and without IDD. While the proportion of adults who used services was higher for those with IDD compared with those without IDD for both years, differences were greatest for mental health emergency visits and hospitalisations; adults with IDD were 6.3 to 10.9 times more likely to use these services than others with no IDD during the pandemic. CONCLUSIONS: During the first COVID-19 year in Ontario, Canada, service use decreased for all service types, except for virtual physician visits. In both years, adults with IDD remained more likely to use services than other adults, with the largest differences in use of mental health hospitalisations and mental health emergency department visits.

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5. Franklin MS, Bush C, Jones KA, Davis NO, French A, Howard J, Greiner MA, Maslow GR. Inequities in Receipt of the North Carolina Medicaid Waiver Among Individuals with Intellectual Disability or Autism Spectrum Disorder. Journal of developmental and behavioral pediatrics : JDBP. 2022.

OBJECTIVE: We examined characteristics associated with receiving the North Carolina Home and Community-Based Services Waiver for intellectual and developmental disabilities (I/DDs) and its association with emergency department (ED) utilization. METHOD: Through analysis of the North Carolina 2017 to 2018 Medicaid claims and enrollment data, we examined characteristics (age, sex, race and ethnicity, geography, diagnosis (intellectual disability [ID] with or without autism spectrum disorders or autism spectrum disorder without ID) associated with receiving the NC I/DD Waiver and the association of this Wavier with ED utilization. We identified patients with at least 1 International Classification of Diseases-10-CM diagnosis code for an ID or autism spectrum disorder. We excluded patients with missing county information and whose enrollment in the NC I/DD Waiver program began after October 1, 2017. RESULTS: Only 22% of 53,531 individuals with I/DD in North Carolina received the Waiver. Non-Hispanic Blacks and Hispanic individuals were less likely to receive the Waiver than non-Hispanic White individuals. Adults (>21 years old), men, and urban residents were more likely to receive the Waiver. Individuals who received the Waiver were 31% less likely to use the ED. CONCLUSION: Innovative strategies are needed to provide equitable access to the NC I/DD Waiver and provide services to the 14,000 people with I/DD currently waiting to receive the Waiver. Through the Waiver, those with I/DD can access preventative and therapeutic outpatient services and decrease their need for ED care. These findings highlight the need for policy reform to address inequities in access to the Waiver for individuals with I/DD.

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6. Hedenius M, Hardiansyah I, Falck-Ytter T. Visual Global Processing and Subsequent Verbal and Non-Verbal Development: An EEG Study of Infants at Elevated versus Low Likelihood for Autism Spectrum Disorder. Journal of autism and developmental disorders. 2022.

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7. Junaid M, Slack-Smith L, Wong K, Bourke J, Baynam G, Calache H, Leonard H. Association between craniofacial anomalies, intellectual disability and autism spectrum disorder: Western Australian population-based study. Pediatric research. 2022.

BACKGROUND: Accurate knowledge of the relationship between craniofacial anomalies (CFA), intellectual disability (ID) and autism spectrum disorder (ASD) is essential to improve services and outcomes. The aim is to describe the association between CFA, ID and ASD using linked population data. METHODS: All births (1983-2005; n = 566,225) including CFA births (comprising orofacial clefts, craniosynostosis, craniofacial microsomia and mandibulofacial dysostosis) surviving to 5 years were identified from the birth, death, birth defects and midwives population data sets. Linked data from these data sets were followed for a minimum of 5 years from birth until 2010 in the intellectual disability database to identify ID and ASD. These associations were examined using a modified Poisson regression. RESULTS: Prevalence of ID and ASD was higher among CFA (especially with additional anomalies) than those without [prevalence ratio 5.27, 95% CI 4.44, 6.25]. It was higher among CFA than those with other gastrointestinal and urogenital anomalies but lower than nervous system and chromosomal anomalies. Children with CFA and severe ID had a higher proportion of nervous system anomalies. CONCLUSIONS: Findings indicate increased ID and ASD among CFA but lower than nervous system and chromosomal anomalies. This population evidence can improve early identification of ID/ASD among CFA and support service planning. IMPACT: Our study found about one in ten children born with craniofacial anomalies (CFA) are later identified with intellectual disability (ID). Prevalence of ID among CFA was higher than those with other gastrointestinal, urogenital, and musculoskeletal birth defects but lower than those with the nervous system and chromosomal abnormalities. Most children with craniofacial anomalies have a mild-to-moderate intellectual disability with an unknown aetiology. On average, intellectual disability is identified 2 years later for children born with non-syndromic craniofacial anomalies than those with syndromic conditions. Our findings can improve the early identification of ID/ASD among CFA and support service planning.

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8. Li X, Zhou P, Li Q, Peng B, Cun Y, Dai Y, Wei H, Liu X, Yu Y, Jiang Z, Fan Q, Zhang Y, Yang T, Chen J, Cheng Q, Li T, Chen L. Regressive Autism Spectrum Disorder: High Levels of Total Secreted Amyloid Precursor Protein and Secreted Amyloid Precursor Protein-α in Plasma. Frontiers in psychiatry. 2022; 13: 809543.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social communication difficulties, repetitive behaviors, and parochial interests. Individuals with regressive ASD (RA), a unique subtype, have poor outcomes. Moreover, there are currently no validated blood-based biomarkers for ASD, hindering early diagnosis and treatment. This study was the first to examine plasma levels of total secreted amyloid precursor protein (sAPPtotal), secreted amyloid precursor protein-α (sAPPα), and secreted amyloid precursor protein-β (sAPPβ) in children diagnosed with RA (n = 23) and compare them with the levels in age-matched children with non-regressive ASD (NRA) (n = 23) and typically developing (TD) controls (n = 23). We found that sAPPtotal and sAPPα levels were significantly higher in children with RA than in children with NRA or in TD controls. In contrast, no difference was observed in sAPPβ levels. In conclusion, increased plasma levels of sAPPtotal and sAPPα may be valuable biomarkers for the early identification of ASD regression. Prospective studies will be conducted using a larger sample to further investigate these differences.

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9. Meng Q, Zhang W, Wang X, Jiao C, Xu S, Liu C, Tang B, Chen C. Human forebrain organoids reveal connections between valproic acid exposure and autism risk. Translational psychiatry. 2022; 12(1): 130.

Valproic acid (VPA) exposure as an environmental factor that confers risk of autism spectrum disorder (ASD), its functional mechanisms in the human brain remain unclear since relevant studies are currently restricted to two-dimensional cell cultures and animal models. To identify mechanisms by which VPA contribute to ASD risk in human, here we used human forebrain organoids (hFOs), in vitro derived three-dimensional cell cultures that recapitulate key human brain developmental features. We identified that VPA exposure in hFOs affected the expression of genes enriched in neural development, synaptic transmission, oxytocin signaling, calcium, and potassium signaling pathways, which have been implicated in ASD. Genes (e.g., CAMK4, CLCN4, DPP10, GABRB3, KCNB1, PRKCB, SCN1A, and SLC24A2) that affected by VPA were significantly overlapped with those dysregulated in brains or organoids derived from ASD patients, and known ASD risk genes, as well as genes in ASD risk-associated gene coexpression modules. Single-cell RNA sequencing analysis showed that VPA exposure affected the expression of genes in choroid plexus, excitatory neuron, immature neuron, and medial ganglionic eminence cells annotated in hFOs. Microelectrode array further identified that VPA exposure in hFOs disrupted synaptic transmission. Taken together, this study connects VPA exposure to ASD pathogenesis using hFOs, which is valuable for illuminating the etiology of ASD and screening for potential therapeutic targets.

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10. Moseley RL, Gregory NJ, Smith P, Allison C, Cassidy S, Baron-Cohen S. Correction to: The relevance of the interpersonal theory of suicide for predicting past-year and lifetime suicidality in autistic adults. Molecular autism. 2022; 13(1): 16.

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11. Mpoulimari I, Zintzaras E. Synthesis of genetic association studies on autism spectrum disorders using a genetic model-free approach. Psychiatric genetics. 2022.

BACKGROUND: Autism spectrum disorder (ASD) is a clinically and genetically heterogeneous group of neurodevelopmental disorders. Despite the extensive efforts of scientists, the etiology of ASD is far from completely elucidated. In an effort to enlighten the genetic architecture of ASDs, a meta-analysis of all available genetic association studies (GAS) was conducted. METHODS: We searched in the Human Genome Epidemiology Navigator (HuGE Navigator) and PubMed for available case-control GAS of ASDs. The threshold for meta-analysis was two studies per genetic variant. The association between genotype distribution and ASDs was examined using the generalized linear odds ratio (ORG). For variants with available allele frequencies, the examined model was the allele contrast. RESULTS: Overall, 57 candidate genes and 128 polymorphisms were investigated in 159 articles. In total 28 genetic polymorphisms have been shown to be associated with ASDs, that are harbored in 19 genes. Statistically significant results were revealed for the variants of the following genes adenosine deaminase (ADA), bone marrow stromal cell antigen-1 (CD157/BST1), Dopamine receptor D1 (DRD1), engrailed homolog 2 (EN2), met proto-oncogene (MET), methylenetetrahydrofolate reductase (MTHFR), solute carrier family 6 member 4 (SLC6A4), Synaptosomal-associated protein, 25kDa (SNAP-25) and vitamin D receptor (VDR). In the allele contrast model of cases versus healthy controls, significant associations were observed for Adrenoceptor Alpha 1B (ADRA1B), acetyl serotonin O – methyltransferase (ASMT), complement component 4B (C4B), dopamine receptor D3 (DRD3), met proto-oncogene (MET), neuroligin 4, X-linked (NLGN4), neurexin 1 (NRXN1), oxytocin receptor (OXTR), Serine/Threonine-Protein Kinase PFTAIRE-1 (PFTK1), Reelin (RELN) and Ras-like without CAAX 2 (RIT2). CONCLUSION: These significant findings provide further evidence for genetic factors’ implication in ASDs offering new perspectives in means of prevention and prognosis.

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12. Rezaei M, Rezaei A, Esmaeili A, Nakhaee S, Azadi NA, Mansouri B. A case-control study on the relationship between urine trace element levels and autism spectrum disorder among Iranian children. Environmental science and pollution research international. 2022.

Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder characterized mainly by qualitative deficiencies in social communication skills, accompanied by repetitive and restricted behavior patterns. This study was conducted to investigate the associations between the risk of ASD development in children and exposure to trace elements (arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), lead (Pb), nickel (Ni), and zinc (Zn)). Two groups of children, including 44 ASD and 35 typically developing (TD) children, were selected, and their fasting urine samples were obtained. The concentration levels of trace elements were assayed using ICP-MS. The results showed that as compared to the TD group, the concentration levels of As (p = 0.002) and Pb (p < 0.001) and also Cr (p < 0.001), Cu (p = 0.001), and Ni (p < 0.001) were significantly higher among ASD children. In terms of gender, boys with ASD showed elevated levels of Cr, Cu, Ni, and Pb, whereas the urine levels of As, Cr, Cu, Ni, and Pb were markedly higher among girls when compared to the non-ASD children. Under the logistic regression model, the risk difference for As, Co, Cr, Cu, Ni, Pb, and Zn remained significant when adjustment was applied for age and gender confounders.

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13. Schmidt KC, Loutaev I, Burlin TV, Thurm A, Sheeler C, Smith CB. Decreased rates of cerebral protein synthesis in conscious young adults with fragile X syndrome demonstrated by L-[1-(11)C]leucine PET. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2022: 271678×221090997.

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. Fragile X mental retardation protein, a putative translation suppressor, is significantly reduced in FXS. The prevailing hypothesis is that rates of cerebral protein synthesis (rCPS) are increased by the absence of this regulatory protein. We have previously reported increased rCPS in the Fmr1 knockout mouse model of FXS. To address the hypothesis in human subjects, we measured rCPS in young men with FXS with L-[1-(11)C]leucine PET. In previous studies we had used sedation during imaging, and we did not find increases in rCPS as had been seen in the mouse model. Since mouse measurements were conducted in awake animals, we considered the possibility that sedation may have confounded our results. In the present study we used a modified and validated PET protocol that made it easier for participants with FXS to undergo the study awake. We compared rCPS in 10 fragile X participants and 16 healthy controls all studied while awake. Contrary to the prevailing hypothesis and findings in Fmr1 knockout mice, results indicate that rCPS in awake participants with FXS are decreased in whole brain and most brain regions by 13-21% compared to healthy controls.

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14. Sun L, Wang X, Wang X, Cui X, Li G, Wang L, Wang L, Song M, Yu L. Genome-wide DNA methylation profiles of autism spectrum disorder. Psychiatric genetics. 2022.

OBJECTIVES: We aimed to identify differentially methylated genes and related signaling pathways in autism spectrum disorder (ASD). METHODS: First, the DNA methylation profile in the brain samples (GSE131706 and GSE80017) and peripheral blood samples (GSE109905) was downloaded from the Gene Expression Omnibus database (GEO) dataset, followed by identification of differentially methylated genes and functional analysis. Second, the GSE109905 data set was used to further validate the methylation state and test the ability to diagnose disease of identified differentially methylated genes. Third, expression measurement of selected differentially methylated genes was performed in whole blood from an independent sample. Finally, protein-protein interaction (PPI) network of core differentially methylated genes was constructed. RESULTS: Totally, 74 differentially methylated genes were identified in ASD, including 38 hypermethylated genes and 36 hypomethylated genes. 15 differentially methylated genes were further identified after validation in the GSE109905 data set. Among these, major histocompatibility complex (HLA)-DQA1 was involved in the molecular function of myosin heavy chain class II receptor activity; HLA-DRB5 was involved in the signaling pathways of cell adhesion molecules, Epstein-Barr virus infection and antigen processing and presentation. In the PPI analysis, the interaction pairs of HLA-DQA1 and HLA-DRB5, FMN2 and ACTR3, and CALCOCO2 and BAZ2B were identified. Interestingly, FMN2, BAZ2B, HLA-DRB5, CALCOCO2 and DUSP22 had a potential diagnostic value for patients with ASD. The expression result of four differentially methylated genes (HLA-DRB5, NTM, IL16 and COL5A3) in the independent sample was consistent with the integrated analysis. CONCLUSIONS: Identified differentially methylated genes and enriched signaling pathway could be associated with ASD.

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15. Tripathi MK, Kartawy M, Ginzburg S, Amal H. Arsenic alters nitric oxide signaling similar to autism spectrum disorder and Alzheimer’s disease-associated mutations. Translational psychiatry. 2022; 12(1): 127.

Epidemiological studies have proven that exposure to Arsenic (AS) leads to the development of many neurological disorders. However, few studies have investigated its molecular mechanisms in the brain. Our previous work has revealed nitric oxide (NO)-mediated apoptosis and SNO reprogramming in the cortex following arsenic treatment, yet the role of NO and S-nitrosylation (SNO) in AS-mediated neurotoxicity has not been investigated. Therefore, we have conducted a multidisciplinary in-vivo study in mice with two different doses of Sodium Arsenite (SA) (0.1 ppm and 1 ppm) in drinking water. We used the novel SNOTRAP-based mass spectrometry method followed by the bioinformatics analysis, Western blot validation, and five different behavioral tests. Bioinformatics analysis of SA-treated mice showed significant SNO-enrichment of processes involved in mitochondrial respiratory function, endogenous antioxidant systems, transcriptional regulation, cytoskeleton maintenance, and regulation of apoptosis. Western blotting showed increased levels of cleaved PARP-1 and cleaved caspase-3 in SA-treated mice consistent with SA-induced apoptosis. Behavioral studies showed significant cognitive dysfunctions similar to those of Autism spectrum disorder (ASD) and Alzheimer’s disease (AD). A comparative analysis of the SNO-proteome of SA-treated mice with two transgenic mouse strains, models of ASD and AD, showed molecular convergence of SA environmental neurotoxicity and the genetic mutations causing ASD and AD. This is the first study to show the effects of AS on SNO-signaling in the striatum and hippocampus and its effects on behavioral characteristics. Finally, further investigation of the NO-dependent mechanisms of AS-mediated neurotoxicity may reveal new drug targets for its prevention.

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16. Viggiano M, D’Andrea T, Cameli C, Posar A, Visconti P, Scaduto MC, Colucci R, Rochat MJ, Ceroni F, Milazzo G, Fucile S, Maestrini E, Bacchelli E. Contribution of CACNA1H Variants in Autism Spectrum Disorder Susceptibility. Frontiers in psychiatry. 2022; 13: 858238.

Autism Spectrum Disorder (ASD) is a highly heterogeneous neuropsychiatric disorder with a strong genetic component. The genetic architecture is complex, consisting of a combination of common low-risk and more penetrant rare variants. Voltage-gated calcium channels (VGCCs or Ca(v)) genes have been implicated as high-confidence susceptibility genes for ASD, in accordance with the relevant role of calcium signaling in neuronal function. In order to further investigate the involvement of VGCCs rare variants in ASD susceptibility, we performed whole genome sequencing analysis in a cohort of 105 families, composed of 124 ASD individuals, 210 parents and 58 unaffected siblings. We identified 53 rare inherited damaging variants in Ca(v) genes, including genes coding for the principal subunit and genes coding for the auxiliary subunits, in 40 ASD families. Interestingly, biallelic rare damaging missense variants were detected in the CACNA1H gene, coding for the T-type Ca(v)3.2 channel, in ASD probands from two different families. Thus, to clarify the role of these CACNA1H variants on calcium channel activity we performed electrophysiological analysis using whole-cell patch clamp technology. Three out of four tested variants were shown to mildly affect Ca(v)3.2 channel current density and activation properties, possibly leading to a dysregulation of intracellular Ca(2+) ions homeostasis, thus altering calcium-dependent neuronal processes and contributing to ASD etiology in these families. Our results provide further support for the role of CACNA1H in neurodevelopmental disorders and suggest that rare CACNA1H variants may be involved in ASD development, providing a high-risk genetic background.

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17. Williams JA, Burgess S, Suckling J, Lalousis PA, Batool F, Griffiths SL, Palmer E, Karwath A, Barsky A, Gkoutos GV, Wood S, Barnes NM, David AS, Donohoe G, Neill JC, Deakin B, Khandaker GM, Upthegrove R. Inflammation and Brain Structure in Schizophrenia and Other Neuropsychiatric Disorders: A Mendelian Randomization Study. JAMA psychiatry. 2022; 79(5): 498-507.

IMPORTANCE: Previous in vitro and postmortem research suggests that inflammation may lead to structural brain changes via activation of microglia and/or astrocytic dysfunction in a range of neuropsychiatric disorders. OBJECTIVE: To investigate the relationship between inflammation and changes in brain structures in vivo and to explore a transcriptome-driven functional basis with relevance to mental illness. DESIGN, SETTING, AND PARTICIPANTS: This study used multistage linked analyses, including mendelian randomization (MR), gene expression correlation, and connectivity analyses. A total of 20 688 participants in the UK Biobank, which includes clinical, genomic, and neuroimaging data, and 6 postmortem brains from neurotypical individuals in the Allen Human Brain Atlas (AHBA), including RNA microarray data. Data were extracted in February 2021 and analyzed between March and October 2021. EXPOSURES: Genetic variants regulating levels and activity of circulating interleukin 1 (IL-1), IL-2, IL-6, C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were used as exposures in MR analyses. MAIN OUTCOMES AND MEASURES: Brain imaging measures, including gray matter volume (GMV) and cortical thickness (CT), were used as outcomes. Associations were considered significant at a multiple testing-corrected threshold of P < 1.1 × 10-4. Differential gene expression in AHBA data was modeled in brain regions mapped to areas significant in MR analyses; genes were tested for biological and disease overrepresentation in annotation databases and for connectivity in protein-protein interaction networks. RESULTS: Of 20 688 participants in the UK Biobank sample, 10 828 (52.3%) were female, and the mean (SD) age was 55.5 (7.5) years. In the UK Biobank sample, genetically predicted levels of IL-6 were associated with GMV in the middle temporal cortex (z score, 5.76; P = 8.39 × 10-9), inferior temporal (z score, 3.38; P = 7.20 × 10-5), fusiform (z score, 4.70; P = 2.60 × 10-7), and frontal (z score, -3.59; P = 3.30 × 10-5) cortex together with CT in the superior frontal region (z score, -5.11; P = 3.22 × 10-7). No significant associations were found for IL-1, IL-2, CRP, or BDNF after correction for multiple comparison. In the AHBA sample, 5 of 6 participants (83%) were male, and the mean (SD) age was 42.5 (13.4) years. Brain-wide coexpression analysis showed a highly interconnected network of genes preferentially expressed in the middle temporal gyrus (MTG), which further formed a highly connected protein-protein interaction network with IL-6 (enrichment test of expected vs observed network given the prevalence and degree of interactions in the STRING database: 43 nodes/30 edges observed vs 8 edges expected; mean node degree, 1.4; genome-wide significance, P = 4.54 × 10-9). MTG differentially expressed genes that were functionally enriched for biological processes in schizophrenia, autism spectrum disorder, and epilepsy. CONCLUSIONS AND RELEVANCE: In this study, genetically determined IL-6 was associated with brain structure and potentially affects areas implicated in developmental neuropsychiatric disorders, including schizophrenia and autism.

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18. Zhang Y, Qin B, Wang L, Zhang K, Song C, Chen J, Cai J, Li T. Corpus Callosum Volumes in Children with Autism Spectrum Disorders: Sex-Associated Differences. Journal of autism and developmental disorders. 2022.

This study aimed to analyze the relationship between sex and corpus callosum (CC) volume in children with autism spectrum disorders (ASD) aged 2-4 years. This prospective study included 50 children with ASD and 50 typically developing (TD) children aged 2-4 years. Midsagittal slices of the CCs of the participants were divided into five subregions using FreeSurfer software. The PMCC, AMCC and TCC volumes were significantly higher in ASD participants than in TD participants, and results were significant in females with ASD rather than in males with ASD (all P < 0.05). In toddlers with ASD, the CC volumes were increased and more pronounced in females than in males. This could be due to overgrowth of axons or/and axonal pruning disorders.

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19. Zhu Y, Nakatani H, Yassin W, Maikusa N, Okada N, Kunimatsu A, Abe O, Kuwabara H, Yamasue H, Kasai K, Okanoya K, Koike S. Application of a Machine Learning Algorithm for Structural Brain Images in Chronic Schizophrenia to Earlier Clinical Stages of Psychosis and Autism Spectrum Disorder: A Multiprotocol Imaging Dataset Study. Schizophrenia bulletin. 2022; 48(3): 563-74.

BACKGROUND AND HYPOTHESIS: Machine learning approaches using structural magnetic resonance imaging (MRI) can be informative for disease classification; however, their applicability to earlier clinical stages of psychosis and other disease spectra is unknown. We evaluated whether a model differentiating patients with chronic schizophrenia (ChSZ) from healthy controls (HCs) could be applied to earlier clinical stages such as first-episode psychosis (FEP), ultra-high risk for psychosis (UHR), and autism spectrum disorders (ASDs). STUDY DESIGN: Total 359 T1-weighted MRI scans, including 154 individuals with schizophrenia spectrum (UHR, n = 37; FEP, n = 24; and ChSZ, n = 93), 64 with ASD, and 141 HCs, were obtained using three acquisition protocols. Of these, data regarding ChSZ (n = 75) and HC (n = 101) from two protocols were used to build a classifier (training dataset). The remainder was used to evaluate the classifier (test, independent confirmatory, and independent group datasets). Scanner and protocol effects were diminished using ComBat. STUDY RESULTS: The accuracy of the classifier for the test and independent confirmatory datasets were 75% and 76%, respectively. The bilateral pallidum and inferior frontal gyrus pars triangularis strongly contributed to classifying ChSZ. Schizophrenia spectrum individuals were more likely to be classified as ChSZ compared to ASD (classification rate to ChSZ: UHR, 41%; FEP, 54%; ChSZ, 70%; ASD, 19%; HC, 21%). CONCLUSION: We built a classifier from multiple protocol structural brain images applicable to independent samples from different clinical stages and spectra. The predictive information of the classifier could be useful for applying neuroimaging techniques to clinical differential diagnosis and predicting disease onset earlier.

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