1. Andreadou MT, Katsaras GN, Talimtzi P, Doxani C, Zintzaras E, Stefanidis I. Association of assisted reproductive technology with autism spectrum disorder in the offspring: an updated systematic review and meta-analysis. European journal of pediatrics. 2021; 180(9): 2741-55.

This study aims to provide an up-to-date meta-analysis of data from studies investigating the risk of bearing a child with autism spectrum disorder (ASD) after being conceived by assisted reproductive technology (ART). The study was conducted according to the PRISMA Statement. PubMed and Scopus databases were searched up to August 2, 2020. Observational studies using a type of conception of assisted reproductive technology and examined as outcome offspring with ASD were included. A random effect model was applied due to the heterogeneity of the studies. Statistical analysis was performed with Stata 13 software. The Newcastle-Ottawa scale was used to assess the methodological quality of the included studies. The search strategy identified 587 potentially relevant studies. A total of 15 studies provided adequate data for statistical comparisons and, therefore, were included in the meta-analysis. Analysis of the subset of studies that examined all offspring and controlled for confounder factors revealed that the use of ART is associated with a higher risk of ASD (RR = 1.11, 95% CI = 1.03-1.19, p < 0.009), while in the case of studies that focused on singletons, a statistically significant association between ART and ASD was not observed (RR = 0.96, 95% CI = 0.82-1.13, p = 0.654).Conclusion: The present meta-analysis confirmed the existing positive correlation between ART and ASD in offspring, suggesting that ART is correlated with a higher risk for bearing a child with ASD. In contrast, this relationship is not confirmed in singletons. High quality prospective studies with a larger number of participants are still required. What is Known: • Studies that investigated the association between ART and ASD in offspring have shown conflicting results. • A previous meta-analysis showed that offspring conceived by ART are 1.35 times more likely to develop ASD than offspring spontaneously conceived. What is New: • This investigation separately considered studies with and without adjustment for confounders. • The findings from the two analyses were similar.

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2. Blaxill M, Rogers T, Nevison C. Autism Tsunami: the Impact of Rising Prevalence on the Societal Cost of Autism in the United States. Journal of autism and developmental disorders. 2021.

The cost of ASD in the U.S. is estimated using a forecast model that for the first time accounts for the true historical increase in ASD. Model inputs include ASD prevalence, census population projections, six cost categories, ten age brackets, inflation projections, and three future prevalence scenarios. Future ASD costs increase dramatically: total base-case costs of $223 (175-271) billion/year are estimated in 2020; $589 billion/year in 2030, $1.36 trillion/year in 2040, and $5.54 (4.29-6.78) trillion/year by 2060, with substantial potential savings through ASD prevention. Rising prevalence, the shift from child to adult-dominated costs, the transfer of costs from parents onto government, and the soaring total costs raise pressing policy questions and demand an urgent focus on prevention strategies.

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3. Caldwell-Harris CL. An Explanation for Repetitive Motor Behaviors in Autism: Facilitating Inventions via Trial-and-Error Discovery. Frontiers in psychiatry. 2021; 12: 657774.

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4. Carter Leno V, Forth G, Chandler S, White P, Yorke I, Charman T, Pickles A, Simonoff E. Behavioural and physiological response to frustration in autistic youth: associations with irritability. Journal of neurodevelopmental disorders. 2021; 13(1): 27.

BACKGROUND: Irritability is a common and impairing occurrence in autistic youth, yet the underlying mechanisms are not well-known. In typically developing populations, differences in frustration response have been suggested as important driver of the behavioural symptoms of irritability. Research exploring the role of frustration response as a risk factor for irritability in autistic populations is limited and often uses parent report or observer ratings; objective measures of frustration response appropriate for use in autistic populations are required to advance the field. METHODS: In the current study, fifty-two autistic adolescents aged 13-17 years from a population-based longitudinal study completed an experimental task designed to induce frustration through exposure to periods of unexpected delay. Behavioural (number of button presses) and physiological (heart rate; HR) metrics were collected during delay periods. Irritability was measured using the parent-rated Affective Reactivity Index (ARI). Analyses used mixed-level models to test whether irritability was associated with different slopes of behavioural and physiological response to experimentally induced frustration during the task. Age and baseline HR (for the physiological data only) were included as covariates. RESULTS: Analyses showed a marginal association between irritability and the slope of behavioural response (incident rate ratio (IRR) =.98, p=.06), and a significant association with the slope of physiological response (b=-.10, p=.04); higher levels of irritability were associated with a dampened behavioural and physiological response, as indicated by flatter slopes of change over the course of the task. The pattern of results largely remained in sensitivity analyses, although the association with physiological response became non-significant when adjusting for IQ, autism symptom severity, and medication use (b=-.10, p=.10). CONCLUSIONS: Results suggest that the current experimental task may be a useful objective measure of frustration response for use with autistic populations, and that a non-adaptive response to frustration may be one biological mechanism underpinning irritability in autistic youth. This may represent an important target for future intervention studies.

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5. Cheong JLY, Olsen JE, Lee KJ, Spittle AJ, Opie GF, Clark M, Boland RA, Roberts G, Josev EK, Davis N, Hickey LM, Anderson PJ, Doyle LW. Temporal Trends in Neurodevelopmental Outcomes to 2 Years After Extremely Preterm Birth. JAMA pediatrics. 2021; 175(10): 1035-42.

IMPORTANCE: Survival of infants born extremely preterm (EP) (<28 weeks' gestation) has increased since the early 1990s. It is necessary to know whether increased survival is accompanied by increased neurodevelopmental disability. OBJECTIVE: To examine changes in major (ie, moderate or severe) neurodevelopmental disability and survival free of major neurodevelopmental disability at 2 years in infants born EP. DESIGN, SETTING, AND PARTICIPANTS: Four prospective longitudinal cohort studies comprising all EP live births at 22 to 27 weeks' gestation from April 1, 2016, to March 31, 2017, and earlier eras (1991-1992, 1997, and 2005), and contemporaneous term-born controls in the state of Victoria, Australia. Among 1208 live births during the periods studied, data were available for analysis of 2-year outcomes in 1152 children: 422 (1991-1992), 215 (1997), 263 (2005), and 252 (2016-2017). Data analysis was performed from September 17, 2020, to April 15, 2021. EXPOSURES: Extreme preterm live birth. MAIN OUTCOMES AND MEASURES: Survival, blindness, deafness, cerebral palsy, developmental delay, and neurodevelopmental disability at 2 years' corrected age. Developmental delay comprised a developmental quotient less than -1 SD relative to the control group means on the Bayley Scales for each era. Major neurodevelopmental disability comprised blindness, deafness, moderate to severe cerebral palsy, or a developmental quotient less than -2 SDs. Individual neurodevelopmental outcomes in each era were contrasted relative to the 2016-2017 cohort using logistic regression adjusted for gestational age, sex, birth weight z score, and sociodemographic variables. Changes in survival free of major neurodevelopmental disability over time were also assessed using logistic regression. RESULTS: Survival to 2 years was highest in 2016-2017 (73% [215 of 293]) compared with earlier eras (1991-1992: 53% [225 of 428]; 1997: 70% [151 of 217]; 2005: 63% [170 of 270]). Blindness and deafness were uncommon (<3%). Cerebral palsy was less common in 2016-2017 (6%) than in earlier eras (1991-1992: 11%; 1997: 12%; 2005: 10%). There were no obvious changes in the rates of developmental quotient less than -2 SDs across eras (1991-1992: 18%; 1997: 22%; 2005: 7%; 2016-2017: 15%) or in rates of major neurodevelopmental disability (1991-1992: 20%; 1997: 26%; 2005: 15%; 2016-2017: 15%). Rates of survival free of major neurodevelopmental disability increased steadily over time: 42% (1991-1992), 51% (1997), 53% (2005), and 62% (2016-2017) (odds ratio, 1.30; 95% CI, 1.15-1.48 per decade; P < .001). CONCLUSIONS AND RELEVANCE: These findings suggest that survival free of major disability at age 2 years in children born EP has increased by an absolute 20% since the early 1990s. Increased survival has not been associated with increased neurodevelopmental disability.

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6. Kang J, Jin Y, Liang G, Li X. Accurate assessment of low-function autistic children based on EEG feature fusion. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2021; 90: 351-8.

Autism spectrum disorder (ASD) is a very serious neurodevelopmental disorder and diagnosis mainly depends on the clinical scale, which has a certain degree of subjectivity. It is necessary to make accurate evaluation by objective indicators. In this study, we enrolled 96 children aged from 3 to 6 years: 48 low-function autistic children (38 males and 10 females; mean±SD age: 4.9±1.1 years) and 48 typically developing (TD) children (38 males and 10 females; mean±SD age: 4.9 ± 1.2 years) to participate in our experiment. We investigated to fuse multi-features (entropy, relative power, coherence and bicoherence) to distinguish low-function autistic children and TD children accurately. Minimum redundancy maximum correlation algorithm was used to choose the features and support vector machine was used for classification. Ten-fold cross validation was used to test the accuracy of the model. Better classification result was obtained. We tried to provide a reliable basis for clinical evaluation and diagnosis for ASD.

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7. Lefebvre A, Cohen A, Maruani A, Amsellem F, Beggiato A, Amestoy A, Moal ML, Umbricht D, Chatham C, Murtagh L, Bouvard M, Leboyer M, Bourgeron T, Delorme R. Discriminant value of repetitive behaviors in families with autism spectrum disorder and obsessional compulsive disorder probands. Autism research : official journal of the International Society for Autism Research. 2021; 14(11): 2373-82.

Repetitive behaviors (RB) represent a wide spectrum of symptoms ranging from sensory-motor stereotypies to complex cognitive rituals, frequently dichotomized as low- and high-order sub-groups of symptoms. Even though these subgroups are considered as phenomenologically distinct in autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD), brain imaging and genetic studies suggest that they have common mechanisms and pathways. This discrepancy may be explained by the frequent intellectual disability reported in ASD, which blurs the RB expressivity. Given the high heritability of RB, that is, the diversity of symptoms expressed in the relatives are dependent on those expressed in their probands, we hypothesize that if RB expressed in ASD or OCD are two distinct entities, then the RB expressed in relatives will also reflect these two dimensions. We thus conduct a linear discriminant analysis on RB in both the relatives of probands with ASD and OCD and subjects from the general population (n = 1023). The discriminant analysis results in a classification of 81.1% of the controls (p < 10(-4) ), but poorly differentiated the ASD and OCD relatives (≈46%). The stepwise analysis reveals that five symptoms attributed to high-order RB and two related to low-order RB (including hypersensitivity) are the most discriminant. Our results support the idea that the difference of RB patterns in the relatives is mild compared with the distribution of symptoms in controls. Our findings reinforce the evidence of a common biological pattern of RB both in ASD and OCD but with minor differences, specific to each of these two neuro-developmental disorders. LAY SUMMARY: Repetitive behaviors (RB), a key symptom in the classification of both OCD and ASD, are phenomenologically considered as distinct in the two disorders, which is in contrast with brain imaging studies describing a common neural circuit. Intellectual disability, which is frequently associated with ASD, makes RB in ASD more difficult to understand as it affects the expression of the RB symptoms. To avoid this bias, we propose to consider the familial aggregation in ASD and OCD by exploring RB in the first-degree relatives of ASD and OCD. Our results highlight the existence of RB expressed in relatives compared to the general population, with a common pattern of symptoms in relatives of both ASD and OCD but also minor differences, specific to each of these two neuro-developmental disorders.

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8. Lodi-Smith J, Rodgers JD, Kozlowski K, Khan S, Marquez Luna V, Long CJ, Donnelly JP, Lopata C, Thomeer ML. Autism Characteristics and Self-Reported Health in Older Adulthood. The journals of gerontology Series B, Psychological sciences and social sciences. 2021; 76(9): 1738-44.

OBJECTIVES: The present research used a continuous measurement approach to extend the evidence that autism is associated with significant struggles in physical health as well as mental health and psychological well-being. METHODS: The relationship of autism characteristics to physical health and psychological well-being was examined in 294 individuals (M age = 70.51, SD age = 8.17, age range = 53-96). The sample is 57.4% female (n = 166) and primarily White (n = 270, 96.8%). The majority of the participants did not identify as having an autism diagnosis (n = 284, 96.6%). Participants completed the Autism-Spectrum Quotient Scale alongside self-report measures of physical health, mental health, and psychological well-being. RESULTS: Autism characteristics correlated strongly with challenges in social engagement due to poor health (r = 0.46), depression (r = 0.39) and anxiety (r = 0.47), limitations due to poor mental health (r = 0.41), satisfaction with life (r = -0.47), and psychological well-being (r = -0.62). DISCUSSION: These findings help shed light on the challenges experienced by individuals aging with elevated autism characteristics. The limitations of this study and prior work on this topic help identify important avenues for future research in this area.

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9. Mahalaxmi I, Subramaniam MD, Gopalakrishnan AV, Vellingiri B. Dysfunction in Mitochondrial Electron Transport Chain Complex I, Pyruvate Dehydrogenase Activity, and Mutations in ND1 and ND4 Gene in Autism Spectrum Disorder Subjects from Tamil Nadu Population, India. Molecular neurobiology. 2021; 58(10): 5303-11.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by impaired social interaction and behavioural abnormalities. Growing evidence proved that impairment in mitochondrial functions could inhibit energy production and may contribute to the onset of ASD. Genetic variants in the genes of mitochondrial DNA (mtDNA) could interrupt the normal energy metabolism and production in the brain which lead to a wide range of structural and functional changes in the brain resulting in ASD. The present study aims to compare the activities of mitochondrial electron transport chain (ETC) complex I, pyruvate dehydrogenase (PDH) and specific mitochondrial DNA gene (MT-ND1 and MT-ND4) variants associated with ASD subjects in the Tamil Nadu population. Mutational analysis revealed that most mutations in ASD subjects showed synonymous type followed by missense in both the ND1 and ND4 genes. Interestingly, we found that the complex I and PDH dysfunctions may have a role in ASD compared to the controls (p ≤ 0.0001). Hence, the results of the present study suggest that mitochondrial dysfunction, specifically the complex I genes, may play a major role in the onset of ASD, concluding that further research on mitochondrial genes are mandatory to unravel the mechanism behind ASD pathogenesis.

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10. Nohelty K, Bradford CB, Hirschfeld L, Miyake CJ, Novack MN. Effectiveness of Telehealth Direct Therapy for Individuals with Autism Spectrum Disorder. Behavior analysis in practice. 2021: 1-16.

The field of applied behavior analysis (ABA) has utilized telehealth for clinical supervision and caregiver guidance with research supporting the use of both modalities. Research demonstrating effectiveness is crucial, as behavior analysts must ensure the services they provide are effective in order to be ethical. With the increased need for patients to access more services via telehealth, due to the novel coronavirus (COVID-19) pandemic, the current study evaluated the efficacy of telehealth direct therapy to teach new skills to individuals with autism spectrum disorder (ASD). This study examined the utility of natural environment teaching and discrete trial training strategies provided over a videoconferencing platform to teach new skills directly to seven individuals with varying ASD severity levels. The targeted skills were taught solely through telehealth direct therapy with varying levels of caregiver support across participants and included skills in the language, adaptive, and social domains. In a multiple baseline design, all seven participants demonstrated mastery and maintenance for all targets; in addition, generalization to family members was assessed for some targets. The evidence suggests that telehealth is a modality that is effective and can be considered for all patients when assessing the appropriate location of treatment.

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11. Savard J, Hirvikoski T, Görts Öberg K, Dhejne C, Rahm C, Jokinen J. Impulsivity in Compulsive Sexual Behavior Disorder and Pedophilic Disorder. Journal of behavioral addictions. 2021; 10(3): 839-47.

BACKGROUND AND AIMS: Impulsivity is regarded as a risk factor for sexual crime reoffending, and a suggested core feature in Compulsive Sexual Behavior Disorder. The aim of this study was to explore clinical (e.g. neurodevelopmental disorders), behavioral and neurocognitive dimensions of impulsivity in disorders of problematic sexuality, and the possible correlation between sexual compulsivity and impulsivity. METHODS: Men with Compulsive Sexual Behavior Disorder (n = 20), and Pedophilic Disorder (n = 55), enrolled in two separate drug trials in a specialized Swedish sexual medicine outpatient clinic, as well as healthy male controls (n = 57) were assessed with the Hypersexual Behavior Inventory (HBI) for sexual compulsivity, and with the Barratt Impulsiveness Scale (BIS) and Connors’ Continuous Performance Test-II (CPT-II) for impulsivity. Psychiatric comorbidity information was extracted from interviews and patient case files. RESULTS: Approximately a quarter of the clinical groups had Attention-Deficit/Hyperactivity Disorder (ADHD) or Autism Spectrum Disorder. Both clinical groups reported more compulsive sexuality (r = 0.73-0.75) and attentional impulsivity (r = 0.36-0.38) than controls (P < 0.05). Based on results on univariate correlation analysis, BIS attentional score, ADHD, and Commissions T-score from CPT-II were entered in a multiple linear regression model, which accounted for 15% of the variance in HBI score (P < 0.0001). BIS attentional score was the only independent positive predictor of HBI (P = 0.001). DISCUSSION: Self-rated attentional impulsivity is an important associated factor of compulsive sexuality, even after controlling for ADHD. Psychiatric comorbidity and compulsive sexuality are common in Pedophilic Disorder. CONCLUSION: Neurodevelopmental disorders and attentional impulsivity - including suitable interventions - should be further investigated in both disorders.

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12. Srinivasan SM, Su WC, Cleffi C, Bhat AN. From Social Distancing to Social Connections: Insights From the Delivery of a Clinician-Caregiver Co-mediated Telehealth-Based Intervention in Young Children With Autism Spectrum Disorder. Frontiers in psychiatry. 2021; 12: 700247.

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13. Worsham W, Dalton S, Bilder DA. The Prenatal Hormone Milieu in Autism Spectrum Disorder. Frontiers in psychiatry. 2021; 12: 655438.

Though the etiology of autism spectrum disorder (ASD) remains largely unknown, recent findings suggest that hormone dysregulation within the prenatal environment, in conjunction with genetic factors, may alter fetal neurodevelopment. Early emphasis has been placed on the potential role of in utero exposure to androgens, particularly testosterone, to theorize ASD as the manifestation of an « extreme male brain. » The relationship between autism risk and obstetric conditions associated with inflammation and steroid dysregulation merits a much broader understanding of the in utero steroid environment and its potential influence on fetal neuroendocrine development. The exploration of hormone dysregulation in the prenatal environment and ASD development builds upon prior research publishing associations with obstetric conditions and ASD risk. The insight gained may be applied to the development of chronic adult metabolic diseases that share prenatal risk factors with ASD. Future research directions will also be discussed.

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14. Yu L, Huang D, Wang S, Wu X, Chen Y, Zhang Y. Evidence of Altered Cortical Processing of Dynamic Lexical Tone Pitch Contour in Chinese Children with Autism. Neuroscience bulletin. 2021; 37(11): 1605-8.

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15. Zhao H, Zhang H, Liu S, Luo W, Jiang Y, Gao J. Association of Peripheral Blood Levels of Cytokines With Autism Spectrum Disorder: A Meta-Analysis. Frontiers in psychiatry. 2021; 12: 670200.

Background: Although increasing evidence suggests an association between alterations in peripheral cytokines and autism spectrum disorder (ASD), a consensus is lacking. To determine whether abnormal cytokine profiles in peripheral blood were associated with ASD, we performed this systemic review and meta-analysis. Methods: A systematic literature search was conducted through the Embase, PubMed, Web of Knowledge, PsycINFO, and Cochrane databases up to 4 June 2020. Clinical studies exploring the aberration of peripheral cytokines of autistic patients and controls were included in our meta-analysis. We pooled extracted data using fixed- or random-effects models based on heterogeneity tests with Comprehensive Meta-analysis software. We converted standardized mean differences to Hedges’ g statistic to obtain the effect sizes adjusted for sample size. Subgroup analyses, sensitivity analyses, meta-regression, and publication bias tests were also carried out. Results: Sixty-one articles (326 studies) were included to assess the association between 76 cytokines and ASD. We conducted our meta-analysis based on 37 cytokines with 289 studies. Since there were fewer than three studies on any of the other 39 cytokines, we only provided basic information for them. The levels of peripheral IL-6, IL-1β, IL-12p70, macrophage migration inhibitory factor (MIF), eotaxin-1, monocyte chemotactic protein-1 (MCP-1), IL-8, IL-7, IL-2, IL-12, tumor necrosis factor-α (TNF-α), IL-17, and IL-4 were defined as abnormal cytokines in the peripheral blood of ASD patients compared with controls. The other 24 cytokines did not obviously change in ASD patients compared with the controls. Conclusions: The findings of our meta-analysis strengthen the evidence for an abnormal cytokine profile in ASD. These abnormal cytokines may be potential biomarkers for the diagnosis and treatment of ASD in the future.

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