1. Aishworiya R, Biag HMB, Salcedo-Arellano MJ, Musa Z, Schneider A, Clark C, Santos E, Tassone F, Hagerman R. Fragile X Syndrome and Fetal Alcohol Syndrome: Occurrence of Dual Diagnosis in a Set of Triplets. J Dev Behav Pediatr;2023 (Aug 8)

BACKGROUND: Fragile X syndrome (FXS) and fetal alcohol syndrome disorders are both common causes of intellectual disability in children. When both conditions are present in the same individual, the resultant phenotype may make identification of clinical issues and management challenging. CASE PRESENTATION: In this case report, we present a case of triplets who had significant in utero alcohol exposure; 2 of whom also have FXS and the other not having the fragile X mutation. The siblings with FXS have subtle differences in the physical phenotype compared with the other one, who has prominent features of partial fetal alcohol syndrome instead. However, all 3 siblings have intellectual impairment (although this is more severe in the 2 with FXS), meet diagnostic criteria for autism spectrum disorder, and present with severe behavioral challenges. The clinical presentation of the 2 siblings with FXS is much more severe as compared to a child with FXS alone, and this is likely due to the additive effect of in utero alcohol exposure and environmental factors. We discuss the combination of these 2 pathologies and how this can affect the overall clinical presentation. CONCLUSION: In the management of children with FXS, evaluation for other risk factors that can have neurobehavioral sequelae is important, and these can affect clinical presentation and prognosis.

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2. Ashby D, Yin L, Jones F, Wright AL, Williams H, Williams C, Deavenport-Saman A, Vanderbilt D, Solomon O. « She Is Stand-Offish Like That »: Black Adults’ Recognition of Child Behaviors Associated with Autism Spectrum Disorder. J Dev Behav Pediatr;2023 (Aug 8)

OBJECTIVE: The purpose of this study is to identify the sociocultural factors in the Black community that contribute to a delay in identification of Black children with autism spectrum disorder (ASD). METHODS: Four focus groups with parents of typically developing children were conducted at 2 Black Churches using a community-partnered participatory research approach and the socioecological model. Participants completed sociodemographic surveys, viewed CDC Autism Training Videos of Black children with ASD, and reported on their behavioral observations. Focus groups were audio recorded and transcribed. Thematic data analysis was conducted using NVivo software. RESULTS: At the individual level, participants interpreted ASD-associated behaviors as a problem of timing of developmental milestones in the course of normative development rather than a sign of a disorder and positive and negative characteristics. At the interpersonal level, the role of grandparents and extended family was important for monitoring child development. At the organizational level, racial concordance with health care providers was seen as critical because of historical mistrust. At the community level, fear of racism and child protective services and inequitable care emerged. At the policy level, there were concerns about access to affordable, high-quality care. CONCLUSION: This study provides insight into the sociocultural factors in the faith-based Black community that may contribute to a delay in identification of Black children with ASD. Health care professionals need additional training to effectively serve Black children and families in the face of historical mistrust and health care inequity.

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3. Chahil G, Bollu PC. Rett Syndrome. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Pradeep Bollu declares no relevant financial relationships with ineligible companies.: StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC., 2023. Rett syndrome (RTT) is a neurodevelopmental disorder in which regression of previously acquired skills follows a period of typical development. RTT can present with a multitude of symptoms including but not limited to a deceleration in head growth, gait abnormalities, loss of purposeful hand movements often replaced with repetitive stereotypical movement (hand-wringing), loss of speech and breathing abnormalities. RTT is associated with a complex phenotype and has been classified into typical, atypical, and variant presentations. Approximately 90% of reported cases of RTT inherit mutations of the methyl-CpG-binding protein 2 (MECP2) gene. Some atypical cases of RTT may result from mutations in cyclin-dependent kinase-like 5 (CDKL5). Mutations in MECP2 have been associated with impacting the development of neurons and axodendritic connections. Jellinger and Seitelberger (1986) were the first neuropathologists to identify and describe the pathology behind RTT. They found that the brain in patients of RTT weighed less, and the neurons of the substantia nigra pars compacta contained less melanin in comparison to the age-matched controls. Although RTT was thought to be exclusive to females, males with the phenotype and MECP2 mutations are now being defined. http://www.ncbi.nlm.nih.gov/pubmed/29489169

4. Demler VF, Sterner EF, Wilson M, Zimmer C, Knolle F. Association between increased anterior cingulate glutamate and psychotic-like experiences, but not autistic traits in healthy volunteers. Sci Rep;2023 (Aug 7);13(1):12792.

Despite many differences, autism spectrum disorder and schizophrenia spectrum disorder share environmental risk factors, genetic predispositions as well as neuronal abnormalities, and show similar cognitive deficits in working memory, perspective taking, or response inhibition. These shared abnormalities are already present in subclinical traits of these disorders. The literature proposes that changes in the inhibitory GABAergic and the excitatory glutamatergic system could explain underlying neuronal commonalities and differences. Using magnetic resonance spectroscopy ((1)H-MRS), we investigated the associations between glutamate concentrations in the anterior cingulate cortex (ACC), the left/right putamen, and left/right dorsolateral prefrontal cortex and psychotic-like experiences (Schizotypal Personality Questionnaire) and autistic traits (Autism Spectrum Quotient) in 53 healthy individuals (26 women). To investigate the contributions of glutamate concentrations in different cortical regions to symptom expression and their interactions, we used linear regression analyses. We found that only glutamate concentration in the ACC predicted psychotic-like experiences, but not autistic traits. Supporting this finding, a binomial logistic regression predicting median-split high and low risk groups for psychotic-like experiences revealed ACC glutamate levels as a significant predictor for group membership. Taken together, this study provides evidence that glutamate levels in the ACC are specifically linked to the expression of psychotic-like experiences, and may be a potential candidate in identifying early risk individuals prone to developing psychotic-like experiences.

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5. Elsheikh MS, Ashaat EA, Ramadan A, Mohamed NH, Elaraby NM, El-Hariri HM, Hashish AF, Nashaat NH. Efficacy of Laser Acupuncture for Children With Autism Spectrum Disorder: Clinical, Molecular, and Biochemical Study. Pediatr Neurol;2023 (Jul 15);147:44-51.

BACKGROUND: Low-level laser acupuncture (LLLA) biostimulation could contribute to improving the symptoms and communication of children manifesting autism spectrum disorder (ASD). Photobiomodulation might influence the level of brain-derived neurotrophic factor (BDNF) and miR-320 expression. The aim was to investigate the influence of LLLA biostimulation on the severity, language abilities, BDNF levels, and miR-320 in a sample of children with ASD. METHODS: The participants with ASD (N = 30) were randomly divided equally into groups: Group I received LLLA therapy twice a week for 12 sessions and Group II did not receive it. Assessments of the severity, language abilities, BDNF level by enzyme-linked immunosorbent assay, and miR-320 expression by reverse transcriptase quantitative polymerase chain reaction were performed before and after the intervention. A comparison between ASD cases (N = 30) before starting the therapy and neurotypical children (N = 15) regarding miR-320 expression was performed. RESULTS: Following the intervention, the severity of ASD was reduced and language performance was elevated in both groups. The improvement in Group I was higher with (P = 0.002; 0.03). The plasma BDNF level was reduced only in Group I (P < 0.001). The expression level of miR-320 in Group I did not show a change (P = 0.641). A significant difference in miR-320 expression between children with ASD and the neurotypical group (P = 0.000) was observed. CONCLUSION: This study introduces LLLA therapy as a safe and promising therapeutic procedure for improving the core manifestations and communication abilities and for modulating BDNF levels in children with ASD. The reduced expression of miR-320 showed a good diagnostic value in children with ASD.

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6. Foster M, Federico A, Klaiman C, Bradshaw J. Early Sleep Differences in Young Infants with Autism Spectrum Disorder. J Dev Behav Pediatr;2023 (Aug 8)

OBJECTIVE: Children with autism spectrum disorder (ASD) experience greater sleep challenges than their neurotypical peers, but sleep patterns for infants later diagnosed with ASD are unknown. This study examined differences in total sleep duration and proportion of sleep experienced at night within the first 6 months of life among infants later diagnosed with ASD, infants who demonstrated subclinical characteristics of ASD and were classified as exhibiting the broad autism phenotype (BAP), and their typically developing (TD) peers. In addition, associations between infant sleep variables and developmental outcomes at 24 months were explored. METHODS: Participants included 79 infants enrolled in a prospective, longitudinal study of the early development of ASD. Between ages 1 week and 6 months, participants completed a monthly retrospective 24-hour sleep log. At 24 months, participants received a comprehensive diagnostic evaluation, including the Autism Diagnostic Observation Schedule-2 and Mullen Scales of Early Learning and Vineland-II and were clinically characterized as ASD, BAP, or TD. RESULTS: When accounting for the influence of age, infants later diagnosed with ASD slept less within the 24-hour period than infants in TD or BAP groups from 0 to 6 months (p = 0.04). Percentage of sleep experienced during nighttime hours did not significantly differ between groups from 0 to 6 months (p = 0.25). Greater nighttime sleep percentage at 6 months predicted higher receptive language (p < 0.001) and fine motor scores (p < 0.0001) at 24 months. Total sleep duration at 6 months did not predict any developmental outcomes at 24 months. CONCLUSION: Findings suggest that differences in sleep may occur among autistic individuals earlier in life than previously documented and have cascading effects on development.

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7. Gao N, Liu Z, Wang H, Shen C, Dong Z, Cui W, Xiong WC, Mei L. Deficiency of Cullin 3, a protein encoded by a schizophrenia and autism risk gene, impairs behaviors by enhancing the excitability of ventral tegmental area (VTA) DA neurons. J Neurosci;2023 (Aug 8)

The dopaminergic neuromodulator system is fundamental to brain functions. Abnormal dopamine (DA) pathway is implicated in psychiatric disorders including schizophrenia (SZ) and autism spectrum disorder (ASD). Mutations in Cullin 3 (CUL3), a core component of the Cullin-RING ubiquitin E3 ligase complex, have been associated with SZ and ASD. However, little is known about the function and mechanism of CUL3 in the DA system. Here, we show that CUL3 is critical for the function of DA neurons and DA-relevant behaviors in male mice. CUL3-deficient mice exhibited hyperactive locomotion, deficits in working memory and sensorimotor gating, and increased sensitivity to psychostimulants. In addition, enhanced DA signaling and elevated excitability of the ventral tegmental area (VTA) DA neurons were observed in CUL3-deficient animals. Behavioral impairments were attenuated by dopamine D2 receptor antagonist haloperidol and chemogenetic inhibition of DA neurons. Furthermore, we identified HCN2, a hyperpolarization-activated and cyclic nucleotide-gated channel, as a potential target of CUL3 in DA neurons. Our study indicates that CUL3 controls DA neuronal activity by maintaining ion channel homeostasis and provides insight into the role of CUL3 in the pathogenesis of psychiatric disorders.Significance StatementThis study provides evidence that Cullin 3, a core component of the Cullin-RING ubiquitin E3 ligase complex that has been associated with ASD and SZ, controls the excitability of DA neurons in mice. Its DA-specific heterozygous deficiency increased spontaneous locomotion, impaired working memory and sensorimotor gating, and elevated response to psychostimulants. We showed that CUL3 deficiency increased the excitability of VTA DA neurons, and inhibiting D2 receptor or DA neuronal activity attenuated behavioral deficits of CUL3-deficient mice. We found HCN2, a hyperpolarization-activated channel, as a target of CUL3 in DA neurons. Our findings reveal CUL3’s role in DA neurons and offer insights into the pathogenic mechanisms of ASD and SZ.

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8. Jayashankar A, Bynum B, Butera C, Kilroy E, Harrison L, Aziz-Zadeh L. Connectivity differences between inferior frontal gyrus and mentalizing network in autism as compared to developmental coordination disorder and non-autistic youth. Cortex;2023 (Jul 14);167:115-131.

Prior studies have compared neural connectivity during mentalizing tasks in autism (ASD) to non-autistic individuals and found reduced connectivity between the inferior frontal gyrus (IFG) and mentalizing regions. However, given that the IFG is involved in motor processing, and about 80% of autistic individuals have motor-related difficulties, it is necessary to explore if these differences are specific to ASD or instead similar across other developmental motor disorders, such as developmental coordination disorder (DCD). Participants (29 ASD, 20 DCD, 31 typically developing [TD]; ages 8-17) completed a mentalizing task in the fMRI scanner, where they were asked to think about why someone was performing an action. Results indicated that the ASD group, as compared to both TD and DCD groups, showed significant functional connectivity differences when mentalizing about other’s actions. The left IFG seed revealed ASD connectivity differences with the: bilateral temporoparietal junction (TPJ), left insular cortex, and bilateral dorsolateral prefrontal cortex (DLPFC). Connectivity differences using the right IFG seed revealed ASD differences in the: left insula, and right DLPFC. These results indicate that connectivity differences between the IFG, mentalizing regions, emotion and motor processing regions are specific to ASD and not a result of potentially co-occurring motor differences.

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9. Lai MC, Saunders NR, Huang A, Artani A, Wilton AS, Zaheer J, Ameis SH, Brown HK, Lunsky Y. Self-Harm Events and Suicide Deaths Among Autistic Individuals in Ontario, Canada. JAMA Netw Open;2023 (Aug 1);6(8):e2327415.

IMPORTANCE: Reasons for elevated suicide risks among autistic people are unclear, with insufficient population-based research on sex-specific patterns to inform tailored prevention and intervention. OBJECTIVES: To examine sex-stratified rates of self-harm events and suicide death among autistic individuals compared with nonautistic individuals, as well as the associated sociodemographic and clinical risk factors. DESIGN, SETTING, AND PARTICIPANTS: This population-based matched-cohort study using linked health administrative databases in Ontario, Canada included all individuals with physician-recorded autism diagnoses from April 1, 1988, to March 31, 2018, each matched on age and sex to 4 nonautistic individuals from the general population. Self-harm events resulting in emergency health care from April 1, 2005, to December 31, 2020, were examined for one cohort, and death by suicide and other causes from April 1, 1993, to December 31, 2018, were examined for another cohort. Statistical analyses were conducted between October 2021 and June 2023. EXPOSURE: Physician-recorded autism diagnoses from 1988 to 2018 from health administrative databases. MAIN OUTCOMES AND MEASURES: Autistic and nonautistic individuals who were sex stratified a priori were compared using Andersen-Gill recurrent event models on self-harm events, and cause-specific competing risk models on death by suicide or other causes. Neighborhood-level income and rurality indices, and individual-level broad diagnostic categories of intellectual disabilities, mood and anxiety disorders, schizophrenia spectrum disorders, substance use disorders, and personality disorders were covariates. RESULTS: For self-harm events (cohort, 379 630 individuals; median age at maximum follow-up, 20 years [IQR, 15-28 years]; median age of first autism diagnosis claim for autistic individuals, 9 years [IQR, 4-15 years]; 19 800 autistic females, 56 126 autistic males 79 200 nonautistic females, and 224 504 nonautistic males), among both sexes, autism diagnoses had independent associations with self-harm events (females: relative rate, 1.83; 95% CI, 1.61-2.08; males: relative rate, 1.47; 95% CI, 1.28-1.69) after accounting for income, rurality, intellectual disabilities, and psychiatric diagnoses. For suicide death (cohort, 334 690 individuals; median age at maximum follow-up, 19 years [IQR, 14-27 years]; median age of first autism diagnosis claim for autistic individuals, 10 years [IQR, 5-16 years]; 17 982 autistic females, 48 956 autistic males, 71 928 nonautistic females, 195 824 nonautistic males), there was a significantly higher crude hazard ratio among autistic females (1.98; 95% CI, 1.11-3.56) and a nonsignificantly higher crude hazard ratio among autistic males (1.34; 95% CI, 0.99-1.82); the increased risks were associated with psychiatric diagnoses. CONCLUSIONS AND RELEVANCE: This cohort study suggests that autistic individuals experienced increased risks of self-harm events and suicide death. Psychiatric diagnoses were significantly associated with the increased risks among both sexes, especially for suicide death, and in partially sex-unique ways. Autism-tailored and autism-informed clinical and social support to reduce suicide risks should consider multifactorial mechanisms, with a particular focus on the prevention and timely treatment of psychiatric illnesses.

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10. Liepinsh E, Svalbe B, Stelfa G, Grinberga S, Zvejniece L, Schiöth HB, Dambrova M. Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels. Mol Autism;2023 (Aug 8);14(1):29.

Deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene was identified in probands with autism spectrum disorder (ASD). TMLHE encodes the first enzyme in carnitine biosynthesis, N6-trimethyllysine dioxygenase (TMLD). Researchers have suggested that carnitine depletion could be important for the development of ASD and cognitive, locomotor and social dysfunctions, but previous findings have been inconclusive regarding the specific role of endogenous carnitine. We developed a mouse knockout model with constitutive TMLD enzyme inactivation that exhibited a significant decrease in the carnitine by more than 90% compared to wild-type (WT) mice. However, we did not observe any significant social, cognitive, or repetitive-behavior changes associated with ASD in the knockout mice; muscle strength and coordination were also not affected. In addition, the life expectancy of knockout mice was similar to that of WT mice. In conclusion, knockout of Tmlh in mice does not induce an ASD phenotype or motor dysfunction despite extremely low carnitine and gamma-butyrobetaine concentrations. Moreover, inactivation of TMLD does not induce a phenotype similar to previously described primary carnitine deficiency; indeed, our results showed that low levels of carnitine sustained adequate energy production, muscle function and social behavior in mice.

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11. Miller CJ, Golovina E, Wicker JS, Jacobsen JC, O’Sullivan JM. De novo network analysis reveals autism causal genes and developmental links to co-occurring traits. Life Sci Alliance;2023 (Oct);6(10)

Autism is a complex neurodevelopmental condition that manifests in various ways. Autism is often accompanied by other conditions, such as attention-deficit/hyperactivity disorder and schizophrenia, which can complicate diagnosis and management. Although research has investigated the role of specific genes in autism, their relationship with co-occurring traits is not fully understood. To address this, we conducted a two-sample Mendelian randomisation analysis and identified four genes located at the 17q21.31 locus that are putatively causal for autism in fetal cortical tissue (LINC02210, LRRC37A4P, RP11-259G18.1, and RP11-798G7.6). LINC02210 was also identified as putatively causal for autism in adult cortical tissue. By integrating data from expression quantitative trait loci, genes and protein interactions, we identified that the 17q21.31 locus contributes to the intersection between autism and other neurological traits in fetal cortical tissue. We also identified a distinct cluster of co-occurring traits, including cognition and worry, linked to the genetic loci at 3p21.1. Our findings provide insights into the relationship between autism and co-occurring traits, which could be used to develop predictive models for more accurate diagnosis and better clinical management.

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12. Murphy JFM. Autism – Houses of the Oireachtas Report. Ir Med J;2023 (Jun 29);116(6):782.

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13. Nasiri M, Parmoon Z, Farahmand Y, Moradi A, Farahmand K, Moradi K, Basti FA, Mohammadi MR, Akhondzadeh S. l-carnitine adjunct to risperidone for treatment of autism spectrum disorder-associated behaviors: a randomized, double-blind clinical trial. Int Clin Psychopharmacol;2023 (Aug 7)

Present study was designed to evaluate the efficacy and safety of l-carnitine as an adjuvant agent to risperidone in the treatment of autism spectrum disorder (ASD)-associated behaviors. In this study, 68 children with confirmed ASD were randomly allocated to receive either l-carnitine (150 mg/day) or matched placebo in addition to risperidone. We utilized the Aberrant Behavior Checklist-Community Edition scale (ABC-C) and a checklist of potential adverse effects to assess changes in behavioral status and safety profile at weeks 0, 5 and 10 of the trial. The primary outcome was defined as a change in the irritability subscale score. Sixty patients with similar baseline characteristics completed the trial period. Although scores of ABC-C subscales significantly decreased in both groups over the trial period, the combination of l-carnitine and risperidone resulted in more reduction on the irritability and hyperactivity subscales compared to the combination of risperidone and placebo (P = 0.033 and P < 0.001, respectively). However, changes in lethargy, stereotypic behavior and inappropriate speech subscales were similar between groups. In conclusion, l-carnitine adjuvant to risperidone could improve irritability and hyperactivity features in children with ASD. Results of this study should be considered preliminary and further clinical trials with larger sample sizes and longer follow-up periods are warranted.

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14. Orm S, Wood J, Corbett B, Fjermestad K. Suicidal Risk Behaviors in Adolescents With Rare Neurodevelopmental Disorders: The Role of Sex, Autistic Traits, and Mental Health Difficulties. J Pediatr Psychol;2023 (Aug 8)

OBJECTIVE: Autistic traits are associated with mental health difficulties and risk of suicidal risk behaviors among adolescents. Little is known about how autistic traits affect the mental health of adolescents with rare neurodevelopmental disorders (RNDs). The aim of this study was to investigate the relationship between autistic traits, mental health difficulties, and suicidal risk behaviors in adolescents with RNDs. METHODS: Parents (N = 93) completed the Child Behavior Checklist, Social Communication Questionnaire, and Social Responsiveness Scale about their adolescent (Mage = 13.1, SD = 2.3, 62.4% females) with an RND (e.g., sex chromosome aneuploidies, Fragile X syndrome, 22q11.2 deletion syndrome). The data were analyzed with hierarchical logistic regression analysis. RESULTS: The prevalence of suicidal risk behaviors (16.1%) was similar to that reported among autistic youth and was higher among boys than girls. More autistic traits were associated with suicidal risk behaviors in bivariate analysis. In multivariate analysis, more anxiety/depressive symptoms were associated with more suicidal risk behaviors and externalizing problems associated with suicidal risk behaviors beyond autistic traits and anxiety/depressive symptoms. CONCLUSION: Adolescents with RNDs are at risk of suicidal risk behaviors, especially those with higher levels of autistic traits, anxiety/depressive symptoms, and externalizing problems. Assessment of autistic traits, mental health difficulties, and suicide risk may be indicated for adolescents with RNDs to determine if corresponding intervention is needed.

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15. Pellicano E, Heyworth M. The Foundations of Autistic Flourishing. Curr Psychiatry Rep;2023 (Aug 8)

PURPOSE OF REVIEW: All people-including Autistic people-deserve to live flourishing lives. But what does a flourishing life look like for Autistic people? We suggest that the hidden biases, methodological errors, and key assumptions of autism science have obscured answers to this question. Here, we seek to initiate a broader discussion about what the foundations for a good Autistic life might be and how this discussion might be framed. RECENT FINDINGS: We identify five ways in which autism science can help us all to secure those foundations, including by (1) giving Autistic well-being prominence in research, (2) amplifying Autistic autonomy, (3) attending better to everyday experiences, (4) acknowledging context, and (5) working in partnership with Autistic people and their families and allies to ensure that they are at the heart of research decision-making. Such an approach would direct the focus of autism research to help shape good Autistic lives.

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16. Sakano H, Castle MS, Kundu P. Cochlear Nucleus Transcriptome of a Fragile X Mouse Model Reveals Candidate Genes for Hyperacusis. Laryngoscope;2023 (Aug 8)

OBJECTIVE: Fragile X Syndrome (FXS) is a hereditary form of autism spectrum disorder. It is caused by a trinucleotide repeat expansion in the Fmr1 gene, leading to a loss of Fragile X Protein (FMRP) expression. The loss of FMRP causes auditory hypersensitivity: FXS patients display hyperacusis and the Fmr1- knock-out (KO) mouse model for FXS exhibits auditory seizures. FMRP is strongly expressed in the cochlear nucleus and other auditory brainstem nuclei. We hypothesize that the Fmr1-KO mouse has altered gene expression in the cochlear nucleus that may contribute to auditory hypersensitivity. METHODS: RNA was isolated from cochlear nuclei of Fmr1-KO and WT mice. Using next-generation sequencing (RNA-seq), the transcriptomes of Fmr1-KO mice and WT mice (n = 3 each) were compared and analyzed using gene ontology programs. RESULTS: We identified 270 unique, differentially expressed genes between Fmr1-KO and WT cochlear nuclei. Upregulated genes (67%) are enriched in those encoding secreted molecules. Downregulated genes (33%) are enriched in neuronal function, including synaptic pathways, some of which are ideal candidate genes that may contribute to hyperacusis. CONCLUSION: The loss of FMRP can affect the expression of genes in the cochlear nucleus that are important for neuronal signaling. One of these, Kcnab2, which encodes a subunit of the Shaker voltage-gated potassium channel, is expressed at an abnormally low level in the Fmr1-KO cochlear nucleus. Kcnab2 and other differentially expressed genes may represent pathways for the development of hyperacusis. Future studies will be aimed at investigating the effects of these altered genes on hyperacusis. LEVEL OF EVIDENCE: Level N/A Laryngoscope, 2023.

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17. Shin KC, Ali G, Ali Moussa HY, Gupta V, de la Fuente A, Kim HG, Stanton LW, Park Y. Deletion of TRPC6, an Autism Risk Gene, Induces Hyperexcitability in Cortical Neurons Derived from Human Pluripotent Stem Cells. Mol Neurobiol;2023 (Aug 8)

Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder linked to numerous rare, inherited, and arising de novo genetic variants. ASD often co-occurs with attention-deficit hyperactivity disorder and epilepsy, which are associated with hyperexcitability of neurons. However, the physiological and molecular mechanisms underlying hyperexcitability in ASD remain poorly understood. Transient receptor potential canonical-6 (TRPC6) is a Ca(2+)-permeable cation channel that regulates store-operated calcium entry (SOCE) and is a candidate risk gene for ASD. Using human pluripotent stem cell (hPSC)-derived cortical neurons, single-cell calcium imaging, and electrophysiological recording, we show that TRPC6 knockout (KO) reduces SOCE signaling and leads to hyperexcitability of neurons by increasing action potential frequency and network burst frequency. Our data provide evidence that reduction of SOCE by TRPC6 KO results in neuronal hyperexcitability, which we hypothesize is an important contributor to the cellular pathophysiology underlying hyperactivity in some ASD.

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18. Taylor JL, DaWalt LS, Burke MM, Slaughter JC, Xu M. Improving parents’ ability to advocate for services for youth with autism: A randomized clinical trial. Autism Res;2023 (Aug 8)

Youth with autism face challenges accessing services as they transition to adulthood. Improving parents’ ability to advocate for services on behalf of their youth may be an effective way to improve service access and ultimately transition outcomes in this group. In this study, we tested whether participating in an advocacy intervention improved parents’ ability to advocate for services for their transition-aged youth with autism. One hundred and eighty-five parents of youth with autism ages 16-26, recruited across three states in the U.S., were randomized to one of two experimental conditions. The treatment condition received the ASSIST program, a 12-week (24-h) group-based intervention. The control condition received the same written materials as the treatment condition. Primary outcomes for this report-parent advocacy ability-were collected at baseline (prior to randomization) and post-test (immediately after the treatment group finished the 12-week program) by survey. After taking ASSIST, the treatment condition had greater gains than controls in knowledge of adult services (B = -1.62, CI = -2.33 to -0.90) and perceived advocacy skills (B = -0.19, CI = -0.33 to -0.04). Participants who had less knowledge, lower perceived advocacy skills, and less active coping styles at baseline had the greatest treatment gains. Findings suggest that ASSIST is effective in improving parent advocacy ability and may be most beneficial for parents who experience greater challenges advocating for their son/daughter with autism. Future research will examine whether gains in parent advocacy ability leads to improvements in service access and post-school outcomes for transition-age youth with autism.

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19. Thom RP, Wu M, Ravichandran C, McDougle CJ. Clozapine for treatment refractory catatonia in individuals with autism spectrum disorder: a retrospective chart review study. Expert Rev Clin Pharmacol;2023 (Aug 8):1-11.

BACKGROUND: Catatonia is increasingly recognized in individuals with autism spectrum disorder (ASD). Empirical data on treating catatonia in this population are limited. The purpose of this study is to provide naturalistic data on the use of clozapine for the treatment of catatonia in patients with ASD. RESEARCH DESIGN AND METHODS: Medical records of 12 individuals with ASD and catatonia who received treatment with clozapine were reviewed. Treatment response to clozapine was rated by assigning a retrospective Clinical Global Impression Improvement scale (CGI-I) score. RESULTS: Mean (SD) and median (IQR) age at initiation of clozapine treatment were 22.1 (7.7) and 20.4 (9.7) years, with a range of 10-39 years. Eleven of the 12 patients had received treatment with lorazepam prior to initiating clozapine and 9 of the 12 patients received concomitant treatment with lorazepam and clozapine. Eleven of the 12 patients (92%; 95% CI: 65%, 99%) responded to clozapine. All 12 patients remained on clozapine at the time of their most recent clinical note. All 12 patients (100%; 95% CI: 76%, 100%) experienced one or more adverse events, the most common of which was sedation (n = 11, 92%). CONCLUSIONS: Overall, clozapine was associated with a high response rate for the treatment of catatonia in patients with ASD. These naturalistic data support the use of clozapine for the treatment of catatonia in patients with ASD for whom lorazepam is either ineffective or partially effective.

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20. Thurman W, Heitkemper E, Hutson T, Preston A, Hecht J. « The System Tends to Scoop You Up and Spit You Out and They’re Done With You »: The Intersection of Intellectual/Developmental Disability and Homelessness From the Perspectives of Service Providers. Qual Health Res;2023 (Aug 7):10497323231186880.

People with intellectual and developmental disabilities (IDD) experience elevated risk for poor health and social outcomes in adulthood and are at risk for experiencing homelessness and housing instability. Although the exact prevalence of IDD among homeless populations is unknown, a small body of literature related to the intersection of IDD and homelessness suggests differential health needs and service use patterns, with a need for targeted health and social services. In this study, we explore the perceptions and experiences of 18 homeless or disability service providers about (a) their clients at the intersection of IDD and homelessness and (b) their role and the services provided at the intersection of IDD and homelessness. Participants struggled to provide appropriate, accessible services for this population, owing to lack of training and awareness of specific needs, fragmented systems, and inadequately funded healthcare and housing support. Our findings also reveal that clients at this intersection have high contact with public systems, which places them at risk for losing their right to self-determination. Recommendations center on systems transformation to facilitate the ability of providers to collaborate and to make data-driven decisions to deliver person-centered care.

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21. Tromans S, Desarkar P. Assessing for autism in adult psychiatry. BJPsych Open;2023 (Aug 8);9(5):e144.

This editorial discusses a study by Nyrenius and colleagues in which they investigated rates of co-occurring psychiatric conditions and functioning in a population of adults referred to a Swedish psychiatric out-patient clinic, comparing those meeting DSM-5 diagnostic criteria for autism with their non-autistic peers.

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