Pubmed du 10/09/23
1. Ciancone-Chama AG, Bonaldo V, Biasini E, Bozzi Y, Balasco L. Gene expression profiling in trigeminal ganglia from Cntnap2(-/-) and Shank3b(-/-) mouse models of autism spectrum disorder. Neuroscience. 2023.
Sensory difficulties represent a crucial issue in the life of autistic individuals. The diagnostic and statistical manual of mental disorders describes both hyper- and hypo-responsiveness to sensory stimulation as a criterion for the diagnosis autism spectrum disorders (ASD). Among the sensory domain affected in ASD, altered responses to tactile stimulation represent the most commonly reported sensory deficits. Although tactile abnormalities have been reported in monogenic cohorts of patients and genetic mouse models of ASD, the underlying mechanisms are still unknown. Traditionally, autism research has focused on the central nervous system as the target to infer the neurobiological bases of such tactile abnormalities. Nonetheless, the peripheral nervous system represents the initial site of processing of sensory information and a potential site of dysfunction in the sensory cascade. Here we investigated the gene expression deregulation in the trigeminal ganglion (which directly receives tactile information from whiskers) in two genetic models of syndromic autism (Shank3b and Cntnap2 mutant mice) at both adult and juvenile ages. We found several neuronal and non-neuronal markers involved in inhibitory, excitatory, neuroinflammatory and sensory neurotransmission to be differentially regulated within the trigeminal ganglia of both adult and juvenile Shank3b and Cntnap2 mutant mice. These results may help in disentangling the multifaced complexity of sensory abnormalities in autism and open avenues for the development of peripherally targeted treatments for tactile sensory deficits exhibited in ASD.
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2. Pedersen EM, Agerbo E, Plana-Ripoll O, Steinbach J, Krebs MD, Hougaard DM, Werge T, Nordentoft M, Børglum AD, Musliner KL, Ganna A, Schork AJ, Mortensen PB, McGrath JJ, Privé F, Vilhjálmsson BJ. ADuLT: An efficient and robust time-to-event GWAS. Nature communications. 2023; 14(1): 5553.
Proportional hazards models have been proposed to analyse time-to-event phenotypes in genome-wide association studies (GWAS). However, little is known about the ability of proportional hazards models to identify genetic associations under different generative models and when ascertainment is present. Here we propose the age-dependent liability threshold (ADuLT) model as an alternative to a Cox regression based GWAS, here represented by SPACox. We compare ADuLT, SPACox, and standard case-control GWAS in simulations under two generative models and with varying degrees of ascertainment as well as in the iPSYCH cohort. We find Cox regression GWAS to be underpowered when cases are strongly ascertained (cases are oversampled by a factor 5), regardless of the generative model used. ADuLT is robust to ascertainment in all simulated scenarios. Then, we analyse four psychiatric disorders in iPSYCH, ADHD, Autism, Depression, and Schizophrenia, with a strong case-ascertainment. Across these psychiatric disorders, ADuLT identifies 20 independent genome-wide significant associations, case-control GWAS finds 17, and SPACox finds 8, which is consistent with simulation results. As more genetic data are being linked to electronic health records, robust GWAS methods that can make use of age-of-onset information will help increase power in analyses for common health outcomes.
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3. Plak R, Rippe R, Merkelbach I, Begeer S. Psychosocial Outcomes in Autistic Children Before and During the COVID-19 Pandemic. Journal of autism and developmental disorders. 2023.
Studies on the impact of the COVID-19 pandemic on autistic children’s psychosocial outcomes have shown mixed results. In the current study we aimed to gain a better insight into the effect of the COVID-19 pandemic by comparing psychosocial outcomes collected pre-pandemic with data collected during the pandemic. We used the Strengths and Difficulties Questionnaire (SDQ) to examine change over time in psychosocial outcomes of autistic children from pre-pandemic (T0) to lockdown I (T1) and lockdown II (T2) in the Netherlands. We expected a deterioration in psychosocial outcomes. There were 224 participants in T0 and T1, of which 141 also participated in T2. The results showed a surprising improvement in psychosocial outcomes from T0 to T1. Special education and female gender were associated with increased difficulties over time, while higher age was associated with decreased difficulties. At the subdomain level we found that emotional problems remained stable, while hyperactivity, conduct problems, and peer problems decreased, and prosocial behavior increased. Attending special education predicted increased peer problems over time, while higher age predicted both decreased conduct problems and increased prosocial behavior over time. The COVID-19 pandemic may have temporarily improved the fit between the psychosocial needs and the environment for children with autism in the Netherlands.
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4. Waizbard-Bartov E, Ferrer E, Heath B, Andrews DS, Rogers S, Kerns CM, Wu Nordahl C, Solomon M, Amaral DG. Changes in the severity of autism symptom domains are related to mental health challenges during middle childhood. Autism : the international journal of research and practice. 2023: 13623613231195108.
For many autistic children, the severity of their autism symptoms changes during middle childhood. We studied whether these changes are associated with the emergence of other mental health challenges such as anxiety and attention-deficit hyperactivity disorder. Children who had increased social-communication challenges had more anxiety and attention-deficit hyperactivity disorder symptoms and disruptive behavior problems than other children. Children who decreased their restricted and repetitive behaviors, on the contrary, had more anxiety. We discuss why these changes in autism symptoms may lead to increases in other mental health concerns.
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5. Williams EH, Thompson NM, McCray G, Chakrabarti B. Autistic traits modulate the influence of face masks on gaze perception. Scientific reports. 2023; 13(1): 14921.
Detecting when others are looking at us is a crucial social skill. Accordingly, a range of gaze angles is perceived as self-directed; this is termed the « cone of direct gaze » (CoDG). Multiple cues, such as nose and head orientation, are integrated during gaze perception. Thus, occluding the lower portion of the face, such as with face masks during the COVID-19 pandemic, may influence how gaze is perceived. Individual differences in the prioritisation of eye-region and non-eye-region cues may modulate the influence of face masks on gaze perception. Autistic individuals, who may be more reliant on non-eye-region directional cues during gaze perception, might be differentially affected by face masks. In the present study, we compared the CoDG when viewing masked and unmasked faces (N = 157) and measured self-reported autistic traits. The CoDG was wider for masked compared to unmasked faces, suggesting that reduced reliability of lower face cues increases the range of gaze angles perceived as self-directed. Additionally, autistic traits positively predicted the magnitude of CoDG difference between masked and unmasked faces. This study provides crucial insights into the effect of face masks on gaze perception, and how they may affect autistic individuals to a greater extent.
