A de novo frameshift pathogenic variant in TBR1 identified in autism without intellectual disability (septembre 2020)
1. Zorn J, Abdoun O, Sonié S, Lutz A. Cognitive Defusion Is a Core Cognitive Mechanism for the Sensory-Affective Uncoupling of Pain During Mindfulness Meditation. Psychosom Med;2021 (Jul-Aug 01);83(6):566-578.
OBJECTIVE: Mindfulness meditation can downregulate the experience of pain. However, its specific underlying regulatory mechanisms are still largely unknown. Here, we aimed to investigate the role of cognitive defusion-a form of psychological distancing from internal experiences-in mindfulness-based pain regulation. METHODS: We implemented a thermal heat paradigm that was designed to amplify the cognitive-affective aspects of pain in 43 novice meditators (2-day formal training; 51.2% women; 53.2 ± 7.0 years old) and 27 expert meditators (>10,000-hour practice; 44.4% women; 51.9 ± 8.4 years old). We collected pain intensity and unpleasantness reports and trait measures of pain catastrophizing assessed by the Pain Catastrophizing Scale (PCS), cognitive defusion assessed by the Drexel Defusion Scale (DDS), and cognitive fusion assessed by the Cognitive Fusion Questionnaire, as well as of several other constructs commonly reported in the literature. RESULTS: Experts reported lower PCS (6.9 ± 5.2 versus 17.2 ± 8.5, p < .001) but higher DDS (39.4 ± 6.4 versus 28.9 ± 6.6, p < .001) than novices. Across participants, the PCS and DDS were negatively correlated and shared unique variance that survived adjusting for other mindfulness-related and cognitive-emotional constructs (β = -0.64, p < .001). Conversely, the relationships between PCS and other commonly reported constructs did not seem specific, as none of the relationships survived adjusting for DDS (adjusted β < 0.25, p > .05). Further supporting the relevance of DDS to pain, both the DDS and PCS specifically predicted pain unpleasantness as opposed to pain intensity. However, DDS seemed to be a more specific predictor of unpleasantness than PCS, as the relationship between DDS and unpleasantness survived adjusting for PCS (adjusted β = -0.33, p = .016), but not vice versa (adjusted β = 0.20, p = .162). We also found that the Cognitive Fusion Questionnaire showed a similar pattern of associations with PCS and pain self-reports to what was found for the DDS, although these associations were less consistent. CONCLUSIONS: Collectively, these findings highlight the central role of cognitive defusion in mindfulness-based pain regulation.
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1. Sapey-Triomphe LA, Reversat J, Lesca G, Chatron N, Bussa M, Mazoyer S, Schmitz C, Sonié S, Edery P. A de novo frameshift pathogenic variant in TBR1 identified in autism without intellectual disability. Hum Genomics;2020 (Sep 18);14(1):32.
BACKGROUND: In order to be able to provide accurate genetic counseling to patients with Autism Spectrum Disorder (ASD), it is crucial to identify correlations between heterogeneous phenotypes and genetic alterations. Among the hundreds of de novo pathogenic variants reported in ASD, single-nucleotide variations and small insertions/deletions were reported in TBR1. This gene encodes a transcription factor that plays a key role in brain development. Pathogenic variants in TBR1 are often associated with severe forms of ASD, including intellectual disability and language impairment. METHODS: Adults diagnosed with ASD but without intellectual disability (diagnosis of Asperger syndrome, according to the DSM-IV) took part in a genetic consultation encompassing metabolic assessments, a molecular karyotype and the screening of a panel of 268 genes involved in intellectual disability, ASD and epilepsy. In addition, the patient reported here went through a neuropsychological assessment, structural magnetic resonance imaging and magnetic resonance spectroscopy measurements. RESULTS: Here, we report the case of a young adult male who presents with a typical form of ASD. Importantly, this patient presents with no intellectual disability or language impairment, despite a de novo heterozygous frameshift pathogenic variant in TBR1, leading to an early premature termination codon (c.26del, p.(Pro9Leufs*12)). CONCLUSION: Based on this case report, we discuss the role of TBR1 in general brain development, language development, intellectual disability and other symptoms of ASD. Providing a detailed clinical description of the individuals with such pathogenic variants should help to understand the genotype-phenotype relationships in ASD.
