Reduced heart rate variability in adults with autism spectrum disorder

Thapa, Rinku; Alvares, Gail A.; Zaidi, Tooba; Thomas, Emma; Hickie, Ian B.; Park, Shin H.; Guastella, Adam J.

doi:10.1002/aur.2104

Cited by 51 publications

(51 citation statements)

References 52 publications

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“…S3; heart rate variability (HRV)], they can be used as equivalent proxies of arousal (43). HRV, which consists of spontaneous modulation of the heart rate in wakefulness, is atypically steady in ASD (44). Here, HRV detected arousal alterations in female RTT patients.…”

Section: Significancementioning

confidence: 59%

Deep learning of spontaneous arousal fluctuations detects early cholinergic defects across neurodevelopmental mouse models and patients

Artoni

Piffer

Vinci

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Neurodevelopmental spectrum disorders like autism (ASD) are diagnosed, on average, beyond age 4 y, after multiple critical periods of brain development close and behavioral intervention becomes less effective. This raises the urgent need for quantitative, noninvasive, and translational biomarkers for their early detection and tracking. We found that both idiopathic (BTBR) and genetic (CDKL5- and MeCP2-deficient) mouse models of ASD display an early, impaired cholinergic neuromodulation as reflected in altered spontaneous pupil fluctuations. Abnormalities were already present before the onset of symptoms and were rescued by the selective expression of MeCP2 in cholinergic circuits. Hence, we trained a neural network (ConvNetACh) to recognize, with 97% accuracy, patterns of these arousal fluctuations in mice with enhanced cholinergic sensitivity (LYNX1-deficient). ConvNetACh then successfully detected impairments in all ASD mouse models tested except in MeCP2-rescued mice. By retraining only the last layers of ConvNetACh with heart rate variation data (a similar proxy of arousal) directly from Rett syndrome patients, we generated ConvNetPatients, a neural network capable of distinguishing them from typically developing subjects. Even with small cohorts of rare patients, our approach exhibited significant accuracy before (80% in the first and second year of life) and into regression (88% in stage III patients). Thus, transfer learning across species and modalities establishes spontaneous arousal fluctuations combined with deep learning as a robust noninvasive, quantitative, and sensitive translational biomarker for the rapid and early detection of neurodevelopmental disorders before major symptom onset.

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Section: Significancementioning

confidence: 59%

Deep learning of spontaneous arousal fluctuations detects early cholinergic defects across neurodevelopmental mouse models and patients

Artoni

Piffer

Vinci

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…The STV and HF (ln) of male Sal, male VPA, and female Sal mice were significantly increased from 4 to 8 weeks of age, whereas these of female VPA mice remained unchanged, suggesting the strong suppression of parasympathetic nervous development in female VPA mice. Several reports revealed that the assessment of the sympathetic and parasympathetic activity using HRV in children with ASD yielded inconsistent results 25 – 27 , 48 . As ASD is a heterogeneous disease 1 , it can be inferred that such diversity occurred because of the characteristics of the population and the environmental factors that were involved in the studies.…”

Section: Discussionmentioning

confidence: 99%

“…ECG analysis of children and adults diagnosed with ASD has revealed lower autonomic nervous activity compared with healthy individuals. This lower activity has been hinted to be associated with the pathology of ASD 25 – 27 . In addition, the sympathetic and parasympathetic interaction is associated with externalizing behavior problems in children with ASD 28 .…”

Section: Introductionmentioning

confidence: 95%

Alterations in the autonomic nerve activities of prenatal autism model mice treated with valproic acid at different developmental stages

Kasahara

Yoshida

Nakanishi

et al. 2020

Sci Rep

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Autism spectrum disorder (ASD) is characterized by impairment of social communication, repetitive behavior and restrictive interest. The risk of ASD is strongly associated with the prenatal period; for instance, the administration of valproic acid (VPA) to pregnant mothers increases risk of ASD in the child. Patients with ASD often exhibit an alteration in the autonomic nervous system. In this study, we assessed the autonomic nervous activity at each prenatal developmental stage of model mice of ASD treated with VPA, to clarify the relationship between timing of exposure and ASD symptoms. The assessment of the autonomic nervous activity was performed based on the analysis of electrocardiography data collected from fetal and adult mice. Interestingly, VPA model mouse fetuses exhibited a significantly lower activity of the sympathetic nervous system. In contrast, sympathetic nervous activity at P0 was significantly higher. In adult VPA model mice, the parasympathetic activity of female VPA mice was suppressed. Moreover, female VPA mice showed reduced the parasympathetic activity after exposure to restraint stress. These results suggest that the autonomic nervous activity of VPA model mice was altered from the fetal stage, and that the assessment of autonomic nervous activities at an early developmental stage could be useful for the understanding of ASD.

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“…1f). Recent studies have suggested lower heart rate variability in ASD compared to controls [12]. Although further investigations are warranted, our results may provide clues for the underlying mechanisms of potential cardiovascular risks in ASD.…”

mentioning

confidence: 55%

MicroRNA profiling in adults with high-functioning autism spectrum disorder

et al. 2019

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and repetitive behaviors. Owing to the difficulty of clinical diagnosis, ASD without intellectual disability (i.e., high-functioning ASD) is often overlooked. MicroRNAs (miRNAs) have been recently recognized as potential biomarkers of ASD as they are dysregulated in various tissues of individuals with ASD. However, it remains unclear whether miRNA expression is altered in individuals with high-functioning ASD. Here, we investigated the miRNA expression profile in peripheral blood from adults with high-functioning ASD, and age and gender-matched healthy controls. We identified miR-6126 as being robustly down-regulated in ASD and correlated with the severity of social deficits. Enrichment analysis of predicted target genes revealed potential association with neurons, synapses, and oxytocin signaling pathways. Our findings may provide insights regarding the molecular clues for recognizing high-functioning ASD.

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Reduced heart rate variability in adults with autism spectrum disorder

Cited by 51 publications

References 52 publications

Deep learning of spontaneous arousal fluctuations detects early cholinergic defects across neurodevelopmental mouse models and patients

Deep learning of spontaneous arousal fluctuations detects early cholinergic defects across neurodevelopmental mouse models and patients

Alterations in the autonomic nerve activities of prenatal autism model mice treated with valproic acid at different developmental stages

MicroRNA profiling in adults with high-functioning autism spectrum disorder

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