Propranolol for treating emotional, behavioural, autonomic dysregulation in children and adolescents with autism spectrum disorders

Sagar-Ouriaghli, Ilyas; Lievesley, Kate; Santosh, Paramala

doi:10.1177/0269881118756245

Cited by 43 publications

(29 citation statements)

References 90 publications

(167 reference statements)

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“…Therefore, it can be useful for treating disorders concerning to emotional and behavioral deficits caused by hyperarousal. Sixteen reports are found in a review about the use of propranolol in ASD ( Sagar-Ouriaghli et al, 2018 ). The results from the eight single-dose clinical trials led to significant improvements in cognitive performance, improvement in semantic networks and functional connectivity.…”

Section: Main Articlementioning

confidence: 99%

“…The remaining eight single case reports and case series showed improvements in anxiety, aggressive, self-injurious and hypersexual behaviors. In no study a negative observation has been reported so far for the treatment with this kind of beta-blocker apart from high dose treatment that caused hypotension ( Sagar-Ouriaghli et al, 2018 ). This can be seen as a treatable side effect.…”

Section: Main Articlementioning

confidence: 99%

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The Generalized Adaptation Account of Autism

2020

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The heterogeneous phenomenology of autism together with diverse patterns of comorbidities led in the past to formulation of manifold theories and hypotheses on different explanatory levels. We scrutinize most recent findings from genetics, neurobiology and physiology and derive testable hypotheses about possible physiological links between domains. With focus on altered sensory perception and neuronal processing in ASD, we assume two intertwined regulatory feedback circuits under the umbrella of genetics and environmental factors. Both regulatory circuits are highly variable between individuals in line with the heterogeneous spectrum of ASD. The circuits set off from altered pathways and connectivity in ASD, fueling HPA-axis activity and distress. In the first circuit altered tryptophan metabolism leads to higher neurotoxic substances and reinforces the excitation:inhibition imbalance in the brain. The second circuit focuses on the impact and interaction with the environment and its rhythms in ASD. With lower melatonin levels, as the pacemaker molecule of the circadian system, we assume misalignment to outer and inner states corroborated from the known comorbidities in ASD. Alterations of the microbiome composition in ASD are supposed to act as a regulatory linking factor for both circuits. Overall, we assume that altered internal balance on cellular and neurophysiological levels is one of the main reasons leading to a lower ability in ASD to adapt to the environment and own internal changing states, leading to the conceptualization of autism as a condition of generalized imbalance in adaptation. This comprehensive framework opens up new perspectives on possible intervention and prevention strategies.

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Section: Main Articlementioning

confidence: 99%

Section: Main Articlementioning

confidence: 99%

The Generalized Adaptation Account of Autism

2020

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“…The use of propranolol is also frequently prescribed to address hyperarousal and social anxiety. Given that the atypical pupillary response co-occurs with respiratory sinus arrhythmia and externalizing behaviors, propranolol has had positive outcomes for addressing these physical indicators of anxiety associated with ASD and for improving functional neural connectivity during cognitive tasks [ 95 , 96 , 97 ].…”

Section: Pupillary Response Modulation Of the Lc-ne System And mentioning

confidence: 99%

Using Pupillometry to Assess the Atypical Pupillary Light Reflex and LC-NE System in ASD

Lynch¹

2018

Behavioral Sciences

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With recent advances in technology, there has been growing interest in use of eye-tracking and pupillometry to assess the visual pathway in autism spectrum disorder (ASD). Within emerging literature, an atypical pupillary light reflex (PLR) has been documented, holding potential for use as a clinical screening biomarker for ASD. This review outlines dominant theories of neuropathology associated with ASD and integrates underlying neuroscience associated with the atypical PLR through a reciprocal model of brainstem involvement and cortical underconnectivity. This review draws from animal models of ASD demonstrating disruption of cranial motor nuclei and brain imaging studies examining arousal and the influence of the locus coeruleus norepinephrine (LC-NE) system on the pupillary response. Pupillometry methods are explained in relation to existing data examining the PLR in ASD and pupillary parameters of constriction latency and tonic pupil diameter as key parameters for investigation. This focused review provides preliminary data toward future work developing pupillometry metrics and offers direction for studies aimed at rigorous study replication using pupillometry with the ASD population. Experimental conditions and testing protocol for capturing pupil parameters with this clinical population are discussed to promote clinical research and translational application.

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“…28,29 Effects of beta-blockers in reducing autism-related emotional and behavioral dysregulation were also reported in a series of case studies. 30,31 Additionally, there are studies exploring the effects of propranolol on functional connectivity. 32,33 To date, few studies have aimed to elucidate the interactive function of the LC and VTA in ASD populations from the perspective of brain neuroimaging.…”

Section: Introductionmentioning

confidence: 99%

Altered Extended Locus Coeruleus and Ventral Tegmental Area Networks in Boys with Autism Spectrum Disorders: A Resting-State Functional Connectivity Study

Huang¹,

Yu²,

Wilson³

et al. 2021

NDT

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Introduction: Previous studies have suggested that cerebral projections of the norepinephrine (NE) and dopamine (DA) systems have important etiology and treatment implications for autism spectrum disorder (ASD). Methods: We used functional magnetic resonance imaging to evaluate spontaneous resting state functional connectivity in boys aged 7-15 years with ASD (n=86) and age-, intelligence quotient-matched typically developing boys (TD, n=118). Specifically, we investigated functional connectivity of the locus coeruleus (LC) and ventral tegmental area (VTA), the main source projection of neurotransmitters NE and DA, respectively. Results: 1) Both the LC and VTA showed reduced connectivity with the postcentral gyrus (PoCG) in boys with ASD, reflecting the potential roles of NE and DA in modulating the function of the somatosensory cortex in boys with ASD. 2) The VTA had increased connectivity with bilateral thalamus in ASD; this alteration was correlated with repetitive and restrictive features. 3) Altered functional connectivity of both the LC and VTA with brain regions such as the angular gyrus (AG), middle temporal gyrus visual area (MT/V5), and occipital face area (OFA) in ASD group. Discussion: Our findings implicate the role of LC-NE and VTA-DA systems from the perspective of functional neuroimaging and may shed light on pharmacological studies targeting NE and DA for the treatment of autism in the future.

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Propranolol for treating emotional, behavioural, autonomic dysregulation in children and adolescents with autism spectrum disorders

Abstract: This review indicates that propranolol holds promise for EBAD and cognitive performance in ASD. Given the lack of good quality clinical trials, randomised controlled trials are warranted to explore the efficacy of propranolol in managing EBAD in ASD.

Cited by 43 publications

References 90 publications

The Generalized Adaptation Account of Autism

The Generalized Adaptation Account of Autism

Using Pupillometry to Assess the Atypical Pupillary Light Reflex and LC-NE System in ASD

Altered Extended Locus Coeruleus and Ventral Tegmental Area Networks in Boys with Autism Spectrum Disorders: A Resting-State Functional Connectivity Study

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