Association of serum allopregnanolone with restricted and repetitive behaviors in adult males with autism

Chew, Leila; Sun, Kai; Sun, Wenchao; Wang, Zhe; Rajadas, Jayakumar; Flores, Ryan; Arnold, E.C.; Jo, Booil; Fung, Lawrence K.

doi:10.1016/j.psyneuen.2020.105039

Cited by 10 publications

(11 citation statements)

References 59 publications

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“…For example, the levels of this neuroactive steroid are decreased in the male, but not the female, brain mouse model of autism spectrum disorder‐like behaviour 126 . In particular, in adult males, a decrease in the levels of this neuroactive steroid is associated with more severe restricted and repetitive behaviour 127 …”

Section: Levels Of Allo Under Physiological and Pathological Conditionsmentioning

confidence: 99%

“…126 In particular, in adult males, a decrease in the levels of this neuroactive steroid is associated with more severe restricted and repetitive behaviour. 127 The plasma levels of ALLO are also decreased in association with post-traumatic stress disorders (PTSD) re-experiencing and depressive symptoms in PTSD patients, as well as with enhanced contextual fear memory and impaired fear extinction in PTSD experimental models. 128,129 Interestingly, in female PTSD patients, the observed low levels of ALLO in the CSF are associated with impairment of the enzyme synthesising this neuroactive steroid (ie, 3α-HSOR).…”

Section: Mood Disordersmentioning

confidence: 99%

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Allopregnanolone: An overview on its synthesis and effects

Diviccaro

Cioffi

Falvo

et al. 2021

J Neuroendocrinology

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Allopregnanolone, a 3α,5α‐progesterone metabolite, acts as a potent allosteric modulator of the γ‐aminobutyric acid type A receptor. In the present review, the synthesis of this neuroactive steroid occurring in the nervous system is discussed with respect to physiological and pathological conditions. In addition, its physiological and neuroprotective effects are also reported. Interestingly, the levels of this neuroactive steroid, as well as its effects, are sex‐dimorphic, suggesting a possible gender medicine based on this neuroactive steroid for neurological disorders. However, allopregnanolone presents low bioavailability and extensive hepatic metabolism, limiting its use as a drug. Therefore, synthetic analogues or a different therapeutic strategy able to increase allopregnanolone levels have been proposed to overcome any pharmacokinetic issues.

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Section: Levels Of Allo Under Physiological and Pathological Conditionsmentioning

confidence: 99%

Section: Mood Disordersmentioning

confidence: 99%

Allopregnanolone: An overview on its synthesis and effects

Diviccaro

Cioffi

Falvo

et al. 2021

J Neuroendocrinology

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“…Remarkably, the severity in the insistence of sameness correlates to high expression levels of GABRB3 (Shao et al., 2003 ) and this reduction in the release of GABA into the striatum also has been related to compulsive behaviors (Chao et al., 2010 ). In this regard, a decrease in the expression of allopregnanolone, a neurosteroid agonist of GABA A receptors, has been related to highly specific interests (higher‐level RRBs) (Chew et al., 2021 ).…”

Section: Biopsychological Correlates Of Higher‐level Behaviorsmentioning

confidence: 99%

Biopsychological correlates of repetitive and restricted behaviors in autism spectrum disorders

et al. 2021

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Background: Autism Spectrum Disorder (ASD) is considered a neurodevelopmental condition that is characterized by alterations in social interaction and communication, as well as patterns of restrictive and repetitive behaviors (RRBs). RRBs are defined as broad behaviors that comprise stereotypies, insistence on sameness, and attachment to objects or routines. RRBs can be divided into lower-level behaviors (motor, sensory, and object-manipulation behaviors) and higher-level behaviors (restrictive interests, insistence on sameness, and repetitive language). According to the DSM-5, the grade of severity in ASD partially depends on the frequency of RRBs and their consequences for disrupting the life of patients, affecting their adaptive skills, and increasing the need for parental support. Methods:We conducted a systematic review to examine the biopsychological correlates of the symptomatic domains of RRBs according to the type of RRBs (lower-or higher-level). We searched for articles from the National Library of Medicine (PubMed) using the terms: autism spectrum disorders, ASD, and autism-related to executive functions, inhibitory control, inflexibility, cognitive flexibility, hyper or hypo connectivity, and behavioral approaches. For describing the pathophysiological mechanism of ASD, we also included animal models and followed PRISMA guidelines. Results: One hundred and thirty-one articles were analyzed to explain the etiology, continuance, and clinical evolution of these behaviors observed in ASD patients throughout life. Conclusions: Biopsychological correlates involved in the origin of RRBs include alterations in a) neurotransmission system, b) brain volume, c) inadequate levels of growth factors, d) hypo-or hyper-neural connectivity, e) impairments in behavioral inhibition, cognitive flexibility, and monitoring and f) non-stimulating environments. Understanding these lower-and higher-level of RRBs can help professionals to improve or design novel therapeutic strategies.

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“…The growing interest in the role of chronic inflammation in neurological disorders is connected to the fact that generalized alterations in oxidative/antioxidant status, as well as immune, endocrine systems, and neuromediator transmission in the brain take place in inflammation [ 134 ]. Immune system disorders may become a new target in autism treatment [ 135 ].…”

Section: Systemic Approaches To the Study Of Autism Spectrum Disordersmentioning

confidence: 99%

Molecular Mechanisms of Aberrant Neuroplasticity in Autism Spectrum Disorders (Review)

Anashkina¹,

Ерлыкина²

2021

Sovrem Tehnol Med

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This review presents the analysis and systematization of modern data on the molecular mechanisms of autism spectrum disorders (ASD) development. Polyetiology and the multifactorial nature of ASD have been proved. The attempt has been made to jointly review and systematize current hypotheses of ASD pathogenesis at the molecular level from the standpoint of aberrant brain plasticity. The mechanism of glutamate excitotoxicity formation, the effect of imbalance of neuroactive amino acids and their derivatives, neurotransmitters, and hormones on the ASD formation have been considered in detail. The strengths and weaknesses of the proposed hypotheses have been analyzed from the standpoint of evidence-based medicine. The conclusion has been drawn on the leading role of glutamate excitotoxicity as a biochemical mechanism of aberrant neuroplasticity accompanied by oxidative stress and mitochondrial dysfunction. The mechanism of aberrant neuroplasticity has also been traced at the critical moments of the nervous system development taking into account the influence of various factors of the internal and external environment. New approaches to searching for ASD molecular markers have been considered.

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Association of serum allopregnanolone with restricted and repetitive behaviors in adult males with autism

Cited by 10 publications

References 59 publications

Allopregnanolone: An overview on its synthesis and effects

Allopregnanolone: An overview on its synthesis and effects

Biopsychological correlates of repetitive and restricted behaviors in autism spectrum disorders

Molecular Mechanisms of Aberrant Neuroplasticity in Autism Spectrum Disorders (Review)

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