Abstract
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by social and communication abnormalities. Heterogeneity in the expression and severity of the core and associated symptoms poses difficulties in classification and the overall clinical approach. Synaptic abnormalities have been observed in preclinical ASD models. They are thought to play a major role in clinical functional abnormalities and might be modified by targeted interventions. An imbalance in excitatory to inhibitory neurotransmission (E/I imbalance), through altered glutamatergic and GABAergic neurotransmission, respectively, is thought to be implicated in the pathogenesis of ASD. Glutamatergic and GABAergic agents have been tested in clinical trials with encouraging results as to efficacy and tolerability. Further studies are needed to confirm the role of E/I modulators in the treatment of ASD and on the safety and efficacy of the current agents.
Highlights
Autism spectrum disorder (ASD) is a group of complex neurodevelopmental disorders characterized by the presence of multiple and persistent deficits in social communication and social interaction associated with restricted interests and stereotyped and repetitive behaviors (American Psychiatric Association, 2013; Grzadzinski et al, 2013)
These findings suggest that memantine can be an effective adjunctive treatment for behavioral problems in children with ASD
Differences in response to the tested agents have been identified across development in subjects with ASD, and the same has been observed about tolerability
Summary
Autism spectrum disorder (ASD) is a group of complex neurodevelopmental disorders characterized by the presence of multiple and persistent deficits in social communication and social interaction associated with restricted interests and stereotyped and repetitive behaviors (American Psychiatric Association, 2013; Grzadzinski et al, 2013). The link between GABA and binocular rivalry dynamics was found absent in ASD pointing to an insufficient GABA inhibitory function (Dunn and Jones, 2020) Based on these findings, research efforts have been directed to identify agents that have the potential to reverse this abnormal signaling, namely, excitation to inhibition (E/I) imbalance from preclinical models to clinical trials. Modulators of E/I imbalance are a group of agents that are used to restore the balance of excitation and inhibition in brain cortical regions that are dysfunctional in ASD patients These agents include compounds that target metabotropic glutamate receptors (mGluR, e.g., mGluR5 antagonists), NMDA receptors (e.g., the NMDA receptor antagonist memantine), or AMPA receptors (with receptor potentiating drugs such as ampakines). Few randomized clinical trial placebo-controlled studies have been performed to date and will be dealt with in the current article (Table 1)
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