GABA system dysfunction in autism and related disorders: from synapse to symptoms

Abstract

Autism spectrum disorders (ASDs) are neurodevelopmental syndromes characterised by repetitive behaviours and restricted interests, impairments in social behaviour and relations, and in language and communication. These symptoms are also observed in a number of developmental disorders of known origin, including Fragile X Syndrome, Rett Syndrome, and Foetal Anticonvulsant Syndrome. While these conditions have diverse etiologies, and poorly understood pathologies, emerging evidence suggests that they may all be linked to dysfunction in particular aspects of GABAergic inhibitory signalling in the brain. We review evidence from genetics, molecular neurobiology and systems neuroscience relating to the role of GABA in these conditions. We conclude by discussing how these deficits may relate to the specific symptoms observed.

Figure 1

A simplified illustration of the major synaptic pathways responsible for GABA synthesis, breakdown, release and reuptake. Abbreviations: gaba = gamma-aminobutyric acid; glu = glutamate; gln = glutamine. GLNase = glutaminase. GAD = glutamate decarboxylase. GABA-T = GABA transaminase. VIAAT = vesicular inhibitory amino acid transporter. GAT = GABA transporter. GABA-A = GABA_A receptor (note: there are numerous subtypes of this receptor, but these are not shown, for simplicity.) GS = glutamine synthetase. Not pictured: GABA_B receptors; GABA_A or GABA_B autoreceptors.