Role of Allopregnanolone in tics severity

our group has recently documented that AP increases tic-like manifestations in several animal models of tic disorders;

furthermore, our results indicate that inhibiting AP synthesis and signalling reduces the exacerbation of tic severity associated with acute stress.

Although the specific mechanisms of these effects remain partially elusive, our findings point to the possibility that the GABAergic activation by AP may also lead to disinhibitory effects, which could interfere with the ability of patients to suppress their tics. (R1)

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The molecular and neurobiological causes of these alterations remain poorly understood, even though several studies have documented a selective loss in cholinergic and parvalbumin-positive GABAergic interneurones in the dorsal striatum of individuals with severe TD.

Building on this evidence, it is possible that a local reduction in striatal interneurones (likely a result of genetic and early-life inflammatory factors) may lead to the formation of “focal disinhibition areas” in the dorsal striatum.

In addition, several lines of research have shown a reduction in GABA content in the cortex of TD patients. (R1)