Tourette syndrome : do reduced histamine levels induce an increase in spontaneous repetitive behaviour?

Abstract

Gilles de la Tourette syndrome (TS) is a disabling neuropsychiatric disorder characterised by persistent motor and vocal tics. Comorbidity of TS with other neuropsychiatric conditions such as obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD) and autism is frequent. TS has a significant genetic contribution and, in this regard, several susceptibility loci have been identified including the histidine decarboxylase (HDC ) gene, which encodes an enzyme that is essential for histamine synthesis. Animal models of human disease are key to identify genetic and, importantly, pharmacological modifiers of phenotypes that mimic those present in the human condition. HDC is highly conserved throughout different species including the fruit fly Drosophila melanogaster. Aiming at uncovering TS-like phenotypes, in the present study we investigated repetitive grooming behaviour in flies that have reduced histamine levels as a result of a mutation in the hdc-encoding gene. We find that histamine deficiency in Drosophila is not associated with an increase in spontaneous repetitive grooming behaviour but rather a decrease. We speculate that the grooming behaviour in Drosophila hdc knockouts is not a translationally relevant TS phenotype. Future work should investigate whether stereotypy can be induced in the same mutants after pharmacological challenge or stress induction.