REGULATION OF COMPULSIVE BEHAVIOURS BY KCNQ1 MIGHT INVOLVE DISRUPTION OF NORMAL THYROID FUNCTION

Although the exact aetiology of obsessive-compulsive disorder (OCD), a neuropsychiatric disorder characterised by intrusive thoughts and repetitive behaviours, is still unknown, recent research in this area has implicated potassium voltage-gated channel subfamily Q member 1 (KCNQ1). Constitutive KCNQ1 homozygous knockout mice display a strong compulsive-like phenotype characterised by behaviours like increased object checking and reduced behavioural flexibility. In contrast, neuron-specific (Cre-Nestin), tamoxifen-induced, conditional KCNQ1 knockout mice do not show these behaviours at adolescence or during adulthood. The precise mechanism by which KCNQ1 inactivation gives rise to the compulsive-like phenotype remains unknown however, these contrasting behavioural observations suggest the phenotype arises outside the brain and/or is neurodevelopmental in origin. Aside from brain, KCNQ1 is also expressed in the thyroid gland where it is believed to influence the biosynthesis of thyroid hormone, which has been linked to neurodevelopment. Here we show how the lack of KCNQ1 disrupts normal thyroid function inducing hypothyroidism. Constitutive KCNQ1 knockout mice have lower plasma triiodothyronine (T3) and thyroxine (T4) levels and higher thyroid-stimulating hormone (TSH) levels, on average compared to age-matched wildtypes of the same sex as measured by ELISAs. From this, it’s possible that hypothyroidism could be causing or contributing to the compulsive-like behaviours observed in the constitutive KCNQ1 KO mouse model. This study furthers our understanding of the link previously made between OCD and KCNQ1 and will direct future studies in this area to consider the influence of thyroid function and its neurodevelopment impact during early life in the generation of compulsive-like behaviours.