Reduced plasma apelin levels in patients with autistic spectrum disorder

BACKGROUND: Dysregulation of the vasopressin (AVP) system has been implicated in the pathogenesis of autistic spectrum disorder (ASD). Apelin is a recently discovered neuropeptide that could counteract AVP actions and whose receptors are colocalized with vasopressin in hypothalamic magnocellular neurons. Aims of the present study were to investigate circulating levels of apelin in patients with ASD and to assess their correlation with plasma AVP concentrations. METHODS: Plasma levels of apelin and AVP were measured in a total of 18 patients with ASD and 21 age- and gender-matched healthy comparison subjects. The Childhood Autism Rating Scale (CARS) was used to assess the severity of autistic symptoms. RESULTS: Significantly reduced levels of apelin (p < 0.001) and elevated concentrations of AVP (p = 0.02) were found in ASD patients as compared to controls. Additionally, a significant inverse correlation between apelin and AVP levels was found within the ASD group (r = -0.61; p = 0.007), but not in healthy participants (r = -0.26; p = 0.25). Multivariate linear regression analysis showed that only AVP concentrations independently predicted apelin values in ASD individuals (beta = -0.42, t = 2.63, p = 0.014). No correlation was seen between apelin levels and CARS scores (r = -0.10; p = 0.68). CONCLUSIONS: Our findings of a significantly reduced peripheral level of apelin coupled with elevated AVP point to a subtle but definite vasopressinergic dysfunction in autism that could play a role in the etiopathophysiology of this disorder in humans.