Positive effect of leptin substitution on mood and behaviour in patients with congenital leptin deficiency

Abstract

SummaryBackgroundStates of starvation are characterized by reduced physical activity and social withdrawal. This has been suggested to be mediated at least in part via reduced leptin concentrations.ObjectiveWe therefore aimed to ascertain if leptin substitution in patients with congenital leptin deficiency (CLD) can improve physical activity and mood.MethodsSeven patients with CLD were filmed prior to and after short‐ and long‐term substitution (2–21 days; 3–4 months) in a play situation. Six independent, blinded investigators ranked each video according to specifically developed scales concerning motor activity, social interaction, emotionality, and mood with higher scores representing improvements.ResultsShort term metreleptin substitution significantly increased mean total score from 17.7 ± 4.1 to 22.6 ± 6.6 (p = 0.039), and mean scores for motor activity (4.1 ± 1.1 to 5.1 ± 1.5, p = 0.023) and social interaction (4.6 ± 1.1 to 6.2 ± 1.7, p = 0.016). After long term substitution means of all four single scales and of total score were even higher than at short‐term follow‐up.During a treatment pause of 3 months in two children, all four scale scores fell below substitution levels and rose again after restart.ConclusionsMetreleptin substitution improved indices of physical activity and psychological wellbeing in patients with CLD. This suggests that reduced leptin concentrations might be in part responsible for emotional and behavioural changes seen during starvation.