Abstract
To examine the hypothesis that normalization of low circulating leptin levels in patients with anorexia nervosa ameliorates hyperactivity, three seriously ill females with hyperactivity were treated off-label with metreleptin (recombinant human leptin) for up to 14 days. Drive for activity, repetitive thoughts of food, inner restlessness, and weight phobia decreased in two patients. Surprisingly, depression improved rapidly in all patients. No serious adverse events occurred. Due to obvious limitations of uncontrolled case series, placebo-controlled clinical trials are mandatory to confirm the observed rapid onset of beneficial effects. Our findings suggest an important role of hypoleptinemia in the mental and behavioral phenotype of anorexia nervosa.
Highlights
Underweight, fear of weight gain, and body image disturbances represent cardinal features of anorexia nervosa (AN)[1,2]
Self-rating scales included Eating Disorders Inventory (EDI50; to allow comparisons with population-based norms we present percentile ranks50,51) and Beck Depression Inventory-II (BDI-II)[52]
Patient B reported no changes in the visual analog scale (VAS)
Summary
Underweight, fear of weight gain, and body image disturbances represent cardinal features of anorexia nervosa (AN)[1,2]. Mental and behavioral symptoms of this eating disorder are intertwined with those of starvation[3], which develops from the prolonged energy restriction characteristic of AN2,4. Ensuing hypoleptinemia represents a key endocrine feature of this eating disorder[3,6,7] and acts as the major signal for the adaptation to starvation[7,8,9,10]. Hyperactivity is a common behavioral manifestation of AN, which has been linked to hypoleptinemia[11,12,13,14], albeit not consistently so[15]. Rodent studies point to a causal link between hyperactivity and low circulating leptin levels[11,16,17,18]. In light of the potential involvement of the reward system in AN20–26, the role of leptin as a strong modulator of this system deserves attention[5,14,16,27,28,29,30] within the context of AN specific psychopathology
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