First Account of Psychological Changes Perceived by a Female with Congenital Leptin Deficiency upon Treatment with Metreleptin

Abstract

Two psychiatric interviews of a 39-year old female with congenital leptin deficiency were conducted to define psychological changes fourteen and 165 days after initiation of treatment with human recombinant leptin (metreleptin). The most pronounced initial experience related to the reduced preoccupation with food. An improved mood was reported by the patient, which she associated with this reduced preoccupation. Her mood remained elevated upon recontact, whereas she was no longer preoccupied with food. Overall, the interviews provides a vivid account of the subjective experiences upon initiation of treatment. Some of the findings bear resemblance to those reported recently in patients with anorexia nervosa who were treated with metreleptin for one to three weeks. This case report provides further evidence that metreleptin has strong psychophamacological effects in patients with absolute or relative leptin deficiency. We strongly recommend profound psychological examinations of patients with congenital leptin deficiency at baseline and after intitiation of treatment with human recombinant leptin to gain further insight into the functions affected by this hormone.

Suggestive Evidence for an Antidepressant Effect of Metreleptin Treatment in Patients with Lipodystrophy

“…These effects of metreleptin treatment on depressive symptoms in LD patients fit with results reported for patients with AN [41, 42]. Taken together with data from patients with AN and a case report of a patient with congenital leptin deficiency [35], our results suggest that metreleptin may have a strong antidepressant effect in patients with hypoleptinemia, irrespective of the cause of leptin deficiency.…”

“…This substantiates our hypothesis that the antidepressant effect of leptin substitution in hypoleptinemia first observed in patients with AN extends to those with LD. Initial evidence suggests that patients with congenital leptin deficiency may also experience a mood improvement upon initiation of metreleptin treatment [ 35 ].…”

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

“…42 In contrast, in a qualitative interview of an adult female patient with CLD, a strong improvement in mood could be demonstrated after 14 days of metreleptin substitution, which persisted to the follow-up on dosing day 150. 37 These results are somewhat in line with previous cursory observations in the three adult patients with CLD published by Licinio et al, who described profound changes in non-ingestive behaviour from very docile and infantile to assertive and adult-like after 2 weeks of metreleptin substitution. 41 The behavioural effects of metreleptin substitution have recently been evaluated in patients with more common causes of hypoleptinemia, namely lipodystrophy and anorexia nervosa.…”

“…In Patient 1, her initial score of 1 in the BDI was in fact so low, that it was impossible for the patient to indicate a significant improvement with this score no matter how much better she might have felt 42 . In contrast, in a qualitative interview of an adult female patient with CLD, a strong improvement in mood could be demonstrated after 14 days of metreleptin substitution, which persisted to the follow‐up on dosing day 150 37 . These results are somewhat in line with previous cursory observations in the three adult patients with CLD published by Licinio et al, who described profound changes in non‐ingestive behaviour from very docile and infantile to assertive and adult‐like after 2 weeks of metreleptin substitution 41 …”

“…30 In addition, leptin's downstream mediator BDNF is a powerful modulator of hippocampal neurogenesis and leptin has been shown to enhance the induction of synaptic plasticity in the hippocampal area, 36 which might be a further mechanism promoting leptin's anti-depressive effect. Alternatively, or in addition, the experience of a cessation of constant feelings of hunger and of the preoccupation with food may entail a feeling of liberation, thereby indirectly boosting mood (as discussed in a previous publication 37 ).…”