Rapid Emergence of Appetite and Hunger Resulting in Weight Gain and Improvement of Eating Disorder Symptomatology during and after Short-Term Off-Label Metreleptin Treatment of a Patient with Anorexia Nervosa

Gradl-Dietsch, Gertraud; Milos, Gabriella; Wabitsch, Martin; Bell, Rebecca; Tschoepe, Franziska; Antel, Jochen

doi:10.1159/000527386

Cited by 25 publications

(32 citation statements)

References 39 publications

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“…There is a growing body of evidence that hypoleptinemia in acute AN influences mood and disorder-related rumination and that experimental, well-monitored metreleptin treatment in patients with AN has the potential to reverse or at least improve these and other somatic and neuropsychiatric symptoms of AN. [22][23][24][25] Furthermore, going beyond associations between hypoleptinemia and rostralmedial amygdala nuclei alterations as documented previously, 29 the current study unveiled an impact of a specific subgroup of rostral-medial amygdala nuclei in mediating the relationship between leptin levels and rumination frequency in acute AN. We acknowledge that the observed mediation effects via volumes of right accessory basal and cortical nuclei are preliminary.…”

Section: Discussionsupporting

confidence: 72%

“…16,17,20,22 Moreover, case studies in patients with AN reported improvements in hyperactivity, weight phobia, mood, and, importantly, foodÀ/weight-related rumination following short-term treatment with recombinant human leptin (metreleptin). [23][24][25] However, the effects of metreleptin on brain structures/functions, potentially leading to its beneficial cognitive-affective impacts, have not been examined in AN to date.…”

Section: Limitationsmentioning

confidence: 99%

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Explicating the role of amygdala substructure alterations in the link between hypoleptinemia and rumination in anorexia nervosa

Wronski,

Hohnemann,

Bernardoni

et al. 2023

Acta Psychiatr Scand

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ObjectiveThe amygdaloid complex plays a pivotal role in emotion processing and has been associated with rumination transdiagnostically. In anorexia nervosa (AN), we previously observed differential reductions of amygdala nuclei volumes (rostral‐medial cluster substantially affected) and, in another study, elevated food−/weight‐related rumination. Both amygdala volumes and rumination frequency correlated with characteristically suppressed leptin levels in AN. Thus, we hypothesized that amygdala nuclei alterations might be associated with AN‐related rumination and potentially mediate the leptin‐rumination relationship in AN.MethodsRumination (food−/weight‐related) was assessed using ecological momentary assessment for a 14‐day period. We employed frequentist and Bayesian linear mixed effects models in females with AN (n = 51, 12–29 years, majority admitted to inpatient treatment) and age‐matched healthy females (n = 51) to investigate associations between rostral‐medial amygdala nuclei volume alterations (accessory basal, cortical, medial nuclei, corticoamygdaloid transitions) and rumination. We analyzed mediation effects using multi‐level structural equation models.ResultsReduced right accessory basal and cortical nuclei volumes predicted more frequent weight‐related rumination in AN; both nuclei fully mediated the effect of leptin on weight‐related rumination. In contrast, we found robust evidence for the absence of amygdala nuclei volume effects on rumination in healthy females.ConclusionThis study provides first evidence for the relevance of specific amygdala substructure reductions regarding cognitive symptom severity in AN and points toward novel mechanistic insight into the relationship between hypoleptinemia and rumination, which might involve the amygdaloid complex. Our findings in AN may have important clinical value with respect to understanding the beneficial neuropsychiatric effects of leptin (treatment) in AN and potentially other psychiatric conditions such as depression.

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Section: Discussionsupporting

confidence: 72%

Section: Limitationsmentioning

confidence: 99%

Explicating the role of amygdala substructure alterations in the link between hypoleptinemia and rumination in anorexia nervosa

Wronski,

Hohnemann,

Bernardoni

et al. 2023

Acta Psychiatr Scand

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“…The first interview was transcribed according to the transcription rules of Dresing and Pehl [ 25 ]. The interview pursued two aims: (i) focus on the subjective experience of the patient upon the initiation of metreleptin treatment and (ii) investigation of the extent of overlap of induced changes with those previously observed in AN patients [ 15 , 16 , 17 ]. Accordingly, the patient was asked to report all observations she had made within the initial 14 days of metreleptin treatment in a non-directive manner; in the second part of the interview, she was systematically questioned as to potential changes in preoccupation with food, sleep, mood, concentration, and spontaneity.…”

Section: Case Historymentioning

confidence: 99%

“…Due to leptin's role in the adaptation to starvation [ 12 ], we postulated that psychological symptoms of starvation, as meticulously delineated in the Minnesota Starvation Study [ 13 ], may result from the hypoleptinemia induced by loss of fat mass [ 14 ]. Indeed, metreleptin treatment of patients with anorexia nervosa (AN) has recently been shown to entail beneficial and rapid-onset cognitive, emotional, and behavioral effects [ 15 , 16 , 17 ]. Thus, preoccupation with food declined within 3–5 days; sleep improved.…”

Section: Introductionmentioning

confidence: 99%

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

Zorn¹,

Antel

Schnurbein³

et al. 2022

Obes Facts

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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.

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“…43 In five patients with acute anorexia nervosa and hypoleptinemia, metreleptin treatment was also associated with a pronounced improvement of depressed mood. 31,32,44 Interestingly however, anorexia nervosa associated hyperactivity decreased under metreleptin substitution. 31,32 This finding is in apparent contrast to the increased ratings of motor activity in our patients with CLD.…”

Section: Mean Total Scorementioning

confidence: 96%

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

et al. 2023

Self Cite

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Background: States 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.Objective: We therefore aimed to ascertain if leptin substitution in patients with congenital leptin deficiency (CLD) can improve physical activity and mood.Methods: Seven patients with CLD were filmed prior to and after short-and longterm 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.Results: Short 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.Conclusions: Metreleptin 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.

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Rapid Emergence of Appetite and Hunger Resulting in Weight Gain and Improvement of Eating Disorder Symptomatology during and after Short-Term Off-Label Metreleptin Treatment of a Patient with Anorexia Nervosa

Cited by 25 publications

References 39 publications

Explicating the role of amygdala substructure alterations in the link between hypoleptinemia and rumination in anorexia nervosa

Explicating the role of amygdala substructure alterations in the link between hypoleptinemia and rumination in anorexia nervosa

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

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

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