Leptin and Ghrelin Levels in Patients With Schizophrenia During Different Antipsychotics Treatment: A Review

Abstract

Energy homeostasis is achieved by the integration of peripheral metabolic signals by the neural circuits involving specific hypothalamic nuclei and brain stem regions. These neural circuits mediate many of the effects of the adipocyte-derived hormone leptin and gut-derived hormone ghrelin. The former is strongly anorexigenic while the latter is the only orexigenic agent active when administered by a peripheral route. Abnormal regulation of these 2 antagonistic regulatory peptides in patients with schizophrenia could play a role in the impairment in the regulation of food intake and energy balance. This bibliographical analysis aims to compare 27 prospective and cross-sectional studies published on circulating leptin and ghrelin levels during acute and chronic administration of antipsychotics treatment, especially atypical ones. Fasting morning leptin levels of schizophrenic patients increase rapidly in the first 2 weeks after atypical antipsychotic (AAP) treatment (mostly olanzapine and clozapine) and remain somehow elevated after that period up to several months. On the contrary, conventional antipsychotics (such as haloperidol) do not interfere with leptin levels. In contrast to leptin, fasting morning ghrelin levels decrease during the first few weeks after the beginning of AAPs treatment while they increase in the longer run. Surprisingly, body weight gain and correlations between the variation of these 2 peptides and adiposity and metabolism-related parameters such as the body mass index and abdominal perimeter were not systematically considered. Finally, an objective evaluation of feeding behavior during antipsychotic treatment remains to be determined.

RETRACTED: Identification of gene ontologies linked to prefrontal–hippocampal functional coupling in the human brain

“…Ghrelin is a metabolic peptide associated with the regulation of appetite and food intake; ghrelin levels in the brain have been found to change with atypical antipsychotic treatment (82). Interestingly, several lines of evidence have linked ghrelin to WM function (83).…”

The role of ghrelin signalling in second-generation antipsychotic-induced weight gain

“…Previous reports have suggested controversial results of the effect of SGAs on circulating ghrelin levels (Sentissi et al, 2008;Jin et al, 2008). One earlier review paper suggested a bi-phasic effect, with downregulated and upregulated ghrelin levels under short-and long-term SGA treatments, respectively (Sentissi et al, 2008).…”

“…One earlier review paper suggested a bi-phasic effect, with downregulated and upregulated ghrelin levels under short-and long-term SGA treatments, respectively (Sentissi et al, 2008). Another review paper has proposed preliminary explanation suggesting that the negative feedback effect of ghrelin secretion is disrupted under SGA treatments in the long-term (Jin et al, 2008).…”

Altered reward anticipation: Potential explanation for weight gain in schizophrenia?

“…They typically concentrate on i) dysregulation of neuroendocrinological circuits (e.g., hormonal regulation by the hypothalamus; Sharma et al, 2014); ii) dysregulation of peripheral hormones (e.g., leptin and ghrelin) implicated in weight homeostasis and in regulation of glucose (De Hert et al, 2009;Mitchell et al, 2013;Sentissi et al, 2008); and iii) the effect of antipsychotic medication on weight (Bak et al, 2014;Deng et al, 2010;Sharma et al, 2014). All of these factors are important.…”