The Role of Leptin in Antipsychotic-Induced Weight Gain: Genetic and Non-Genetic Factors

Abstract

Schizophrenia is a chronic and disabling mental illness affecting millions of people worldwide. A greater proportion of people with schizophrenia tends to be overweight. Antipsychotic medications have been considered the primary risk factor for obesity in schizophrenia, although the mechanisms by which they increase weight and produce metabolic disturbances are unclear. Several lines of research indicate that leptin could be a good candidate involved in pathways linking antipsychotic treatment and weight gain. Leptin is a circulating hormone released by adipocytes in response to increased fat deposition to regulate body weight, acting through receptors in the hypothalamus. In this work, we reviewed preclinical, clinical, and genetic data in order to infer the potential role played by leptin in antipsychotic-induced weight gain considering two main hypotheses: (1) leptin is an epiphenomenon of weight gain; (2) leptin is a consequence of antipsychotic-induced “leptin-resistance status,” causing weight gain.

Antipsychotic treatment is associated with inflammatory and metabolic biomarkers alterations among first‐episode psychosis patients: A 7‐month follow‐up study

“…The elevation of C‐peptide apparently reflects problems in insulin processing after treatment with antipsychotic drugs. With respect to leptin, we replicated previous results (Panariello, Polsinelli, Borlido, Monda, & De Luca, ; Pérez‐Iglesias et al, ; Potvin et al, ) demonstrating that long‐term antipsychotic treatment is associated with elevated leptin level. There is agreement by researchers that leptin increase during antipsychotic treatment is a result of weight gain rather than a direct impact of atypical antipsychotics on leptin physiology (Jin, Meyer, Mudaliar, & Jeste, ; Panariello et al, ; Potvin, Zhornitsky, & Stip, ).…”

Leptin and the brain: Influences on brain development, cognitive functioning and psychiatric disorders

“…Several studies have identified a role for leptin in antipsychotic-related weight gain [154][155][156][157][158][159][160][161][162][163][164]. In a review of 27 studies, it was concluded that atypical antipsychotics cause a rapid rise in leptin levels in the first weeks of treatment, which then remain elevated long-term, in contrast to conventional antipsychotics which did not appear to affect leptin levels [164].…”

Leptin and psychiatric illnesses: does leptin play a role in antipsychotic-induced weight gain?

“…Regarding the increase in food intake, it has been shown that atypical antipsychotics can modulate metabolic homeostasis in the hypothalamus, through effects on receptors of neurotransmitters such as serotonin (5-hydroxytryptamine 2c, 1b, 1a, 6), dopamine (D2), histamine (H1 and H3), adrenaline (alpha 2) and acetylcholine (M3) [7,[11][12][13]. Nevertheless, the exact mechanism of weight gain appears to be a more complex association of various neurobiological and metabolic pathways [14]. However, aside from these widespread and well-known theories on the pathophysiology of AIWG, there is growing interest in the implication of hormones involved in the food intake process, such as leptin [14,15].…”