Sabela Casado

Gambling disorder (GD) is a modestly prevalent and severe condition for which neurobiology is not yet fully understood. Although alterations in signals involved in energy homeostasis have been studied in substance use disorders, they have yet to be examined in detail in GD. The aims of the present study were to compare different endocrine and neuropsychological factors between individuals with GD and healthy controls (HC) and to explore endocrine interactions with neuropsychological and clinical variables. A case–control design was performed in 297 individuals with GD and 41 individuals without (healthy controls; HCs), assessed through a semi-structured clinical interview and a psychometric battery. For the evaluation of endocrine and anthropometric variables, 38 HCs were added to the 41 HCs initially evaluated. Individuals with GD presented higher fasting plasma ghrelin (p < 0.001) and lower LEAP2 and adiponectin concentrations (p < 0.001) than HCs, after adjusting for body mass index (BMI). The GD group reported higher cognitive impairment regarding cognitive flexibility and decision-making strategies, a worse psychological state, higher impulsivity levels, and a more dysfunctional personality profile. Despite failing to find significant associations between endocrine factors and either neuropsychological or clinical aspects in the GD group, some impaired cognitive dimensions (i.e., WAIS Vocabulary test and WCST Perseverative errors) and lower LEAP2 concentrations statistically predicted GD presence. The findings from the present study suggest that distinctive neuropsychological and endocrine dysfunctions may operate in individuals with GD and predict GD presence. Further exploration of endophenotypic vulnerability pathways in GD appear warranted, especially with respect to etiological and therapeutic potentials.

Data gleaned recently shows that ghrelin, a stomach derived peptide, and liver-expressed-antimicrobial peptide 2 (LEAP-2) play opposite roles on food intake. However, the data available with LEAP-2 in relation to in vivo studies are still very scanty and some key questions regarding the interplay among ghrelin and LEAP-2 remain to be answered. In this work, using rats and mice, we study fasting-induced food intake as well as testing the effect of diet exposure, e.g., standard diet and high fat diet, in terms of ghrelin-induced food intake. The anorexigenic effect of LEAP-2 on fasting induced food intake appears to be dependent on energy stores, being more evident in ob/ob than in wild type mice and also in animals exposed to high fat diet. On the other hand, LEAP-2 administration markedly inhibited ghrelin-induced food intake in lean, obese (ob/ob and DIO) mice, aged rats and GH-deficient dwarf rats. In contrast, the inhibitory effect on glucose levels can only be observed in some specific experimental models indicating that the mechanisms involved are likely to be quite different. Taken together from these data, LEAP-2 emerged as a potential candidate to be therapeutically useful in obesity.