Are Signals Regulating Energy Homeostasis Related to Neuropsychological and Clinical Features of Gambling Disorder? A Case–Control Study

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.