Association of central serotonin transporter availability with HPA axis responsiveness in human obesity and non-obesity controls

Ziel/Aim Alterations of serotonergic signalling and hypothalamic-pituitary-adrenal (HPA) axis activity are implicated in the pathogenesis of human obesity. We aimed to investigate the relation of serotonin transporter (SERT) availability and HPA responsiveness in heavily obese but otherwise healthy subjects (OB) compared to non-obesity controls (NOC).

Methodik/Methods Twenty-eight OB (21 females; age 36.6 ± 10.6 years; body mass index [BMI] 41.2 ± 5.1 kg/m²) were compared to twelve healthy NOC (8 females; age 35.8±SD 7.4 years; BMI 22.4 ± 2.3 kg/m²), matched for age and sex. All participants underwent positron emission tomography (PET) and HPA testing. The SERT selective tracer[¹¹C]DASB was applied and parametric images of the binding potential (BP_ND) were calculated using the multilinear reference tissue model and evaluated by both atlas-based volume of interest (VOI) analysis, as well as by voxel-based analysis (SPM8). HPA axis responsiveness was investigated using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test, and curve indicators were derived for cortisol and adrenocorticotropic hormone (ACTH).

Ergebnisse/Results OB subjects showed significant positive correlations of ACTH curve parameters with SERT BP in the caudate nucleus (ACTH-AUC: r = .54, p = .003). In NOC, cortisol indicators correlated significantly with BP_ND in the hippocampus (cortisol-AUC: r = .59, p = .04).

Schlussfolgerungen/Conclusions The present study supports a relationship of SERT availability with HPA axis responsiveness. Normally, HPA activity is linked to 5-HTT availability of cortico-limbic structures. In comparison, OB individuals show associations with subcortical areas which are known to be involved in processing reward and salience.

Publication History

Article published online:
08 April 2021