Abstract
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Objectives Stress and impulsivity are involved in feeding control thus potentially acting as main contributors to an increased risk of obesity. The brain NA system modulates both and is altered in obesity as well. This is the first study to combine pharmacological stress testing, assessments of impulsivity and inhibition control together with in vivo imaging of central NAT by means of PET and [11C]MRB in heavily obese individuals (BMI>35).
Methods Ten obese subjects (OB, BMI 42±4, age 34±9 yrs, 4f, no comorbidities) and ten normal-weight, healthy controls (C, BMI 24±2, 33±8 yrs, 4f) underwent 120-min dynamic PET (ECAT EXACT HR+) acquisition after IV application of 357±14 and 361±7 MBq [11]MRB, respectively. Kinetic modeling of regional TACs was performed using MRTM2 (occipital reference region) to estimate BPND based on individual PET-MR coregistration. VOI data were plotted against the Barrett Impulsivity scale (BIS-11), behavioral inhibition scale (BIS) and dexamethasone suppression/CRH stimulation test read-outs to measure hypothalamic-pituitary-adrenal (HPA) axis.
Results BPND did not differ between OB and C on a group-level whereas discrimination analysis revealed significant differences with reclassification rates of 100% (OB) and 90% (C). Also, BIS-11 and BIS were similar in OB and C (p=.67 and p=.35), and OB showed HPA axis hyperactivity (i.e. cortisol secretion p=.02) correlated with BIS-11 total score in the hippocampus (r=-.76; p=.01), with BIS in the thalamus (r=.81, p<.001), with ACTH and cortisol in the hypothalamus (r=-.88, p<.001 and r=-.83, p<.001, respectively).
Conclusions These correlations indicate changes in NAT levels and thus an altered NA tone related to stress reactivity and impulse control in distinct brain areas including the hypothalamus, the hippocampus, and the thalamus in obesity.