Elsmarieke van de Giessen

Lower striatal dopamine D2/3 receptor availability in obese compared with non-obese subjects

BackgroundObesity is a result of a relative excess in energy intake over energy expenditure. These processes are controlled by genetic, environmental, psychological and biological factors. One of the factors involved in the regulation of food intake and satiety is dopaminergic signalling. A small number of studies have reported that striatal dopamine D2/D3 receptor [D2/3R] availability is lower in morbidly obese subjects.MethodsTo confirm the role of D2/3R in obesity, we measured striatal D2/3R availability, using [123I]IBZM SPECT, in 15 obese women and 15 non-obese controls.ResultsStriatal D2/3R availability was 23% (p = 0.028) lower in obese compared with non-obese women.ConclusionThis study is an independent replication of the finding that severely obese subjects have lower striatal D2/3R availability. Our findings invigorate the evidence for lower striatal D2/3R availability in obesity and confirm the role of the striatal dopaminergic reward system in obesity.

Dopamine D2/3 receptor availability and amphetamine-induced dopamine release in obesity

Introduction: The neurotransmitter dopamine is important in the regulation of food intake. It is hypothesised that obese people experience less reward from food due to lower striatal dopamine release, which consequently leads to overeating. This study is the first to assess whether obese subjects have blunted striatal dopamine release. Method: We measured striatal dopamine D2/3 receptor (DRD2/3) availability and amphetamine-induced striatal dopamine release in 15 obese and 15 age-matched, normal-weight women using [123I]iodobenzamide single photon emission computed tomography (SPECT) imaging. In addition, correlations with food craving were examined. Results: Baseline striatal DRD2/3 availability was lower in obese subjects (0.91±0.16) compared to controls (1.09±0.16; p=0.006). Amphetamine-induced dopamine release was significant in controls (7.5%±9.2; p=0.007) and not in obese subjects (1.2%±17.7; p=0.802), although the difference in release between groups (d=0.45) was not significant. Dopamine release positively correlated with the trait food craving in obese subjects. Conclusion: This study replicates previous findings of lower striatal DRD2/3 availability in obesity and provides preliminary data that obesity is associated with blunted dopamine release. The positive correlation between dopamine release and food craving in obesity may seem contradictory with the latter finding but is presumably related to heterogeneity within the obese subjects.

Reduced dopamine transporter binding predates impulse control disorders in Parkinson's disease

Impulse control disorders (ICD) are relatively common in Parkinsons disease (PD) and generally are regarded as adverse effects of dopamine replacement therapy, although certain demographic and clinical risk factors are also involved. Previous single‐photon emission computed tomography (SPECT) studies showed reduced ventral striatal dopamine transporter binding in Parkinson patients with ICD compared with patients without. Nevertheless, these studies were performed in patients with preexisting impulse control impairments, which impedes clear‐cut interpretation of these findings. We retrospectively procured follow‐up data from 31 medication‐naïve PD patients who underwent dopamine transporter SPECT imaging at baseline and were subsequently treated with dopamine replacement therapy. We used questionnaires and a telephone interview to assess medication status and ICD symptom development during the follow‐up period (31.5 ± 12.0 months). Eleven patients developed ICD symptoms during the follow‐up period, eight of which were taking dopamine agonists. The PD patients with ICD symptoms at follow‐up had higher baseline depressive scores and lower baseline dopamine transporter availability in the right ventral striatum, anterior‐dorsal striatum, and posterior putamen compared with PD patients without ICD symptoms. No baseline between‐group differences in age and disease stage or duration were found. The ICD symptom severity correlated negatively with baseline dopamine transporter availability in the right ventral and anterior‐dorsal striatum. The results of this preliminary study show that reduced striatal dopamine transporter availability predates the development of ICD symptoms after dopamine replacement therapy and may constitute a neurobiological risk factor related to a lower premorbid dopamine transporter availability or a more pronounced dopamine denervation in PD patients susceptible to ICD.

Free-choice and no-choice high-fat diets affect striatal dopamine D2/3 receptor availability, caloric intake, and adiposity.

Different types of high‐fat (HF) diets are used to study diet‐induced obesity (DIO) in rodents and this has led to different phenotypes. This study assesses whether different HF diets differentially affect striatal dopamine D2/3 receptor (DRD2/3) availability, as decreased striatal DRD2/3 availability has been implicated in obesity in relation to reward deficiency for food. Thirty rats were randomized to either a free‐choice HF diet (HF‐choice), a premixed HF diet (HF‐no‐choice), or a standard chow diet for 28 days. Striatal DRD2/3 was measured using 123I‐IBZM storage phosphor imaging at day 29. DRD2/3 availability was significantly decreased in the dorsal striatum in the HF‐choice rats compared to chow rats, but not in HF‐no‐choice rats. Additionally, caloric intake of the HF‐choice rats was significantly higher than that of HF‐no‐choice rats and serum leptin and percentage abdominal fat store weight of total body weight were significantly higher in the HF‐choice rats compared to chow rats. These preliminary results suggest that the choice element in HF diets, which is possibly related to the motivational aspects of eating, leads to overconsumption and to a distinct state of obesity. These results are relevant for future studies on DIO when considering choice of diet type.

No association between striatal dopamine transporter binding and body mass index: A multi-center European study in healthy volunteers

INTRODUCTION Dopamine is one among several neurotransmitters that regulate food intake and overeating. Thus, it has been linked to the pathophysiology of obesity and high body mass index (BMI). Striatal dopamine D(2) receptor availability is lower in obesity and there are indications that striatal dopamine transporter (DAT) availability is also decreased. In this study, we tested whether BMI and striatal DAT availability are associated. METHODS The study included 123 healthy individuals from a large European multi-center database. They had a BMI range of 18.2-41.1 kg/m(2) and were scanned using [(123)I]FP-CIT SPECT imaging. Scans were analyzed with both region-of-interest and voxel-based analysis to determine the binding potential for DAT availability in the caudate nucleus and putamen. A direct relation between BMI and DAT availability was assessed and groups with high and low BMI were compared for DAT availability. RESULTS No association between BMI and striatal DAT availability was found. CONCLUSION The lack of an association between BMI and striatal DAT availability suggests that the regulation of striatal synaptic dopamine levels by DAT plays no or a limited role in the pathophysiology of overweight and obesity.

Being impulsive and obese increases susceptibility to speeded detection of high-calorie foods.

OBJECTIVE Overeating and obesity are associated with impulsivity. In studies among patients with a substance use disorder, impulsivity was found to be associated with substance-related attentional bias. This study examined whether obesity, impulsivity and food craving are associated with an attentional bias for high-calorie food. METHODS Obese (n = 185, mean BMI = 38.18 ± 6.17) and matched healthy-weight (n = 134, mean BMI = 22.35 ± 1.63) men (27.9%) and women (72.1%), aged 18-45 years, took part in the study. Participants were tested on several self-report and behavioral measures of impulsivity (i.e., response inhibition and reward sensitivity) and self-reported trait craving. In addition, they performed a visual search task to measure attentional bias for high- and low-caloric foods. RESULTS Self-reported impulsivity influenced the relationship between weight status and detection speed of high- and low-caloric food items: High-impulsive participants with obesity were significantly faster than high-impulsive healthy-weight participants in detecting a high-caloric food item among neutral items, whereas no such difference was observed among low-impulsive participants. No significant effects were found on low-caloric food items, for trait craving or any of the behavioral measures of impulsivity. CONCLUSION Self-reported impulsivity, but not trait craving or behavioral measures of impulsivity, is associated with an attentional bias for high-caloric foods, but only in people with obesity. It is in particular the speedy detection of high-caloric foods in the environment that characterizes the impulsive person with obesity, which in turn may cause risky eating patterns in a society were high-caloric food is overly present.

A Cochrane review on brain [18F]FDG PET in dementia: limitations and future perspectives

1. Nuclear Medicine Unit, IRCCS San Martino – IST, Dept of Health Sciences, University of Genoa, Italy 2. Department of Medical Imaging, Geneva University and Geneva University Hospitals, Geneva, Switzerland 3. Department of Nuclear Medicine, University of Amsterdam, Academic Medical Center, Amsterdam, The Netherlands. 4. Nuclear Medicine Department, Clinica Universidad de Navarra, University of Navarra, Pamplona, Spain 5. Inserm, U1077, Caen, France; Universite de Caen Basse-Normandie, UMR-S1077, Caen, France; Ecole Pratique des Hautes Etudes, UMR-S1077, Caen, France; CHU de Caen, U1077, Caen, France 6. Klinik und Poliklinik fur Nuklearmedizin, Universitat zu Koln, Koln, Germany 7. Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany 8. Department of Radiology & Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands 9. Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark 10. Institute of Biostructure and Bioimaging, CNR, Naples, Italy 11. INSERM UMR 825 Universite de Toulouse; UPS; Imagerie cerebrale et handicaps neurologiques; CHU Purpan, Place du Dr Baylac, F-31059 Toulouse Cedex 9, France 12. Institute of Cognitive Sciences and Technologies, CNR, Rome, Italy 13. Department of Nuclear Medicine, Karolinska Hospital, Stockholm, Sweden

Association of central serotonin transporter availability and body mass index in healthy Europeans.

UNLABELLED Serotonin-mediated mechanisms, in particular via the serotonin transporter (SERT), are thought to have an effect on food intake and play an important role in the pathophysiology of obesity. However, imaging studies that examined the correlation between body mass index (BMI) and SERT are sparse and provided contradictory results. The aim of this study was to further test the association between SERT and BMI in a large cohort of healthy subjects. METHODS 127 subjects of the ENC DAT database (58 females, age 52 ± 18 years, range 20-83, BMI 25.2 ± 3.8 kg/m(2), range 18.2-41.1) were analysed using region-of-interest (ROI) and voxel-based approaches to calculate [(123)I]FP-CIT specific-to-nonspecific binding ratios (SBR) in the hypothalamus/thalamus and midbrain/brainstem as SERT-specific target regions. RESULTS In the voxel-based analysis, SERT availability and BMI were positively associated in the thalamus, but not in the midbrain. In the ROI-analysis, the interaction between gender and BMI showed a trend with higher correlation coefficient for men in the midbrain albeit not significant (0.033SBRm(2)/kg, p=0.1). CONCLUSIONS The data are in agreement with previous PET findings of an altered central serotonergic tone depending on BMI, as a probable pathophysiologic mechanism in obesity, and should encourage further clinical studies in obesity targeting the serotonergic system.

Genetic polymorphisms in the DRD2, DRD3, and SLC6A3 gene in elderly patients with delirium†

Dopamine excess appears to be critical in the final common pathway of delirium. The aim of this study was to investigate whether genetic polymorphisms in three dopamine‐related genes (the dopamine receptor 2 (DRD2), dopamine receptor 3 (DRD3), and the dopamine transporter (SLC6A3) gene) were associated with delirium. Patients aged 65 years and older acutely admitted to the medical department or to the surgical department following hip fracture were included. Delirium was diagnosed by the Confusion Assessment Method. Sixteen single nucleotide polymorphisms (SNPs) and one variable number of tandem repeats in the SLC6A3 gene, nine SNPs in the DRD2 gene, and six SNPs in the DRD3 gene were genotyped. Fifty percent of the 115 surgical patients and 34% of the 605 medical patients experienced delirium. Delirious patients were older and had more frequently pre‐existing functional and cognitive impairment (P < 0.001). After correction for multiple testing, one SNP in the SLC6A3 gene (rs393795) was associated with reduced risk of delirium (P = 0.032). Adjusted for age, cognitive impairment, and functional impairment, three SNPs in the DRD2 gene and seven SNPs in the SLC6A3 gene were associated with delirium; none of these associations was significant after correction for multiple testing. Variations in the SLC6A3 gene and possibly the DRD2 gene were associated with delirium. Although validation of these results is needed our results support a role for the dopamine transporter and dopamine receptor 2 in the pathogenesis of delirium.

Striatal dopamine D2/3 receptor availability increases after long-term bariatric surgery-induced weight loss.

In several studies reduced striatal dopamine D2/3 receptor (D2/3R) availability was reported in obese subjects compared to lean controls. Whether this is a reversible phenomenon remained uncertain. We previously determined the short-term effect of Roux-en-Y gastric bypass surgery (RYGB) on striatal D2/3R availability (using [(123)I]IBZM SPECT) in 20 morbidly obese women. Striatal D2/3R availability was lower compared to controls at baseline, and remained unaltered after 6 weeks, despite significant weight loss. To determine whether long-term bariatric surgery-induced weight loss normalizes striatal D2/3R binding, we repeated striatal D2/3R binding measurements at least 2 years after RYGB in 14 subjects of the original cohort. In addition, we assessed long-term changes in body composition, eating behavior and fasting plasma levels of leptin, ghrelin, insulin and glucose. Mean body mass index declined from 46±7kg/m(2) to 32±6kg/m(2), which was accompanied by a significant increase in striatal D2/3R availability (p=0.031). Striatal D2/3R availability remained significantly reduced compared to the age-matched controls (BMI 22±2kg/m(2); p=0.01). Changes in striatal D2/3R availability did not correlate with changes in body weight/fat, insulin sensitivity, ghrelin or leptin levels. Scores on eating behavior questionnaires improved and changes in the General Food Craving Questionnaire-State showed a borderline significant correlation with changes in striatal D2/3R availability. These findings show that striatal D2/3R availability increases after long-term bariatric-surgery induced weight loss, suggesting that reduced D2/3R availability in obesity is a reversible phenomenon.