Jan Booij

University of Amsterdam, Amsterdamo, North Holland, Netherlands

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Publications (277)1157.69 Total impact

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    ABSTRACT: Stress is an important risk factor in the etiology of psychotic disorder. Preclinical work has shown that stress primarily increases dopamine (DA) transmission in the frontal cortex. Given that DA-mediated hypofrontality is hypothesized to be a cardinal feature of psychotic disorder, stress-related extrastriatal DA release may be altered in psychotic disorder. Here we quantified for the first time stress-induced extrastriatal DA release and the spatial extent of extrastriatal DA release in individuals with non-affective psychotic disorder (NAPD). Twelve healthy volunteers (HV) and 12 matched drug-free NAPD patients underwent a single infusion [18F]fallypride positron emission tomography scan during which they completed the control and stress condition of the Montreal Imaging Stress Task. HV and NAPD did not differ in stress-induced [18F]fallypride displacement and the spatial extent of stress-induced [18F]fallypride displacement in medial prefrontal cortex (mPFC) and temporal cortex (TC). In the whole sample, the spatial extent of stress-induced radioligand displacement in right ventro-mPFC, but not dorso-mPFC or TC, was positively associated with task-induced subjective stress. Psychotic symptoms during the scan or negative, positive and general subscales of the Positive and Negative Syndrome Scale were not associated with stress-induced [18F]fallypride displacement nor the spatial extent of stress-induced [18F]fallypride displacement in NAPD. Our results do not offer evidence for altered stress-induced extrastriatal DA signaling in NAPD, nor altered functional relevance. The implications of these findings for the role of the DA system in NAPD and stress processing are discussed.
    Translational Psychiatry 04/2015; 5(4). DOI:10.1038/tp.2015.37 · 4.36 Impact Factor
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    ABSTRACT: Extended-release naltrexone (XRNT), an opioid receptor antagonist, is successfully used in the treatment of opioid dependence. However, naltrexone treatment of opioid-dependent patients may reduce striatal dopamine transporter (DAT) availability and cause depression and anhedonia. The aim of this study is to investigate changes in striatal DAT availability and symptoms of depression (Beck Depression Inventory (BDI)) and anhedonia (Snaith Hamilton Pleasure Scale (SHAPS)) before and during XRNT treatment. At baseline, ten detoxified heroin-dependent patients and 11 matched healthy controls underwent [(123)I]FP-CIT single photon emission computed tomography (SPECT) imaging to assess striatal DAT binding. Patients underwent a second SPECT scan 2 weeks after an intramuscular injection with XRNT. At baseline, the mean binding potential (BPND) in the putamen was at a trend level lower and the mean BDI score was significantly higher in heroin patients (n = 10) than in controls (n = 11) (3.45 ± 0.88 vs. 3.80 ± 0.61, p = 0.067, d = -0.48 and 12.75 ± 7.40 vs. 5.20 ± 4.83, p = 0.019, d = 1.24, respectively). Post hoc analyses in subgroups with negative urine analyses for opioids and cocaine showed significantly lower baseline putamen BPND in heroin patients (n = 8) than controls (n = 10) (3.19 ± 0.43 vs. 3.80 ± 0.64, p = 0.049, d = -1.03). XRNT treatment in heroin patients was not significantly associated with changes in striatal DAT availability (p = 0.348, d = 0.48), but the mean BDI score after XRNT treatment was significantly lower than before treatment (7.75 ± 7.21 vs. 12.75 ± 7.40, p = 0.004, d = -0.68). The results of this study suggest that XRNT treatment does not reduce striatal DAT availability and has no significant effect on anhedonia, but is associated with a significant reduction of depressive symptoms.
    Psychopharmacology 03/2015; DOI:10.1007/s00213-015-3891-4 · 3.99 Impact Factor
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    ABSTRACT: The muscarinic M1 receptor (M1R) is highly involved in cognition and selective M1 agonists have pro-cognitive properties. Loss of the M1R has been found in post-mortem brain tissue of several neuropsychiatric disorders which may be related to symptoms of cognitive dysfunction. (123)I-iododexetimide is used for imaging muscarinic acetylcholine receptors (mAchRs). Considering its high brain uptake and intense binding in M1R-rich brain areas, (123)I-iododexetimide may be an attractive radiopharmaceutical to image the M1R. To date, the binding affinity and selectivity of (123)I-iododexetimide for the mAchR subtypes has not been characterized, nor its brain distribution studied intensively. Therefore, this study aims to address these topics. In the current study, the in vitro affinity and selectivity of (127)I-iododexetimide (cold-labelled iododexetimide), as well as it's functional antagonist properties (GTPy35S assay), were assessed on recombinant human M1-M5Rs. Distributions of (127)I-iododexetimide and (123)I-iododexetimide in the brain were evaluated using liquid chromatography-mass spectrometry and storage phosphor imaging, respectively, ex vivo in rats, wild-type mice, and M1-M5 knock-out (KO) mice. Inhibition of (127)I-iododexetimide and (123)I-iododexetimide binding in M1R-rich brain areas by the M1/4R agonist xanomeline, or the antipsychotics olanzapine (M1R antagonist) and haloperidol (low M1R affinity) was assessed in rats ex-vivo. Results : In vitro, (127)I-iododexetimide displayed high affinity for the M1R (pM range), with modest selectivity over other mAchRs. In bio distribution studies in rats, ex vivo (127)I-iododexetimide binding was much higher in M1R-rich brain areas, such as cortex and striatum, compared to cerebellum (devoid of M1Rs). In M1 KO mice, but not M2-M5 KO mice, (127)I-iododexetimide binding was strongly reduced in frontal cortex compared to wild-type mice. Finally, both acute administration of an M1/4R agonist xanomeline and M1R antagonist olanzapine were able to inhibit ex vivo (123)I-iododexetimide, and (123)I-iododexetimide binding in M1-rich brain areas in rats, while administration of haloperidol had no effect. The current results suggest (123)I-iododexetimide preferentially binds to the M1R in vivo and can be displaced by M1R ligands. (123)I-iododexetimide may therefore be a useful imaging tool to further evaluate M1R changes in neuropsychiatric disorders, as a potential stratifying biomarker, or as clinical target engagement biomarker to assess M1R. Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 01/2015; 56(2). DOI:10.2967/jnumed.114.147488 · 5.56 Impact Factor
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    ABSTRACT: The opioid receptor antagonist naltrexone is successfully used in the treatment of opioid and alcohol dependence. However, questions have been raised about possible anhedonic side effects, because the opioid system is directly involved in hedonic responses to natural rewarding activities, possibly due to its indirect effects on the striatal dopamine transporter (DAT). In order to test this hypothesis, 30 rats were randomized to either a 10-day treatment with 3 mg/kg short-acting naltrexone or vehicle. No significant differences between the groups were found in striatal DAT availability, cumulative food intake (for 48 or 72 h), body weight gain and abdominal fatpad weight. Thus, the results of this study suggest that (sub)chronic treatment with short-acting naltrexone does not induce possible anhedonic effects. However, it cannot be ruled out the anhedonic effect of naltrexone is only short-lived and thus not detected in the current study. Therefore, future studies are needed to study possible acute anhedonic effects at several time points shortly after short-acting naltrexone administration and to directly compare the possible anhedonic effects of long-acting with those of short-acting opioid antagonists. © The Author(s) 2015.
    Journal of Psychopharmacology 01/2015; DOI:10.1177/0269881114565380 · 2.81 Impact Factor
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    ABSTRACT: In specialized movement disorder centers, Parkinson's disease (PD) is wrongly diagnosed in 6 to 25% of cases. To improve the accuracy of the clinical diagnosis, it is necessary to have a reliable and practical reference standard. Dopamine transporter single-photon emission computed tomography (DAT SPECT) imaging might have the potential (high diagnostic accuracy and practical to use) to act as reference standard in detecting nigrostriatal cell loss in patients with (early stage) parkinsonism. We performed a systematic review to evaluate if DAT SPECT imaging can be used as such. Relevant studies were searched in the MEDLINE and EMBASE databases. Studies were selected when they met the following criteria: (1) all patients were adults with a clinical diagnosis of PD or clinically uncertain parkinsonism and (2) the study reported original data. In addition, studies needed to fulfill one of the two following criteria: (1) patients underwent at least one DAT SPECT and had a neuropathological confirmed diagnosis and (2) patients underwent at least two DAT SPECT scans, performed at least 2 years apart. The search identified 1,649 articles. Eight studies fulfilled our selection criteria and were included in this review. There was only one study including patients with diagnostic uncertainty. Sensitivity and specificity of DAT SPECT imaging to detect nigrostriatal cell loss were 98%. The other studies included patients with a diagnosis of PD in whom there was no uncertainty. In these studies, sensitivity was 100%. Our systematic review indicates that DAT SPECT imaging seems to be accurate to detect nigrostriatal cell loss in patients with parkinsonism.
    01/2015; 5:12. DOI:10.1186/s13550-015-0087-1
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    ABSTRACT: For imaging of dopamine D2/3 receptors, agonist tracers are favoured over antagonists because they are more sensitive to detection of dopamine release and because they may selectively label the high-affinity receptor state. We have developed novel D2/3 receptor selective agonists that can be radiolabelled with [(123)I], which label is advantageous over most other labels, such as carbon-11, as it has a longer half-life. Particularly, we considered (R) N-[7-hydroxychroman-2-yl]-methyl 4-iodobenzyl amine (compound 1) as an attractive candidate for development as it shows high binding affinity to D2/3 receptors in vitro, and here we report on the characterization of this first [(123)I]-labelled D2/3 receptor agonist radiopharmaceutical intended for SPECT imaging. The appropriate tin precursor for [(123)I]-1 was developed and was successfully radiolabelled with iodine-123 giving a moderate yield (30-35%) and a good purity (>95%) for [(123)I]-1. In biodistribution experiments in Wistar rats intravenous injection of [(123)I]-1 resulted in a fast brain uptake, where the observed binding in the D2/3 receptor-rich striatum was slightly higher than that in the cerebellum 30 min to 4 h p.i. Storage phosphor imaging experiments, however, did not show specific D2/3 receptor binding. In conclusion, despite promising in vitro data for 1, neither specific ex vivo binding nor high signal-to-noise ratios were found in rodents for [(123)I]-1.
    12/2014; 2014:507012. DOI:10.1155/2014/507012
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    ABSTRACT: Background. Minor stresses measured in daily life have repeatedly been associated with increased momentary psychotic experiences, both in individuals with psychotic disorders and in persons who are genetically at an increased risk for these disorders. Severe hearing impairment (SHI) is an environmental risk factor for psychotic disorder, possibly due to the experience of social exclusion. The aim of the current study is to investigate whether people with SHI exhibit higher levels of psychotic reactivity to social stressors in daily life than normal-hearing controls and whether this reactivity is associated with decreased baseline dopamine (DA) D2/3 receptor availability and/or elevated DA release following a dexamphetamine challenge. Method. We conducted an experience sampling study in 15 young adults with SHI and 19 matched normal-hearing controls who had previously participated in a single photon emission computed tomography study measuring DA D2/3 receptor availability and DA release in response to dexamphetamine. Results. The association between social stress and momentary psychotic experiences in daily life was stronger among SHI participants than among normal-hearing controls. Interactions between social stress and baseline striatal DA D2/3 receptor availability or DA release were not significant in multilevel models of momentary psychotic experiences including age, sex and tobacco use. Conclusions. While both elevated striatal DA release and elevated psychotic stress reactivity have been found in the same population defined by an environmental risk factor, SHI, their inter-relationship cannot be established. Further research is warranted to clarify the association between biological and psychological endophenotypes and psychosis risk.
    Psychological Medicine 12/2014; DOI:10.1017/S0033291714002797 · 5.43 Impact Factor
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    ABSTRACT: Dopamine D2/3 receptor (D2/3R) agonist positron emission tomography (PET) tracers are better suited for the imaging of synaptic dopaminergic neurotransmission than D2/3R antagonists, and may also offer the opportunity to study in vivo the high-affinity state of D2/3R (D2/3RHigh). Aiming to develoP (18)F-labeled D2/3R agonists suitable for widespread clinical application, we report here on the synthesis, in vitro and in vivo evaluation evaluation of a D2/3R-agonist ligand from the aminomethyl chromane (AMC) class - (R)-2-[(4-(18)F-fluorobenzylamino)methyl]chroman-7-ol ((18)F-AMC20). In vitro affinities of AMC20 towards dopaminergic receptor subtypes were measured in membrane homogenates prepared from HEK293 cells expressing human dopamine receptors. Agonism of AMC20 was assessed in the arrestin recruitment assay in CHO-K1 cells expressing D2RLong receptors. D2/3R-specific binding of (18)F-AMC20 was evaluated in brain slices of Sprague-Dawley rats by in vitro autoradiography and in living rats by in vivo small-animal PET imaging and ex vivo autoradiography. PET data were analyzed with one and two-tissue compartmental models (1TCM/2TCM), simplified reference tissue model (SRTM) and Logan graphical analysis. Specificity of binding was tested by blocking D2/3R with raclopride (co-incubation with 10 μM in-vitro, administration of 1.0 mg/kg in vivo). In membrane homogenates AMC20 demonstrated picomolar affinity at D2RHigh (mean Ki = 85 pM) and excellent selectivity against D2RLow (mean Ki = 84 nM, 988-fold selectivity) and D1-like receptors (mean Ki = 5062 nM at D1R). The efficacy of AMC20 was 90% of that of dopamine in the arrestine recruitment assay. Up to 70% of total binding of (18)F-AMC20 in the D2/3R-rich striatum in rat brain slices was D2/3R-specific, in living rats the uptake ratio between the striatum and the D2/3R-poor cerebellum reached 2.0-2.5, depending on the measurement method. Radiometabolites of (18)F-AMC20 did not enter the brain. Striatal binding potential (BPND) of (18)F-AMC20 varied between 0.49 and 0.59 depending on the estimation method. Pre-treatment with 1 mg/kg raclopride reduced the apparent specific binding of (18)F-AMC20 in the striatum. (18)F-AMC20 shows specific binding to D2/3R in the striatum of living rats. Further optimization of the chemical structure of (18)F-AMC20 can lead to (18)F-labeled D2/3 agonist PET tracers more suitable for in vivo clinical application. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 12/2014; DOI:10.2967/jnumed.114.145466 · 5.56 Impact Factor
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    ABSTRACT: Background Most studies investigating the role of personality as a risk factor for the development of opioid dependence compare dependent opioid users with healthy controls who never used heroin. In order to understand the potential protective role of personality, it is crucial to compare illicit opioid users who never became dependent with dependent opioid users. Aims This study aims to examine the role of personality as a risk factor for opioid use and as a protective factor for the development of opioid dependence. Methods Comparing personality factors between three groups: (1) 161 never-dependent illicit opioid users who have been using illicit opioids but never became opioid dependent; (2) 402 dependent opioid users in methadone maintenance treatment or heroin-assisted treatment; and (3) 135 healthy controls who never used heroin. Personality was assessed with a short version of Cloninger's Temperament and Character Inventory. Results Never-dependent opioid users reported more Novelty Seeking and Harm Avoidance and less Self-Directedness and Cooperativeness than healthy controls and more Reward Dependence and Self-Directedness, and less Harm Avoidance than dependent opioid users. Furthermore, never-dependent opioid users reported more Self-Transcendence than both dependent opioid users and healthy controls. Conclusions Never-dependent opioid users may have started to use opioids partly due to their tendency to seek novel and/or spiritual experiences (high Novelty Seeking, high Self-Transcendence) and their tendency to avoid aversive stimuli (high Harm Avoidance), whereas they may have been protected against the development of dependence by their need for social approval (high Reward Dependence) and their self-efficacy (high Self-Directedness).
    Drug and Alcohol Dependence 12/2014; 145. DOI:10.1016/j.drugalcdep.2014.09.783 · 3.28 Impact Factor
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    ABSTRACT: Several studies demonstrated improvement of depressive symptoms in treatment resistant depression (TRD) after administering dopamine agonists which suggest abnormal dopaminergic neurotransmission in TRD. However, the role of dopaminergic signaling through measurement of striatal dopamine D2/3 receptor (D2/3R) binding has not been investigated in TRD subjects. We used [123I]IBZM single photon emission computed tomography (SPECT) to investigate striatal D2/3R binding in TRD. We included 6 severe TRD patients, 11 severe TRD patients on antipsychotics (TRD AP group) and 15 matched healthy controls. Results showed no significant difference (p = 0.75) in striatal D2/3R availability was found between TRD patients and healthy controls. In the TRD AP group D2/3R availability was significantly decreased (reflecting occupancy of D2/3Rs by antipsychotics) relative to TRD patients and healthy controls (p<0.001) but there were no differences in clinical symptoms between TRD AP and TRD patients. This preliminary study therefore does not provide evidence for large differences in D2/3 availability in severe TRD patients and suggests this TRD subgroup is not characterized by altered dopaminergic transmission. Atypical antipsychotics appear to have no clinical benefit in severe TRD patients who remain depressed, despite their strong occupancy of D2/3Rs.
    PLoS ONE 11/2014; 9(11):e113612. DOI:10.1371/journal.pone.0113612 · 3.53 Impact Factor
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    ABSTRACT: Dexamphetamine (dAMPH) is a stimulant drug that is widely used recreationally as well as for treatment of attention deficit hyperactivity disorder (ADHD). Although animal studies have shown neurotoxic effects of dAMPH on the dopaminergic system, little is known about such effects on the human brain. Here, we studied the dopaminergic system at multiple physiological levels in recreational dAMPH users and age, gender and IQ-matched dAMPH-naïve healthy controls. We assessed baseline D2/3 receptor availability, in addition to changes in DA release using single-photon emission computed tomography (SPECT) and DA functionality using pharmacological magnetic resonance imaging (phMRI) following a dAMPH challenge. Also, the subjective responses to the challenge were determined. dAMPH users displayed significantly lower striatal DA D2/3 receptor binding compared to healthy controls. In dAMPH users we further observed a blunted DA release and DA functionality to an acute dAMPH challenge, as well as a blunted subjective response. Finally, the lower D2/3 availability, the more pleasant the dAMPH administration was experienced by control subjects, but not by dAMPH users. Thus, in agreement with preclinical studies, we show that recreational use of dAMPH in human subjects is associated with dopaminergic system dysfunction. These findings warrant further (longitudinal) investigations, and call for caution when using this drug recreationally and for ADHD.Neuropsychopharmacology accepted article preview online, 14 November 2014. doi:10.1038/npp.2014.301.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 11/2014; 40(5). DOI:10.1038/npp.2014.301 · 7.83 Impact Factor
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    ABSTRACT: 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. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
    Health Psychology 11/2014; DOI:10.1037/hea0000167 · 3.95 Impact Factor
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    ABSTRACT: Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug-naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross-sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single-photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [123I]FP-CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age-moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD. © 2014 International Parkinson and Movement Disorder Society
    Movement Disorders 10/2014; DOI:10.1002/mds.26051 · 5.63 Impact Factor
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    ABSTRACT: An increased risk for psychosis is observed in people with hearing impairment. According to the social defeat hypothesis, the long-term experience of exclusion leads to enhanced baseline activity and/or sensitization of the dopamine system and puts the individual at increased risk for psychosis.
    JAMA Psychiatry 10/2014; 71(12). DOI:10.1001/jamapsychiatry.2014.1325 · 12.01 Impact Factor
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    ABSTRACT: 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/m2, range 18.2–41.1) were analyzed using region-of-interest (ROI) and voxel-based approaches to calculate [123I]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 (0.03 SBR⁎m2/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.
    European Neuropsychopharmacology 08/2014; 24(8). DOI:10.1016/j.euroneuro.2014.05.005 · 5.40 Impact Factor
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    ABSTRACT: Establishing an early, accurate diagnosis is fundamental for appropriate clinical management of patients with movement disorders or dementia. Ioflupane (123)I Injection (DaTscan, (123)I-ioflupane) is an important adjunct to support the clinical diagnosis. Understanding individual-reader diagnostic performance of (123)I-ioflupane in a variety of clinical scenarios is essential.
    Journal of Nuclear Medicine 06/2014; 55(8). DOI:10.2967/jnumed.114.140228 · 5.56 Impact Factor
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    ABSTRACT: Apart from binding to the dopamine transporter (DAT), [(123)I]FP-CIT shows moderate affinity for the serotonin transporter (SERT), allowing imaging of both monoamine transporters in a single imaging session in different brain areas. The aim of this study was to systematically evaluate extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls. SPECT data from 103 healthy controls with well-defined criteria of normality acquired at 13 different imaging centres were analysed for extrastriatal binding using volumes of interest analysis for the thalamus and the pons. Data were examined for gender and age effects as well as for potential influence of striatal DAT radiotracer binding. Thalamic binding was significantly higher than pons binding. Partial correlations showed an influence of putaminal DAT binding on measured binding in the thalamus but not on the pons. Data showed high interindividual variation in extrastriatal binding. Significant gender effects with 31 % higher binding in women than in men were observed in the thalamus, but not in the pons. An age dependency with a decline per decade (±standard error) of 8.2 ± 1.3 % for the thalamus and 6.8 ± 2.9 % for the pons was shown. The potential to evaluate extrastriatal predominant SERT binding in addition to the striatal DAT in a single imaging session was shown using a large database of [(123)I]FP-CIT scans in healthy controls. For both the thalamus and the pons, an age-related decline in radiotracer binding was observed. Gender effects were demonstrated for binding in the thalamus only. As a potential clinical application, the data could be used as a reference to estimate SERT occupancy in addition to nigrostriatal integrity when using [(123)I]FP-CIT for DAT imaging in patients treated with selective serotonin reuptake inhibitors.
    European Journal of Nuclear Medicine 05/2014; 41(10). DOI:10.1007/s00259-014-2785-8 · 4.53 Impact Factor
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    ABSTRACT: Preclinical imaging with SPECT combined with CT or MRI is used more and more frequently and has proven to be very useful in translational research. In this article, an overview of current preclinical research applications and trends of SPECT combined with CT or MRI, mainly in tumour imaging and neuroscience imaging, is given and the advantages and disadvantages of the different approaches are described. Today SPECT and CT systems are often integrated into a single device (commonly called a SPECT/CT system), whereas at present combined SPECT and MRI is almost always carried out with separate systems and fiducial markers to combine the separately acquired images. While preclinical SPECT/CT is most widely applied in oncology research, SPECT combined with MRI (SPECT/MRI when integrated in one system) offers the potential for both neuroscience applications and oncological applications. Today CT and MRI are still mainly used to localize radiotracer binding and to improve SPECT quantification, although both CT and MRI have additional potential. Future technology developments may include fast sequential or simultaneous acquisition of (dynamic) multimodality data, spectroscopy, fMRI along with high-resolution anatomic MRI, advanced CT procedures, and combinations of more than two modalities such as combinations of SPECT, PET, MRI and CT all together. This will all strongly depend on new technologies. With further advances in biology and chemistry for imaging molecular targets and (patho)physiological processes in vivo, the introduction of new imaging procedures and promising new radiopharmaceuticals in clinical practice may be accelerated.
    European journal of nuclear medicine and molecular imaging 05/2014; 41 Suppl 1(S1):S36-49. DOI:10.1007/s00259-013-2685-3 · 5.22 Impact Factor
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    ABSTRACT: 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 [(123)I]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.
    Journal of Psychopharmacology 04/2014; 28(9). DOI:10.1177/0269881114531664 · 2.81 Impact Factor
  • Schizophrenia Research; 04/2014

Publication Stats

6k Citations
1,157.69 Total Impact Points

Institutions

  • 1998–2015
    • University of Amsterdam
      • • Department of Nuclear Medicine
      • • Faculty of Medicine AMC
      Amsterdamo, North Holland, Netherlands
  • 1997–2015
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Nuclear Medicine
      Amsterdamo, North Holland, Netherlands
  • 2014
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
    • Università degli Studi di Bari Aldo Moro
      Bari, Apulia, Italy
  • 2010
    • Lancaster University
      Lancaster, England, United Kingdom
  • 2000–2008
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 2002–2003
    • VU University Medical Center
      • Department of Neurology
      Amsterdam, North Holland, Netherlands
  • 1995–2003
    • VU University Amsterdam
      • Department of Neurology
      Amsterdamo, North Holland, Netherlands