Biomedical subjects

Jan Booij

Publications and source records attributed to Jan Booij.

32 records · Page 2Linked to original sources

PubMed2004

Cerebral blood flow changes during script-driven imagery in police officers with posttraumatic stress disorder.

BACKGROUND: Functional brain imaging studies in posttraumatic stress disorder (PTSD) have focused mostly on war or sexual abuse victims, many of whom also had comorbid disorders. The aim of this study was to examine the neuronal circuitry underlying responses to script-driven imagery in traumatized police officers with and without PTSD and with low comorbidity rates. METHODS: In a case-matched control study, 30 traumatized police officers with and without PTSD underwent clinical assessment and (99m)technetium-hexa-methyl-propylene-amine-oxime single photon emission computed tomography scanning with neutral and trauma scripts. Statistical parametric mapping was applied to analyze changes in regional cerebral blood flow. RESULTS: The main findings were significantly less activation in the medial frontal gyrus and more activation in the right cuneus in the PTSD group relative to the trauma-exposed control group in reaction to trauma versus neutral scripts. Within the PTSD group, subjects showed less activation in the superior temporal gyrus, left lentiform nucleus, left middle frontal gyrus, and left inferior frontal gyrus in reaction to trauma scripts. CONCLUSIONS: We confirmed previous findings of dysfunction of the medial frontal gyrus in PTSD in a new population with low comorbidity rates. Other alterations were found in certain brain structures involved in emotional, memory, linguistic, visuospatial, and motor processing.

Adult↗

PubMed2004

Mood disorders and serotonin transporter density in ecstasy users--the influence of long-term abstention, dose, and gender.

RATIONALE: Neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") on the serotonin (5-HT) system have been described in animals and humans, but little is known about long-term effects of ecstasy use on mood. OBJECTIVES: To investigate short-term and long-term effects of ecstasy use on mood and its association with 5-HT neurotoxicity, dose, and gender in humans. METHODS: Fifteen moderate ecstasy users, 23 heavy ecstasy users, 16 former heavy ecstasy users and 15 drug-using, but ecstasy-naive controls were included. Mood was assessed using the Composite International Diagnostic Interview (CIDI) and the Beck Depression Inventory (BDI). Outcomes were correlated with 5-HT transporter (SERT) density, assessed with [123I]beta-CIT single photon emission computed tomography (SPECT). RESULTS: The prevalence of mood disorders assessed by CIDI did not differ between all groups. The overall test for differences in BDI scores between groups was near significance (P=0.056), with BDI scores higher in former heavy ecstasy users than in ecstasy-naive controls (P=0.045). BDI scores were correlated with the total number of ecstasy tablets used (r=0.310; P=0.021). No associations between CIDI or BDI outcomes and SERT density or gender were observed. CONCLUSIONS: These results suggest that ecstasy use is not associated with clinical depression (CIDI). However, the number of ecstasy tablets taken lifetime was associated with higher BDI scores for depressive mood, and this relationship seemed to persist after ecstasy use had stopped. We did not find that depressed mood in ecstasy users was associated with decrease in SERT density. Prospective studies are needed to establish the causal relationship between ecstasy use and depressed mood.

Adolescent↗

PubMed2004

Idiopathic hyposmia as a preclinical sign of Parkinson's disease.

Olfactory dysfunction is an early and common symptom in Parkinson's disease (PD). In an effort to determine whether otherwise unexplained (idiopathic) olfactory dysfunction is associated with an increased risk of developing PD, we designed a prospective study in a cohort of 361 asymptomatic relatives (parents, siblings, or children) of PD patients. A combination of olfactory detection, identification, and discrimination tasks was used to select groups of hyposmic (n = 40) and normosmic (n = 38) individuals for a 2-year clinical follow-up evaluation and sequential single-photon emission computed tomography (SPECT), using [123I]beta-CIT as a dopamine transporter ligand, to assess nigrostriatal dopaminergic function at baseline and 2 years from baseline. A validated questionnaire, sensitive to the presence of parkinsonism, was used in the follow-up of the remaining 283 relatives. Two years from baseline, 10% of the individuals with idiopathic hyposmia, who also had strongly reduced [123I]beta-CIT binding at baseline, had developed clinical PD as opposed to none of the other relatives in the cohort. In the remaining nonparkinsonian hyposmic relatives, the average rate of decline in dopamine transporter binding was significantly higher than in the normosmic relatives. These results indicate that idiopathic olfactory dysfunction is associated with an increased risk of developing PD of at least 10%.

Aged↗

PubMed2004

Validity of in vivo [123I]beta-CIT SPECT in detecting MDMA-induced neurotoxicity in rats.

This study investigated the ability of a high-resolution pinhole single-photon emission computed tomography (SPECT) system, with [(123)I]beta-CIT as a radiotracer, to detect 3,4-methelenedioxymethamphetamine (MDMA, 'Ecstasy')-induced loss of serotonin transporters (SERTs) in the living rat brain. In vivo striatal and thalamic [(123)I]beta-CIT binding ratios, representing specific binding to dopamine and serotonin transporters, respectively, were determined 7 days before as well as 10 days after treatment of rats with neurotoxic doses of MDMA using SPECT. At the end of the experiment, radioactivity ratios were also determined ex vivo, and compared to control data. Both in vivo and ex vivo, thalamic, but not striatal, uptake ratios were statistical significantly reduced after MDMA treatment. These data show that [(123)I]beta-CIT SPECT may be able to detect MDMA-induced loss of SERTs. Therefore, this may be a promising technique to perform serial studies on MDMA-induced serotonergic neurotoxicity in living small animals.

Animals↗

PubMed2004

Synthesis and evaluation of iodinated TZTP-derivatives as potential radioligands for imaging of muscarinic M2 receptors with SPET.

A series of iodinated thiadiazolyltetrahydro-1-methyl-pyridine (TZTP) compounds was synthesized and evaluated in vitro and in vivo as potential radioligands for imaging of the muscarinic M2 receptor subtype with SPET. One of these compounds, 5-(E)-iodopentenylthio-TZTP, has high in vitro affinity (Ki = 4.9 nM) and moderate selectivity for the muscarinic M2 receptor subtype. Although the uptake pattern in the biodistribution studies in rats is consistent with muscarinic M2 receptor disribution, specific in vivo binding to these receptors could not be demonstrated. The usefulness of this tracer in human SPET imaging may therefore be limited.

Animals↗

PubMed2004

Subjective experience and dopamine D2 receptor occupancy in patients treated with antipsychotics: clinical implications.

OBJECTIVES: This paper gives an overview of studies on the association between dopaminergic neurotransmission and the subjective experience of patients with schizophrenia. METHODS: We undertook a review of the literature. RESULTS: Dopaminergic neurotransmission may be relevant for subjective experience. Higher striatal D2 receptor occupancy by typical and atypical antipsychotics is related to worse subjective experience, more severe negative symptoms, and depression. Individuals with lower baseline dopamine function are at an increased risk for dysphoric responses during antipsychotic therapy with dopaminergic-blocking drugs. There is preliminary evidence that a window of striatal D2 receptor occupancy between 60% and 70% is optimal for the subjective experience of patients. These occupancies are often reached even with low dosages of antipsychotic drugs. CONCLUSIONS: Reaching an optimal dopamine D2 receptor occupancy is clinically relevant, since subjective experience associated with antipsychotic medication is related to medication compliance. Antipsychotic drug dosages often need to be lower than levels in common use.

Antipsychotic Agents↗

PubMed2003

Imaging of striatal dopamine transporters in rat brain with single pinhole SPECT and co-aligned MRI is highly reproducible.

A recently developed pinhole high-resolution SPECT system was used to measure striatal to non-specific binding ratios in rats (n = 9), after injection of the dopamine transporter ligand (123)I-FP-CIT, and to assess its test/retest reproducibility. For co-alignment purposes, the rat brain was imaged on a 1.5 Tesla clinical MRI scanner using a specially developed surface coil. The SPECT images showed clear striatal uptake. On the MR images, cerebral and extra-cerebral structures could be easily delineated. The mean striatal to non-specific [(123)I]FP-CIT binding ratios of the test/retest studies were 1.7 +/- 0.2 and 1.6 +/- 0.2, respectively. The test/retest variability was approximately 9%. We conclude that the assessment of striatal [(123)I]FP-CIT binding ratios in rats is highly reproducible.

Animals↗

PubMed2003

Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study.

OBJECTIVE: The authors tested the hypothesis that a dopamine D(2) receptor occupancy level between 60% and 70% in patients with recent-onset schizophrenia would result in optimal subjective experience. In addition, they sought preliminary evidence on whether subjective experience is better with low-dose olanzapine than with low-dose haloperidol. METHOD: Subjects (N=24) who met DSM-IV criteria for schizophrenia were randomly assigned to 6 weeks of double-blind treatment with either olanzapine, 7.5 mg/day, or haloperidol, 2.5 mg/day. Subjective experience, psychopathology, and extrapyramidal symptoms were assessed at baseline and at endpoint. After 6 weeks, D(2) receptor occupancy was assessed with [(123)I]iodobenzamide single photon emission computed tomography. RESULTS: The two study groups were similar at baseline. After 6 weeks, patients receiving olanzapine had a significantly lower mean dopamine D(2) receptor occupancy (51.0%, range=36%-67%) than those given haloperidol (65.5%, range=45%-75%). Receptor occupancy between 60% and 70% was associated with optimal subjective experience, and subjective experience improved significantly in the haloperidol group. CONCLUSIONS: A level of D(2) receptor occupancy between 60% and 70% is optimal for subjective experience of patients with recent-onset schizophrenia. Substantial interindividual variation in D(2) receptor occupancy was seen at fixed low-dose levels of olanzapine and haloperidol. Olanzapine, 7.5 mg/day, showed no superior subjective response over haloperidol, 2.5 mg/day. Olanzapine may need to be dosed higher than 7.5 mg/day for most patients with recent-onset schizophrenia, and haloperidol needs to be individually titrated in the very low dose range to reach optimal occupancy.

Adolescent↗

PubMed2002

Validity of [123I]beta-CIT SPECT in detecting MDMA-induced serotonergic neurotoxicity.

Recent [123I]beta-CIT single-photon emission computed tomography (SPECT) studies revealed decreased serotonin transporters (SERT) density in the brain of humans with a history of MDMA ("Ecstasy") use. However, [123I]beta-CIT SPECT has until now not been validated as a method for detecting such serotonergic lesions. Therefore, the present study was undertaken. Following baseline [123I]beta-CIT SPECT scans, a rhesus monkey was treated with MDMA (5 mg/kg, s.c. twice daily for 4 consecutive days). SPECT studies 4, 10, and 31 days after MDMA treatment revealed decreases in [123I]beta-CIT binding ratios in the SERT-rich brain region studied (hypothalamic/midbrain region), with SERT density reduced by 39% in this brain region 31 days after treatment. Data obtained with SPECT studies correlated well with SERT density determined with autoradiography after sacrifice of the animal (-34%). In addition, ex vivo [123I]beta-CIT binding studies in rats 1 week after treatment with neurotoxic doses of MDMA (20 mg/kg s.c. twice daily for 4 consecutive days) revealed significant reductions in [123I]beta-CIT binding in SERT-rich regions (including the hypothalamus) when compared to saline-treated rats. The combined results of these studies indicate that SPECT imaging of SERT with [123I]beta-CIT can detect changes in SERT density secondary to MDMA-induced neurotoxicity in the hypothalamic/midbrain region, and possibly other brain regions.

Animals↗

PubMed2002

Posttraumatic tremor without parkinsonism in a patient with complete contralateral loss of the nigrostriatal pathway.

We present a patient with posttraumatic tremor who did not show any [(123)I]FP-CIT uptake in the contralateral putamen and caudate. The absence of hypokinesia and rigidity is surprising in the presence of a striatal dopaminergic denervation that is even more severe than in Parkinson's disease. An explanation, therefore, could be that the lesion in the subthalamic nucleus in our patient prevented the onset of a Parkinson syndrome.

Adult↗

PubMed2002

Imaging of dopamine transporters in rats using high-resolution pinhole single-photon emission tomography.

To date, the vast majority of investigations on the dopaminergic system in small animals have been in vitro studies. In comparison with in vitro studies, single-photon emission tomography (SPET) or positron emission tomography (PET) imaging of the dopaminergic system in small animals has the advantage of permitting repeated studies within the same group of animals. Dopamine transporter imaging is a valuable non-invasive tool with which to investigate the integrity of dopaminergic neurons. The purpose of this study was to investigate the feasibility of assessing dopamine transporter density semi-quantitatively in rats using a recently developed high-resolution pinhole SPET system. This system was built exclusively for imaging of small animals. In this unique single-pinhole system, the animal rotates instead of the collimated detector. The system has proven to have a high spatial resolution. We performed SPET imaging with [(123)I]FP-CIT to quantify striatal dopamine transporters in rat brain. In all seven studied control rats, symmetrical striatal binding to dopamine transporters was seen 2 h after injection of the radiotracer, with striatal-to-cerebellar binding ratios of approximately 3.5. In addition, test/retest variability of the striatal-to-cerebellar binding ratios was studied and found to be 14.5%. Finally, in unilaterally 6-hydroxydopamine-lesioned rats, striatal binding was only visible on the non-lesioned side. Quantitative analysis revealed that striatal-to-cerebellar SPET ratios were significantly lower on the lesioned (mean binding ratio 2.2 +/- 0.2) than on the non-lesioned (mean ratio 3.1 +/- 0.4) side. The preliminary results of this study indicate that semi-quantitative assessment of striatal dopamine transporter density using our recently developed high-resolution single-pinhole SPET system is feasible in living rat brain.

Animals↗

PubMed2002

The acute and chronic effects of MDMA ("ecstasy") on cortical 5-HT2A receptors in rat and human brain.

While the pre-synaptic effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin (5-HT) neurons have been studied extensively, little is known about its effects on post-synaptic 5-HT(2) receptors. Therefore, cortical 5-HT(2A) receptor densities and 5-HT concentration were studied in MDMA treated rats (10 mg/kg s.c.). Furthermore, 5-HT(2A) post-synaptic receptor densities in the cerebral cortex of recent as well as ex-MDMA users were studied using [123I]R91150 SPECT. In rats we observed a decrease followed by a time-dependent recovery of cortical 5-HT(2A) receptor densities, which was strongly and positively associated with the degree of 5-HT depletion. In recent MDMA users, post-synaptic 5-HT(2A) receptor densities were significantly lower in all cortical areas studied, while 5-HT(2A) receptor densities were significantly higher in the occipital cortex of ex-MDMA users. The combined results of this study suggest a compensatory upregulation of post-synaptic 5-HT(2A) receptors in the occipital cortex of ex-MDMA users due to low synaptic 5-HT levels.

Adolescent↗

PubMed2001

Use of amphetamine by recreational users of ecstasy (MDMA) is associated with reduced striatal dopamine transporter densities: a [123I]beta-CIT SPECT study--preliminary report.

RATIONALE: Tablets sold as ecstasy often contain not only 3,4-methylenedioxymethamphetamine (MDMA) but other compounds well known to cause dopaminergic neurotoxicity, such as (meth)amphetamine. Furthermore, the use of ecstasy in the Netherlands is often combined with the use of amphetamine. However, little is known about the effects of ecstasy use or the combination of ecstasy and amphetamine use on dopamine (DA) neurones in the human brain. OBJECTIVES: This study was designed to investigate the effects of ecstasy as well as the combined use of ecstasy and amphetamine on the density of nigrostriatal DA neurones. METHODS: [123I]beta-CIT SPECT was used to quantify striatal DA transporters. Striatal [123I]beta-CIT binding ratios of control subjects ( n=15) were compared with binding ratios of ecstasy users ( n=29) and individuals with a history of combined ecstasy and amphetamine use ( n=9) after adjustment for age. RESULTS: Striatal [123I]beta-CIT binding ratios were significantly lower in combined ecstasy and amphetamine users compared to sole ecstasy users (6.75 versus 8.46, respectively: -20.2%, P=0.007). Binding ratios were significantly higher in ecstasy users when compared to controls (8.46 versus 7.47, respectively: +13.2%, P=0.045). CONCLUSIONS: These initial observations suggest that the sole use of ecstasy is not related to dopaminergic neurotoxicity in humans. In contrast, the reported use of amphetamine by regular users of ecstasy seems to be associated with a reduction in nigrostriatal DA neurones.

Adolescent↗

PubMed2001

Investigating the potential neurotoxicity of Ecstasy (MDMA): an imaging approach.

Human users of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') users may be at risk of developing MDMA-induced neuronal injury. Previously, no methods were available for directly evaluating the neurotoxic effects of MDMA in the living human brain. However, development of in vivo neuroimaging tools has begun to provide insights into the effects of MDMA in the human brain. In this review, contributions of brain imaging studies on the potential neurotoxic effects of MDMA and functional consequences are highlighted. An overview is given of PET, SPECT and MR spectroscopy studies, most of which show evidence of neuronal injury in MDMA users. Different neuroimaging tools are discussed that have investigated potential functional consequences of MDMA-induced 5-HT neurotoxic lesions. Finally, the contribution of brain imaging in future studies is discussed, emphasising the crucial role it will play in our understanding of MDMA's short- and long-term effects in the human brain. Copyright 2001 John Wiley & Sons, Ltd.

Journal Article↗