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Biomedical subjects

Jan Booij

Publications and source records attributed to Jan Booij.

At least 19 recordsLinked to original sources
PubMed2006

Gender differences in Parkinson's disease.

OBJECTIVE: To investigate gender differences in basic disease characteristics, motor deterioration and nigrostriatal degeneration in Parkinson's disease (PD). METHODS: We studied 253 consecutive PD patients who were not receiving levodopa or dopamine agonists (disease duration < or = 10 years). We investigated the influence of gender and oestrogen status on: (1) age at onset, (2) presenting symptom, (3) severity and progression of motor symptoms (Unified Parkinson's Disease Rating Scale III (UPDRS-III) scores) and (4) amount and progression of nigrostriatal degeneration ([123I]FP-CIT single photon emission computed tomography measurements). RESULTS: Age at onset was 2.1 years later in women (53.4 years) than in men (51.3 years). In women, age at onset correlated positively with parity, age at menopause and fertile life span. Women more often presented with tremor (67%) than men (48%). Overall, patients presenting with tremor had a 3.6 year higher age at onset and a 38% slower UPDRS-III deterioration. Mean UPDRS-III scores at disease onset were equal for both genders, as was the rate of deterioration. Women had a 16% higher striatal [123I]FP-CIT binding than men at symptom onset and throughout the course of PD. CONCLUSIONS: Our results suggest that, in women, the development of symptomatic PD may be delayed by higher physiological striatal dopamine levels, possibly due to the activity of oestrogens. This could explain the epidemiological observations of a lower incidence and higher age at onset in women. Women also presented more often with tremor which, in turn, is associated with milder motor deterioration and striatal degeneration. Taken together, these findings suggest a more benign phenotype in women with PD.

Adult↗
PubMed2006

A prospective cohort study on sustained effects of low-dose ecstasy use on the brain in new ecstasy users.

It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use. We prospectively studied sustained effects (>2 weeks abstinence) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR techniques and self-report questionnaires on psychopathology as part of the NeXT (Netherlands XTC Toxicity) study. Outcomes of proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging (DTI), perfusion-weighted imaging (PWI), and questionnaires on depression, impulsivity, and sensation seeking were compared in 30 subjects (12M, 21.8+/-3.1 years) in two sessions before and after first ecstasy use (1.8+/-1.3 tablets). Interval between baseline and follow-up was on average 8.1+/-6.5 months and time between last ecstasy use and follow-up was 7.7+/-4.4 weeks. Using 1H-MRS, no significant changes were observed in metabolite concentrations of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), and creatine (Cr), nor in ratios of NAA, Cho, and mI relative to Cr. However, ecstasy use was followed by a sustained 0.9% increase in fractional anisotropy (FA) in frontoparietal white matter, a 3.4% decrease in apparent diffusion (ADC) in the thalamus and a sustained decrease in relative regional cerebral blood volume (rrCBV) in the thalamus (-6.2%), dorsolateral frontal cortex (-4.0%), and superior parietal cortex (-3.0%) (all significant at p<0.05, paired t-tests). After correction for multiple comparisons, only the rrCBV decrease in the dorsolateral frontal cortex remained significant. We also observed increased impulsivity (+3.7% on the Barratt Impulsiveness Scale) and decreased depression (-28.0% on the Beck Depression Inventory) in novel ecstasy users, although effect sizes were limited and clinical relevance questionable. As no indications were found for structural neuronal damage with the currently used techniques, our data do not support the concern that incidental ecstasy use leads to extensive axonal damage. However, sustained decreases in rrCBV and ADC values may indicate that even low ecstasy doses can induce prolonged vasoconstriction in some brain areas, although it is not known whether this effect is permanent. Additional studies are needed to replicate these findings.

Adolescent↗
PubMed2006

Sepiapterin reductase deficiency an autosomal recessive DOPA-responsive dystonia.

The diagnosis of a 14-year-old girl with a new homoallelic mutation in the sepiapterin reductase (SR) gene is reported. Initially she presented at the age of 2 with hypotonia and mild cognitive developmental delay, and was diagnosed as having mild methylmalonic aciduria, which was recently identified as methylmalonylCoA racemase deficiency, a new defect in valine-isoleucine metabolism. After a 12-year progression of her neurologic condition, which had made her wheelchair-bound at the age of 6, dystonia with diurnal variation had become apparent. At the age of 14 this finding led to rapid diagnosis of SR deficiency. The diagnostic approach with CSF neurotransmitter and pterins analysis and combined phenylalanine/BH(4) loading test, and finally measurement of sepiapterin in CSF is illustrative for the diagnosis of SR deficiency. As in all other patients with this new defect, very low levels of homovanillic acid and 5-hydroxyindoleacetic acid and high levels of biopterin and sepiapterin in the CSF are the diagnostic hallmark. The girl improved dramatically on treatment with L-DOPA and 5-hydroxytryptophan. The initial diagnosis of methylmalonic aciduria may afterwards be considered to have not significantly contributed to her clinical condition and only has led to a long delay of the clinically relevant diagnosis of SR deficiency. Although the clinical condition of this recently recognized autosomal recessive defect in pterin metabolism is complex and many symptoms can occur in variable severity and time of onset, dystonia with diurnal variation is a characteristic finding, as shown in nearly all patients described so far. The rapid and favourable response on treatment with L-DOPA warrants the classification of SR deficiency as another autosomal recessive type of DOPA-responsive dystonia (DRD). This classification is important to improve the awareness of clinicians that more than one metabolic defect can underlie the phenotype of a DOPA-responsive dystonic disorder and that dystonia should always trigger a rapid diagnosis of the underlying neurotransmitter synthesis defect, in view of the excellent treatability of a DRD.

Adolescent↗
PubMed2006

Repeated administration of D-amphetamine induces loss of [123I]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study.

UNLABELLED: In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or methamphetamine (METH) may induce loss of binding to striatal DATs in rats by using an experimental biodistribution study design and a SPECT tracer for the DAT ([123I]FP-CIT). METHODS: Groups of male rats (n = 10 per group) were treated with D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a day for 5 consecutive days. Five days later, [123I]FP-CIT was injected intravenously, and 2 h later, the rats were sacrificed and radioactivity was assayed. RESULTS: In d-AMPH but not METH-treated rats, striatal [123I]FP-CIT uptake was significantly lower (approximately 17%) than in the control group. CONCLUSION: These data show that [123I]FP-CIT can be used to detect AMPH-induced changes in DAT binding and may validate the use of DAT radiotracers to study AMPH-induced changes in striatal DAT binding in vivo.

Amphetamine↗
PubMed2006

No-carrier-added versus carrier-added123I-metaiodobenzylguanidine for the assessment of cardiac sympathetic nerve activity.

PURPOSE: No-carrier-added (nca) MIBG is primarily associated with specific uptake (i.e. uptake-1 mechanism). We evaluated the hypothesis that nca MIBG will be less influenced by changes in extra-neuronal uptake (i.e. uptake-2 mechanism) compared with carrier-added (ca) MIBG. METHODS: No-carrier-added MIBG was compared with ca MIBG of two different manufacturers (ca MIBG-1 and ca MIBG-2, with a specific activity of 200 Mq/mumol and 40 MBq/mumol MIBG respectively) in rats (n=6 per group): controls, blocking uptake-1 (desipramine) and blocking uptake-2 (phenoxybenzamine hydrochloride). Dedicated pinhole SPECT was performed 2 h after injection of the radiotracer. After SPECT, biodistribution was assessed [% injected dose per gram tissue (%ID)]. RESULTS: No-carrier-added MIBG had the highest absolute cardiac uptake. Although a clear trend was observed, nca MIBG was not statistically significantly different from ca MIBG-1 (0.31+/-0.05 %ID vs 0.25+/-0.01 %ID,p=0.05). Blocking uptake-1 resulted in a significant decrease in absolute cardiac uptake only for nca MIBG (0.22+/-0.03 %ID,p=0.004). Blocking uptake-2 resulted in a significant reduction in ca MIBG-1 cardiac uptake (0.14+/-0.02 %ID,p=0.0001), but not in the cardiac uptake of nca MIBG or MIBG-2. SPECT showed the highest relative cardiac uptake for nca MIBG. Poor contrast between myocardium and surrounding tissue hampered assessment of relative cardiac uptake on SPECT of both ca MIBG-1 and ca MIBG-2. CONCLUSION: No-carrier-added MIBG yields a higher myocardial uptake than ca MIBG and is associated with a higher specific as well as a lower non-neuronal uptake. We therefore conclude that for the scintigraphic assessment of the myocardial sympathetic nervous system, nca MIBG is to be preferred over ca MIBG.

3-Iodobenzylguanidine↗
PubMed2006

Brain kinetics of the new selective serotonin transporter tracer [(123)I]ADAM in healthy young adults.

UNLABELLED: Recently, the tracer (123)I-2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine ([(123)I]ADAM) has been developed for selective imaging of serotonin transporters (SERTs) with single photon emission computed tomography (SPECT). The purpose of this study was to develop an [(123)I]ADAM SPECT protocol for clinical studies in young adults. METHODS: We examined the time course of [(123)I]ADAM binding to central SERTs in eight healthy young volunteers up to 6 h postinjection. RESULTS: We found that the time of peak-specific [(123)I]ADAM binding was highly variable among subjects, but specific binding in the SERT-rich (hypo)thalamus peaked within 5 h postinjection in all subjects. Moreover, in this brain area, binding ratios of specific to nonspecific binding did not significantly change between 3 and 6 h postinjection, and peaked 5 h postinjection. CONCLUSIONS: Five hours postinjection may be optimal for single-scan [(123)I]ADAM SPECT studies in humans, but more work is needed to assess the accuracy of the 5-h tissue ratio as a measure of SERT in the brain.

Adult↗
PubMed2006

Neuroimaging findings with MDMA/ecstasy: technical aspects, conceptual issues and future prospects.

Users of ecstasy (3,4-methylenedioxymethamphetamine; MDMA) may be at risk of developing MDMA-induced injury to the serotonin (5-HT) system. Previously, there were no methods available for directly evaluating the neurotoxic effects of MDMA in the living human brain. However, development of in vivoneuroimaging tools have begun to provide insights into the effects of ecstasy on the human brain. Single photon emission computed tomography (SPECT), positron emission computed tomography (PET) and proton magnetic resonance spectroscopy (1H-MRS) studies which have evaluated ecstasy's neurotoxic potential will be reviewed and discussed in terms of technical aspects, conceptual issues and future prospects. Although PET and SPECT may be limited by several factors such as the low cortical uptake and the use of a non-optimal reference region (cerebellum) the few studies conducted so far provide suggestive evidence that people who heavily use ecstasy are at risk of developing subcortical, and probably also cortical reductions in serotonin transporter (SERT) densities, a marker of 5-HT neurotoxicity. There seem to be dose-dependent and transient reductions in SERT for which females may be more vulnerable than males. 1H-MRS appears to be a less sensitive technique for studying ecstasy's neurotoxic potential. Whether individuals with a relatively low ecstasy exposure also demonstrate loss of SERT needs to be determined. Because most studies have had a retrospective design, in which evidence is indirect and differs in the degree to which any causal links can be implied, longitudinal studies in human ecstasy users are needed to draw definite conclusions.

Amphetamine-Related Disorders↗
PubMed2006

Memory function and serotonin transporter promoter gene polymorphism in ecstasy (MDMA) users.

Although 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) has been shown to damage brain serotonin (5-HT) neurons in animals and possibly humans, little is known about the long-term consequences of MDMA-induced 5-HT neurotoxic lesions on functions in which 5-HT is involved, such as cognitive function. Because 5-HT transporters play a key element in the regulation of synaptic 5-HT transmission it may be important to control for the potential covariance effect of a polymorphism in the 5-HT transporter promoter gene region (5-HTTLPR) when studying the effects of MDMA as well as cognitive functioning. The aim of the study was to investigate the effects of moderate and heavy MDMA use on cognitive function, as well as the effects of long-term abstention from MDMA, in subjects genotyped for 5-HTTLPR. A second aim of the study was to determine whether these effects differ for females and males. Fifteen moderate MDMA users (<55 lifetime tablets), 22 heavy MDMA+ users (>55 lifetime tablets), 16 ex-MDMA+ users (last tablet > 1 year ago) and 13 controls were compared on a battery of neuropsychological tests. DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods.A significant group effect was observed only on memory function tasks (p = 0.04) but not on reaction times (p = 0.61) or attention/executive functioning (p = 0.59). Heavy and ex-MDMA+ users performed significantly poorer on memory tasks than controls. In contrast, no evidence of memory impairment was observed in moderate MDMA users. No significant effect of 5-HTTLPR or gender was observed. While the use of MDMA in quantities that may be considered "moderate" is not associated with impaired memory functioning, heavy use of MDMA use may lead to long lasting memory impairments. No effect of 5-HTTLPR or gender on memory function or MDMA use was observed.

Adult↗
PubMed2006

Ecstasy use and self-reported depression, impulsivity, and sensation seeking: a prospective cohort study.

Although there are indications that ecstasy users have higher levels of depression, impulsivity, and sensation seeking, it is unknown whether these are consequences of ecstasy use or predisposing factors for starting ecstasy use. We prospectively assessed the predictive value of depression, impulsivity, and sensation seeking on future first time ecstasy use. We also assessed whether depression, impulsivity, and sensation seeking had changed after first ecstasy use. Depression, impulsivity, and sensation seeking were assessed using self-report questionnaires in 188 ecstasy-naive volunteers with high probability for future ecstasy use. After a mean follow-up of 17 months, measurements were repeated in 59 incident ecstasy users (mean 6.0 tablets) and 61 matched persistent ecstasy-naive volunteers. Only experience seeking (subscale of the sensation seeking scale) predicted future ecstasy use (OR -- 1.05, 95% CI 1.00 to 1.10), but after adjustment for potential confounders this was not significant anymore. At follow-up, significant effects of ecstasy use on the general and the disinhibition subscale of the sensation seeking scale were observed (after adjustment for potential confounders: regression coefficient B 0.51, 95% CI 0.20 to 0.83 and B -- 3.25, 95% CI 1.74 to 4.76, respectively). These data indicate that depression, impulsivity, and sensation seeking do not predict first time ecstasy use in a population of young adults with the intention to start using ecstasy and that low level ecstasy use does not seem to cause depression or impulsivity. However, low level ecstasy use may increase (certain aspects of) sensation seeking.

Adolescent↗
PubMed2005

Occupancy of dopamine D2 receptors by antipsychotic drugs is related to nicotine addiction in young patients with schizophrenia.

RATIONALE: Occupancy of dopamine D2 receptors by antipsychotic drugs depends on the individual availability of D2 receptors and on the dose and type of antipsychotic medication. It has been suggested that a low availability of these receptors may increase the risk for addictive behavior. OBJECTIVE: This study aims to show that patients with relatively high occupancy of D2 receptors by antipsychotic drugs are more prone to nicotine consumption. METHODS: Striatal D2 receptor occupancy by equivalent doses of olanzapine or risperidone was assessed with [123I]iodobenzamide single-photon emission computed tomography (SPECT) in 36 patients with schizophrenia. Smoking status at the time of SPECT imaging was assessed. The number of cigarettes used in the following three consecutive years was estimated with the Life Chart Schedule (LCS). RESULTS: There was a positive and significant relation between D2 receptor occupancy following treatment with olanzapine (n=19) or risperidone (n=12) and the number of cigarettes smoked in three consecutive years (r=0.60, p<0.001) in patients who smoked. There was a significant difference in the percentage of D2 occupancy for smokers (mean 74.3%, SD 12.8, n=31) and nonsmokers (mean 49.8%, SD 9.1, n=5). CONCLUSION: Frequency of cigarette smoking in schizophrenic patients treated with antipsychotic medication is significantly and negatively related to the availability of striatal D2 receptors.

Adult↗
PubMed2005

The role of dopamine in human addiction: from reward to motivated attention.

There is general consensus among preclinical researchers that dopamine plays an important role in the development and persistence of addiction. However, the precise role of dopamine in addictive behaviors is far from clear and only a few clinical studies on the role of dopamine in human addiction have been conducted so far. The present paper reviews studies addressing the role of dopamine in humans. There is substantial and consistent evidence that dopamine is involved in the experience of drug reward in humans. Dopamine may also be involved in motivational processes such as drug craving. However, given the inconsistent findings of studies using dopamine receptor (ant)agonists, the role of dopamine in the experience of craving is far from resolved. Recent theories claiming that dopamine signals salience and makes the brain paying attention to biological relevant stimuli may provide an interesting framework for explaining addictive behaviors. There is accumulating evidence that patients with drug and alcohol addiction have an aberrant focus on drug-related stimuli. Although there is some preliminary support for the role of dopamine in these attention processes, more studies have to be carried out in order to test the validity of these theories in human subjects.

Attention↗
PubMed2005

Pinhole SPECT imaging of dopamine transporters correlates with dopamine transporter immunohistochemical analysis in the MPTP mouse model of Parkinson's disease.

The in vivo analysis of dopaminergic degeneration in animal models of Parkinson's disease (PD), using pinhole single photon emission computed tomography (SPECT), ideally should afford a serial study design, enabling the analysis of the degenerative process as well as the potential neuroprotective and/or restorative properties of drugs over time in living animals. Previously, we demonstrated that striatal dopamine transporter (DAT) levels in rats could be analyzed reproducibly, using pinhole SPECT with the DAT probe [(123)I]N-omega-fluoropropyl-2beta-carbomethoxy-3beta-{4-iodophenyl}nortropane (FP-CIT). However, the capacity of this approach to accurately detect a range of striatal DAT levels in the most widely used animal model of PD, i.e., the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse, remains to be determined. For this purpose, various levels of DAT were induced by treating c57BL/6J mice for 1, 3, or 5 days with MPTP (25 mg/kg ip), respectively. [(123)I]FP-CIT SPECT scans were performed 5 days after the last MPTP injection. Mice were perfused 6 days after the last MPTP injection, and the SPECT data were compared to ex vivo striatal and nigral DAT levels as measured by immunohistochemistry within the same animals. The analysis of striatal DAT levels using SPECT and DAT immunohistochemistry yielded highly comparable results on the percentage of DAT reduction in each MPTP group. The in vivo data showed a decrease of specific striatal to non-specific binding ratios by 59%, 82%, and 76% in mice treated for 1, 3, and 5 days, respectively. Moreover, a strong, positive correlation was observed between the in vivo and ex vivo parameters. The present study provides the first evidence that [(123)I]FP-CIT pinhole SPECT allows the accurate detection of a range of striatal DAT (i.e., losses of approximately 60-80%) levels in mice. Since such large dopaminergic lesions could be detected, this SPECT method may at least be useful for analyzing neuroprotective treatment with a clear-cut positive (i.e., complete protection) or negative (i.e., not any protection) effect. Whether this method is also useful for analyzing more subtle effects of neuroprotective treatment (partial protection) remains to be established, by studying mice with small dopaminergic lesions.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2005

Early-stage [123I]beta-CIT SPECT and long-term clinical follow-up in patients with an initial diagnosis of Parkinson's disease.

PURPOSE: Previous studies using dopamine transporter single-photon emission computed tomography (SPECT) to try and distinguish between patients with idiopathic Parkinson's disease (IPD) and patients with atypical parkinsonian syndromes (APS) have mainly focussed on patients with an already established clinical diagnosis of several years' duration. Differences in the pattern of striatal involvement between IPD and APS have been found in only few studies. We hypothesized that distinguishing SPECT features might be most pronounced at an early disease stage, and the purpose of the present study was to investigate this hypothesis. METHODS: The study included 72 patients with an initial clinical diagnosis of IPD, supported by decreased striatal [(123)I]beta-CIT binding on baseline SPECT. In ten patients, the diagnosis was changed to APS over a mean follow-up period of 62 months. We retrospectively compared the patterns of striatal involvement on the baseline SPECT scans between the group of patients (re)diagnosed with APS and the remaining 62 patients in whom a diagnosis of IPD was maintained. RESULTS: In the group of patients with APS, baseline [(123)I]beta-CIT binding in both caudate nuclei was lower than in the group of patients with IPD. In addition, putamen to caudate binding ratios were higher in the group of APS patients. In spite of these differences, individual binding values showed considerable overlap between the groups. CONCLUSION: [(123)I]beta-CIT SPECT scanning in early-stage, untreated parkinsonian patients revealed a relative sparing of the caudate nucleus in patients with IPD as compared to patients later (re)diagnosed with APS. Nevertheless, the pattern of striatal involvement appears to have little predictive value for a later re-diagnosis of APS in individual cases.

Cocaine↗
PubMed2005

The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance.

This paper describes the objectives and methods of The Netherlands XTC Toxicity (NeXT) study focussing on the causality, course, and clinical relevance of ecstasy neurotoxicity. Previous studies suggest that ecstasy (3,4 methylene-dioxymethamphetamine, MDMA, XTC) is toxic toward brain serotonin axons, but most of these studies have serious methodological limitations. The current study is a combination of different approaches with three substudies: (1) a crosssectional substudy among heavy ecstasy users and controls with variation in drug use, which will provide information about potential neurotoxic consequences of ecstasy in relation to other drugs; (2) a prospective cohort substudy in ecstasy-naive subjects with high risk for future ecstasy use, which will provide information on the causality and short-term course of ecstasy use and potential neurotoxicity, and (3) a retrospective cohort substudy in lifetime ecstasy users and matched controls of an existing epidemiological sample that will provide information on long-term course and outcome of ecstasy use in the general population. Neurotoxicity is studied using (a) different imaging techniques (beta-CIT SPECT, 1H-MR spectroscopy, diffusion tensor imaging, perfusion weighted imaging and functional magnetic resonance imaging), and (b) neuropsychological and psychiatric assessments of memory, depression, and personality. The combined results will lead to conclusions that can be used in prevention messages, clinical decision making, and the development of an (inter)national ecstasy policy.

Adolescent↗
PubMed2005

Rigidity and bradykinesia reduce interlimb coordination in Parkinsonian gait.

OBJECTIVE: To assess the influence of rigidity and bradykinesia and the extent of dopaminergic degeneration on interlimb coordination during walking in early, drug-naive patients with Parkinsons disease (PD). DESIGN: The interlimb coordination was examined during a systematic manipulation of walking speed on a treadmill. The phase relations between arm and leg movements were related to the clinical measures of rigidity and bradykinesia as well as to the extent of dopaminergic degeneration. SETTING: Movement disorders outpatient clinic (including motion analysis laboratory) and a nuclear medicine department of a university hospital. PARTICIPANTS: Twenty-nine early and drug-naive PD patients. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The interlimb coordination during walking was evaluated by studying the (continuous) relative phase relations between movements of arms and legs. The clinical assessment of rigidity and bradykinesia was performed by using the Unified Parkinson Disease Rating Scale. The dopaminergic degeneration was expressed as striatal 2beta-carboxymethoxy-3beta-(4-iodophenyl) tropane (beta-CIT) single-photon emission computed tomography (SPECT) binding. RESULTS: The mean relative phase between arm and leg movements increased significantly with walking speed in all patients. Significant correlations were found between the rigidity and bradykinesia and the coordination measures ( P </=.007), as well as contralateral striatal [ 123 I]beta-CIT SPECT binding and coordination measures ( P <.001), in terms of asymmetry indices. CONCLUSIONS: Early, drug-naive PD patients in this sample were able to adapt their coordination patterns when walking speed was systematically manipulated. However, bradykinesia and rigidity as well as the extent of degeneration of the dopaminergic system were associated with a limited adaptive ability (flexibility) in movement coordination. The combination of a drug treatment that controls bradykinesia and rigidity and a physical therapy exercise programs possibly using external cues mechanisms are required to obtain relevant effects on gait in PD patients.

Adult↗
PubMed2005

Validation of [(123)I]beta-CIT SPECT to assess serotonin transporters in vivo in humans: a double-blind, placebo-controlled, crossover study with the selective serotonin reuptake inhibitor citalopram.

Disturbances in the serotonin (5-HT) system are associated with various neuropsychiatric disorders. The 5-HT system can be studied in vivo by measuring 5-HT transporter (SERT) densities using (123)iodine-labeled 2beta-carbomethoxy-3beta(4-iodophenyl)tropane ([(123)I]beta-CIT) and single photon emission computed tomography (SPECT). Validation of this technique is important because [(123)I]beta-CIT does not bind selectively to SERTs. Some studies have validated this technique in vivo in the human brain in SERT-rich areas, but the technique has not been validated yet in SERT-low cortical areas. The aim of this study was to further validate [(123)I]beta-CIT SPECT in assessing SERTs in vivo in humans in both SERT-rich and SERT-low areas. A double-blind, placebo-controlled, crossover design was used with the selective 5-HT reuptake inhibitor (SSRI) citalopram. Six male subjects underwent two [(123)I]beta-CIT SPECT sessions: one after pretreatment with citalopram and one after placebo. Scans were acquired 4 h and 22-27 h p.i., and both region-of-interest and voxel-by-voxel analyses were performed. Citalopram reduced [(123)I]beta-CIT binding ratios in SERT-rich midbrain and (hypo)thalamus. Binding ratios were also lower after citalopram in SERT-low cortical areas, but statistical significance was only reached in several cortical areas using voxel-by-voxel analysis. In addition, citalopram increased binding ratios in the DAT-rich striatum and increased absolute uptake in the cerebellum. The results show that [(123)I]beta-CIT SPECT is a valid technique to study SERT binding in vivo in human brain in SERT-rich areas. Although we provide some evidence that [(123)I]beta-CIT SPECT may be used to measure SERTs in SERT-low cortical areas, these measurements must be interpreted with caution.

Adolescent↗