beta-CIT Binding Research Articles

Venlafaxine alters microvascular perfusion, [123I]-beta-CIT binding and BDI scores in flushing postmenopausal women

BackgroundAlthough 70% of postmenopausal women suffer from hot flashes the pathophysiology is poorly understood. The serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine provides relief of flushing although the mechanism is unknown and could involve a central effect and/or a peripheral effect. Using single photon emission computed tomography (SPECT) we studied the central serotonin transporter (SERT) in vivo using [123I]-beta-carbomethoxy-3-β-(4-iodophenyl)tropane (beta-CIT) and, as previous studies have shown that reactivity of the skin blood vessels is enhanced in those who flush, we examined cutaneous microvascular perfusion. MethodsCutaneous microvascular perfusion was assessed in 31 postmenopausal women, with flushing, using laser Doppler imaging with iontophoresis (LDI+ION), before and after 8 weeks of treatment with venlafaxine. A sub-group of 14 of these women also had SPECT imaging at both time points to evaluate the availability of SERT in the brain. Flush frequency and score was recorded, and Beck Depression Inventory (BDI) II scores were assessed before and after treatment. ResultsFollowing treatment with venlafaxine, there was a significant reduction in the [123I]-beta-CIT binding ratio, BDI scores, flushing and endothelial dependent perfusion response. [123I]-Beta-CIT reduction was associated with BDI reduction (r2=0.54; F=8.8; p=0.004), but not flushing reduction or perfusion reduction. ConclusionsVenlafaxine resulted in a decrease in BDI II scores with an associated reduction in [123I]-beta-CIT binding in a group of non-depressed women. It also improved flush frequency and severity which may be as a result of decreases seen in enhanced cutaneous microvascular perfusion.

High resolution micro‐SPECT scanning in rats using 125I β‐CIT: Effects of chronic treatment with carbamazepine

Carbamazepine (CBZ) is a first-line antiepileptic agent with mood-stabilizing effects in bipolar disorder. It has been reported to influence extracellular concentrations of serotonin and dopamine, suggesting an interaction with monoamine transporters. We have investigated this effect using in vivo single photon emission computed tomography (SPECT) in rats. Adult male rats received 3 mg/kg/h CBZ via mini-osmotic pump. After 14 days continuous treatment, animals underwent two consecutive SPECT scans, using 125I beta-CIT as a radiotracer to label serotonin transporter (SERT) and dopamine transporter (DAT) sites in the brain. Pharmacologic distinction was enabled by 125I beta-CIT SPECT imaging in rats acutely exposed to the serotonin and dopamine transporter inhibitors, fluoxetine and GBR12909. The interaction between CBZ and 125I beta-CIT binding to SERT and DAT was investigated using in vitro autoradiography. Carbamazepine (10 microm) did not affect binding of 125I beta-CIT to isolated rat brain slices, thereby excluding a direct effect on ligand binding to SERT and DAT. SPECT studies with fluoxetine and GBR12909 highlighted SERT binding in thalamus, hippocampus, centromedial nuclei, and occipital cortex, and DAT binding in the caudate. Prolonged treatment with CBZ failed to influence 125I beta-CIT binding to either SERT or DAT in any of the brain regions examined. This study employed the novel technique of small animal SPECT imaging to investigate the effects of CBZ on monoamine transporters in rat brain. Following prolonged treatment, the drug was without effect on SERT or DAT availability. The mechanism by which CBZ exerts its mood stabilizing effects remains elusive.

Loss of thalamic serotonin transporters in early drug-naïve Parkinson’s disease patients is associated with tremor: an [123I]β-CIT SPECT study

In vitro studies revealed serotonin transporter (5-HTT) decline in Parkinson’s disease (PD). Yet, few studies investigated thalamic 5-HTT in vivo and its effect on PD heterogeneity. We analyzed thalamic [123I]β-CIT binding (mainly reflecting 5-HTT binding) in 32 drug-naïve PD patients and 13 controls with SPECT. Twenty-six patients were examined twice (17 months apart). Based on UPDRS scores, we identified subgroups of patients with moderate/severe tremor (PDT) and without tremor (PDWT) at the time of clinical diagnosis. Additionally, depressive symptoms were evaluated using the Beck Depression Inventory (BDI) at baseline. Mean thalamic specific to non-specific [123I]β-CIT binding ratio was lower in patients when compared to controls, and further decreased during follow-up. At baseline, average thalamic ratio was significantly lower in the PDT than in the PDWT subgroup. No correlation was found between BDI scores and thalamic binding ratios. Our findings show decline of [123I]β-CIT binding to thalamic 5-HTT in PD and its possible contribution to tremor onset.

Validation of [123I]β-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.

Serotonin and dopamine transporter availabilities correlate with the loudness dependence of auditory evoked potentials in patients with obsessive-compulsive disorder.

Brain monoaminergic function is involved in the pathophysiology of psychiatric disorders. The loudness dependence (LD) of the N1/P2 component of auditory evoked potentials has been proposed as a noninvasive indicator of central serotonergic function, whereas single photon emission computed tomography (SPECT) and [123I]beta-CIT can be used to visualize both serotonin (SERT) and dopamine transporters (DAT). The aim of the study was to correlate LD and SPECT measures in patients with obsessive-compulsive disorder, a condition with evidence for a serotonergic dysfunction. A total of 10 subjects received both neurophysiological and imaging investigations. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities. The LD of the relevant subcomponents (tangential dipoles) was investigated using dipole source analysis. SPECT was performed 20-24 h after injection of a mean 140 MBq [123I]beta-CIT. As a measure of brain SERT and DAT availabilities, a ratio of specific to nonspecific [123I]beta-CIT binding for the midbrain . pons region (SERT) and the striatum (DAT) was used. The LD of the right tangential dipole correlated significantly with both SERT and DAT availabilities (Pearson's correlations: rho = 0.69, p < 0.05, and rho = 0.80, p < 0.01, respectively). The correlations remained significant after controlling for the effects of age, gender, and severity of clinical symptoms. Associations between LD and both SERT and DAT availabilities further validate the use of neurophysiological approaches as noninvasive indirect measures of neurochemical brain function and point at a hypothesized interconnection of central monoaminergic systems.

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%.

Abnormalities of dopaminergic neurotransmission in SCA2: a combined 123I-betaCIT and 123I-IBZM SPECT study.

Extrapyramidal features may occur in spinocerebellar ataxias consistent with neuropathological evidence of nigrostriatal involvement. Recently, striatal dopaminergic neurotransmission was found to be abnormal in the uncommon parkinsonian presentation of spinocerebellar ataxia type 2 (SCA2). We have investigated, therefore, striatal dopamine transporter and D2 receptor function in a series of 9 patients with the more common ataxic presentation of SCA2 using single photon emission computed tomography and beta-CIT as well as IBZM. Age-matched healthy subjects and patients with Parkinson's disease (PD) served as controls. All except 1 SCA2 patient exhibited slowness of limb movements without rigidity or rest tremor. In addition, cervical dystonia was present in 5 and dystonic head tremor in 2 SCA2 patients. Striatocerebellar (S/C) ratios of beta-CIT binding were significantly reduced in SCA2 patients compared to control subjects, and they were within the range of PD patients. S/C ratios of IBZM binding were significantly reduced in SCA2 patients compared to control subjects. We conclude that dopaminergic neurotransmission is impaired in the ataxic presentation of SCA2, with a prominent loss of striatal dopamine transporter function. Both slowness of limb movements as well as dystonia in the ataxic SCA2 phenotype may reflect dysfunction not only at cerebellar but also at basal ganglia level.

Depletion and restoration of endogenous monoamines affects beta-CIT binding to serotonin but not dopamine transporters in non-human primates.

The radioligand [123I]beta-CIT binds to dopamine transporters in striatum and to serotonin transporters in brainstem. Endogenous dopamine or serotonin may compete with radioligand binding at monoamine transporters. We used alpha-methyl-p-tyrosine (AMPT) to block dopamine production and measured [123I]beta-CIT binding before and after endogenous dopamine was restored by IV administration of the dopamine precursor L-dihydroxyphenylalanine (L-DOPA) in rhesus monkeys. P-chlorophenylalanine (pCPA) was used to inhibit serotonin production, and [123I]beta-CIT binding was assessed before and after IV administration of the serotonin precursor 5-hydroxy-L-tryptophan (L-5-HTP) restored endogenous serotonin. Pretreatment with benserazide blocked peripheral decarboxylization in both paradigms. Serotonin restoration measurably displaced [123I]beta-CIT binding to brainstem serotonin transporters but not to striatal dopamine transporters. Restoration of dopamine apparently did not affect [123I] beta-CIT binding to striatal dopamine transporters. However, dopamine restoration reduced radioligand binding to brainstem serotonin transporters, most likely due to dopamine release from serotonin neurons following L-DOPA administration. The higher striatal density of dopamine transporters relative to dopamine concentrations may explain why [123I] beta-CIT displacement by endogenous dopamine was not observed. This study indicates that [123I]beta-CIT binding in brainstem (raphe area) is affected by endogenous serotonin release in vivo and that L-DOPA treatment may cause serotonin neurons in the brainstem to corelease dopamine.

Measuring the rate of progression of Parkinson's disease over a 5-year period with beta-CIT SPECT.

Recent imaging studies suggest a rapid degeneration of the dopaminergic system in early Parkinson's disease (PD), followed by a slowing of the degenerative process in advanced disease. In the present study, a group of early-stage PD patients underwent three sequential [123I]beta-CIT SPECT studies to assess the decline of striatal dopamine transporter binding over a 5-year period. Twenty-one of a cohort of 24 early PD patients who participated in an earlier longitudinal beta-CIT SPECT imaging study [Mov Disord 2002;17:45-53] were included. Scan intervals were 26 +/- 11 months (scan 1-2) and 38 +/- 15 months (scan 2-3), respectively. The relative annual rate of decline of striatal beta-CIT binding from age-expected normal values at the time of Scan 1 was used as primary outcome variable. The relative annual decline of striatal binding from Scan 1 to Scan 2 (4.5 +/- 4.6%) and from Scan 2 to Scan 3 (3.0 +/- 3.0%) was not significantly different. The non-significant difference in progression rate was due mainly to the rapid early decline of striatal binding in 1 patient who subsequently developed a severe dysexecutive dementia syndrome. These data are not suggestive of substantial change in the course of dopaminergic degeneration in PD within the first 5 to 7 years after symptom onset.

Periodic leg movements in patients with Parkinson's disease are associated with reduced striatal dopamine transporter binding.

We used single photon emission computed tomography (SPECT) to study striatal [(123)I]beta-CIT binding and polysomnography to study periodic leg movements during sleep (PLMS) in eleven patients with idiopathic Parkinson's disease (PD). The reduced striatal [(123)I]beta-CIT binding was significantly correlated with the number of PLMS. We propose that striatal dopaminergic nerve cell loss is involved in the increased number of PLMS in PD patients.

Effect of glutamatergic systems on in vivo binding of [(125)I]beta-CIT in the brain of a rat model of Parkinson's disease.

The effect of MK-801, a noncompetitive NMDA receptor antagonist, on both in vivo and in vitro binding of [(125)I]beta-CIT (RTI-55) was investigated in a rat model of Parkinson's disease. The binding experiments were performed 2 weeks after unilateral intranigral microinjection of 6-hydroxydopamine (6-OHDA). In the in vitro binding study, no alterations in [(125)I]beta-CIT binding in rat brain sections were observed after addition of MK-801, 0.03 microM or 3 microM, to the incubation medium. However, in vivo [(125)I]beta-CIT binding to the dopamine transporter in both nonlesioned and 6-OHDA-lesioned striatum was significantly increased by pretreatment with MK-801. In vivo [(125)I]beta-CIT binding to the serotonin (5HT) transporter in nonlesioned cerebral cortex, hypothalamus, and thalamus was also significantly increased by MK-801. However, the degree of change in the specific binding of [(125)I]beta-CIT induced by MK-801 was smaller in the lesioned cerebral cortex. Kinetic analysis, by a simplified three-compartment model with the cerebellum as the reference region, revealed that these alterations in the in vivo [(125)I]beta-CIT binding induced by MK-801 were mainly due to changes in the rate constants of in vivo binding, the input rate constant, k(3), and the output rate constant, k(4). These results indicate that the glutamatergic system significantly affects the function of dopamine transporters in the degenerated dopaminergic neurons in Parkinson's disease.

Unaltered Dopamine Transporter Availability in Adult Attention Deficit Hyperactivity Disorder

The authors examined whether patients with attention deficit hyperactivity disorder (ADHD) have altered striatal dopamine transporter levels, which may explain psychostimulant effects in this disorder. Single photon emission computed tomography and [(123)I]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT) were used to assess dopamine transporter availability in nine adult patients with ADHD (eight of whom were stimulant naive) and nine age- and gender-matched healthy comparison subjects. Striatal [(123)I]beta-CIT binding did not differ significantly between the ADHD and comparison subjects. The findings suggest that a hypothesized dysregulation of dopamine function in ADHD does not entail altered dopamine transporter levels.

SPECT imaging of striatal pre- and postsynaptic dopaminergic status in restless legs syndrome with periodic leg movements in sleep.

Restless legs syndrome (RLS) is a common sleep-related disorder principally characterised by leg paresthesia associated with an irresistible urge to move. A majority of RLS patients experience periodic leg movements during sleep (PLMS) and wakefulness. Pharmacological evidence suggests that RLS-PLMS may be caused by a central nervous system dopaminergic (DA) dysfunction. The aim of the present study was to evaluate the striatal pre- and postsynaptic DA status in patients suffering from both RLS and PLMS, by means of [123I] beta-CIT and [123I]IBZM SPECT respectively. Ten drug-naïve patients and ten age-matched controls participated in this study. All participants were recorded for at least one night of polysomnography before the SPECT studies. No difference was seen in DA transporter ([123I] beta-CIT) binding between RLS-PLMS patients (MD=4.89) and controls (MD=4.81; p=0.81). The study of the striatal D2-receptor binding ([123I]IBZM) revealed a significantly lower binding in patients (MD= 1.72) compared with controls (MD=1.85; p=0.006). These results support the hypothesis that a central DA dysfunction is involved in the physiopathology of RLS-PLMS. Several mechanisms may be responsible for the decrease of the D2-receptor binding. However, since [123I] beta-CIT binding is normal, a decreased number of D2-receptors or a decreased affinity of D2-receptors for [123I]IBZM is more likely than an increased level of synaptic DA with attendant downregulation of D2-receptors.

Progression of dopaminergic degeneration in Parkinson's disease and atypical parkinsonism: a longitudinal beta-CIT SPECT study.

Atypical parkinsonian syndromes (APS) such as multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration are characterized by poor response to antiparkinsonian medication and rapid clinical deterioration. We used SPECT and [123I]beta-CIT as a label of dopamine transporters to study the progression of presynaptic dopaminergic degeneration in Parkinson's disease (PD) and APS. Twenty-four PD patients with short disease duration (2.4 +/- 1.5 years), 12 PD patients with long disease duration (9.2 +/- 2.6 years), 10 patients with APS (disease duration 2.1 +/- 1.5 years), and nine patients with essential tremor (ET) underwent sequential [123I]beta-CIT SPECT imaging with an interval of 25.5 +/- 10.3 (13-63) months. The age-related decline of striatal beta-CIT binding was studied cross-sectionally in 30 healthy subjects. The ratio of striatum/cerebellum -1 at 20 hours after tracer injection, reflecting specific-to-nondisplaceable binding, was used as the primary SPECT outcome measure. At scan 1, striatal beta-CIT binding was reduced in PD patients with short disease duration (-42% compared with age-corrected normal values) and long disease duration (-51%), and APS (-36%), but normal in ET. During the observation period striatal beta-CIT binding significantly declined in patients with APS (14.9% per year) and short duration PD (7.1% per year), whereas PD patients with long disease duration and patients with ET showed no significant change of striatal beta-CIT binding between scans 1 and 2. The relative annual reduction from age-corrected normal values at the time of scan 1 was significantly higher in patients with APS than in PD patients with short disease duration (9.6 vs. 4.3%, P = 0.004). These results demonstrate a rapid decline of striatal beta-CIT binding in patients with atypical parkinsonian syndromes, exceeding the reduction in PD. The dopaminergic degeneration in PD appears to slow down during the course of the disease. SPECT with [123I]beta-CIT is a sensitive marker of disease progression in parkinsonian disorders.

Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons

3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational drug that has been shown to damage brain serotonin neurons in high doses. However, effects of moderate MDMA use on serotonin neurons have not been studied, and sex differences and the long-term effects of MDMA use on serotonin neurons have not been identified. We investigated the effects of moderate and heavy MDMA use, sex differences, and long-term effects of MDMA use on serotonin neurons in different brain regions. By means of flyers posted in "rave" venues in Amsterdam, the Netherlands, we recruited 15 moderate MDMA users, 23 heavy MDMA users, 16 ex-MDMA users who had stopped using MDMA for more than 1 year, and 15 controls who claimed never to have used MDMA. We studied the effects of MDMA on brain serotonin neurons using 123iodine-2beta-carbomethoxy-3beta-(4-iodophenyl) tropane ([123I]beta-CIT)-a radioligand that binds with high affinity to serotonin transporters. Density of binding (expressed as a ratio of region-of-interest binding over binding in the cerebellum) was calculated by single-photon-emission computed tomography (SPECT). We saw significant effects of group and group by sex (p=0.041 and p=0.022, respectively) on overall [123I]beta-CIT binding ratios. In heavy MDMA users, significant decreases in overall binding ratios were seen in women (p<0.01) but not men (p=0.587). In female ex-MDMA users, overall densities of serotonin transporters were significantly higher than in heavy MDMA users (p=0.004), but not higher than in controls (p=0.524). Our results indicate that heavy use of MDMA is associated with neurotoxic effects on serotonin neurons, that women might be more susceptible than men, and that MDMA-induced neurotoxic changes in several brain regions of female ex-MDMA users are reversible.

Rigidity decreases resting tremor intensity in Parkinson's disease: A [(123)I]beta-CIT SPECT study in early, nonmedicated patients.

Tremor is one of the clinical hallmarks of Parkinson's disease (PD). Although it is accepted that other classic symptoms of PD such as rigidity and bradykinesia result from a degeneration of the nigrostriatal system and subsequent reduction in striatal dopamine, the pathophysiology of resting tremor remains unclear. The majority of recent single photon emission computed tomography (SPECT) and positron emission tomography (PET) studies, using various radioligands, demonstrated significant correlation between striatal radioligand bindings and the degree of parkinsonian symptoms such as rigidity and bradykinesia, but not tremor. We investigate the relationship between the degeneration of the nigrostriatal pathway and the appearance of resting tremor, taking into account the possible interference of rigidity with the resting tremor. Thirty early and drug-naïve PD patients were examined. Tremor and rigidity of the arms were assessed using UPDRS, and the power of tremor was estimated using spectral analysis of tremor peaks. [(123)I]beta-CIT SPECT was used to assess degeneration of the dopaminergic system in PD patients. A comparison between asymmetry indices showed that in terms of both tremor and rigidity, the most affected arm corresponded significantly with the contralateral striatum, having the largest reduction in radioligand binding. Furthermore, tremor power accounted for a significant part of variance in the contralateral striatum, suggesting a relationship between this PD symptom and the degeneration of the dopaminergic system. Further, the degree of tremor was reduced with increasing rigidity. However, correcting for the influence of rigidity, the significant contribution of tremor in the variance in the contralateral striatal [(123)I]beta-CIT binding disappeared. When the confounding influence of rigidity is taken into account, no significant direct relationship between dopaminergic degeneration and the degree of tremor could be found. Other pathophysiological mechanisms should be similarly investigated in order to further our understanding of the origin of resting tremor in PD.

Cortical serotonin transporter density and verbal memory in individuals who stopped using 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"): preliminary findings.

Although the popular drug 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") has been shown to damage brain serotonin (5-HT) neurons in animals, the fate and functional consequences of 5-HT neurons after MDMA injury are not known in humans. We investigated the long-term effects of MDMA use on cortical 5-HT neurons in humans and memory function, because brain 5-HT has been implicated in memory function. Twenty-two recent MDMA users, 16 ex-MDMA users who had stopped using MDMA for more than 1 year, and 13 control subjects. The effects of MDMA use on cortical 5-HT neurons was studied by means of single-photon emission computed tomography with iodine 123-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl) tropane ([(123)I]beta-CIT) by quantification of brain 5-HT transporter densities. Verbal memory performance was assessed with the Rey Auditory Verbal Learning Test. Mean cortical [(123)I]beta-CIT-labeled 5-HT transporter density was significantly lower in recent MDMA users than in controls (1.17 vs. 1.28 [-9%]) but not in ex-MDMA users (1.24 vs. 1.28 [-3%]). Recent and ex-MDMA users recalled significantly fewer words than did controls on the immediate recall (47.0 and 48.0 vs 60.0, respectively; P =.001) as well as the delayed recall (9.8 and 10.1 vs. 13.1, respectively; P =.003). Greater use of MDMA was associated with greater impairment in immediate verbal memory. However, memory performance was not associated with [(123)I]beta-CIT binding to cortical 5-HT transporters or duration of abstinence from MDMA. The present study suggests that, while the neurotoxic effects of MDMA on 5-HT neurons in the human cortex may be reversible, the effects of MDMA on memory function may be long-lasting.

In Vivo Evidence for Differential Association of Striatal Dopamine and Midbrain Serotonin Systems With Neuropsychiatric Symptoms in Parkinson's Disease

Parkinson's disease affects various neurotransmitter systems. Using SPECT, the authors measured [(123)I]beta-CIT binding ratios of the caudate, putamen, medial thalamus, and dorsal midbrain over cerebellum in 16 patients with Parkinson's disease, and examined correlations with clinical ratings. Whereas striatal binding ratios (reflecting regional dopamine transporter densities) were associated with motor symptoms, dorsal midbrain binding ratios (reflecting regional serotonin transporter densities) were significantly correlated with the mentation, behavior, and mood subscale of the Unified Parkinson's Disease Rating Scale. These findings indicate that degeneration of the nigrostriatal dopaminergic neurons and a dysfunctional serotonergic raphe system contribute differentially to motor deficits and neuropsychiatric symptoms in Parkinson's disease.

Multimodal SPECT and MRT imaging data analysis for an improvement in the diagnosis of idiopathic Parkinson's syndrome

Parkinson's disease (PD) is characterized by a degeneration of nigrostriatal dopaminergic neurons, which can be imaged with 123I-labeled 2 beta-carbomethoxy-3 beta-(4-iodophenyl) tropane ([123I]beta-CIT) and single-photon emission computed tomography (SPECT). However, the quality of the region of interest (ROI) technique used for quantitative analysis of SPECT data is compromised by limited anatomical information in the images. We investigated whether the diagnosis of PD can be improved by combining the use of SPECT images with morphological image data from magnetic resonance imaging (MRI)/computed tomography (CT). We examined 27 patients (8 men, 19 women; aged 55 +/- 13 years) with PD (Hoehn and Yahr stage 2.1 +/- 0.8) by high-resolution [123I]beta-CIT SPECT (185-200 MBq, Ceraspect camera). SPECT images were analyzed both by a unimodal technique (ROIs defined directly within the SPECT studies) and a multimodal technique (ROIs defined within individual MRI/CT studies and transferred to the corresponding interactively coregistered SPECT studies). [123I]beta-CIT binding ratios (cerebellum as reference), which were obtained for heads of caudate nuclei (CA), putamina (PU), and global striatal structures were compared with clinical parameters. Differences between contra- and ipsilateral (related to symptom dominance) striatal [123I]beta-CIT binding ratios proved to be larger in the multimodal ROI technique than in the unimodal approach (e.g., for PU: 1.2 vs. 0.7). Binding ratios obtained by the unimodal ROI technique were significantly correlated with those of the multimodal technique (e.g., for CA: y = 0.97x + 2.8; r = 0.70; P < 0.001). Concerning the correlations between SPECT data and clinical parameters, the significance levels in the multimodal ROI technique, for example, for the correlation between CA and the UPDRScom subscore (r = -0.49 vs. -0.32). These results show that the impact of [123I]beta-CIT SPECT for diagnosing PD is affected by the method used to analyze the SPECT images. The described multimodal approach, which is based on coregistration of SPECT and morphological imaging data, leads to improved determination of the degree of this dopaminergic disorder.

SPECT and PET imaging of the dopaminergic system in Parkinson's disease.

This paper gives an overview of the clinical importance of SPECT and PET imaging of the dopaminergic system in the differential diagnosis and for the determination of the progression rate of Parkinson's disease (PD). D2 receptor imaging can help to differentiate multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) from PD. In patients treated with neuroleptics it is possible to determine the rate of striatal D2 receptor blockade using this technique. This occupancy rate parallels the occurrence of parkinsonian side effects. Its measurement helps in the selection of newer atypical neuroleptics, which can be used to treat drug-induced psychosis in PD because they do not aggravate parkinsonian symptoms. Imaging of dopaminergic neurons with [123I]beta-CIT SPECT or [18F]DOPA PET is a way to visualize and quantify the nigrostriatal dopaminergic lesion in PD. Findings correlate with clinical rating scales and demonstrate the feasibility of detecting the preclinical lesion in patients with hemiparkinson or familial PD. [123I]beta-CIT SPECT can easily distinguish patients with essential tremor and patients with "lower body parkinsonism" due to a subcortical vascular encephalopathy. MSA and PSP cannot be separated from PD with this method alone. Longitudinal studies with [123I]beta-CIT SPECT and [18F]DOPA PET can quantify the progression rate in PD. SPECT results from our own group show a low rate of progression in patients with a long duration of disease and a more marked progression rate in patients with shorter disease duration. In the former group regions in the striatum with higher beta-CIT binding at the time of the first SPECT scan decline faster than regions with lower binding. These findings suggest a curvilinear course of progression which starts at different time points in different striatal regions and which levels off after several years of disease duration. These findings are in line with data from PET studies and underline the importance of an early start of neuroprotective strategies. Preliminary data from PET and SPECT studies in early PD suggest that dopamine agonists might have a slight neuroprotective effect and might slow down the rate of progression of the disease.