Frontal dopamine D(2/3) receptor binding in drug-naive first-episode schizophrenic patients correlates with positive psychotic symptoms and gender.

BACKGROUND: The aim of the study was to examine extrastriatal dopamine D(2/3) receptor binding and psychopathology in schizophrenic patients, and to relate binding potential (BP) values to psychopathology. METHODS: Twenty-five drug-naive schizophrenic patients and 20 healthy controls were examined with single-photon emission computerized tomography (SPECT) using the D(2/3)-receptor ligand [123I]epidepride. RESULTS: In the hitherto largest study on extrastriatal D(2/3) receptors we detected a significant correlation between frontal D(2/3) BP values and positive schizophrenic symptoms in the larger group of male schizophrenic patients, higher frontal BP values in male (n = 17) compared to female (n = 8) patients, and - in accordance with this - significantly fewer positive schizophrenic symptoms in the female patients. No significant differences in BP values were observed between patients and controls; the patients, however, had significantly higher BP in the right compared to the left thalamus, whereas no significant hemispheric imbalances were observed in the healthy subjects. CONCLUSIONS: The present data are the first to confirm a significant correlation between frontal D(2/3) receptor BP values and positive symptoms in male schizophrenic patients. They are in agreement with the hypothesis that frontal D(2/3) receptor activity is significant for positive psychotic symptoms. Additionally, the data support a thalamic hemispheric imbalance in schizophrenia.     

Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia.

BACKGROUND: The clinical efficacy of dopamine D2 receptor antagonism on the psychotic symptoms of schizophrenia has been widely demonstrated. However, most in vivo imaging studies have not been able to detect significant changes in striatal D2 receptors in schizophrenia. On the other hand, a number of studies have reported abnormalities in the cerebral cortex of schizophrenia. The aim of this study was to examine the extrastriatal D2 receptors of patients with schizophrenia. METHODS: Eleven drug-naive male patients with schizophrenia were examined with positron emission tomography using carbon 11-labeled FLB 457. Symptoms were assessed using the Brief Psychiatric Rating Scale. Eighteen healthy controls were used for comparison. Region-of-interest analysis was performed using the reference tissue method, and binding potential (BP) was used for the index of dopamine D2 receptor binding. RESULTS: The BP value was significantly lower, by about 12.5%, in the anterior cingulate cortex in drug-naive patients with schizophrenia than in healthy controls. A significant negative correlation was observed between BP in the anterior cingulate cortex and the positive symptom score on Brief Psychiatric Rating Scale. CONCLUSIONS: The lower BP values indicate fewer D2 receptors in the anterior cingulate cortex in patients with schizophrenia. Alterations in D2 receptor function in the extrastriatal region may underlie the positive symptoms of schizophrenia.     

Lack of sex differences in striatal dopamine D2 receptor binding in drug-naive schizophrenic patients: an IBZM-SPECT study

Differences in antipsychotic treatment response, clinical course and outcome of schizophrenia could be related to gender-related cerebral differences in anatomy and function. The aim of the study was to assess sex differences in the striatal dopamine D2 receptor binding in 15 drug-naive schizophrenic patients (seven males, eight females) using (123)I-IBZM single photon emission computed tomography. Basal ganglia/frontal cortex (BG/FC) uptake ratios were obtained. No significant differences were found in global, left and right BG/FC ratios or laterality indices between males and females. No correlation was found between BG/FC ratios and age, duration of illness or scores on symptom rating scales. Our data indicate a lack of sex differences in striatal D2 receptor binding in drug-naive schizophrenic patients and do not support previous reports of left lateralized striatal asymmetry in male schizophrenic patients.     

The role of extrastriatal dopamine D2 receptors in schizophrenia.

Despite numerous studies on extrastriatal regions involved in schizophrenia, studies on the functional implications of dopamine (DA) D2 receptors in the extrastriatal regions, including the cortex and thalamus, are limited. We review postmortem and in vivo human imaging studies as well as animal studies, focusing on the function of extrastriatal DA D2 receptors and their role in the pathophysiology of schizophrenia. Based on recent findings, cortical DA D2 receptors may interact with the gamma-aminobutyric acid system to modulate DA transmission, and thalamic DA D2 receptors are likely to participate in sensory gating function into the prefrontal cortex. We have found decreased DA D2 receptors in the anterior cingulate cortex and thalamic subregions of patients with schizophrenia. These observations may suggest that alterations of extrastriatal DA D2 receptors are involved in dysregulation of DA transmission and sensory signals from the thalamus to the cortex. Excessive excitatory signals from the thalamus might flow into the cortical neurotransmission system, aggravating dysregulation of DA transmission in both the striatal and extrastriatal regions in schizophrenia. These notions suggest the need for future investigations of extrastriatal DA D2 receptor function to gain important clues regarding the pathogenesis and of possible treatments for schizophrenia.     

Decreased expression of reelin receptor VLDLR in peripheral lymphocytes of drug-naive schizophrenic patients

Reelin, a secretory protease that plays major roles in neurodevelopment and synaptic plasticity, may also play a role in the pathogenesis of schizophrenia. The present study was undertaken to examine whether the expression of two receptors for reelin, very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor type 2 (ApoER2), were abnormal in peripheral blood lymphocytes of schizophrenic patients. In this study, we measured the mRNA levels of VLDLR and ApoER2 in blood lymphocytes from patients with schizophrenia (drug-naive patients (n=20) and medicated patients (n=20)) and age-and gender-matched healthy controls (n=40) using quantitative real-time RT-PCR. Furthermore, we examined the correlation between mRNA levels and clinical variables in patients. Levels of VLDLR mRNA in drug-naive, unmedicated patients with schizophrenia were significantly lower than those of controls. In contrast, levels of ApoER2 mRNA in drug-naive patients did not differ from those of controls, although the levels of ApoER2 mRNA in medicated patients were significantly lower than those of controls. Interestingly, levels of VLDLR mRNA in drug-naive patients showed significant increases with respect to baseline after six months of antipsychotic treatment, whereas levels of ApoER2 mRNA were significantly lower than baseline after six months of treatment. In all patients, there was a negative correlation between VLDLR mRNA levels and the severity of clinical symptoms. Our findings suggest that peripheral VLDLR mRNA levels may serve as a reliable peripheral biological marker of schizophrenia, and that the reelin-VLDLR/ApoER2 signaling pathway plays a role in the pathophysiology of schizophrenia.     

The role of dopamine for the pathophysiology of schizophrenia

Since decades, experimental approaches and clinical experience have suggested a dopaminergic system's dysregulation playing an important role within the pathophysiology of schizophrenia. This paper summarizes the actual standard of knowledge of the physiological fundamentals and hypothesized dysbalances of the dopamine (DA) system with respect to schizophrenia including interaction with other neurotransmitter systems (glutamate, GABA). The assumed functional role of DA with respect to physiological and illness-associated cognitive performance, especially working memory, reward, and motivation, as it was assessed by fMRI studies, is presented. A third focus concentrates on giving a short survey of SPECT and PET studies measuring the amount of the striatal and extrastriatal DA, the striatal and extrastriatal dopamine D2 receptor, and the dopamine transporter (DAT) comparing first-episode, drug-na?ve, treated, and relapsing schizophrenic patients and healthy control persons.     

Electroencephalographic sleep abnormalities in schizophrenia. Relationship to positive/negative symptoms and prior neuroleptic treatment.

Polysomnographic abnormalities in schizophrenia are not well characterized and their associations with schizophrenic symptomatology have not been adequately assessed. To address these issues, we recorded electroencephalographic sleep in 20 drug-naive schizophrenics, 20 drug-free but previously medicated schizophrenics, and 15 normal controls. Drug-naive and previously medicated patients had significantly greater impairment of sleep continuity and shorter rapid eye movement latency when compared with controls. In the previously medicated group, findings were significantly influenced by duration of drug-free status. Rapid eye movement latency was inversely correlated with the severity of negative symptoms (r = -.52) but was unrelated to depressive symptoms. Slow-wave sleep did not differ between schizophrenic patients and normal controls and was unrelated to any clinical parameter. Mechanisms underlying the observed associations between rapid eye movement sleep abnormalities and negative symptoms in the acute phase of schizophrenic illness need to be explored.     

Midbrain dopamine D2/3 receptor binding in schizophrenia

Several studies suggest that dysregulation of dopaminergic transmission in the midbrain and thalamus may contribute to the symptomatology of schizophrenia. The objective of this study was to examine the putative alteration of dopamine D_2/3 receptor densities in the thalamus and midbrain of drug-naïve schizophrenic patients. We used the high-affinity single-photon emission tomography ligand [¹²³I]epidepride for imaging D_2/3 receptor binding sites in six neuroleptic-naïve schizophrenic patients, and seven healthy controls. Schizophrenic symptoms were evaluated by the Positive and Negative Syndrome Scale. Significantly lower D_2/3 values were observed in the midbrain of patients with schizophrenia compared to controls (P = 0.02). No statistically significant difference was observed in the thalamus between two groups. Negative correlations were found between thalamic D_2/3 receptor binding and general psychopathological schizophrenic symptoms (r from ?0.78 to ?0.92). These observations implicate altered dopaminergic activity in the midbrain of schizophrenic patients.     

Associated alterations of striatal dopamine D2/D3 receptor and transporter binding in drug-naive patients with schizophrenia: a dual-isotope SPECT study

OBJECTIVE: In vivo imaging studies have revealed deregulated presynaptic or postsynaptic function of the midbrain dopaminergic system in patients with schizophrenia. To further delineate the neuropathological involvement of the presynaptic and postsynaptic dopamine neurons in schizophrenia, the authors examined brain D(2)-family receptor and dopamine transporter binding simultaneously in patients with drug-naive schizophrenia using the dual-isotope single photon emission computed tomography (SPECT) imaging technique. METHOD: Eleven patients with schizophrenia and 12 healthy comparison subjects were recruited. Striatal dopamine D(2)/D(3) receptor was measured with SPECT and [(123)I]iodobenzamide ([(123)I]IBZM), while dopamine transporter was measured with SPECT and [(99m)Tc]TRODAT-1. RESULTS: Striatal D(2)/D(3) receptor and dopamine transporter binding were unaltered in these drug-naive patients with schizophrenia. Nonetheless, D(2)/D(3) receptor binding measures were positively correlated with dopamine transporter binding measures in these patients but not in the comparison subjects. CONCLUSIONS: The associated presynaptic and postsynaptic disturbances of midbrain dopamine neurons could be clinically relevant in drug-naive patients with schizophrenia.     

D2/D3 dopamine receptor binding with [F-18]fallypride in thalamus and cortex of patients with schizophrenia

BACKGROUND: Abnormalities in the dopaminergic system are implicated in schizophrenia. [F-18]fallypride is a highly selective, high affinity PET ligand well suited for measuring D2/D3 receptor availability in the extrastriatal regions of the brain including thalamus, prefrontal, cingulate, and temporal cortex, brain regions implicated in schizophrenia with other imaging modalities. METHODS: Resting [F-18]fallypride PET studies were acquired together with anatomical MRI for accurate coregistration and image analysis on 15 drug na?ve schizophrenics (10 men, 5 women, mean age 28.5 years) and 15 matched controls (9 men, 6 women, mean age 27.4 years). Dopamine D2/D3 receptor levels were measured as binding potential (BP). The fallypride BP images of each subject were spatially normalized and subsequently smoothed for group comparison. Measures of significance between the schizophrenic and control groups were determined using statistical parametric mapping (SPM). The medial dorsal nucleus and pulvinar were also traced on coregistered MRI for detailed assessment of BP in these regions. RESULTS: The thalamus of patients with schizophrenia had lower [F-18]fallypride BP than normal controls and this was the brain area with the greatest difference (range -8.5% to -27.2%). Left medial dorsal nucleus and left pulvinar showed the greatest decreases (-21.6% and -27.2% respectively). The patients with schizophrenia also demonstrated D2/D3 BP reduction in the amygdala region, cingulate gyrus, and the temporal cortices. CONCLUSIONS: These findings suggest that drug na?ve patients with schizophrenia have significant reductions in extrastratial D2/D3 receptor availability. The reductions were most prominent in regions of the thalamus, replicating other studies both with high affinity D2/D3 ligands and consistent with FDG-PET studies, further supporting the hypothesis of thalamic abnormalities in this patient population.     

Decreased 5-HT1A receptor binding in amygdala of schizophrenia.

BACKGROUND: On the basis of postmortem data and the pharmacological action of atypical antipsychotics, serotonin-1A receptors are of interest in the study of the pathophysiology of schizophrenia. To investigate serotonin-1A receptors in schizophrenia and their relation to symptoms, we measured the availability of serotonin-1A receptors in patients with schizophrenia using positron emission tomography with [carbonyl-(11)C]WAY-100635. METHODS: Serotonin-1A receptor binding of 11 patients with schizophrenia (8 drug-naive and 3 drug-free) was compared with that of 22 age-matched and gender-matched healthy control subjects. Symptoms were assessed using the Positive and Negative Syndrome Scale. Serotonin-1A receptor binding in selected regions of interest was quantified by binding potential obtained by the reference tissue method. RESULTS: The regional binding potential value was lower in the amygdala by about 19% in patients with schizophrenia than in normal controls. A significant negative correlation was observed between binding potential in the amygdala and the negative and depression/anxiety symptom scores on the five-symptom subscale of the Positive and Negative Syndrome Scale. CONCLUSIONS: Decreased serotonin-1A receptor binding in the amygdala may underlie the affective components included in the symptoms of negative and depression/anxiety in schizophrenia.     

Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients

Several lines of evidence suggest that D-serine, an endogenous agonist of the glycine site on the NMDA receptors, might play a role in the pathophysiology of schizophrenia. The purpose of this study was to determine whether levels of D- and L-serine or D-serine ratio (D-serine/total serine) in cerebrospinal fluid (CSF) were altered in first episode and drug-naive schizophrenic patients. The CSF levels of D- and L-serine in 25 male first episode and drug-naive schizophrenic patients and 17 age-matched male healthy subjects were measured using a column-switching high performance liquid chromatography system. The percentage of D-serine in the total serine of patients was significantly (z = -2.01, p = 0.044) lower than that of controls. This study suggests that synthetic or metabolic pathways of D-serine may be abnormal in the brain of drug-naive schizophrenic patients, supporting the NMDA receptor dysfunction hypothesis of schizophrenia.     

Muscarinic cholinergic hyperactivity in schizophrenia. Relationship to positive and negative symptoms

Based on the implication of increased muscarinic ACh activity in the production of negative symptoms, the association of decreasing cholinergic activity with positive symptoms, and the covariance of positive and negative symptoms in the psychotic phase of schizophrenia, a model of (DA) dopaminergic/(ACh) cholinergic interactions in schizophrenia was recently formulated. It suggests that DA/ACh balance is of central importance in schizophrenic pathophysiology and that muscarinic ACh activity increases in an attempt to maintain this balance in the face of increasing DA activity that occurs in the psychotic phase of the illness. The model further suggests that the muscarinic system exerts a damping influence on the emergence of positive symptoms associated with DA hyperactivity, but that this compensatory increase in muscarinic activity is accompanied by an intensification of negative symptoms. In the present study, we tested two important postulates of this model. We tested the prediction that muscarinic activity is increased in schizophrenia by comparing the effect of biperiden, an antimuscarinic M-1 agent, on REM latency in 12 drug-free schizophrenic inpatients and matched normal controls. We found that biperiden caused a smaller increase in REM latency in schizophrenic patients, suggesting that muscarinic activity is increased in schizophrenia. We tested the prediction that an anticholinergic agent would increase positive symptoms and decrease negative symptoms by studying the effect of 8 mg of biperiden/day for 2 days on positive and negative symptoms (assessed by the BPRS) in 30 medication-free schizophrenic inpatients.(ABSTRACT TRUNCATED AT 250 WORDS)     

首发精神分裂症患者心灵理论损伤的研究

背景 心灵理论(又称心理理论)是社会认知中最重要的认知成分之一,现在已经成为认知神经科学界关注的热点之一.目前的研究均证实精神分裂症患者存在心灵理论的损害,并且这种损害和其精神病性症状有一定的相关性.然而目前的研究大多集中在慢性或是服过药的精神分裂症患者中,尚不能完全排除药物的影响.因此本研究采用两种不同的心灵理论任务,并结合神经心理学背景测查对首发、未服药的精神分裂症患者进行了测试.以了解这种心灵理论的损害是否可以在首发、未服药的精神分裂症患者中得到重复.临床上以阴性症状为主的精神分裂症患者往往表现出更为明显的认知功能的损害,因此本研究还对以阴性症状为主的精神分裂症患者(阴性亚组)和以阳性症状为主的精神分裂症患者(阳性亚组)的心灵理论任务成绩及神经心理学背景测查成绩进行了比较.方法 对52例首发、未服药、能合作的精神分裂症患者和64名健康被试进行了眼区任务和失言觉察任务的心灵理论能力测查,采用言语流畅性和数字广度(包括顺背数字和倒背数字)任务对所有研究对象进行了神经心理学背景测试.采用阳性症状和阴性症状量表(PANSS)对精神分裂症患者的精神病性症状进行了评定.52例精神分裂症患者按照PANSS量表的复合量表分(阳性症状总分减阴性症状总分)进行了分组(复合量表分＞0者为阳性亚组,＜0者为阴性亚组),其中27例为阳性亚组,25例为阴性亚组.结果 在需要心灵理论认知成分加工的心理状态阅读任务和失言觉察问题得分上,以及言语流畅性成绩中精神分裂症组的成绩显著低于健康对照组,精神分裂症患者阴性亚组的心理状态阅读任务和言语流畅性成绩显著低于阳性亚组.心灵理论成绩和阴性症状总分呈显著负相关并和言语流畅性成绩呈显著正相关.结论 首发、未服药的精神分裂症患者存在心灵理论能力的损害,并且这种损害可能与其额叶功能的障碍有关.两种不同亚型的精神分裂症患者可能存在着不同形式的心灵理论的损害.     

Schizophrenia and the D1 receptor: Focus on negative symptoms

Lynch, Minda R.: Schizophrenia and the Dl receptor: Focus on negative symptoms. Prog. Meuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 797–832.

1. 1. Negative symptoms have been associated with structural impairment in the PFC, and hypothesized to arise from a central hypodopaminergic substrate.

2. 2. Corticofugal PFC neurons, which are inhibited by VTA DA innervation, exert a tonic excitatory modulation on DA activity in the NAS.

3. 3. Lesions of ascending DA forebrain projections “uncouple” the functional link between D1 and D2 receptors, permitting independent activation of D1 sites in generating behavioral output.

4. 4. A previously identified absence of this D1/D2 link in schizophrenic brain suggests that functional activation of PFC Dl receptors may induce hyperinhibition of descending corticofugal efferents to the NAS.

5. 5. Consequent hypoactivity of DA in the NAS is proposed to give rise to negative symptoms of schizophrenia, and low dose DA agonist treatments may mimic behavioral features of this symptom profile via direct PFC Dl stimulation.

6. 6. It follows that clozapine's efficacy for negative symptoms may be attributable, in part, to blockade of PFC Dl receptors, with subsequent enhancement of glutamate-facilitated NAS DA activity.

Low dopamine d(2) receptor binding in subregions of the thalamus in schizophrenia

OBJECTIVE: Several structural and functional brain imaging studies have pointed to a disturbance of thalamic subnuclei in patients with schizophrenia. The dopamine hypothesis of schizophrenia has, however, not been thoroughly examined in terms of this complex structure, which has connections with most brain regions of central interest in schizophrenia research. The aim of the present study was to examine dopamine D(2) receptor binding in subregions of the thalamus in patients with schizophrenia. METHOD: The authors used positron emission tomography and the radioligand [(11)C]FLB457 to examine dopamine D(2) receptor binding in thalamic subregions of 10 drug-naive patients with schizophrenia. Binding potential was calculated by the reference tissue method and used as an index for dopamine D(2) receptor binding. Comparisons were made with 19 healthy subjects. Subregions of interest were defined on individual magnetic resonance images using a percentage-based operational approach. Clinical symptoms were rated by using the Brief Psychiatric Rating Scale (BPRS). RESULTS: The [(11)C]FLB457 binding potential was lower in the central medial and posterior subregions of the thalamus in patients with schizophrenia. At a functional level, there was a significant negative correlation between binding potential and BPRS positive symptom scores. CONCLUSIONS: The subregions with low D(2) receptor binding comprise primarily the dorsomedial nucleus and pulvinar, two important components in circuitries previously suggested in the pathophysiology of schizophrenia. Aberrant dopaminergic neurotransmission in thalamic subregions might be a mechanism underlying positive symptoms in schizophrenia.     

Dopamine D2 receptor occupancy by olanzapine or risperidone in young patients with schizophrenia

A crucial characteristic of antipsychotic medication is the occupancy of the dopamine (DA) D2 receptor. We assessed striatal DA D2 receptor occupancy by olanzapine and risperidone in 36 young patients [31 males, 5 females; mean age 21.1 years (16-28)] with first episode schizophrenia, using [123I]iodobenzamide (IBZM) SPECT. The occupancy of DA D2 receptors was not significantly different between olanzapine and risperidone. However, in subgroups of most prescribed doses, DA D2 occupancy was higher in the risperidone 4-mg group (79%) compared to the olanzapine 15-mg group (62%). [123I]IBZM binding ratios decreased with olanzapine dose (r = -0.551; P < 0.01), indicating higher DA D2 receptor occupancy with higher olanzapine dose. Akathisia and positive symptoms were correlated with [123I]IBZM binding ratio (r = -0.442; P < 0.01; and r = -0.360; P < 0.05, respectively). Prolactin (PRL) levels were elevated in the risperidone, but not in the olanzapine group, at comparable D2 receptor occupancy levels. In the olanzapine group, PRL levels were correlated with [123I]IBZM binding ratio (r = -0.551; P < 0.01). In conclusion, both olanzapine and risperidone induce a high striatal D2 receptor occupancy, dependent on dose and group formation. The lower incidence of prolactin elevation with olanzapine, compared to risperidone, may not be attributed to a lower D2 receptor occupancy.     

Effects of (S)-ketamine on striatal dopamine: a [11C]raclopride PET study of a model psychosis in humans

Administration of the N-methyl-D-aspartate (NMDA) antagonist S-ketamine in normals produces a psychosis-like syndrome including several positive and negative symptoms of schizophrenic disorders (Abi-Saab WM, D'Souza DC, Moghaddam B, Krystal JH. The NMDA antagonist model for schizophrenia: promise and pitfalls. Pharmacopsychiatry 1998;31:104-109). Given the clinical efficacy of dopamine (DA) D2 receptor antagonists in the treatment of positive symptoms, it is conceivable that S-ketamine-induced psychotic symptoms are partially due to a secondary activation of dopaminergic systems. To date, animal and human studies of the effects of NMDA antagonists on striatal DA levels have been inconsistent. The present study used positron emission tomography (PET) to determine whether a psychotomimetic dose of S-ketamine decreases the in vivo binding of [11C]raclopride to striatal DA D2 receptors in humans (n = 8). S-ketamine elicited a psychosis-like syndrome, including alterations in mood, cognitive disturbances, hallucinations and ego-disorders. S-ketamine decreased [11C]raclopride binding potential (BP) significantly in the ventral striatum (-17.5%) followed by the caudate nucleus (-14.3%) and putamen (-13.6%), indicating an increase in striatal DA concentration. The change in raclopride BP in the ventral striatum correlated with heightened mood ranging from euphoria to grandiosity. These results provide evidence that the glutamatergic NMDA receptor may contribute to psychotic symptom formation via modulation of the DA system.     

精神分裂症中枢NE和DA相互作用与症状学及相关因素分析

应用高压液相色谱（ＨＰＬＣ）对６７例精神分裂症脑脊液中多巴胺（ＤＡ）、去甲肾上腺素（ＮＥ）进行测试，以ＮＥ／ＤＡ为相互作用指标，并以其中位数将受试者分为高ＮＥ／ＤＡ比值组（１５例）和低ＮＥ／ＤＡ比值组（５２例）。结果发现，低比值组的ＢＰＲＳ及其阳性症状显著高于高比值组，且ＮＥ／ＤＡ与之呈显著性负相关。同时还发现，高、低比值组的阴、阳性亚型构成有显著性差异，低比值组年龄明显低于高比值组，但未发现两组在家族史、性别之差异。本研究结合ＮＥ／ＤＡ意义进行了讨论     

Normal IPT and IBZM SPECT in drug-naive and levodopa-treated idiopathic restless legs syndrome

Fourteen drug-naive and 11 levodopa-treated patients with idiopathic restless legs syndrome (RLS), and 10 controls age-matched to each RLS group separately were examined with polysomnography (PSG), [(123)I]-(N)-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ((123)I-IPT) SPECT, and [(123)I]-(S)-2-hydroxy-3-iodo-6-methoxy-[(1-ethyl-2-pyrrolidinyl)methyl] benzamide ((123)I-IBZM) SPECT. Drug-naive and levodopa-treated patients with RLS and controls showed similar striatal dopamine transporter and dopamine D(2)-receptor binding, the latter declining with age. The authors conclude that striatal dopamine transporter and receptor density is normal in drug-naive and levodopa-treated patients with RLS.