Decreased striatal dopamine transporter binding assessed with [123I] FP-CIT in first-episode schizophrenic patients with and without short-term antipsychotic-induced parkinsonism

Mateos, J.J.; Lomeña, Francisco; Parellada, Eduard; Font, Mireia; Fernández, Estrella; Pavı́a, Javier; Prats, Alberto; Pons, F; Bernardo, Miquel

doi:10.1007/s00213-005-2250-2

Cited by 40 publications

(23 citation statements)

References 32 publications

(31 reference statements)

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“…On the other hand, some studies clearly showed a significant decrease of DAT binding in patients with schizophrenia, in young antipsychotic-free patients [41] as well as in chronic medicated patients [42]. Using recent [123I] FP-CIT tracer, in two independent studies, Mateos and co-workers [43,44] reported and confirmed that DAT binding was lower in antipsychotic-naive first episode patients than in healthy subjects, at baseline and after a 4-weektreatment period. Interestingly, in a 4-year follow up study, Mané and co-workers [45] reported a specific relation between striatal DAT number and negative symptoms suggesting that there is a close relationship between DAT number and clinical features of patients.…”

Section: Imaging Striatal Dopamine Transporter (Dat)mentioning

confidence: 77%

Abnormal Striatal Dopamine Transmission in Schizophrenia

Fecteau¹,

Suaud-Chagny²

2013

Current Medicinal Chemistry

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Despite numerous revisions and reformulations, dopamine (DA) hypothesis of schizophrenia remains a pivotal neurochemical hypothesis of this illness. The aim of this review is to expose and discuss findings from positron emission tomography (PET) or singlephoton-emission computed tomography (SPECT) studies investigating DA function in the striatum of medicated, drug-naïve or drug-free patients with schizophrenia and in individuals at risk compared with healthy volunteers.DA function was studied at several levels: i) at a presynaptic level where neuroimaging studies investigating DOPA uptake capacity clearly show an increase of DA synthesis in patients with schizophrenia; ii) at a synaptic level where neuroimaging studies investigating dopamine transporter availability (DAT) does not bring any evidence of dysfunction; iii) and finally, neuroimaging studies investigating DA receptor density show a mild increase of D2 receptor density in basic condition and, an hyperreactivity of DA system in dynamic condition.These results are discussed regarding laterality, sub-regions of striatum and implications for the at-risk population. Striatal DA abnormalities are now clearly demonstrated in patients with schizophrenia and at risk population and could constitute an endophenotype of schizophrenia. Subtle sub-clinical striatal DA abnormalities in at risk population could be a biomarker of transition from a vulnerability state to the expression of frank psychosis.

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Section: Imaging Striatal Dopamine Transporter (Dat)mentioning

confidence: 77%

Abnormal Striatal Dopamine Transmission in Schizophrenia

Fecteau¹,

Suaud-Chagny²

2013

Current Medicinal Chemistry

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“…Results on striatal DAT binding in schizophrenic subjects have been inconsistent, with reports of either elevated (11,12), reduced (9,11,16), or unaltered (7,8,10,(13)(14)(15) DAT binding. Interestingly, also in medicated patients, either unaltered (8), decreased (9,16), or increased DAT binding (12) has been observed.…”

Section: Discussionmentioning

confidence: 99%

“…If endogenous dopamine displaces exogenous radioligands or competes with them for presynaptic binding sites, this may have implications for DAT imaging studies in Parkinsonian subjects, who are treated with pharmacologic compounds that lead to an increased availability of dopamine in the synaptic cleft. Moreover, DAT binding is increasingly assessed in schizophrenic patients (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Because neuroleptics such as haloperidol increase endogenous dopamine concentrations, radioligand binding to the DAT may be severely confounded in medicated schizophrenic patients.…”

mentioning

confidence: 99%

Pretreatment with Haloperidol Reduces¹²³I-FP-CIT Binding to the Dopamine Transporter in the Rat Striatum: An In Vivo Imaging Study with a Dedicated Small-Animal SPECT Camera

Nikolaus¹,

Antke²,

Kley³

et al. 2009

J Nucl Med

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Synaptic dopamine is mainly regulated by presynaptic dopamine transporter (DAT) activity. We hypothesized that variations in synaptic dopamine are reflected by variations of DAT radioligand binding. The effect of haloperidol, which increases synaptic dopamine concentrations, was therefore assessed in the rat striatum using 123 I-N-v-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl)-nortropane ( 123 I-FP-CIT) as a DAT radioligand. Methods: Striatal 123 I-FP-CIT binding was measured in 24 rats under baseline conditions (no pretreatment) and at 1 h after injection of haloperidol or a vehicle (1 mg/kg) using a small-animal SPECT camera. Results: Baseline equilibrium ratios (V 3 $) were 1.32 6 0.24 (mean 6 SD). After the haloperidol injection, V 3 $ decreased to 0.99 6 0.38 (P 2-tailed , 0.0001), corresponding to a mean reduction of DAT binding by 25%. Conclusion: Our results are indicative of competition between the DAT ligand 123 I-FP-CIT and synaptic dopamine elevated by haloperidol, suggesting that the assessment of 123 I-FP-CIT binding may be suitable to study variations in synaptic dopamine in vivo.

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“…34,36,39,42 However, the pooled meta-analysis indicated no statistical evidence for a significant difference between the 2 groups (Hedges' g = �0.244, CI 95% from �0.676 to 0.188, Z = �1.106, P = .269, figure 3). The striatal DAT density schizophrenia/control ratio ranged from 0.87 to 1.51, with an average value of 0.95.…”

Section: Dopamine Transporter Density In the Striatummentioning

confidence: 99%

“…31,38,39 Laruelle et al 31 found a trend level association in patients with schizophrenia between low striatal DAT density and severity of negative symptoms. 31 Schmitt et al found that hallucinations were inversely correlated with striatal DAT density in the subgroup of schizophrenic patients with predominantly positive symptoms.…”

Section: Psychotic Symptomsmentioning

confidence: 99%

Striatal Presynaptic Dopamine in Schizophrenia, Part I: Meta-Analysis of Dopamine Active Transporter (DAT) Density

Fusar‐Poli

Meyer‐Lindenberg

2012

Schizophrenia Bulletin

106

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Background: Striatal dopaminergic neurotransmission has been postulated to be fundamental to the emergence of key symptoms of schizophrenia, such as psychotic symptoms, and is targeted by currently available dopaminergic drugs. A specific marker of the integrity of presynaptic dopamine neurons in the striatum, the density of striatal dopamine terminals, can be quantified through molecular neuroimaging of the dopamine active transporter (DAT). However, the currently available results using this approach in schizophrenia are inconsistent. Methods: Thirteen Single Photon Emission Tomography or Positron Emission Tomography (PET) studies investigating DAT density in the striatum of schizophrenic patients and matched controls were included in a quantitative meta-analysis. Binding potentials in the striatum, caudate, and putamen, as well as demographic, clinical, and methodological variables, were extracted from each publication. Hedges' g was used as a measure of effect size. Results: The overall database contained 202 subjects with schizophrenia and 147 controls, well matched with respect to sociodemographic variables. Striatal DAT density was not significantly different between patients and controls. Similar negative findings were regionally confirmed in the putamen and caudate. There was no moderating effect for external factors. Conclusions: Our meta-analysis uncovered no evidence indicating altered density of striatal dopamine terminals in schizophrenia. Moreover, striatal DAT density did not seem to be influenced by antipsychotic medication or illness duration. Our data suggest that altered integrity of striatal dopaminergic synapses is not critical for the emergence of schizophrenia or its treatment. These findings should be useful in further refining dopaminergic hypotheses of schizophrenia.

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Decreased striatal dopamine transporter binding assessed with [123I] FP-CIT in first-episode schizophrenic patients with and without short-term antipsychotic-induced parkinsonism

Abstract: Our first-episode schizophrenic patients with and without DIP after short-term risperidone treatment have a decreased striatal DAT binding assessed with [(123)I] FP-CIT. This alteration could be related to the schizophrenic disease or may be secondary to the antipsychotic treatment.

Cited by 40 publications

References 32 publications

Abnormal Striatal Dopamine Transmission in Schizophrenia

Abnormal Striatal Dopamine Transmission in Schizophrenia

Pretreatment with Haloperidol Reduces¹²³I-FP-CIT Binding to the Dopamine Transporter in the Rat Striatum: An In Vivo Imaging Study with a Dedicated Small-Animal SPECT Camera

Striatal Presynaptic Dopamine in Schizophrenia, Part I: Meta-Analysis of Dopamine Active Transporter (DAT) Density

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Decreased striatal dopamine transporter binding assessed with [123I] FP-CIT in first-episode schizophrenic patients with and without short-term antipsychotic-induced parkinsonism

Abstract: Our first-episode schizophrenic patients with and without DIP after short-term risperidone treatment have a decreased striatal DAT binding assessed with [(123)I] FP-CIT. This alteration could be related to the schizophrenic disease or may be secondary to the antipsychotic treatment.

Cited by 40 publications

References 32 publications

Abnormal Striatal Dopamine Transmission in Schizophrenia

Abnormal Striatal Dopamine Transmission in Schizophrenia

Pretreatment with Haloperidol Reduces123I-FP-CIT Binding to the Dopamine Transporter in the Rat Striatum: An In Vivo Imaging Study with a Dedicated Small-Animal SPECT Camera

Striatal Presynaptic Dopamine in Schizophrenia, Part I: Meta-Analysis of Dopamine Active Transporter (DAT) Density

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Pretreatment with Haloperidol Reduces¹²³I-FP-CIT Binding to the Dopamine Transporter in the Rat Striatum: An In Vivo Imaging Study with a Dedicated Small-Animal SPECT Camera