Lower striatal dopamine transporter binding in neuroleptic-naive schizophrenic patients is not related to antipsychotic treatment but it suggests an illness trait

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

doi:10.1007/s00213-006-0570-5

Cited by 62 publications

(35 citation statements)

References 44 publications

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“…49 The second study enrolled antipsychotic-naïve first-episode patients and investigated them at baseline and after 4 weeks of risperidone treatment and confirmed a null effect of antipsychotic on striatal DAT density. 42 These results are in line with animal models showing that chronic administration of clozapine, risperidone, or haloperidol did not alter DAT density in rats. 50,51 These consistent results are in interesting contrast to preclinical findings that show that D2 receptors are a critical regulator of synaptic arborization, 52 with pronounced increases in synaptic density seen under chronic D2 blockade 53 and in D2 receptor knockout mice.…”

Section: Discussionsupporting

confidence: 79%

“…20,21 Three studies included in the present database uncovered significant striatal DAT decreases in schizophrenic subjects as compared with controls. 34,39,42 The decreased DAT density was attributed to a higher loss of dopamine neuron integrity, in line with the neurotoxic hypothesis of striatal hyperdopaminergia. Conversely, one study found greater DAT density in schizophrenic patients as compared with controls.…”

Section: Discussionsupporting

confidence: 49%

“…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%

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

Fusar‐Poli

Meyer‐Lindenberg

2012

Schizophrenia Bulletin

107

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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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Section: Discussionsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 49%

Section: Dopamine Transporter Density In the Striatummentioning

confidence: 99%

See 1 more Smart Citation

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

Fusar‐Poli

Meyer‐Lindenberg

2012

Schizophrenia Bulletin

107

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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: 76%

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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“…Laakso et al 51 Mateos et al 59 Schmitt et al 60 Arakawa et al 61 Mateos Figure 3. Studies of dopamine transporter availability.…”

Section: Discussionmentioning

confidence: 99%

The Nature of Dopamine Dysfunction in Schizophrenia and What This Means for Treatment

Howes

Kambeitz

Kim

et al. 2012

Arch Gen Psychiatry

840

646

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Lower striatal dopamine transporter binding in neuroleptic-naive schizophrenic patients is not related to antipsychotic treatment but it suggests an illness trait

Cited by 62 publications

References 44 publications

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

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

Abnormal Striatal Dopamine Transmission in Schizophrenia

The Nature of Dopamine Dysfunction in Schizophrenia and What This Means for Treatment

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