Presynaptic dopaminergic function in the striatum of schizophrenic patients

doi:10.1016/S0920-9964(96)00102-8

Schizophrenia Research

Volume 23, Issue 2, 7 February 1997, Pages 167-174

https://doi.org/10.1016/S0920-9964(96)00102-8 Get rights and content

Abstract

The dopaminergic hypothesis of schizophrenia postulates increased brain dopaminergic activity. Two previous studies reported increased ¹⁸F-DOPA uptake with positron emission tomography in schizophrenic patients (n = 5, n = 7). In the present study, striatal dopaminergic function was assessed in vivo in six untreated schizophrenics and seven control subjects, comparable for age and sex. The ¹⁸F-fluoro-L-DOPA (¹⁸F-DOPA) uptake rate constant K_i was determined in the caudate and putamen using coregistered positron emission tomography and magnetic resonance imaging. No difference between groups for mean K_i was found. The variability of the ¹⁸F-DOPA uptake values was higher in the caudate (p<0.01) and in the putamen (p<0.001) in schizophrenic patients than in control subjects, suggesting that schizophrenia is a disorder involving heterogeneous states of the striatal presynaptic dopaminergic function.

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In addition, the F-18-DOPA-PET showed abnormal lateralization in one patient (Lauer et al., 2001). The remaining investigations included only one patient with catatonia as part of a cohort of 6, 10, and 7 patients with SCZ, respectively (Dao-Castellana et al., 1997; Hietala et al., 1995, 1999). In particular, all three studies showed a reduced dopamine binding affinity in the striatum compared to patients with SCZ without catatonia or HC.
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Catatonia is characterized by structural, functional, perfusion, and metabolic cortico-subcortical abnormalities. However, the majority of studies and case reports included in this systematic review are affected by considerable heterogeneity, both in terms of populations and neuroimaging techniques, which calls for a cautious interpretation. Further elucidation, through future neuroimaging research, could have great potential to improve the description of the neural motor and psychomotor mechanisms underlying catatonia.
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One of the most enduring neurochemical theories of schizophrenia focus upon dysregulation of dopaminergic neurotransmission. Studies have shown that patients with schizophrenia, when having psychotic symptoms, show a heightened synthesis of dopamine, a heightened dopamine release in response to an impulse, and a heightened level of synaptic dopamine [77–81]. Kapur [42] in his seminal paper proposed that a dysregulated, hyperdopaminergic state at a ‘brain’ level, leads to an aberrant assignment of salience to the elements of one’s experience at a ‘mind’ level.
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Dopamine activity has been associated with the response to antipsychotic treatment. Our study used a four-parameter model to test the association between the striatal decarboxylation rate of ¹⁸F-DOPA to ¹⁸F-dopamine (k₃) and the effect of treatment on psychotic symptoms in antipsychotic-naïve patients with first-episode psychosis. We further explored the effect of treatment with a partial dopamine D₂ receptor agonist (aripiprazole) on k₃ and dopamine synthesis capacity (DSC) determined by the four-parameter model and by the conventional tissue reference method.
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Presynaptic dopaminergic function in the striatum of schizophrenic patients

Abstract

J. Psychiatry Res.

Brain Res. Rev.

Life Sci.

Lancet

J. Psychiat. Res.

Psychiatry Res. Neuroimaging

Science

Positron emission tomography after MPTP: observations relating to the cause of Parkinson's disease

Nature

DA receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs

Science

3H-Flupenthixol binding in post-mortem brains of schizophrenics: evidence for a selective increase in dopamine D2 receptors

Psychopharmacology

D2 dopamine receptors in neuroleptic-naive schizophrenic patients: a positron emission tomography study with 11C raclopride

Arch. Gen. Psychiatry

Cerebral metabolism of 6-18F-fluoro-L-3,4-dihydroxyphenylalanine in the primate

J. Neurochem.

Modeling neuroreceptor binding of radioligands in vivo

Conception neurologique du syndrome catatonique

Encéphale

Striatal D2 dopamine receptor characteristics in neuroleptic-naive schizophrenic patients studied with positron emission tomography

Arch. Gen. Psychiatry

Monoamine neurotransmitter interactions in drug-free and neuroleptic-treated schizophrenics

Arch Gen Psychiatry

The positive and negative syndrome scale (PANSS) for schizophrenia

Schizophr. Bull.

3H-Spiperone binding sites in post-mortem brain from schizophrenic patients: relationship to neuroleptic drug treatment, abnormal movements, and positive symptoms

J. Neural Transm.

Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects

³H-Flupenthixol binding in post-mortem brains of schizophrenics: evidence for a selective increase in dopamine D2 receptors

Cerebral metabolism of 6-¹⁸F-fluoro-L-3,4-dihydroxyphenylalanine in the primate

³H-Spiperone binding sites in post-mortem brain from schizophrenic patients: relationship to neuroleptic drug treatment, abnormal movements, and positive symptoms