Elsevier

Biological Psychiatry

Volume 65, Issue 12, 15 June 2009, Pages 1091-1093
Biological Psychiatry

Brief Report
Baseline and Amphetamine-Stimulated Dopamine Activity Are Related in Drug-Naïve Schizophrenic Subjects

https://doi.org/10.1016/j.biopsych.2008.12.007Get rights and content

Background

Previous studies demonstrated increased striatal dopamine (DA) release after amphetamine challenge and increased striatal baseline occupancy of D2 receptors in patients with schizophrenia compared with control subjects. We report here on the relationship between these two aspects of DA release in drug-naïve patients with schizophrenia (SCZ) and matched healthy control subjects (HC).

Methods

Six drug-naïve SCZ and eight HC underwent single-photon emission computed tomography (SPECT) scans after bolus followed by constant infusion of (S)-(-)-3-[123I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([123I]IBZM) under three conditions to determine the equilibrium specific to non-displaceable binding potential (BPND) for striatal D2 at baseline, after amphetamine administration and after DA depletion.

Results

Amphetamine induced decrease in BPND was positively correlated with BPND increase after DA depletion in SCZ (p = .02) but not in HC (p = .44). Additionally, both were significantly increased.

Conclusions

In drug-naïve patients with schizophrenia but not in control subjects, stimulated and baseline DA release are both increased and positively correlated. At the neuronal level this association suggests that capacity for storage in presynaptic terminals, measured with the amphetamine paradigm, and baseline intrasynaptic DA release, measured with the α-methyl-para-tyrosine (αMPT) paradigm, are associated in schizophrenia, both consistent with increased midbrain DA cells activity.

Section snippets

Subjects

The protocol was approved by the institutional review boards of the New York State Psychiatric Institute and Columbia Presbyterian Medical Center. Patients and control subjects were subgroups from our previous study of baseline D2R occupancy by DA in schizophrenia (11). Patients were diagnosed with schizophrenia according to the DSM-IV. Only antipsychotic-naïve patients experiencing a first episode of illness were included. Control subjects were matched for age, gender, ethnicity, and parental

Results

Six drug-naïve patients experiencing a first episode of illness and eight healthy control subjects completed the study. One additionally recruited patient was withdrawn from the study due to side effects of αMPT. Subject characteristics are shown in Table 1.

Average BPND values for the three scans are shown in Table 2. The decrease in BPND after amphetamine administration was 18 ± 7% in patients and 10 ± 5% in control subjects compared with the baseline scan (p = .03). The increase in BPND after

Discussion

This study shows for the first time that amphetamine-induced DA release and baseline D2R occupancy by DA are very tightly correlated in drug-naïve patients with schizophrenia but not in control subjects. Furthermore, as previously shown, both measures are higher in patients compared with control subjects, detectable even in this small sample of subjects. This is the first report of a relationship between the changes in radioligand binding after amphetamine and those after αMPT within the same

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