Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort.
OBJECTIVE
The authors previously observed an increase in striatal dopamine transmission following amphetamine challenge in 15 untreated patients with schizophrenia compared to 15 matched healthy subjects. The purpose of this study was to replicate this finding in a new cohort of schizophrenic patients and healthy subjects.


METHODS
Fifteen patients with schizophrenia and 15 healthy subjects matched for age, gender, ethnicity, and parental socioeconomic status were recruited for this study. Patients fulfilled DSM-IV criteria for schizophrenia, had no history of alcohol or substance abuse or dependence, and were neuroleptic free for a minimum of 21 days. Amphetamine-induced dopamine release was assessed by the reduction in dopamine D2 receptor availability induced by an acute amphetamine challenge (0.3 mg/kg, intravenous bolus). Reduction in D2 receptor availability was measured with single photon emission computed tomography and the D2 receptor radiotracer [123I]IBZM.


RESULTS
No differences were observed between patients with schizophrenia and the comparison group in D2 receptor availability at baseline. Patients with schizophrenia exhibited a significantly larger reduction in D2 receptor availability following acute amphetamine challenge than the comparison group. In this study, the effect size was smaller than in the first study. Excess dopamine release following amphetamine was associated with transient emergence or worsening of positive symptoms.


CONCLUSIONS
In this new cohort of subjects the authors replicated their initial observation of a dysregulation of striatal dopamine release in schizophrenia.
Abi-Dargham
A
A
Department of Psychiatry, Yale University, New Haven, Conn., USA. aadar@neuron.cpmc.columbia.edu
Gil
R
R
Krystal
J
J
Baldwin
R M
RM
Seibyl
J P
JP
Bowers
M
M
van Dyck
C H
CH
Charney
D S
DS
Innis
R B
RB
Laruelle
M
M
D000328:Adult; D000661:Amphetamine / Q000494:pharmacology; D001549:Benzamides; D015331:Cohort Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D015899:Tomography, Emission-Computed, Single-Photon
D001549:Benzamides; D011759:Pyrrolidines; D011954:Receptors, Dopamine; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D000661:Amphetamine; D004298:Dopamine