TY - JOUR
T1 - Presynaptic Striatal Dopamine Dysfunction in People at Ultra-high Risk for Psychosis
T2 - Findings in a Second Cohort
AU - Egerton, Alice
AU - Chaddock, Christopher A.
AU - Winton-Brown, Toby T.
AU - Bloomfield, Michael A. P.
AU - Bhattacharyya, Sagnik
AU - Allen, Paul
AU - McGuire, Philip K.
AU - Howes, Oliver D.
N1 - Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
PY - 2013/7/15
Y1 - 2013/7/15
N2 - Background: Using positron emission tomography (PET), we previously observed increases in 3,4-dihydroxy-6-[F-18]fluoro-L-phenylalanine (F-18-DOPA) uptake in the striatum of subjects at ultra-high risk (UHR) for psychosis, indicating elevated presynaptic dopamine synthesis capacity. The purpose of this study was to test if this finding would be replicated in a second UHR cohort.Methods: F-18-DOPA PET was used to estimate dopamine synthesis capacity in the striatum of an entirely new cohort of 26 individuals at UHR for psychosis (14 males, mean +/- SD age = 22.7 +/- 4.7 years) and 20 healthy volunteers matched for age and gender (11 males, mean +/- SD age = 24.5 +/- 4.5 years).Results: Dopamine synthesis capacity was elevated in the whole [t(44) = 2.6; p = .01, effect size = .81] and associative striatum [t(44) = 2.6; p = .01, effect size = .73] of UHR compared with control subjects. When the two samples were combined to give a final sample of 32 control and 50 UHR subjects, the higher levels of dopamine synthesis capacity in the UHR group reached significance across the whole [F(1,81) = 11.0; p = .001], associative [F(1,81) = 12.7; p = .001], and sensorimotor [F(1,81) = 4.7; p = .03], but not the limbic [F(1,81) = 2.1; p = .2], striatum.Conclusions: The findings indicate that elevated dopamine synthesis capacity in the dorsal striatum is a robust feature of individuals at UHR for psychosis and provide further evidence that dopaminergic abnormalities precede the onset of psychosis.
AB - Background: Using positron emission tomography (PET), we previously observed increases in 3,4-dihydroxy-6-[F-18]fluoro-L-phenylalanine (F-18-DOPA) uptake in the striatum of subjects at ultra-high risk (UHR) for psychosis, indicating elevated presynaptic dopamine synthesis capacity. The purpose of this study was to test if this finding would be replicated in a second UHR cohort.Methods: F-18-DOPA PET was used to estimate dopamine synthesis capacity in the striatum of an entirely new cohort of 26 individuals at UHR for psychosis (14 males, mean +/- SD age = 22.7 +/- 4.7 years) and 20 healthy volunteers matched for age and gender (11 males, mean +/- SD age = 24.5 +/- 4.5 years).Results: Dopamine synthesis capacity was elevated in the whole [t(44) = 2.6; p = .01, effect size = .81] and associative striatum [t(44) = 2.6; p = .01, effect size = .73] of UHR compared with control subjects. When the two samples were combined to give a final sample of 32 control and 50 UHR subjects, the higher levels of dopamine synthesis capacity in the UHR group reached significance across the whole [F(1,81) = 11.0; p = .001], associative [F(1,81) = 12.7; p = .001], and sensorimotor [F(1,81) = 4.7; p = .03], but not the limbic [F(1,81) = 2.1; p = .2], striatum.Conclusions: The findings indicate that elevated dopamine synthesis capacity in the dorsal striatum is a robust feature of individuals at UHR for psychosis and provide further evidence that dopaminergic abnormalities precede the onset of psychosis.
KW - Dopamine
KW - imaging
KW - positron emission tomography
KW - psychosis
KW - schizophrenia
KW - striatum
KW - POSITRON-EMISSION-TOMOGRAPHY
KW - HIGH-CLINICAL-RISK
KW - SYNTHESIS CAPACITY
KW - SCHIZOPHRENIA
KW - BRAIN
KW - PET
KW - TRANSMISSION
KW - AMPHETAMINE
KW - RELEASE
KW - SCALE
KW - Acknowledged-BRC
KW - Acknowledged-BRC-13/14
U2 - 10.1016/j.biopsych.2012.11.017
DO - 10.1016/j.biopsych.2012.11.017
M3 - Article
C2 - 23312565
SN - 0006-3223
VL - 74
SP - 106
EP - 112
JO - Biological psychiatry
JF - Biological psychiatry
IS - 2
ER -