Presynaptic Striatal Dopamine Dysfunction in People at Ultra-high Risk for Psychosis:: Findings in a Second Cohort

Alice Egerton; Christopher A. Chaddock; Toby T. Winton-Brown; Michael A.P. Bloomfield; Sagnik Bhattacharyya; Paul Allen; Philip McGuire; Oliver Howes

doi:10.1016/j.biopsych.2012.11.017

Presynaptic Striatal Dopamine Dysfunction in People at Ultra-high Risk for Psychosis: Findings in a Second Cohort

Alice Egerton, Christopher A. Chaddock, Toby T. Winton-Brown, Michael A.P. Bloomfield, Sagnik Bhattacharyya, Paul Allen, Philip McGuire, Oliver Howes

Research output: Contribution to journal › Article

Abstract

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.

Original language	English
Pages (from-to)	106-112
Journal	Biological Psychiatry
Volume	74
Issue number	2
DOIs	https://doi.org/10.1016/j.biopsych.2012.11.017
Publication status	Published - 2013

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10.1016/j.biopsych.2012.11.017

http://dx.doi.org/10.1016/j.biopsych.2012.11.017

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@article{0bb7d26617564bfe978ac3275c00d596,

title = "Presynaptic Striatal Dopamine Dysfunction in People at Ultra-high Risk for Psychosis:: Findings in a Second Cohort",

abstract = "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.",

author = "Alice Egerton and Chaddock, {Christopher A.} and Winton-Brown, {Toby T.} and Bloomfield, {Michael A.P.} and Sagnik Bhattacharyya and Paul Allen and Philip McGuire and Oliver Howes",

year = "2013",

doi = "10.1016/j.biopsych.2012.11.017",

language = "English",

volume = "74",

pages = "106--112",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier",

number = "2",

}

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

AU - Howes, Oliver

PY - 2013

Y1 - 2013

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.

U2 - 10.1016/j.biopsych.2012.11.017

DO - 10.1016/j.biopsych.2012.11.017

M3 - Article

SN - 0006-3223

VL - 74

SP - 106

EP - 112

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 2

ER -