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Heterogeneity of striatal dopamine function in schizophrenia: meta-analysis of variance

Brugger, Stefan P, Angelescu, I, Abi-Dargham, A, Mizrahi, R, Shahrezaei, V and Howes, O 2020. Heterogeneity of striatal dopamine function in schizophrenia: meta-analysis of variance. Biological Psychiatry 87 (3) , pp. 215-224. 10.1016/j.biopsych.2019.07.008

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Background It has been hypothesized that dopamine function in schizophrenia exhibits heterogeneity in excess of that seen in the general population. However, this hypothesis has never been systematically tested. Method We employed meta-analysis of variance to investigate inter-individual variability of striatal dopaminergic function in patients with schizophrenia and healthy controls. We included 65 studies reporting molecular imaging measures of dopamine synthesis or release capacities, D2/3 receptor (D2/3R) or transporter (DAT) availabilities, or synaptic dopamine levels, in 983 patients and 968 controls. Variability differences were quantified using variability ratio (VR) and coefficient of variation ratio. Results Inter-individual variability of striatal D2/3R (VR=1.26, p<.0001) and DAT availabilities (VR=1.31, p=.01), and synaptic dopamine levels (VR=1.38, p=.045), but not dopamine synthesis (VR=1.12, p=.13) or release (VR=1.08, p=.70) capacities, were significantly greater in patients. . Findings were robust to variability measure. Mean dopamine synthesis (g=0.65, p=.004) and release (g=0.66, p=.03) capacities, as well as synaptic levels (g=0.78, p=.0006) were greater in patients overall, but mean synthesis capacity did not differ relative to controls in treatment resistant patients (p>0.3). Mean D2/3R (g=0.17, p=.14) and DAT (g=-0.20, p=.28) availabilities did not differ between groups. Conclusions Our findings demonstrate significant heterogeneity of striatal dopamine function in schizophrenia. They suggest that while elevated dopamine synthesis and release capacities may be core features of the disorder, altered D2/3R and DAT availabilities, and synaptic dopamine levels, may occur only in a subgroup of patients. This heterogeneity may contribute to variation in treatment response and side-effects.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher: Elsevier
ISSN: 0006-3223
Date of First Compliant Deposit: 18 September 2019
Date of Acceptance: 10 July 2019
Last Modified: 24 Nov 2020 19:15

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