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Altered mesocorticolimbic functional connectivity in psychotic disorder: an analysis of proxy genetic and environmental effects

Published online by Cambridge University Press:  25 March 2015

S. C. T. Peeters ,
E. H. B. M. Gronenschild ,
V. van de Ven ,
P. Habets ,
R. Goebel ,
J. van Os ,
M. Marcelis  and
for Genetic Risk and Outcome of Psychosis (G.R.O.U.P.)
S. C. T. Peeters
Affiliation:
Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, the Netherlands
E. H. B. M. Gronenschild
Affiliation:
Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, the Netherlands
V. van de Ven
Affiliation:
Department of Cognitive Neuroscience, Maastricht University, Maastricht, the Netherlands
P. Habets
Affiliation:
Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, the Netherlands
R. Goebel
Affiliation:
Department of Cognitive Neuroscience, Maastricht University, Maastricht, the Netherlands
J. van Os
Affiliation:
Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, the Netherlands Division of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, UK
M. Marcelis*
Affiliation:
Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, the Netherlands Institute for Mental Health Care Eindhoven (GGzE), Eindhoven, the Netherlands
*
*Address for correspondence: M. Marcelis, M.D., Ph.D., Department of Psychiatry and Psychology, Maastricht University Medical Centre, PO Box 616 (Vijv1), 6200 MD Maastricht, the Netherlands. (Email: m.marcelis@maastrichtuniversity.nl)
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Abstract

Background

Altered dopaminergic neurotransmission in the mesocorticolimbic (MCL) system may mediate psychotic symptoms. In addition, pharmacological dopaminergic manipulation may coincide with altered functional connectivity (fc) ‘in rest’. We set out to test whether MCL-fc is conditional on (familial risk for) psychotic disorder and/or interactions with environmental exposures.

Method

Resting-state functional magnetic resonance imaging data were obtained from 63 patients with psychotic disorder, 73 non-psychotic siblings of patients with psychotic disorder and 59 healthy controls. With the nucleus accumbens (NAcc) as seed region, fc within the MCL system was estimated. Regression analyses adjusting for a priori hypothesized confounders were used to assess group differences in MCL connectivity as well as gene (group) × environmental exposure interactions (G × E) (i.e. to cannabis, developmental trauma and urbanicity).

Results

Compared with controls, patients and siblings had decreased fc between the right NAcc seed and the right orbitofrontal cortex (OFC) as well as the left middle cingulate cortex (MCC). Siblings showed decreased connectivity between the NAcc seed and lentiform nucleus compared with patients and controls. In addition, patients had decreased left NAcc connectivity compared with siblings in the left middle frontal gyrus. There was no evidence for a significant interaction between group and the three environmental exposures in the model of MCL-fc.

Conclusions

Reduced NAcc–OFC/MCC connectivity was seen in patients and siblings, suggesting that altered OFC connectivity and MCC connectivity are vulnerability markers for psychotic disorder. Differential exposure to environmental risk factors did not make an impact on the association between familial risk and MCL connectivity.

Keywords

Dopaminefunctional magnetic resonance imaginggene–environment interactionpsychotic disordersiblings
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 10 , July 2015 , pp. 2157 - 2169
Copyright
Copyright © Cambridge University Press 2015 

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