Neural correlates of reward processing in adults with 22q11 deletion syndrome.

Esther D A Van Duin,Therese Van Amelsvoort,Fabiana Da Silva Alves,Koen Schruers,Liesbet Goossens,Nicole Schmitz,Dennis Hernaus

doi:10.1186/s11689-016-9158-5

Esther D A Van Duin, Therese Van Amelsvoort + Show 5 more

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https://doi.org/10.1186/s11689-016-9158-5

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Abstract

Background22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic neurotransmission in 22q11DS, which may contribute to the increased vulnerability for psychosis. A dysfunctional motivational reward system is considered one of the salient features in psychosis and thought to be related to abnormal dopaminergic neurotransmission. The functional anatomy of the brain reward circuitry has not yet been investigated in 22q11DS.MethodsThis study aims to investigate neural activity during anticipation of reward and loss in adult patients with 22q11DS. We measured blood-oxygen-level dependent (BOLD) activity in 16 patients with 22q11DS and 12 healthy controls during a monetary incentive delay task using a 3T Philips Intera MRI system. Data were analysed using SPM8.ResultsDuring anticipation of reward, the 22q11DS group alone displayed significant activation in bilateral middle frontal and temporal brain regions. Compared to healthy controls, significantly less activation in bilateral cingulate gyrus extending to premotor, primary motor and somatosensory areas was found.During anticipation of loss, the 22q11DS group displayed activity in the left middle frontal gyrus and anterior cingulate cortex, and relative to controls, they showed reduced brain activation in bilateral (pre)cuneus and left posterior cingulate.Within the 22q11DS group, COMT Val hemizygotes displayed more activation compared to Met hemizygotes in right posterior cingulate and bilateral parietal regions during anticipation of reward. During anticipation of loss, COMT Met hemizygotes compared to Val hemizygotes showed more activation in bilateral insula, striatum and left anterior cingulate.ConclusionsThis is the first study to investigate reward processing in 22q11DS. Our preliminary results suggest that people with 22q11DS engage a fronto-temporal neural network. Compared to healthy controls, people with 22q11DS primarily displayed reduced activity in medial frontal regions during reward anticipation. COMT hemizygosity affects responsivity of the reward system in this condition. Alterations in reward processing partly underlain by the dopamine system may play a role in susceptibility for psychosis in 22q11DS.

Highlights

Psychotic disorders, including schizophrenia, are potentially devastating lifelong illnesses that are disabling and costly to patients, families, communities and healthcare systems
Gender distribution was not significantly different between the two groups (22q11DS M/F ratio 8/8; controls M/F ratio 8/4; p = 0.46, Fisher’s exact test). 22q11 deletion syndrome (22q11DS) patients and healthy controls differed in total intelligence quotient (IQ) scores (HC 110 (10) and 22qDS 77 (10), p < 0.001)
COMT genotype effects on 22q11DS reward processing In line with previous studies investigating reward anticipation with functional magnetic resonance imaging (fMRI) in healthy controls [19, 68], we found an effect of COMT genotype on reward processing

Summary

Introduction

Psychotic disorders, including schizophrenia, are potentially devastating lifelong illnesses that are disabling and costly to patients, families, communities and healthcare systems. Symptoms typically emerge during late adolescence, and the estimated lifetime prevalence and incidence is approximately 0.3–0.7 % [1]. Treatment advances in these heterogeneous disorders have been limited by insufficient mechanistic understanding of the underlying pathophysiology. Several functional magnetic resonance imaging (fMRI) studies have demonstrated alterations in the brain reward network in patients with, and at clinical high risk for, psychosis, primarily in the striatal motivational system [8,9,10,11,12,13]

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