Elevated regional cerebral blood flow in adults with 22q11.2 deletion syndrome

Abstract

Objectives

Recurrent chromosome 22q11.2 deletions cause 22q11 deletion syndrome (22q11DS), a multisystem disorder associated with high rates of schizophrenia. Neuroanatomical changes on brain MRI have been reported in relation to 22q11DS. However, to date no 22q11DS neuroimaging studies have examined cerebral blood flow (CBF). This exploratory case-control study seeks to identify differences in regional cerebral blood flow between 22q11DS subjects and controls, and their association with psychotic symptoms.

Methods

This study of 23 adults used arterial spin labelling MRI to investigate voxel-wise CBF in 22q11DS individuals compared with age- and sex-matched healthy controls.

Results

Four significant clusters, involving the right and left putamen, right fusiform gyrus and left middle temporal gyrus, delineated significantly elevated CBF in individuals with 22q11DS compared to controls. Post-hoc analysis determined that this elevation in CBF trended with psychotic symptom diagnosis within the 22q11DS group.

Conclusions

These findings suggest possible relevance to schizophrenia risk and support further functional neuroimaging studies of 22q11DS with larger sample sizes to improve our understanding of the underlying pathophysiology.

Keywords:

• DiGeorge syndrome
• cerebral perfusion
• schizophrenia
• imaging
• genetics

Acknowledgements

The authors thank the adults with 22q11.2 deletion syndrome and their involved families for their contributions to this and related research studies.

Disclosure statement

NJB receives consulting fees from Nobias Therapeutics, Inc.

Additional information

Funding

This work was supported by the Canadian Institutes of Health Research [MOP-97800, MOP-111238, PJT-148924] and the Canada Research Chairs Program (Anne S. Bassett), a Brain Canada Mental Health Training Award (Nancy J. Butcher), and a Canadian Institutes of Health Research Frederick Banting and Charles Best Canada Graduate Scholarship (Nancy J. Butcher). Maurice Pasternak is supported by a School of Graduate Studies University-Wide Award scholarship funding from the Institute of Medical Science, University of Toronto. Anne S. Bassett is supported by the Dalglish Family Chair in 22q11.2 Deletion Syndrome at the University Health Network and University of Toronto. HJMMM is supported by the Dutch Heart Foundation [03-004-2020-T049], by the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 research and innovation program [ASPIRE E!113701], provided by the Netherlands Enterprise Agency (RvO), and by the EU Joint Program for Neurodegenerative Disease Research, provided by the Netherlands Organisation for health Research and Development and Alzheimer Nederland [DEBBIE JPND2020-568-106]. MM reports grant funding from the Ontario Brain Institute, the Canadian Institutes of Health Research, Woman’s Brain Health Initiative, Brain Canada, Weston Brain Institute and Washington University. MM has received personal fees for serving on a Scientific Advisory Committee for Ionis Pharmaceuticals, Alector Pharmaceuticals, Wave Life Sciences, and Biogen Canada, outside of this submitted work. MM has received royalties from Henry Stewart Talks, outside of this submitted work. MM is a clinical trial site investigator for Roche, and Alector Pharmaceuticals, outside of this submitted work.