Functional Dysconnectivity in Ventral Striatocortical Systems in 22q11.2 Deletion Syndrome
Journal
Schizophrenia Bulletin
ISSN
0586-7614
1745-1701
Date Issued
2021
Author(s)
Ángeles Tepper
Analía Cuiza
Luz María Alliende
Carlos Mena
Juan Pablo Ramirez-Mahaluf
Claudia Ornstein
Rosemarie Fritsch
Ruben Nachar
Alfonso González-Valderrama
Juan Pablo Cruz
Cristian Tejos
Alex Fornito
Nicolas Crossley
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:title>Abstract</jats:title>
<jats:p>22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental disorder that represents one of the greatest known risk factors for psychosis. Previous studies in psychotic subjects without the deletion have identified a dopaminergic dysfunction in striatal regions, and dysconnectivity of striatocortical systems, as an important mechanism in the emergence of psychosis. Here, we used resting-state functional MRI to examine striatocortical functional connectivity in 22q11.2DS patients. We used a 2 × 2 factorial design including 125 subjects (55 healthy controls, 28 22q11.2DS patients without a history of psychosis, 10 22q11.2DS patients with a history of psychosis, and 32 subjects with a history of psychosis without the deletion), allowing us to identify network effects related to the deletion and to the presence of psychosis. In line with previous results from psychotic patients without 22q11.2DS, we found that there was a dorsal to ventral gradient of hypo- to hyperstriatocortical connectivity related to psychosis across both patient groups. The 22q11.2DS was additionally associated with abnormal functional connectivity in ventral striatocortical networks, with no significant differences identified in the dorsal system. Abnormalities in the ventral striatocortical system observed in these individuals with high genetic risk to psychosis may thus reflect a marker of illness risk.</jats:p>
<jats:p>22q11.2 deletion syndrome (22q11.2DS) is a genetic neurodevelopmental disorder that represents one of the greatest known risk factors for psychosis. Previous studies in psychotic subjects without the deletion have identified a dopaminergic dysfunction in striatal regions, and dysconnectivity of striatocortical systems, as an important mechanism in the emergence of psychosis. Here, we used resting-state functional MRI to examine striatocortical functional connectivity in 22q11.2DS patients. We used a 2 × 2 factorial design including 125 subjects (55 healthy controls, 28 22q11.2DS patients without a history of psychosis, 10 22q11.2DS patients with a history of psychosis, and 32 subjects with a history of psychosis without the deletion), allowing us to identify network effects related to the deletion and to the presence of psychosis. In line with previous results from psychotic patients without 22q11.2DS, we found that there was a dorsal to ventral gradient of hypo- to hyperstriatocortical connectivity related to psychosis across both patient groups. The 22q11.2DS was additionally associated with abnormal functional connectivity in ventral striatocortical networks, with no significant differences identified in the dorsal system. Abnormalities in the ventral striatocortical system observed in these individuals with high genetic risk to psychosis may thus reflect a marker of illness risk.</jats:p>
Cite this document
Tepper, Á., Cuiza, A., Alliende, L. M., Mena, C., Ramirez-Mahaluf, J. P., Iruretagoyena, B., Ornstein, C., Fritsch, R., Nachar, R., González-Valderrama, A., Undurraga, J., Cruz, J. P., Tejos, C., Fornito, A., Repetto, G., & Crossley, N. (2022). Functional dysconnectivity in ventral striatocortical systems in 22q11. 2 deletion syndrome. Schizophrenia Bulletin, 48(2), 485-494. https://doi.org/10.1093/schbul/sbab139
Subjects
schizophrenia
;
functional connectivity
;
22q11ds
;
dopaminergic systems
;
striatal connectivity
;
genetic risk to psychosis
;
adolescent
;
digeorge syndrome
;
female
;
humans
;
magnetic resonance imaging
;
male
;
mental status and dementia tests
;
ventral striatum
;
young adult
;
adult
;
article
;
chromosome deletion 22q11
;
controlled study
;
female
;
functional connectivity
;
functional magnetic resonance imaging
;
gene deletion
;
genetic association
;
genetic risk
;
human
;
major clinical study
;
male
;
positive and negative syndrome scale
;
psychosis
;
schizophrenia
;
young adult
;
adolescent
;
anatomy and histology
;
complication
;
dementia assessment
;
digeorge syndrome
;
nuclear magnetic resonance imaging
;
pathophysiology
;
procedures
;
ventral striatum