Disrupted working memory circuitry and psychotic symptoms in 22q11.2 deletion syndrome

C A Montojo; A Ibrahim; K H Karlsgodt; C Chow; A E Hilton; R K Jonas; T K Vesagas; C E Bearden

doi:10.1016/j.nicl.2014.01.010

Disrupted working memory circuitry and psychotic symptoms in 22q11.2 deletion syndrome

Neuroimage Clin. 2014 Jan 31:4:392-402. doi: 10.1016/j.nicl.2014.01.010. eCollection 2014.

Authors

C A Montojo¹, A Ibrahim², K H Karlsgodt³, C Chow², A E Hilton⁴, R K Jonas², T K Vesagas², C E Bearden⁵

Affiliations

¹ Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, University of California, Los Angeles, Los Angeles, CA 90095, USA ; Department of Psychology, 1285 Franz Hall, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Feinstein Institute for Medical Research, Zucker Hillside Hospital, North Shore-LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA.
⁴ Department of Psychology, 1285 Franz Hall, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, University of California, Los Angeles, Los Angeles, CA 90095, USA ; Department of Psychology, 1285 Franz Hall, University of California, Los Angeles, Los Angeles, CA 90095, USA ; Brain Research Institute, 695 Charles E Young Drive S, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Abstract

22q11.2 deletion syndrome (22q11DS) is a recurrent genetic mutation that is highly penetrant for psychosis. Behavioral research suggests that 22q11DS patients exhibit a characteristic neurocognitive phenotype that includes differential impairment in spatial working memory (WM). Notably, spatial WM has also been proposed as an endophenotype for idiopathic psychotic disorder, yet little is known about the neurobiological substrates of WM in 22q11DS. In order to investigate the neural systems engaged during spatial WM in 22q11DS patients, we collected functional magnetic resonance imaging (fMRI) data while 41 participants (16 22q11DS patients, 25 demographically matched controls) performed a spatial capacity WM task that included manipulations of delay length and load level. Relative to controls, 22q11DS patients showed reduced neural activation during task performance in the intraparietal sulcus (IPS) and superior frontal sulcus (SFS). In addition, the typical increases in neural activity within spatial WM-relevant regions with greater memory load were not observed in 22q11DS. We further investigated whether neural dysfunction during WM was associated with behavioral WM performance, assessed via the University of Maryland letter-number sequencing (LNS) task, and positive psychotic symptoms, assessed via the Structured Interview for Prodromal Syndromes (SIPS), in 22q11DS patients. WM load activity within IPS and SFS was positively correlated with LNS task performance; moreover, WM load activity within IPS was inversely correlated with the severity of unusual thought content and delusional ideas, indicating that decreased recruitment of working memory-associated neural circuitry is associated with more severe positive symptoms. These results suggest that 22q11DS patients show reduced neural recruitment of brain regions critical for spatial WM function, which may be related to characteristic behavioral manifestations of the disorder.

Keywords: Copy number variation; Endophenotype; Executive function; Psychosis; Velocardiofacial syndrome.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adolescent
Adult
Brain / physiopathology*
Connectome / methods
DiGeorge Syndrome / physiopathology*
Female
Humans
Magnetic Resonance Imaging / methods
Male
Memory Disorders / physiopathology*
Memory, Short-Term*
Nerve Net / physiopathology*
Neural Pathways / physiopathology
Psychotic Disorders / diagnosis
Psychotic Disorders / physiopathology*
Reproducibility of Results
Sensitivity and Specificity
Spatial Memory
Young Adult

Abstract

Publication types

MeSH terms

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