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Disrupted working memory circuitry and psychotic symptoms in 22q11.2 deletion syndrome.
Neuroimage Clin 2014; 4:392-402NC

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.

Authors+Show Affiliations

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.Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, University of California, Los Angeles, Los Angeles, CA 90095, USA.Feinstein Institute for Medical Research, Zucker Hillside Hospital, North Shore-LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA.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.Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, University of California, Los Angeles, Los Angeles, CA 90095, USA.Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, University of California, Los Angeles, Los Angeles, CA 90095, USA.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24567911

Citation

Montojo, C A., et al. "Disrupted Working Memory Circuitry and Psychotic Symptoms in 22q11.2 Deletion Syndrome." NeuroImage. Clinical, vol. 4, 2014, pp. 392-402.
Montojo CA, Ibrahim A, Karlsgodt KH, et al. Disrupted working memory circuitry and psychotic symptoms in 22q11.2 deletion syndrome. Neuroimage Clin. 2014;4:392-402.
Montojo, C. A., Ibrahim, A., Karlsgodt, K. H., Chow, C., Hilton, A. E., Jonas, R. K., ... Bearden, C. E. (2014). Disrupted working memory circuitry and psychotic symptoms in 22q11.2 deletion syndrome. NeuroImage. Clinical, 4, pp. 392-402. doi:10.1016/j.nicl.2014.01.010.
Montojo CA, et al. Disrupted Working Memory Circuitry and Psychotic Symptoms in 22q11.2 Deletion Syndrome. Neuroimage Clin. 2014;4:392-402. PubMed PMID: 24567911.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disrupted working memory circuitry and psychotic symptoms in 22q11.2 deletion syndrome. AU - Montojo,C A, AU - Ibrahim,A, AU - Karlsgodt,K H, AU - Chow,C, AU - Hilton,A E, AU - Jonas,R K, AU - Vesagas,T K, AU - Bearden,C E, Y1 - 2014/01/31/ PY - 2013/09/04/received PY - 2014/01/18/revised PY - 2014/01/21/accepted PY - 2014/2/26/entrez PY - 2014/2/26/pubmed PY - 2014/2/26/medline KW - Copy number variation KW - Endophenotype KW - Executive function KW - Psychosis KW - Velocardiofacial syndrome SP - 392 EP - 402 JF - NeuroImage. Clinical JO - Neuroimage Clin VL - 4 N2 - 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. SN - 2213-1582 UR - https://www.unboundmedicine.com/medline/citation/24567911/Disrupted_working_memory_circuitry_and_psychotic_symptoms_in_22q11_2_deletion_syndrome_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-1582(14)00011-4 DB - PRIME DP - Unbound Medicine ER -