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

[22q11.2 deletion syndrome]

22 q 11 .2 deletion syndrome (22 q 11 DS ) is a recurrent genetic mutation that is highly penetrant for psychosis . Behavioral research suggests that 22 q 11 DS 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 22 q 11 DS . In order to investigate the neural systems engaged during spatial WM in 22 q 11 DS patients , we collected functional magnetic resonance imaging (fMRI ) data while 41 participants (16 22 q 11 DS patients , 25 demographically matched controls ) performed a spatial capacity WM task that included manipulations of delay length and load level . Relative to controls , 22 q 11 DS 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 22 q 11 DS . 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 22 q 11 DS 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 22 q 11 DS patients show reduced neural recruitment of brain regions critical for spatial WM function , which may be related to characteristic behavioral manifestations of the disorder .

Diseases
Validation

Diseases presenting "psychosis" symptom

22q11.2 deletion syndrome

child syndrome

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

sneddon syndrome

This symptom has already been validated