Pathways to understanding psychosis through rare – 22q11.2DS - and common variants

Copy Number Variant Risk Scores Associated With Cognition, Psychopathology, and Brain Structure in Youths in the Philadelphia Neurodevelopmental Cohort

“…Many so-called genomic disorders, historically characterized by sets of clinical features and now linked to specific recurrent CNVs, are associated with autism, schizophrenia, and intellectual disability . For example, up to 25% of individuals with 22q11.2 deletion syndrome develop schizophrenia . Multiple recurrent CNVs have also been associated with cognitive outcomes and depressive symptoms in adults .…”

“…[1][2][3][4][5] For example, up to 25% of individuals with 22q11.2 deletion syndrome develop schizophrenia. 6 Multiple recurrent CNVs have also been associated with cognitive outcomes 7,8 and depressive symptoms in adults. 9 However, most clinically relevant CNVs are ultra-rare, with frequencies too low for sufficiently powered tests of genomewide association.…”

Neuropsychological Profile of 25 Brazilian Patients with 22q11.2 Deletion Syndrome: Effects of Clinical and Socioeconomic Variables

“…A significant discrepancy between the verbal comprehension and perceptual organization indexes has been reported since the first studies on 22q11.2SD [10,12,13,17], particularly in pediatric samples [17]. Studies with larger cohorts of patients have reported declines, particularly in verbal IQ, with increasing age [17,18]. Our results, therefore, reinforce previous evidence that in individuals with 22q11.2DS, verbal reasoning may be better developed in early stages of development, while working memory [49,50], perceptual organization [12,13], and processing speed [51] constitute areas of cognitive weakness.…”

“…A significant discrepancy (three to eight points on the standard scale) between verbal and performance IQs is reported in almost 75% of individuals, with better performance in the verbal domain [10,11,[15][16][17]. There is evidence of a decline in verbal IQ scores with age, possibly associated with the emergence of psychiatric symptoms [15,16,18].…”

“…Neuropsychological findings include deficits in a wide range of cognitive functions, such as attention, executive functioning, and visuospatial processing [11,17,[19][20][21][22][23]. Correlates of cognitive and intellectual deficits have been attributed to volumetric alterations in patients with 22q11.2DS [24][25][26][27], as well as to the emergence of psychotic symptoms [18,28,29].…”