Figure 1.

Effects of CNVs on cognitive and behavioral dimensions

(A) RGDs and dimensional phenotyping, current knowledge, and hypotheses. NPD CNVs affect multiple cognitive and behavioral dimensions and increase the risk for ASD, SZ, and ID, albeit with different effect sizes. This scenario incorporates key features of the genomic architecture of psychiatric disorders including polygenicity, phenotypic variability -also referred to as pleiotropy- and genetic overlap between conditions, cognitive and behavioral dimensions. In this scenario, combinations in different proportions of common dimensions lead to different clinical manifestations classified as psychiatric diagnoses. The 4 dimensions described in figure 1A may approximately align with RDoC dimensions: Cognitive ability → Cognitive systems; Disorganized thought/perceptual abnormalities → perception (a (sub)construct of the cognitive systems domain); Social responsiveness → Systems for social processes; Anxiety-mood → Negative valence.

(B) Effects of 1q21.1, 16p11.2 and 22q11.2 deletions and duplications on neurocognitive and behavioral functioning. Measures are standardized to control mean and standard deviation. For visualization purposes, scores are converted to absolute, positive values to highlight impairments in CNV groups compared to controls (Z=0 indicated by vertical dashed line). Behavioral measures = scales from Child Behavior Checklist (CBCL). Social responsiveness was assessed by the Social Responsiveness Scale (SRS). Sample sizes: 1q21.1 Del n =11, 1q21.1 Dup n = 12 (REF); 16p11.2 Del n = 137, 16p11.2 Dup n = 127 (11); 22q11.2 Del n = 99, 22q11.2 Dup n = 34 (21); combined controls n = 214.