Background 22q11. (ages 17C26) are needed. Resting-state networks (RSNs) in 22q11DS during this stage of brain development may thus provide insight into the dynamic changes in functional integration that influence the incidence of prodromal symptoms and neurocognitive deficits characteristic of this syndrome. Methods Independent component analysis (ICA) was performed to identify RSNs in a combined sample of 55 individuals with 22q11DS (27 males; age range 17C26) and 29 controls (17 males; age range 17C23, consisting of 8 siblings without the deletion and 21 typically developed individuals) from two research sites. We conducted a full factorial analysis to determine group differences between 22q11DS and controls. A Poisson regression analysis was conducted in the 22q11DS group to determine relationships of rs-fMRI network connectivity with psychiatric symptoms based on factors of the 18-item Brief Psychiatric Rating Scale. Nonparametric Spearman correlations were performed to test associations between within-network functional connectivity (FC) and performance on measures of verbal memory (California Verbal Learning Test) and executive function (Behavior Rating Inventory of Executive Function Adult version) in 22q11DS. Results Between-group network connectivity analyses revealed significant differences in 9 RSNs. Decreased network FC in 22q11DS was observed in the following networks: high-level visual processing network (HLVPN), low-level visual processing network (LLVPN), visual/precuneus network, left frontal-parietal network (LFPN), right frontal-parietal network (RFPN), and self-referential network (SRN). In contrast, greater network FC in 22q11DS was observed in subclusters of the 102036-29-3 IC50 LLVPN, visual/precuneus network, limbic network (LN), default mode network (DMN), and visuospatial processing network (VSPN). Increased functional connectivity of the right cuneus (visual/precuneus network) and right superior parietal lobule (DMN) in 22q11DS was positively associated with both thought disturbance and disorganization factors of the Brief Psychiatric Rating Scale (BPRS). Decreased functional connectivity in the left posterior cingulate (LLVPN) was associated with higher thought disturbance scores in 22q11DS. No associations with our neurocognitive measures passed correction for multiple comparisons (Bonferroni-corrected tests between siblings and controls were conducted for age, gender, and full scale IQ, where Therefore, since siblings did not differ in demographic measures, we combined them into one control group. All participants from both subsamples were native English speakers. Exclusion criteria for the SUNY sample included seizure disorder, fetal exposure to alcohol or drugs, parent-reported elevated lead levels or birth weight under 2500 grams, loss of consciousness lasting longer than 15?minutes, paramagnetic implants, or orthodontic braces. Potential controls with a IL1A personal or family history of schizophrenia or bipolar disorder were also excluded. Exclusion criteria for the UCLA subsample included additional neurological or medical condition that could affect imaging measures, insufficient fluency in English, substance or alcohol abuse and/or dependence within the last 6?months, and any condition that is a contraindication for MRI acquisition. Additional details of exclusion criteria for the UCLA subsample can be found in . Details of this sample have been described elsewhere . Additionally, our control group did not meet criteria for a psychotic disorder, based on information gathered from the administration of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID; ) for both sites. Diagnosis of 22q11DS in the SUNY subgroup was confirmed by fluorescence in situ hybridization (FISH). In the UCLA subgroup, 22q11DS diagnosis was confirmed by either FISH or array comparative genomic hybridization (CGH). Within the combined 22q11DS group, 24 were treated with one or more antipsychotic, stimulant, antidepressant, antianxiety, or mood stabilizing medications at the time of their scan. Two controls were treated with an antidepressant, antianxiety, or stimulant medication at the time of their scan. Due to the fact that data were taken from an ongoing longitudinal study, control participants in the SUNY study who presented with 102036-29-3 IC50 an anxiety disorder were excluded from the first timepoint; however, those who later developed an anxiety disorder were not. (The current report is based on 102036-29-3 IC50 data acquired at the fourth timepoint of the SUNY study.) Controls with ADHD/learning disability were not excluded from the SUNY sample at any timepoint, in order to maximize comparability between the control sample and the higher functioning participants in the 22q11DS group. Based on tests, demographic variables did 102036-29-3 IC50 not differ significantly between sites for either patients or controls. Table?1 contains information regarding demographics and medication for all 84 participants included in our group analysis. Additional information regarding participant characteristics between sites can 102036-29-3 IC50 be found in Additional file 1: Table S1. The institutional review boards of SUNY Upstate.