IMPORTANCE Psychosis-risk studies have examined help-seeking adolescents and young adults. Population-based studies evaluating psychotic symptoms and neurocognitive performance across childhood are needed for "growth charting" cognitive development. We hypothesized that psychosis spectrum youths have delayed neurocognitive age relative to chronological age. We expected larger lags with increased symptom severity and in late adolescence and early adulthood.OBJECTIVES To examine neurocognitive age and compare typically developing participants with psychosis spectrum participants. DESIGN, SETTING, AND PARTICIPANTSThe Philadelphia Neurodevelopmental Cohort is a genotyped sample, with electronic medical records, enrolled in the study of brain behavior. In an academic and children's hospital health care network, a structured psychiatric evaluation was performed and a computerized neurocognitive battery administered to evaluate performance in several domains. From 18 344 youths in the recruitment pool who were aged 8 to 21 years, physically and cognitively capable of participating, and proficient in English, participants were randomly selected with stratification for age, sex, and ethnicity. A total of 9138 participants were enrolled in the study between November 1, 2009, and November 30, 2011, and 2321 endorsed psychotic symptoms: 1423 significant (psychosis spectrum) and 898 limited (psychosis limited). They had no comorbid medical conditions. They were compared with 981 participants endorsing significant other psychiatric symptoms and with 1963 typically developing children with no psychiatric or medical disorders. MAIN OUTCOMES AND MEASURESThe computerized neurocognitive battery provides accuracy and speed measures on 12 tests and speed measures alone on 2, yielding 26 measures used in a regression analysis to predict chronological age. Prediction was performed on the entire set and separately for each domain (executive, episodic memory, complex cognition, social cognition, and sensorimotor speed).RESULTS Throughout childhood and adolescence, the psychosis spectrum group had lower predicted age compared with the typically developing group and the group with other psychiatric symptoms. The psychosis spectrum group had a greater developmental lag than the psychosis limited group. The lags were most pronounced for complex cognition and social cognition and were smallest for sensorimotor speed.CONCLUSIONS AND RELEVANCE Individuals who endorse psychotic symptoms are neurocognitively delayed across the age range; this delay relates to symptom severity and is not prominent in other psychiatric disorders. Combined clinical and neurocognitive assessment can facilitate early detection and targeted intervention to delay or ameliorate disease progression.

Background Sustained high-level cognitive performance is of paramount importance for the success of space missions, which involve environmental, physiological and psychological stressors that may affect brain functions. Despite subjective symptom reports of cognitive fluctuations in spaceflight, the nature of neurobehavioral functioning in space has not been clarified. Methods We developed a computerized cognitive test battery (Cognition) that has sensitivity to multiple cognitive domains and was specifically designed for the high-performing astronaut population. Cognition consists of 15 unique forms of 10 neuropsychological tests that cover a range of cognitive domains including emotion processing, spatial orientation, and risk decision making. Cognition is based on tests known to engage specific brain regions as evidenced by functional neuroimaging. Here we describe the first normative and acute total sleep deprivation data on the Cognition test battery as well as several efforts underway to establish the validity, sensitivity, feasibility, and acceptability of Cognition. Results Practice effects and test-retest variability differed substantially between the 10 Cognition tests, illustrating the importance of normative data that both reflect practice effects and differences in stimulus set difficulty in the population of interest. After one night without sleep, medium to large effect sizes were observed for 3 of the 10 tests addressing vigilant attention (Cohen’s d=1.00), cognitive throughput (d=0.68), and abstract reasoning (d=0.65). Conclusions In addition to providing neuroimaging-based novel information on the effects of spaceflight on a range of cognitive functions, Cognition will facilitate comparing the effects of ground-based analogs to spaceflight, increase consistency across projects, and thus enable meta-analyses.

The 22q11.2 deletion syndrome (22q11DS) presents with medical and neuropsychiatric manifestations including neurocognitive deficits. Quantitative neurobehavioral measures linked to brain circuitry can help elucidate genetic mechanisms contributing to deficits. To establish the neurocognitive profile and neurocognitive “growth charts”, we compared cross-sectionally 137 individuals with 22q11DS ages 8–21 to 439 demographically matched non-deleted individuals with developmental delay (DD) and medical comorbidities and 443 typically developing (TD) participants. We administered a computerized neurocognitive battery that measures performance accuracy and speed in executive, episodic memory, complex cognition, social cognition and sensorimotor domains. The accuracy performance profile of 22q11DS showed greater impairment than DD, who were impaired relative to TD. Deficits in 22q11DS were most pronounced for face memory and social cognition, followed by complex cognition. Performance speed was similar for 22q11DS and DD, but 22q11DS individuals were differentially slower in face memory and emotion identification. The growth chart, comparing neurocognitive age based on performance relative to chronological age, indicated that 22q11DS participants lagged behind both groups from the earliest age assessed. The lag ranged from less than a year to over three years depending on chronological age and neurocognitive domain. The greatest developmental lag across the age range was for social cognition and complex cognition, with the smallest for episodic memory and sensorimotor speed, where lags were similar to DD. The results suggest that 22q11.2 microdeletion confers specific vulnerability that may underlie brain circuitry associated with deficits in several neuropsychiatric disorders and thereby help identify potential targets and developmental epochs optimal for intervention.

Background Chromosome 22q11.2 deletion syndrome (22q11DS) is a promising model for studying psychosis risk. Direct comparisons of psychosis features between 22q11DS and non-deleted (ND) individuals are limited by inconsistency and small samples. In the largest study to date, we compare 22q11DS to ND in comorbidities, functioning, cognition, and psychosis features across the full range of overall severity. Methods ND youths (n=150) aged 9-24 were matched to 22q11DS (n=150) on age and sex, stratifying for presence of psychosis-spectrum disorder. Individuals were evaluated for psychosis using the Structured Interview for Prodromal Syndromes (SIPS), and for ADHD, substance-related, and mood disorders. Differential item functioning analysis addressed whether 22q11DS differ from ND in the probability of clinically significant ratings while holding constant the overall level of psychosis. Results Onset of psychosis-proneness was similar among 22q11DS (mean=11.0 years) and ND (mean=12.1 years). Accounting for higher overall psychosis symptoms, 22q11DS participants were still more likely to manifest impaired stress tolerance, avolition, and ideational richness; ND were more likely to exhibit unusual thoughts, persecutory ideas, and bizarre thinking. Cognition was impaired in 22q11DS, but did not correlate with symptoms except ideational richness. Comorbid anxiety disorders were more likely in psychosis-spectrum 22q11DS; substance-related disorders were more likely in ND. GAF was similar in 22q11DS and ND, except among those with low total SIPS scores. Conclusions Individuals with 22q11DS share overarching similarities with ND in psychosis symptoms and age of onset for psychosis-proneness; this continues to support the 22q11DS model as a valuable window into mechanisms contributing to psychosis.

Visuospatial processing is a commonly assessed neurocognitive domain, with deficits linked to dysfunction in right posterior regions of the brain. With the growth of large-scale clinical research studies there is an increased need for efficient and scalable assessments of neurocognition, including visuospatial processing. The purpose of the current study was to use a novel method that combines item response theory (IRT) and computerized adaptive testing (CAT) approaches to create an abbreviated form of the computerized Penn Line Orientation Test (PLOT). The 24-item PLOT was administered to 8,498 youths (aged 8 to 21) as part of the Philadelphia Neurodevelopmental Cohort study and, by web-based data collection, in an independent sample of 4,593 adults from Great Britain as part of a television documentary. IRT-based CAT simulations were used to select the best PLOT items for an abbreviated form by performing separate simulations in each group and choosing only items that were selected as useful (i.e., high item discrimination and in the appropriate difficulty range) in at least one of the simulations. Fifteen items were chosen for the final, short form of the PLOT, indicating substantial agreement among the models in how they evaluated each item's usefulness. Moreover, this abbreviated version performed comparably to the full version in tests of sensitivity to age and sex effects. This abbreviated version of the PLOT cuts administration time by 50% without detectable loss of information, which points to its feasibility for large-scale clinical and genomic studies.