Polygenic risk for schizophrenia and measured domains of cognition in individuals with psychosis and controls

Shafee, Rebecca; Nanda, Pranav; Padmanabhan, Jaya; Tandon, Neeraj; Alliey‐Rodriguez, Ney; Kalapurakkel, Sreeja; Weiner, Daniel J.; Gur, Raquel E.; Keefe, Richard S.E.; Hill, S. Kristian; Bishop, Jeffrey R.; Clementz, Brett A.; Tamminga, Carol A.; Gershon, Elliot S.; Pearlson, Godfrey D.; Keshavan, Matcheri S.; Sweeney, John A.; McCarroll, Steven A.; Robinson, Elise

doi:10.1038/s41398-018-0124-8

Cited by 65 publications

(54 citation statements)

References 62 publications

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“…GWAS studies have found a significant genetic overlap between cognition and schizophrenia [18][19][20] , and a recent study by Toulopoulou et al 21 showed that the variance in schizophrenia liability explained by PRS was partially mediated through cognitive deficit.…”

Section: Introductionmentioning

confidence: 99%

Jumping To Conclusions, General Intelligence, And Psychosis Liability: Findings From The Multi-Centre EU-GEI Case-Control Study

Tripoli

Quattrone

Ferraro³

et al. 2019

Preprint

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AbstractBackgroundThe “jumping to conclusions” (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.Methods817 FEP patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC (assessed by the number of beads drawn on the probabilistic reasoning “beads” task) and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.ResultsThe estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia Polygenic Risk Score (SZ PRS) was non-significantly associated with a higher number of beads drawn (B= 0.47, 95% CI −0.21 to 1.16, p=0.17); whereas IQ PRS (B=0.51, 95% CI 0.25 to 0.76, p<0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with higher level of psychotic-like experiences (PLE) in controls, including after controlling for IQ (B= −1.7, 95% CI −2.8 to −0.5, p=0.006), but did not relate to delusions in patients.Conclusionsthe JTC reasoning bias in psychosis is not a specific cognitive deficit but is rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to psychotic-like experiences, independent of IQ. The work has potential to inform interventions targeting cognitive biases in early psychosis.

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Section: Introductionmentioning

confidence: 99%

Jumping To Conclusions, General Intelligence, And Psychosis Liability: Findings From The Multi-Centre EU-GEI Case-Control Study

Tripoli

Quattrone

Ferraro³

et al. 2019

Preprint

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“…The composite score of the CMINDS, applied by Nakahara et al [27] , also showed a significant negative correlation between SZ-PRS and general cognitive abilities. Further reviewed studies have not been able to show a significant association between SZ-PRS and general cognitive abilities in cases [29,35] . Interestingly, Shafee et al [29] found a significant association between general cognitive abilities and SZ-PRS in the non-psychiatric group.…”

Section: General Cognitive Abilitiesmentioning

confidence: 87%

“…Interestingly, Shafee et al [29] found a significant association between general cognitive abilities and SZ-PRS in the non-psychiatric group. Therefore, they assumed that cognitive decrease in patients was due to morbid factors like disease progression, protective effects, treatment effects and possible substance abuse [29] .…”

Section: General Cognitive Abilitiesmentioning

confidence: 99%

“…Nakahara et al, 2018 [27] • C: N = 136 Ranlund et al, 2017 [28] • Shafee et al, 2018 [29] Bipolar-Schizophrenia Network for Intermediate Phenotypes: van Os et al, 2017 [30] Genetic Risk and Outcome of Psychosis: • IQ (information, block design, digit symbol coding, arithmetic (WAIS); baseline & 3-year follow-up) • IQ (information (every third item), block design (uneven items), digit symbol coding, arithmetic (uneven items) (WAIS-III short form); 6-year follow-up)…”

Section: Author and Year Sample Domain (Test) *Significantmentioning

confidence: 99%

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Let’s Talk about the Association between Schizophrenia Polygenic Risk Scores and Cognition in Patients and the General Population: A Review

2018

J Psychiatry Brain Sci

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In the late 19th century, Emil Kraepelin divided endogenous psychosis into manic-depressive psychosis and dementia praecox. The latter term described individuals with schizophrenia and highlights cognitive deficits as a core feature of this illness. Since first degree relatives show lower cognitive performance than healthy controls, but better performance than patients, cognitive functions are discussed as potential endophenotypes for schizophrenia. During the last years, several studies have explored the relationship between schizophrenia polygenic risk scores and cognition both in individuals with psychiatric diseases and the general population. Current research shows mixed results for specific cognitive domains as well as general cognitive abilities and intelligence. These ambiguous results in parts might be due to the heterogeneity of neuropsychological tests used to measure various cognitive domains. Most studies are also underpowered, given the small to moderate effects of schizophrenia polygenic risk scores on cognition. As sufficient sample sizes become more and more available by international consortia and national registries, future studies will probably shed light on the biological relationship between schizophrenia and cognition.

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“…The SZ PRS has been linked with prodromal motor deficits (7), as well as cognitive decline lower educational attainment in the general population (8,9). However, it is unclear whether SZ PRS predicts either cognition or cognitive decline in people with psychotic disorders (10).…”

Section: Introductionmentioning

confidence: 99%

Schizophrenia Polygenic Risk Score and 20-Year Course of Illness in Psychotic Disorders

Jonas

Lencz

et al. 2019

Preprint

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250 words Main Text: 3484 words Abstract Understanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnostics and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically-and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms (β = 0.21), lower GAF (β = -0.28), and worse cognition (β = -0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20years (AUC = 0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a powerful tool for diagnosis and treatment planning.

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Polygenic risk for schizophrenia and measured domains of cognition in individuals with psychosis and controls

Cited by 65 publications

References 62 publications

Jumping To Conclusions, General Intelligence, And Psychosis Liability: Findings From The Multi-Centre EU-GEI Case-Control Study

Jumping To Conclusions, General Intelligence, And Psychosis Liability: Findings From The Multi-Centre EU-GEI Case-Control Study

Let’s Talk about the Association between Schizophrenia Polygenic Risk Scores and Cognition in Patients and the General Population: A Review

Schizophrenia Polygenic Risk Score and 20-Year Course of Illness in Psychotic Disorders

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