Neurocognitive predictors of transition to psychosis: medium- to long-term findings from a sample at ultra-high risk for psychosis

BackgroundIndividuals at ultra-high risk (UHR) for psychosis show reduced neurocognitive performance across domains but it is unclear which reductions are associated with transition to frank psychosis. The aim of this study was to investigate differences in baseline neurocognitive performance between UHR participants with (UHR-P) and without transition to psychosis (UHR-NP) and a healthy control (HC) group and examine neurocognitive predictors of transition over the medium to long term.MethodA sample of 325 UHR participants recruited consecutively from the Personal Assessment and Crisis Evaluation (PACE) Clinic in Melbourne and 66 HCs completed a neurocognitive assessment at baseline. The UHR group was followed up between 2.39 and 14.86 (median = 6.45) years later. Cox regression was used to investigate candidate neurocognitive predictors of psychosis onset.ResultsThe UHR group performed more poorly than the HC group across a range of neurocognitive domains but only performance on digit symbol coding and picture completion differed between the groups. The risk of transition was only significantly associated with poorer performance on visual reproduction [hazard ratio (HR) 0.919, 95% confidence interval (CI) 0.876–0.965, p = 0.001] and matrix reasoning (HR 0.938, 95% CI 0.883–0.996, p = 0.037). These remained significant even after controlling for psychopathology at baseline.ConclusionsThis study is the longest follow-up of an UHR sample to date. UHR status was associated with poorer neurocognitive performance compared to HCs on some tasks. Cognition at identification as UHR was not a strong predictor of risk for transition to psychosis. The results suggests the need to include more experimental paradigms that isolate discrete cognitive processes to better understand neurocognition at this early stage of illness.

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Intelligence trajectories in individuals at ultra-high risk for psychosis: An 8-year longitudinal analysis

10.31234/osf.io/45tpn ◽

2021 ◽

Author(s):

Nicholas Cheng ◽

Ashleigh Lin ◽

Stephen C. Bowden ◽

Caroline Gao ◽

Alison R. Yung ◽

...

Keyword(s):

High Risk ◽

Psychotic Disorder ◽

Fluid Intelligence ◽

Block Design ◽

Small Sample ◽

Linear Mixed Effects ◽

Ultra High Risk ◽

Matrix Reasoning

Background: Cognitive impairment is a well-documented predictor of transition to a full-threshold psychotic disorder amongst individuals at ultra-high risk (UHR) for psychosis. However, less is known about whether change in cognitive functioning differs between those who do and do not transition to a psychotic disorder. Studies to date have not examined trajectories in intelligence constructs (e.g., acquired knowledge and fluid intelligence), which have demonstrated marked impairments in individuals with schizophrenia. This study aimed to examine intelligence trajectories using longitudinal data from three time-points, spanning an average of eight years.Methods: Participants (N=139) at UHR for psychosis completed the Wechsler Abbreviated Scale of Intelligence (WASI) at each follow-up. Linear mixed-effects models mapped changes in WASI Full-Scale IQ (FSIQ) and T-scores on Vocabulary, Similarities, Block Design, and Matrix Reasoning subtests.Results: The sample showed stable and improving trajectories for FSIQ and all subtests. There were no significant differences in trajectories between those who did and did not transition to psychosis and between individuals with good and poor functional outcomes. However, although not significant, the trajectories of the acquired knowledge subtests diverged between transitioned and non-transitioned individuals (β=−0.12, 95% CI [−0.29, 0.05] for Vocabulary and β=−0.14, 95% CI [−0.33, 0.05] for Similarities). Conclusions: There was no evidence for long-term deterioration in intelligence trajectories in this UHR sample. As the small sample of individuals who transitioned may have limited our ability to detect subtle differences, future studies with larger sample sizes are needed to explore potential differences in intelligence trajectories between UHR transition groups.

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Peripheral levels of superoxide dismutase and glutathione peroxidase in youths in ultra-high risk for psychosis: a pilot study

CNS Spectrums ◽

10.1017/s1092852917000803 ◽

2017 ◽

Vol 24 (03) ◽

pp. 333-337 ◽

Cited By ~ 5

Author(s):

Maiara Zeni-Graiff ◽

Adiel C. Rios ◽

Pawan K. Maurya ◽

Lucas B. Rizzo ◽

Sumit Sethi ◽

...

Keyword(s):

Oxidative Stress ◽

At Risk ◽

Superoxide Dismutase ◽

High Risk ◽

Glutathione Peroxidase ◽

Healthy Control Group ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Ultra High Risk ◽

Healthy Control

IntroductionOxidative stress has been documented in chronic schizophrenia and in the first episode of psychosis, but there are very little data on oxidative stress prior to the disease onset.ObjectiveThis work aimed to compare serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in young individuals at ultra-high risk (UHR) of developing psychosis with a comparison healthy control group (HC).MethodsThirteen UHR subjects and 29 age- and sex-matched healthy controls (HC) were enrolled in this study. Clinical assessment included the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I) or the Kiddie-SADS-Present and Lifetime Version (K-SADS-PL), and the Global Assessment of Functioning (GAF) scale. Activities of SOD and GPx were measured in serum by the spectrophotometric method using enzyme-linked immunosorbent assay kits.ResultsAfter adjusting for age and years of education, there was a significant lower activity of SOD and lower GPX activity in the UHR group compared to the healthy control group (rate ratio [RR]=0.330, 95% CI 0.187; 0.584, p<0.001 and RR=0.509, 95% CI 0.323; 0.803, p=0.004, respectively). There were also positive correlations between GAF functioning scores and GPx and SOD activities.ConclusionOur results suggest that oxidative imbalances could be present prior to the onset of full-blown psychosis, including in at-risk stages. Future studies should replicate and expand these results.

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Lymphadenectomy in Early-Stage Intermediate-/High-Risk Endometrioid Endometrial Cancer: Clinical Characteristics and Outcomes in an Australian Cohort

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001039 ◽

2017 ◽

Vol 27 (7) ◽

pp. 1379-1386 ◽

Cited By ~ 1

Author(s):

Rhonda Farrell ◽

Suzanne C. Dixon ◽

Jonathan Carter ◽

Penny M. Webb

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

High Risk ◽

Adjuvant Treatment ◽

Cox Regression ◽

Early Stage ◽

Cox Regression Analysis ◽

Cancer Study ◽

Stage Ib ◽

Australian Cohort

ObjectiveThe role of lymphadenectomy (LND) in early-stage endometrial cancer (EC) remains controversial. Previous studies have included low-risk patients and nonendometrioid histologies for which LND may not be beneficial, whereas long-term morbidity after LND is unclear. In a large Australian cohort of women with clinical early-stage intermediate-/high-risk endometrioid EC, we analyzed the association of LND with clinicopathological characteristics, adjuvant treatment, survival, patterns of disease recurrence, and morbidity.Materials and MethodsFrom a larger prospective study (Australian National Endometrial Cancer Study), we analyzed data from 328 women with stage IA grade 3 (n = 63), stage IB grade 1 to 3 (n = 160), stage II grade 1 to 3 (n = 71), and stage IIIC1/2 grade 1 to 3 (n = 31/3) endometrioid EC. Overall survival (OS) was estimated using Kaplan-Meier methods. The association of LND with OS was assessed using Cox regression analysis adjusted for age, stage, grade, and adjuvant treatment. The association with risk of recurrent disease was analyzed using logistic regression adjusted for age, stage, and grade. Morbidity data were analyzed using χ2 tests.ResultsMedian follow-up was 45.8 months. Overall survival at 3 years was 93%. Lymphadenectomy was performed in 217 women (66%), 16% of this group having positive nodes. Median node count was 12. There were no significant differences in OS between LND and no LND groups, or by number of nodes removed. After excluding stage IB grade 1/2 tumors, there was no association between LND and OS among a “high-risk” group of 190 women with a positive node rate of 24%. However, a similar cohort (n = 71) of serous EC in the Australian National Endometrial Cancer Study had improved survival after LND. Women who underwent LND had significantly higher rates of critical events (5% vs 0%, P = 0.02) and lymphoedema (23% vs 4%, P < 0.0001).ConclusionsIn this cohort with early-stage intermediate-/high-risk endometrioid EC, LND did not improve survival but was associated with significantly increased morbidity.

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Dose-response association of implantable device-measured physical activity with long-term cardiac death and all-cause mortality in patients at high risk of sudden cardiac death: a cohort study

International Journal of Behavioral Nutrition and Physical Activity ◽

10.1186/s12966-020-01026-2 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Xiaoyao Li ◽

Shuang Zhao ◽

Keping Chen ◽

Wei Hua ◽

Yangang Su ◽

...

Keyword(s):

Physical Activity ◽

Older Adults ◽

High Risk ◽

Sudden Cardiac Death ◽

Dose Response ◽

Cardiac Death ◽

Cox Regression ◽

Cardiac Resynchronization ◽

All Cause Mortality

Abstract Background Cardiovascular implantable electronic devices (CIEDs) with physical activity (PA) recording function can continuously and automatically collect patients’ long-term PA data. The dose-response association of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRTD)-measured PA with cardiovascular outcomes in patients at high risk of sudden cardiac death (SCD) was investigated. Methods In total, 822 patients fulfilling the inclusion criteria were included and divided into three groups according to baseline PA tertiles: tertile 1 (< 8.04%, n = 274), tertile 2 (8.04–13.24%, n = 274), and tertile 3 (> 13.24%, n = 274). The primary endpoint was cardiac death, the secondary endpoint was all-cause mortality. Results During a mean follow-up of 59.7 ± 22.4 months, cardiac death (18.6% vs 8.8% vs 5.5%, tertiles 1–3, P < 0.001) and all-cause mortality (39.4% vs 20.4% vs 9.9%, tertiles 1–3, P < 0.001) events decreased according to PA tertiles. Compared with patients younger than 60 years old, older patients had a lower average PA level (9.6% vs 12.8%, P < 0.001) but higher rates of cardiac death (13.2% vs 8.1%, P = 0.024) and all-cause mortality (28.4% vs 16.7%, P < 0.001) events. Adjusted multivariate Cox regression analyses showed that a higher tertile of PA was associated with a lower risk of cardiac death (hazard ratio (HR) 0.41, 95% confidence interval (CI): 0.25–0.68, tertile 2 vs tertile 1; HR 0.28, 95% CI: 0.15–0.51, tertile 3 vs tertile 1, Ptrend < 0.001). Similar results were observed for all-cause mortality. The dose-response curve showed an inverse non-linear pattern, and a significant reduction in endpoint risk was observed at the low-moderate PA level. The HR for cardiac death was reduced by half with 12.32% PA (177 min), and the HR for all-cause mortality was reduced by half with 11.92% PA (172 min). Subgroup analysis results indicated that older adults could benefit from PA and the range for achieving optimal benefits might be lower. Conclusions PA monitoring may aid in long-term management of patients at high risk of SCD. More PA will generate better survival benefits, but even low-moderate PA is already good especially for older adults, which is relatively easy to achieve.

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Long-term employment among people at ultra-high risk for psychosis

Schizophrenia Research ◽

10.1016/j.schres.2016.11.033 ◽

2017 ◽

Vol 184 ◽

pp. 26-31 ◽

Cited By ~ 13

Author(s):

Jack Cotter ◽

Ashleigh Lin ◽

Richard J. Drake ◽

Andrew Thompson ◽

Barnaby Nelson ◽

...

Keyword(s):

High Risk ◽

Ultra High Risk

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Long-term follow-up of women enrolled in a randomized trial of adjuvant chemotherapy for early stage ovarian cancer (ICON1)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.5509 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 5509-5509 ◽

Cited By ~ 15

Author(s):

A. C. Swart

Keyword(s):

Ovarian Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Adjuvant Treatment ◽

Early Stage ◽

Risk Groups ◽

P Value ◽

Long Term Follow Up

5509 Background: ICON1 and a meta-analysis of all relevant trials demonstrated an improvement in 5 year recurrence-free and overall survival (RFS and OS) for women with early-stage epithelial ovarian cancer (ES EOC) treated with adjuvant chemotherapy compared to no adjuvant chemotherapy. We aimed to determine if this initial benefit is maintained long-term and whether benefit is different with different risk groups of patients defined by stage, grade and histology. Method: 477 women with ES EOC were recruited from centres in Italy (271 women) UK (195) Switzerland (11) between August 1991 and January 2000. 5-year results were presented at ASCO 2001. Systematic long-term follow up was planned and completed in May 2006. Results: With a median follow-up of 9.2 years, 168 women have developed recurrent disease or died and 144 women have died. The Hazard Ratio (HR) for RFS of 0.70 in favour of adjuvant chemotherapy (95% CI 0.52–0.95 p= 0.023) translated into an improvement of 10-year absolute RFS of 10% from 57 to 67%. For OS, HR was 0.74 (95% CI 0.53–1.02 p= 0.066), a corresponding improvement in 10-year absolute OS of 8% from 64% to 72%. 26% of patients died from causes other than ovarian cancer. Stage I patients were grouped as low (Ia, grade 1), medium (Ia grade 2, Ib or Ic grade 1) and high risk (Ia, grade 3, Ib or IC grade 2 or 3, any clear cell). The test of interaction between risk groups and adjuvant treatment for RFS and OS was 0.055 and 0.13, respectively. The HR, 95%CI and p value are summarised in the table . Conclusions The long-term benefit of adjuvant treatment on RFS is confirmed. There is clear evidence that adjuvant chemotherapy reduces the risk of recurrence/death or death alone in high-risk patients but not in the low-risk group. [Table: see text] [Table: see text]

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Breast Cancer Index and risk stratification in luminal subtypes: A trans-ATAC study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.534 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 534-534

Author(s):

Ivana Sestak ◽

Yi Zhang ◽

Catherine A. Schnabel ◽

Jack M. Cuzick ◽

Mitchell Dowsett

Keyword(s):

Breast Cancer ◽

High Risk ◽

Cox Regression ◽

Early Stage ◽

Risk Groups ◽

Low Risk ◽

Luminal A ◽

Prognostic Information ◽

Prognostic Performance ◽

Breast Cancer Index

534 Background: The Breast Cancer Index (BCI) is a gene-expression based signature that provides prognostic information for overall (0-10 years) and late (5-10 years) distant recurrence (DR) and prediction of extended endocrine benefit in hormone receptor positive (HR+) early stage breast cancer. The current analysis aims to further characterize, correlate and compare the prognostic performance of BCI in luminal subtypes based on immunohistochemical classification. Methods: 670 postmenopausal women with HR+, LN- disease from the TransATAC cohort were included in this analysis. Luminal A-like tumors (LumA) were identified as those with ER+ and/or PR+ and HER2 -, and Ki67 < 20% by IHC. All other tumors were classified as Luminal B-like (LumB) for this analysis. Primary endpoint was DR. Cox regression models were used to examine BCI prognostic performance according to luminal subtype, adjusting for the clinicopathological model Clinical Treatment Score (CTS). Results: 452 (67.5%) patients were classified as LumA and 218 (32.5%) as LumB. BCI was highly prognostic in LumA cancers (adjusted HR = 1.57 (1.23-1.96), P < 0.001, ΔLR-χ2= 14.09), but not in LumB tumors (adjusted HR = 1.20 (0.94-1.52, P = 0.14, ΔLR-χ2= 2.23). In LumA, 10-year DR risks in BCI intermediate and high risk groups were very similar (25.6% (16.4-38.6) and 25.3% (13.5-44.3), respectively) and significantly different from BCI low (3.9% (2.1-7.0); HR = 7.47 (3.50-15.96) and HR = 8.13 (3.27-20.23), respectively). In LumB, 10-year DR risks in BCI low and BCI intermediate risk groups (13.8% (6.8-26.9) and 14.6% (8.3-24.9), respectively) were very similar and significantly lower than for the BCI high (29.1% (20.0-41.1)). Lum subtyping was only prognostic in the BCI low risk group (LumA vs. LumB: HR = 4.27 (1.65-11.02)) but not in the other two BCI risk groups. Conclusions: BCI provided significant prognostic information in Lum A subtype. These results show that BCI intermediate and high risk had similar risk of DR in LumA tumors, while shared similarly low risk of DR as BCI-low in LumB tumors. Further evaluation is needed to elucidate the distinct mechanisms underlying each classification system.

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Value of clinical treatment score post-5 years (CTS5) for late relapse risk assessment in patients with early-stage HER2+ breast cancer (BC) in the north central cancer treatment group (NCCTG) N9831 (Alliance) trial.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.529 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 529-529

Author(s):

Tanmayi Pai ◽

Angelica Gil ◽

Yaohua Ma ◽

Zhuo Li ◽

Pooja Advani ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Tumor Size ◽

Cox Regression ◽

Early Stage ◽

Low Risk ◽

Late Relapse ◽

Intermediate Risk ◽

Relapse Risk ◽

Significant Difference

529 Background: Multiple prognostic models exist to predict late relapse risk in early stage hormone receptor-positive (HR+) breast cancer (BC). The CTS5 is one such model that has been validated in HR+ HER2-negative BC. The value of this model in HR+ HER2+ has not been established. Here, we assessed CTS5 in patients (pts) with early stage HER2+ BC treated in the NCCTG N9831 (Alliance) trial. Methods: Pts with stage I-III HER2+ HR+ BC who survived ≥ 5 years were included. The online CTS5 calculator was used to determine CTS5 score and risk group (low, intermediate, and high) based on age, tumor size, grade, and number of involved nodes. Kaplan-Meier (KM) estimates, Cox regression models, and C index were used for analysis. Results: From 3,130 pts, 1,204 pts met the criteria and were included. Median age was 49 (22-79) years and median tumor size was 2.4 (0.1-12) cm. 63.6% had grade 3 tumors, 33.6% grade 2, and 2.8% grade 1. Median follow up was 10.89 (5.01-15.32) years. Based on CTS5, 821 (68.2%) pts were classified as high risk, 289 (24%) as intermediate risk, and 94 (7.8%) as low risk. Overall, using univariate Cox regression analysis, there was no statistically significant difference in recurrence free survival (RFS) among pts with intermediate vs. low (HR 0.47 95%CI 0.18-1.22, p = 0.12) and high vs. low (HR1.23 95%CI0.57-2.67, p = 0.6) with the C index of 0.58. Among pts who received concurrent trastuzumab (H) with HR+ BC, there was also no statistical difference in RFS between high vs. low (HR 0.68 95%CI0.24-1.97, p = 0.48) with the C index of 0.55. Paradoxically, pts with intermediate risk had better RFS than low risk (HR 0.18 95%CI0.03-0.97, p = 0.05). As a continuous variable, there is also no significant improvement in RFS per 1 unit increase in CTS5 score (HR 1.19 95%CI 0.73-1.96, p = 0.49) with the C index of 0.54. After 5 years, 7.06% (n = 30/425) of HR+ pts treated with concurrent H recurred. Conclusions: The CTS5 model is not prognostic in pts with early stage HR+ HER2+ BC receiving adjuvant H. While most HR+ HER2+ pts are classified as high risk by CTS5, the recurrence between years 5-10 was low in pts who received adjuvant H. This study highlights the need to develop a new predictive model for risk of late relapse in this specific group of pts to enable clinicians to determine which pts would benefit from extended adjuvant endocrine therapy. Support: BCRF-19-161, U10CA180821, Genentech. https://acknowledgments.alliancefound.org Clinical trial information: NCT00005970 .

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