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Assessment of a Person-Level Risk Calculator to Predict New-Onset Bipolar Spectrum Disorder in Youth at Familial Risk

Published on Aug 1, 2017in JAMA Psychiatry15.92
· DOI :10.1001/jamapsychiatry.2017.1763
Danella Hafeman16
Estimated H-index: 16
(University of Pittsburgh),
John Merranko7
Estimated H-index: 7
(University of Pittsburgh)
+ 11 AuthorsBoris Birmaher6
Estimated H-index: 6
(University of Pittsburgh)
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Abstract
Importance Early identification of individuals at high risk for the onset of bipolar spectrum disorder (BPSD) is key from both a clinical and research perspective. While previous work has identified the presence of a bipolar prodrome, the predictive implications for the individual have not been assessed, to date. Objective To build a risk calculator to predict the 5-year onset of BPSD in youth at familial risk for BPSD. Design, Setting, and Participants The Pittsburgh Bipolar Offspring Study is an ongoing community-based longitudinal cohort investigation of offspring of parents with bipolar I or II (and community controls), recruited between November 2001 and July 2007, with a median follow-up period of more than 9 years. Recruitment has ended, but follow-up is ongoing. The present analysis included offspring of parents with bipolar I or II (aged 6-17 years) who had not yet developed BPSD at baseline. Main Outcomes and Measures This study tested the degree to which a time-to-event model, including measures of mood and anxiety, general psychosocial functioning, age at mood disorder onset in the bipolar parent, and age at each visit, predicted new-onset BPSD. To fully use longitudinal data, the study assessed each visit separately, clustering within individuals. Discrimination was measured using the time-dependent area under the curve (AUC), predicting 5-year risk; internal validation was performed using 1000 bootstrapped resamples. Calibration was assessed by comparing observed vs predicted probability of new-onset BPSD. Results There were 412 at-risk offspring (202 [49.0%] female), with a mean (SD) visit age of 12.0 (3.5) years and a mean (SD) age at new-onset BPSD of 14.2 (4.5) years. Among them, 54 (13.1%) developed BPSD during follow-up (18 with BD I or II); these participants contributed a total of 1058 visits, 67 (6.3%) of which preceded new-onset BPSD within the next 5 years. Using internal validation to account for overfitting, the model provided good discrimination between converting vs nonconverting visits (AUC, 0.76; bootstrapped 95% CI, 0.71-0.82). Important univariate predictors of outcome (AUC range, 0.66-0.70) were dimensional measures of mania, depression, anxiety, and mood lability; psychosocial functioning; and parental age at mood disorder. Conclusions and Relevance This risk calculator provides a practical tool for assessing the probability that a youth at familial risk for BPSD will develop new-onset BPSD within the next 5 years. Such a tool may be used by clinicians to inform frequency of monitoring and treatment options and for research studies to better identify potential participants at ultra high risk of conversion.
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  • Citations (25)
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References36
Newest
#1Paolo Fusar-Poli (NIHR: National Institute for Health Research)H-Index: 62
#2Grazia Rutigliano (UniPi: University of Pisa)H-Index: 13
Last.Philip McGuire ('KCL': King's College London)H-Index: 105
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#1Tania Perich (Black Dog Institute)H-Index: 9
#2Phoebe Lau (Black Dog Institute)H-Index: 7
Last.Basia Radlinska (Black Dog Institute)H-Index: 1
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Cited By25
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#1Alex S. Cohen (LSU: Louisiana State University)H-Index: 57
#2Taylor L. Fedechko (LSU: Louisiana State University)H-Index: 1
Last.Brita Elvevåg (University of Tromsø)H-Index: 13
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#1Gianni L. Faedda (McLean Hospital)H-Index: 33
#2Ross J. Baldessarini (Harvard University)H-Index: 99
Last.M. Hillegers (UU: Utrecht University)H-Index: 4
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#1Antonin Sebela (First Faculty of Medicine, Charles University in Prague)H-Index: 2
#2Marian Kolenic (Charles University in Prague)H-Index: 2
Last.Michal Goetz (Charles University in Prague)H-Index: 6
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#1Nadine M. Melhem (University of Pittsburgh)H-Index: 32
#2Giovanna Porta (University of Pittsburgh)H-Index: 22
Last.J. John Mann (Columbia University)H-Index: 108
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#1Danella Hafeman (University of Pittsburgh)H-Index: 16
#2Henry W. Chase (University of Pittsburgh)H-Index: 22
Last.John Merranko (University of Pittsburgh)H-Index: 7
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