Bipolar Spectrum Disorder in Youth Predicted By New Risk Calculator

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The calculator was able to predict new-onset BPSD based on factors including anxiety, manic symptoms, and depressive symptoms.
The calculator was able to predict new-onset BPSD based on factors including anxiety, manic symptoms, and depressive symptoms.

Researchers have designed a risk calculator to predict the 5-year risk of new-onset bipolar spectrum disorder (BPSD) in youth with familial risk for BPSD, according to a study published in JAMA Psychiatry 1.

Danella M Hafeman, MD, PhD, from the department of psychiatry at the University of Pittsburgh in Pennsylvania, and colleagues conducted a cohort study composed of 412 at-risk offspring of parents with bipolar I or II (BD I or II) (age 6 to 17) who had not yet developed BPSD at baseline.

“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,” commented Dr Hafeman.

The researchers chose participants from The Pittsburgh Bipolar Offspring Study, an ongoing community-based cohort investigation of offspring of parents with bipolar disorder I or II recruited between November 2001 and July 2007, with a median follow-up period of more than 9 years. Parents and their children were interviewed using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL) for non-mood disorders, the K-SADS Mania Rating Scales (KMRS), and the depression items from the K-SADS-Present Version (KDRS). Follow-up evaluations were performed every 2 years to assess for the onset of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) disorders.

The researchers used assessment as the unit of analysis, allowing them to use presenting symptoms at baseline and follow-up visits, and to model the time to new-onset BPSD separately from each assessment.

Of the 412 participants, 54 (13.1%) developed new-onset BPSD (9 BD I, 9 BD II, and 36 bipolar disorder-not otherwise specified [BD-NOS]) during follow-up visits. The participants attended a total of 1058 visits with a median of 2 years between visits, and of these visits, 104 participants (9.8%) were “converting,” meaning that they preceded the onset of BPSD over the remaining follow-up period (median, 5.9 years). Of the participants, 67 (6.3%) converted to BPSD within the next 5 years.

After internal validation, the risk calculator differentiated between converting vs nonconverting visits with a 5-year area under the curve (AUC) of 0.76 (95% Cl, 0.71-0.82), indicating good discrimination.

The calculator was able to predict new-onset BPSD based on anxiety, manic symptoms, depressive symptoms, mood lability, poor general psychosocial functioning, and earlier parental age.

“While risk calculators have been used widely in nonpsychiatric medical disorders, the development of such models in psychiatry has been limited,” wrote Dr Hafeman. “This study developed the first risk calculator to predict the onset of BPSD in youth at familial risk, to our knowledge, and one of the first risk calculators for us in psychiatry.”

Summary and Clinical Applicability

The risk calculator provides a tool for assessing the probability that an offspring of a parent with BP I or II will develop new-onset BPSD within the next 5 years.

Physicians may use the calculator to provide prognostic information to the patient and his or her family, as well as moderate frequency of monitoring and early intervention.

Limitations and Disclosures

  • The sample was not clinically recruited, but rather selected without regard to symptoms in the offspring.
  • It is unknown how the risk calculator would perform in individuals without a familial history of BD, as the calculator was intentionally built using a group of offspring of parents with BD.
  • While the risk calculator was internally validated with state-of-the-art methods, it was not externally validated.
  • The sample included many participants with new-onset BPSD, but few had BP I or II.
  • Follow-up visits were scheduled every 2 years, so the precise timing of BPSD onset is unknown.


Hafeman DM, Merranko J, Goldstein TR, et al. Assessment of a person-level risk calculator to predict new-onset bipolar spectrum disorder in youth at familial risk [published online July 5, 2017]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.1763

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