Daniel M. Keller, PhD

April 08, 2013

NICE, France — Interleukin 6 (IL-6), a cytokine with widespread functions, including proinflammatory ones, is emerging as a biomarker of disease severity in a number of conditions and now in staging bipolar disorder.

"The present study supports the distinction between 2 clusters in bipolar patients," said study investigator Iria Grande, MD, from the Bipolar Disorders Unit of the Hospital Clinic, University of Barcelona, Spain.

The staging model of bipolar disorder posits a progression from prodrome to more severe and refractory presentations. Among the biomarkers she investigated, "only [IL-6] shows us in the logistic regression...a relationship between the early and the late stage," she said.

Dr. Grande reported the findings here at EPA 2013: 21st European Congress of Psychiatry.

To validate the staging model and correlate IL-6 levels with stage, the researchers compared 125 patients with bipolar disorder with 25 first-degree relatives who were control participants. Both groups were aged 18 years or older.

Patients had a confirmed bipolar diagnosis and were euthymic, as determined by the Hamilton Depression Rating Score and the Young Mania Rating Scale for the previous month. Control individuals had no psychiatric diagnosis. The groups were well matched for age, sex, ethnicity, education, and occupational status. However, the Functioning Assessment Short Test (FAST) score for the patient group was 21.06 vs 4 for control individuals (P < .001), as would be expected.

Of the patients with bipolar disorder, 68.7% were type I, 15.7% were type II, 15.7% were unspecified, and 27% had psychiatric comorbidities.

Early-stage patients had fewer episodes (11 vs 16), a later age of onset (35 vs 19 years), a shorter elapsed time since the first episode (8 vs 29 years), and a lower FAST score (22 vs 31) compared with late-stage patients.

In a logistic regression analysis of various biomarkers — specifically, brain-derived neurotrophic factor, thiobarbituric acid reactive substances (byproducts of lipid peroxidation as a marker of oxidative stress), and IL-6 — only IL-6 significantly correlated with bipolar disorder when compared with control participants (odds ratio, 2.033; 95% confidence interval, 1.076 - 3.843; P = .029).

In an analysis of 109 patients, IL-6 was significantly associated with the number of episodes per year (P = .012), age at first episode (P = .033), and age (P < .001).

If borne out, the ability of IL-6 to distinguish stages of bipolar disorder may be clinically useful. "Early-stage bipolar patients typically have better functioning, fewer episodes, older age of onset of the disorder, as well as lower levels of IL-6," Dr. Grande said.

"Late-stage bipolar [patients] present a higher number of episodes and clinical correlates of a more severe disorder in terms of ability to function, as well as in terms of bodily changes such as increased inflammatory states."

Insight Into Disease Evolution

Session chairman Antoine Pelissolo, MD, PhD, professor of psychiatry at Pitié-Salpˆtrière Hospital in Paris, France, who was not involved in the study, commented to Medscape Medical News that in general, it is important to study biomarkers in psychiatry "because biological psychiatry for the moment [does not have] many implications in clinical practice, but now I think that these approaches are very interesting to describe the evolution of patients."

In the specific case of bipolar disorder, staging is "not that easy...and I think that biological markers for severity made a good correlation" in this study, he noted.

He added that given the time constraints of the presentation, one limitation was that no information was presented on the treatments used for these patients, "because the treatments can have an impact on the measures."

Dr. Grande and Dr. Pelissolo have disclosed no relevant financial relationships.

EPA 2013: 21st European Congress of Psychiatry: Abstract 1588. Presented April 7, 2013.

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