MIAMI BEACH – Elevated levels of the same cytokine* were seen in three serious mental illnesses, but each illness had separate and distinct patterns of inflammatory markers, according to a study of immune function and mental illness.
Dr. David R. Goldsmith and colleagues conducted a meta-analysis that pooled results of three dozen studies of outpatients with bipolar disorder, schizophrenia, and major depression, to search for commonalities and differences in immune system activation.
The results were presented in a poster session at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.
Dr. David R. Goldsmith
Dr. Goldsmith, chief resident for the research track at Emory University’s department of psychiatry and behavioral sciences, Atlanta, and his collaborators looked at 36 studies examining individuals with major depressive disorder (MDD) (12 studies), euthymic bipolar disorder (14 studies), and chronic schizophrenia (10 studies). It is the first meta-analysis to pool results from studies of blood cytokine levels in outpatients with three serious mental illnesses, he said.
Serious mental illness is associated with immune activation, and previous studies have found activation of various cytokines in many mental illnesses. In the acute phase of mental illness, elevations have been found in both interleukin-6 (IL-6) and the cytokine receptor SIL-2R; for MDD and schizophrenia, cytokine levels are acutely increased, tend to decrease with treatment, and eventually rise again, he said.
However, Dr. Goldsmith and his collaborators found that only the cytokine* IL-6 was significantly elevated, compared with healthy controls, for all three illnesses included in the meta-analysis (P < .01 for all). IL-6 is associated with acute and chronic inflammation. For MDD and schizophrenia, two other cytokines were significantly elevated in the meta-analysis: the soluble IL-2 receptor (SIL–2R), a cytokine receptor associated with T-cell activation; and IL-1 beta, a cytokine produced by activated macrophages (P < .01 for all interactions, except P = .01 for IL-1 beta in bipolar disorder.)
For all three disorders, several inflammatory cytokines were significantly elevated, compared with healthy subjects.
Dr. Goldsmith noted some limitations of the meta-analysis. For example, there was a high degree of variability across studies in collection and storage techniques. In addition, no consistent set of tests exists to assess inflammation in mental illness, so the measures obtained varied from study to study. Potential confounders such as smoking and substance abuse were difficult to account for as well. The study limitations highlight the need for “a common set of inflammatory markers that must carefully be studied in order to understand the role of the cytokines in chronic psychiatric disorders and inform novel treatment decisions that may only be relevant to a subset of patients,” he noted.
Going forward, more uniform data collection and larger datasets should help delineate the association between inflammation and serious mental illness. “Despite the heterogeneity of the data, we do see some signal for the role of persistent immune activation, which we think will be important for some people with mental illness,” Dr. Goldsmith said in an interview.Dr. Goldsmith received the Janssen Pharmaceuticals Academic Research Mentoring Award in 2014. He reported no other conflicts of interest.
*Correction, 7/10/2015: An earlier version of this story mischaracterized an inflammatory marker. IL-6 is a cytokine.
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