Inflammatory burden increased in overweight bipolar disorder patients

By Joanna Lyford, Senior medwireNews Reporter

Breakdown of the amino acid tryptophan is increased in euthymic, overweight individuals with bipolar disorder, show preliminary results from the BIPFAT study.

The finding supports a role for inflammatory mediators in the pathophysiology of obesity and metabolic disease in people with bipolar disorder, say Eva Reininghaus (Medical University of Graz, Austria) and fellow researchers.

The ongoing BIPFAT study was designed to explore the pathways that underlie the increased frequency of overweight and the metabolic syndrome in patients with bipolar disorder, with a particular focus on inflammation. The participants were 78 euthymic patients with bipolar disorder, of whom 54 were overweight (body mass index >25 kg/m²), and 156 mentally healthy controls, of whom 76 were overweight.

All had blood samples taken and assessed for markers of inflammatory monoamine biosynthesis – namely, tryptophan and kynurenine – as a proxy of dysregulated inflammatory homeostasis.

Reporting interim findings in Bipolar Disorders, Reininghaus et al reveal that levels of kynurenine were significantly higher in bipolar disorder patients compared with healthy controls, at 3.13 vs 2.59 µmol/L, as was the kynurenine-to-tryptophan ratio (an estimate of tryptophan breakdown), at 52.80 vs 45.23.

The same was true when the analysis was restricted to overweight individuals, with bipolar disorder patients having significantly higher levels of kynurenine (3.37 vs 2.77 µmol/L) and a higher kynurenine-to-tryptophan ratio (55.80 vs 48.87) than controls.

Among the patients with bipolar disorder, levels of kynurenine were significantly higher in those who were overweight compared with those of normal weight (3.37 vs 2.58 µmol/L), as was the kynurenine-to-tryptophan ratio (55.80 vs 46.06). The same was true among healthy controls.

The researchers say that the increased kynurenine levels and kynurenine-to-tryptophan ratio “indicate that tryptophan breakdown is increased in the euthymic state of [bipolar disorder], in general, despite the absence of symptoms (or overt psychopathology).”

They believe their findings provide “indirect evidence of increased activity of tryptophan-degrading indoleamine 2,3-dioxygenase in euthymic individuals with [bipolar disorder], underscoring the role of inflammatory mediators as a causative and/or consequent factor.”

They conclude: “More robust abnormalities in the overweight subsample underscore the additional inflammatory burden of medical comorbidity and suggest a shared pathophysiology as well as a mechanism mediating [bipolar disorder] and cardiovascular disease.”

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