Peripheral zinc and neopterin concentrations are associated with mood severity in bipolar disorder in a gender-specific manner

Psychiatry Res. 2017 Sep;255:52-58. doi: 10.1016/j.psychres.2017.05.022. Epub 2017 May 17.


Bipolar disorder (BD) is a recurrent, episodic mood disorder for which there are no current diagnostic, prognostic or theranostic biomarkers. Two peripheral markers of the acute phase immune response, zinc and neopterin, are consistently associated with severity of depression in literature. Given gender differences in clinical presentation of BD and in inflammatory processes, we aimed to explore the interaction between gender and immune biomarkers to predict mood severity in BD. Participants with DSM IV BD I and II were recruited through the Pennsylvania Psychiatric Institute during an acute mood episode. Healthy controls (HC) were recruited through advertisements. Participants fasted for at least 6h when blood was drawn for biomarkers. We found that zinc concentrations were significantly lower in the BD group at baseline (p<.05), and there was also a significant interaction between gender and zinc (p<.05), associated with depression severity. Also, we found a significant interaction between gender and neopterin, associated with mania severity (p<.05). We found that mania severity was associated with neopterin in men, while depression severity was positively associated with zinc in women. Our report bears replication in larger samples and highlights the potential for differences in the underlying pathophysiology between men and women with BD.

Keywords: Biological marker; Bipolar depression; Gender; Inflammation; Zinc.

MeSH terms

  • Adult
  • Affect / physiology
  • Biomarkers / blood
  • Bipolar Disorder / blood*
  • Bipolar Disorder / psychology
  • Female
  • Humans
  • Male
  • Neopterin / blood*
  • Severity of Illness Index*
  • Sex Factors*
  • Zinc / blood*


  • Biomarkers
  • Neopterin
  • Zinc