Neurotrophins, cytokines and oxidative stress mediators, and mood state in bipolar disorder: systematic review and meta-analyses

Background
A reliable biomarker signature for bipolar disorder sensitive to illness phase would be of considerable clinical benefit. Among circulating blood-derived markers there has been a significant amount of research into inflammatory markers, neurotrophins and oxidative stress markers.

Aims
To synthesise and interpret existing evidence of inflammatory markers, neurotrophins and oxidative stress markers in bipolar disorder focussing on the mood phase of illness.

Methods
Following PRISMA guidelines, a systematic review was conducted for studies investigating peripheral biomarkers in bipolar compared to healthy controls. We searched MEDLINE, Embase, PsycInfo, SciELO and Web of Science, and separated studies by bipolar mood phase (mania, depression and euthymia). Extracted data on each biomarker in separate mood phases were synthesised using random effects model meta-analyses.

Results
53 studies were included, comprising 2,467 cases and 2,360 controls. Fourteen biomarkers were identified from meta-analyses of 3 or more studies. No biomarker differentiated mood phase in bipolar individually. Biomarker meta-analyses suggest a combination of hsCRP / IL-6, BDNF / TNF-α and sTNFR1 can differentiate specific mood phase in bipolar. Several other biomarkers of interest were identified.

Conclusions
Combining biomarker results could differentiate bipolar from healthy controls and indicate a specific mood phase signature. Future research should seek to test these combinations of biomarkers in longitudinal studies.