Heart rate variability in bipolar disorder: A systematic review and meta-analysis

•Heart rate variability (HRV) reflects the balance in the autonomous nervous system.•This is the first systematic review and meta-analysis on HRV in bipolar disorder.•HRV is reduced in bipolar disorder compared with healthy individuals.•Methodological issues in individual studies limit the evidence.•HRV may represent an objective diagnostic candidate marker in bipolar disorder.

BackgroundHeart rate variability (HRV) has been suggested reduced in bipolar disorder (BD) compared with healthy individuals (HC). This meta-analysis investigated: HRV differences in BD compared with HC, major depressive disorder or schizophrenia; HRV differences between affective states; HRV changes from mania/depression to euthymia; and HRV changes following interventions.MethodsA systematic review and meta-analysis reported according to the PRISMA guidelines was conducted. MEDLINE, Embase, PsycINFO, The Cochrane Library and Scopus were searched. A total of 15 articles comprising 2534 individuals were included.ResultsHRV was reduced in BD compared to HC (g = -1.77, 95% CI: −2.46; −1.09, P < 0.001, 10 comparisons, n = 1581). More recent publication year, larger study and higher study quality were associated with a smaller difference in HRV. Large between-study heterogeneity, low study quality, and lack of consideration of confounding factors in individual studies were observed.ConclusionsThis first meta-analysis of HRV in BD suggests that HRV is reduced in BD compared to HC. Heterogeneity and methodological issues limit the evidence. Future studies employing strict methodology are warranted.