Non-linear analysis of the heart rate variability in characterization of manic and euthymic phases of bipolar disorder

Background: - Bipolar Disorder (BD) has been associated with autonomic nervous system (ANS) dysregulation, with a consequent increase in mortality. Recent work highlights the non-linear analysis of ANS function. Our objective was to compare ANS modulation using recurrence plots (RP) and symbolic analysis (SA) in manic and euthymic phases of BD to controls. Methods: - Eighteen male patients (33.1 ± 12.0 years) were assessed during mania and at discharge in the euthymic phase compared and to a healthy group matched by age (33.9 ± 10.8 years). Electrocardiographic series (1000 RR intervals, at rest, in supine position) were captured using Polar Advantage RS800CX equipment and Heart Rate Variability (HRV) was analysed using RP and SA. Statistical analysis was performed using ANOVA with Tukey's post-test. The threshold for statistical significance was set at P < 0.05 and Cohen's d effect size was also quantified considering d > 0.8 as an important effect. The study was registered into the Clinical Trials Registration (ClinicalTrials.gov: NCT01272518). Results: Manic group presented significantly higher linearity before treatment (P<0.05) compared to controls considering RP variables. Cohen's d values had a large effect size ranging from 0.888 to 1.227. In the manic phase, SA showed predominance of the sympathetic component (OV%) with reduction of the parasympathetic component (2LV% and 2UV%) with reversion post treatment including higher Shannon Entropy (SE) indicating higher complexity. Limitations: - short follow-up (1 month) and small number of patients. Conclusions: - Non-linear analyzes may be used as supplementary tools for understanding autonomic function in BD during mania and after drug treatment.