Multidimensional analysis of heart rate variability and burden of illness in bipolar disorder

Patients with bipolar disorder (BD) face disproportionate rates of cardiovascular disease. While several mechanisms have been proposed for this association, both are multifactorial and heterogeneous illnesses, and it is unlikely that any individual factor can account for a significant portion of their association. Potential mediators have been mostly studied in isolation even though they are interrelated. Furthermore, few studies have accounted for baseline cardiovascular functioning or burden of illness. We sought to analyze the association between burden of illness, phase of the illness (e.g., depressive) and heart rate variability (HRV) in 48 patients diagnosed with BD using canonical correlation analysis. We hypothesized that the association between burden of illness and HRV measures would be different depending on the clinical phase (i.e., euthymia, depression or (hypo)mania). A longer duration of (hypo)manic episodes was associated with higher rates of hypertension and increased sympathetic activation, along with lower rates of migraine and family history of suicide. In the second canonical variable, a later age at onset of (hypo)manic episodes was associated with higher parasympathetic activity. Small sample size; while the magnitudes of correlations for these top functions were large, none of the models were statistically significant. There are different dimensions to the association between burden of illness and HRV in BD. The first dimension could comprise higher sympathetic activation in the context of longer (hypo)manic episodes, with lower rates for clinical variables that have been associated with a predominant depressive polarity (e.g., family history of suicide and migraine). • Association between illness burden and heart rate variability vary by phase. • Higher sympathetic activation in longer (hypo)manias. • Lower sympathetic activation in predominantly depressive course.