Association between bipolar episodes and fluid and electrolyte homeostasis: A retrospective longitudinal study

Objectives: Imbalance of fluid and electrolyte homeostasis has been suggested to be associated with the neuropathological processes underlying bipolar disorder. However, longitudinal data regarding the association of bipolar episodes with fluid balance are still lacking. We hypothesized that mania may be associated with a relative fluid retention and hemodilution, and depression with a relative hemoconcentration. Methods: Patients with bipolar disorder (n = 43) admitted to a mental health center, both with depressive and manic episodes, were retrospectively followed between 2005 and 2013. Fluid balance and electrolyte serum indices were compared between their manic and depressive episodes. We adjusted for physical and psychiatric comorbidities and for psychotropic treatment, using two-way analysis of variance with repeated measures. Results: There was a significant reduction in serum fluid balance indices during mania compared to depression: mean hemoglobin concentration 13.9 ± 1.4 g/dL versus 14.5 ± 1.4 g/dL, paired t = -4.2, p < 0.0005; mean hematocrit 41.1 ± 4.1% versus 42.3 ± 3.7%, paired t = -3.0, p < 0.005; mean albumin concentration 4.2 ± 0.3 g/dL versus 4.5 ± 0.3 g/dL, paired t = -4.5, p < 0.0001; and mean sodium concentration 140.3 ± 2.0 mEq/L versus 141.0 ± 2.0 mEq/L, paired t = -2.1, p = 0.04, respectively. Controlling for physical and psychiatric comorbidities and psychotropic treatment did not alter these associations. Conclusions: Our results support the notion of an imbalance of fluid and electrolyte homeostasis among bipolar episodes, which is suggestive for relative hemoconcentration during depressive episodes and relative hemodilution during manic episodes. These findings may eventually lead to novel therapeutic targets.