Lifetime burden of mood swings and activation of brain norepinephrine turnover in patients with treatment-refractory depressive illness

Background: We tested if duration and intensity of episodes in treatment-resistant affectively ill patients were related to cerebrospinal fluid (CSF) concentrations of monoamine metabolites. Method: In retrospective life charts were recorded every previous episode of 37 patients with severe treatment-refractory affective disorders. ‘Accumulated burden of mood swings’ (ABMS, sum of each episode length×episode depth) was used to estimate the accumulated illness burden. Homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were analyzed in CSF of all patients and compared with 27 healthy controls. Data were analyzed using multiple regression analysis. Results: CSF MHPG contributed strongly significant and positively to the ABMS. Limitations: The retrospective nature of the study. Conclusion: CSF concentrations of MHPG is positively related to ABMS over life. Thus, a specific involvement of norepinephrine in the long-term burden of affective illness is a likely reality.