Altered brain dopamine metabolism is a trait marker for bipolar disorder

Abstract

Pharmacological treatment, imaging, and neurochemistry studies identify altered dopamine signaling in bipolar disorder. Our previous work has shown higher concentration of homovanillic acid (HVA), the end metabolite of dopamine, in cerebrospinal fluid (CSF) from individuals with bipolar disorder compared to healthy controls. Here, we analyzed HVA concentrations from a follow-up visit in 103 adults with bipolar disorder and 57 controls from our first cohort. Further, we analyzed CSF monoamine metabolite concentrations in a second cohort of 152 adults with bipolar disorder and 55 controls. At the follow-up visit for the first cohort, HVA was higher in individuals with bipolar disorder (278 ± 102 nmol/L, p = 0.003) compared with controls (232 ± 83 nmol/L). In the second cohort, individuals with bipolar disorder had higher HVA (272 ± 97 nmol/L, p = 0.001) and lower 3-methoxy-4-hydroxyphenylglycol (MHPG, 40 ± 9 nmol/L, p = 0.002) concentrations than controls (HVA, 231 ± 71 nmol/L and MHPG, 45 ± 9 nmol/L). Baseline and follow-up measures of monoamine metabolites showed medium to high correlation to each other but did not predict course of illness. We failed to replicate the association of HVA concentration and psychotic symptoms but confirmed lower 5-hydroxyindoleacetic acid (5-HIAA) concentration in individuals treated with antidepressants. In conclusion, we confirmed high HVA concentration in CSF in patients with bipolar disorder compared to a control group. Previous work suggest that this is a feature shared with ADHD but distinct from schizophrenia and major depressive disorder. The role of increased HVA concentration in the course of illness in bipolar disorder remains unclear.