Lower CSF HVA and 5-HIAA in bipolar disorder type 1 with a history of childhood ADHD

Bipolar disorder with childhood attention-deficit hyperactivity disorder (ADHD) is a subphenotype characterized by earlier age of onset, more frequent mood episodes, more suicide attempts, and more interpersonal violence than pure bipolar patients. The aim of this study was to test the biological validity of using childhood ADHD to subgroup bipolar disorder. The monoamine metabolites, homovanillinic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were determined in the cerebrospinal fluid (CSF) of 53 euthymic patients with bipolar disorder type 1, with (N = 17) and without (N = 36) a history of childhood ADHD. In addition to structured clinical interviews, childhood ADHD was assessed by a next of kin using the Autism-Tics, ADHD and other comorbidities questionnaire (A-TAC), and by patients themselves using the Wender Utah rating scale (WURS-25). Current ADHD symptoms were assessed by the Brown attention-deficit disorder scale (Brown ADD). Bipolar patients with childhood ADHD had significantly lower CSF concentration (mean +/- A SD nmol/l) of HVA (89.0 +/- A 32.5 vs. 115.8 +/- A 47.1, P = 0.039) and 5-HIAA (88.7 +/- A 38.5 vs. 116 +/- A 47.9, P = 0.021) than pure bipolar patients. CSF MHPG did not differ between the groups. The WURS-25 score correlated negatively with both HVA (r = -0.27, P = 0.048) and 5-HIAA (r = -0.30, P = 0.027). Likewise, the Brown ADD total score correlated negatively with both HVA (r = -0.34, P = 0.013) and 5-HIAA (r = -0.35, P = 0.011). These findings indicate different monoaminergic function in patients with and without childhood ADHD in bipolar disorder type 1. This lends biological support to the notion that those with childhood ADHD represent a valid subphenotype of bipolar disorder.