Journal of Neural Transmission

, Volume 116, Issue 12, pp 1667–1674 | Cite as

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

  • Eleonore Rydén
  • Christian Johansson
  • Kaj Blennow
  • Mikael Landén
Biological Child and Adolescent Psychiatry - Original Article


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 ± SD nmol/l) of HVA (89.0 ± 32.5 vs. 115.8 ± 47.1, P = 0.039) and 5-HIAA (88.7 ± 38.5 vs. 116 ± 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.


Attention-deficit hyperactivity disorder Bipolar disorder Homovanillic acid Hydroxyindoleacetic acid Methoxyhydroxyphenylglycol 



The authors would like to thank the study coordinator Martina Wennberg for skilful assistance, and Dr Caroline Nilsson for the assessment of bipolar patients. Financial support was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and the Karolinska Institutet, and through grants from the Swedish Medical Research Council (K2008-62x-14647-06-3), the S:t Göran Foundation, the Söderström-Königska Foundation, the Thuring Foundation, the Swedish Psychiatry Foundation, the Swedish Society for Medical Research and the Karolinska Institutet. This work was not financially supported.

Conflict of interest statement



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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Eleonore Rydén
    • 1
  • Christian Johansson
    • 1
  • Kaj Blennow
    • 2
  • Mikael Landén
    • 1
    • 2
  1. 1.Section of Psychiatry, Department of Clinical NeuroscienceKarolinska InstitutetStockholmSweden
  2. 2.Institute of Neuroscience and PhysiologyThe Sahlgrenska Academy at Gothenburg UniversityGothenburgSweden

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