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

  • Biological Child and Adolescent Psychiatry - Original Article
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Abstract

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.

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References

  • American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders: DSM-IV. American Psychiatric Association, Washington

    Google Scholar 

  • Arnsten AF, Li BM (2005) Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry 57(11):1377–1384

    Article  CAS  PubMed  Google Scholar 

  • Åsberg M (1997) Neurotransmitters and suicidal behavior. The evidence from cerebrospinal fluid studies. Ann NY Acad Sci 836:158–181

    Article  PubMed  Google Scholar 

  • Åsberg M, Wagner A (1986) Biochemical effects of antidepressant treatment—studies of monoamine metabolites in cerebrospinal fluid and platelet [3H]imipramine binding. Ciba Found Symp 123:57–83

    PubMed  Google Scholar 

  • Berk M, Dodd S et al (2007) Dopamine dysregulation syndrome: implications for a dopamine hypothesis of bipolar disorder. Acta Psychiatr Scand Suppl 116(434):41–49

    Article  Google Scholar 

  • Berrettini WH, Nurnberger JI Jr et al (1985) Cerebrospinal fluid and plasma monoamines and their metabolites in euthymic bipolar patients. Biol Psychiatry 20(3):257–269

    Article  CAS  PubMed  Google Scholar 

  • Blennow K, Wallin A et al (1993) Cerebrospinal fluid monoamine metabolites in 114 healthy individuals 18–88 years of age. Eur Neuropsychopharmacol 3(1):55–61

    Article  CAS  PubMed  Google Scholar 

  • Brown TE (ed) (1996) Brown Attention-Deficit Disorder Scales for adolescents and adults. The Psychological Corporation, San Antonio

    Google Scholar 

  • Brown GL, Linnoila MI (1990) CSF serotonin metabolite (5-HIAA) studies in depression, impulsivity, and violence. J Clin Psychiatry 51(Suppl):31–41 discussion 42–43

    PubMed  Google Scholar 

  • Elia J, Devoto M (2007) ADHD genetics: 2007 update. Curr Psychiatry Rep 9(5):434–439

    Article  PubMed  Google Scholar 

  • Engström G, Alling C et al (1999) Reduced cerebrospinal HVA concentrations and HVA/5-HIAA ratios in suicide attempters. Monoamine metabolites in 120 suicide attempters and 47 controls. Eur Neuropsychopharmacol 9(5):399–405

    Article  PubMed  Google Scholar 

  • Faraone SV, Biederman J et al (1997) Attention-deficit disorder and conduct disorder: longitudinal evidence for a familial subtype. Psychol Med 27(2):291–300

    Article  CAS  PubMed  Google Scholar 

  • Faraone SV, Glatt SJ et al (2003) The genetics of pediatric-onset bipolar disorder. Biol Psychiatry 53(11):970–977

    Article  PubMed  Google Scholar 

  • Gerner RH, Fairbanks L et al (1984) CSF neurochemistry in depressed, manic, and schizophrenic patients compared with that of normal controls. Am J Psychiatry 141(12):1533–1540

    CAS  PubMed  Google Scholar 

  • Gerra G, Leonardi C et al (2007) Homovanillic acid (HVA) plasma levels inversely correlate with attention-deficit hyperactivity and childhood neglect measures in addicted patients. J Neural Transm 114(12):1637–1647

    Article  CAS  PubMed  Google Scholar 

  • Hansson SL, Svanström Röjvall A et al (2005) Psychiatric telephone interview with parents for screening of childhood autism—tics, attention-deficit hyperactivity disorder and other comorbidities (A-TAC): preliminary reliability and validity. Br J Psychiatry 187:262–267

    Article  PubMed  Google Scholar 

  • Iversen SD, Iversen LL (2007) Dopamine: 50 years in perspective. Trends Neurosci 30(5):188–193

    Article  CAS  PubMed  Google Scholar 

  • Jokinen J, Nordström AL et al (2009) CSF 5-HIAA and DST non-suppression: orthogonal biologic risk factors for suicide in male mood disorder inpatients. Psychiatry Res 165(1–2):96–102

    Article  CAS  PubMed  Google Scholar 

  • Kahn RS, Davidson M et al (1993) Effect of neuroleptic medication on cerebrospinal fluid monoamine metabolite concentrations in schizophrenia. Serotonin–dopamine interactions as a target for treatment. Arch Gen Psychiatry 50(8):599–605

    CAS  PubMed  Google Scholar 

  • Kessler RC, Adler L et al (2005) The World Health Organization Adult ADHD Self-Report Scale (ASRS): a short screening scale for use in the general population. Psychol Med 35(2):245–256

    Article  PubMed  Google Scholar 

  • Kessler RC, Adler L et al (2006) The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 163(4):716–723

    Article  PubMed  Google Scholar 

  • Kogan JN, Otto MW et al (2004) Demographic and diagnostic characteristics of the first 1000 patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Bipolar Disord 6(6):460–469

    Article  PubMed  Google Scholar 

  • Krause J (2008) SPECT and PET of the dopamine transporter in attention-deficit/hyperactivity disorder. Expert Rev Neurother 8(4):611–625

    Article  CAS  PubMed  Google Scholar 

  • Kummer A, Teixeira AL (2008) Dopamine and bipolar disorder. Acta Psychiatr Scand 117(5):398 author reply 398–399

    Article  CAS  PubMed  Google Scholar 

  • Levy F (2004) Synaptic gating and ADHD: a biological theory of comorbidity of ADHD and anxiety. Neuropsychopharmacology 29(9):1589–1596

    Article  CAS  PubMed  Google Scholar 

  • Li D, Sham PC et al (2006) Meta-analysis shows significant association between dopamine system genes and attention-deficit hyperactivity disorder (ADHD). Hum Mol Genet 15(14):2276–2284

    Article  CAS  PubMed  Google Scholar 

  • Mann JJ (2003) Neurobiology of suicidal behaviour. Nat Rev Neurosci 4(10):819–828

    Article  CAS  PubMed  Google Scholar 

  • Montgomery SA, Åsberg M (1979) Montgomery–Asberg Depression Rating Scale. A new depression scale designed to be sensitive to change. Br J Psychiatry 134:382–389

    CAS  Google Scholar 

  • Nierenberg AA, Miyahara S et al (2005) Clinical and diagnostic implications of lifetime attention-deficit/hyperactivity disorder comorbidity in adults with bipolar disorder: data from the first 1000 STEP-BD participants. Biol Psychiatry 57(11):1467–1473

    Article  PubMed  Google Scholar 

  • Nordström P, Samuelsson M et al (1994) CSF 5-HIAA predicts suicide risk after attempted suicide. Suicide Life Threat Behav 24(1):1–9

    PubMed  Google Scholar 

  • Reimherr FW, Wender PH et al (1984) Cerebrospinal fluid homovanillic acid and 5-hydroxy-indoleacetic acid in adults with attention-deficit disorder, residual type. Psychiatry Res 11(1):71–78

    Article  CAS  PubMed  Google Scholar 

  • Reimherr FW, Marchant BK et al (2005) Emotional dysregulation in adult ADHD and response to atomoxetine. Biol Psychiatry 58(2):125–131

    Article  CAS  PubMed  Google Scholar 

  • Rydén E, Thase ME et al (2009) A history of childhood attention-deficit hyperactivity disorder (ADHD) impacts clinical outcome in adult bipolar patients regardless of current ADHD. Acta Psychiatr Scand 120(3):239–246

    Article  PubMed  Google Scholar 

  • Sachs GS, Baldassano CF et al (2000) Comorbidity of attention-deficit hyperactivity disorder with early- and late-onset bipolar disorder. Am J Psychiatry 157(3):466–468

    Article  CAS  PubMed  Google Scholar 

  • Sachs GS, Thase ME et al (2003) Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry 53(11):1028–1042

    Article  PubMed  Google Scholar 

  • Sandra Kooij JJ, Marije Boonstra A et al (2008) Reliability, validity, and utility of instruments for self-report and informant report concerning symptoms of ADHD in adult patients. J Atten Disord 11(4):445–458

    Article  CAS  PubMed  Google Scholar 

  • Sher L, Carballo JJ et al (2006) A prospective study of the association of cerebrospinal fluid monoamine metabolite levels with lethality of suicide attempts in patients with bipolar disorder. Bipolar Disord 8(5 Pt 2):543–550

    Article  CAS  PubMed  Google Scholar 

  • Spencer TJ, Biederman J et al (2007) Further evidence of dopamine transporter dysregulation in ADHD: a controlled PET imaging study using altropane. Biol Psychiatry 62(9):1059–1061

    Article  CAS  PubMed  Google Scholar 

  • Staller JA, Faraone SV (2007) Targeting the dopamine system in the treatment of attention-deficit/hyperactivity disorder. Expert Rev Neurother 7(4):351–362

    Article  CAS  PubMed  Google Scholar 

  • Swanson JM, Kinsbourne M et al (2007) Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis. Neuropsychol Rev 17(1):39–59

    Article  PubMed  Google Scholar 

  • Tamam L, Karakus G et al (2008) Comorbidity of adult attention-deficit hyperactivity disorder and bipolar disorder: prevalence and clinical correlates. Eur Arch Psychiatry Clin Neurosci 258(7):385–393

    Article  PubMed  Google Scholar 

  • Träskman L, Åsberg M et al (1981) Monoamine metabolites in CSF and suicidal behavior. Arch Gen Psychiatry 38(6):631–636

    PubMed  Google Scholar 

  • Träskman-Bendz L, Åsberg M et al (1989) Biochemical aspects of suicidal behavior. Prog Neuropsychopharmacol Biol Psychiatry 13(Suppl):S35–S44

    Article  PubMed  Google Scholar 

  • Van Der Poel F (1977) Evidence for a probenecid-sensitive transport system of acid monoamine metabolites from subarachnoid space. Psychopharmacology (Berl) 52(1):35–40

    Article  Google Scholar 

  • Virkkunen M, Nuutila A et al (1987) Cerebrospinal fluid monoamine metabolite levels in male arsonists. Arch Gen Psychiatry 44(3):241–247

    CAS  PubMed  Google Scholar 

  • Ward MF, Wender PH et al (1993) The Wender Utah Rating Scale: an aid in the retrospective diagnosis of childhood attention-deficit hyperactivity disorder. Am J Psychiatry 150(6):885–890

    CAS  PubMed  Google Scholar 

  • Wender PH, Wolf LE et al (2001) Adults with ADHD. An overview. Ann NY Acad Sci 931:1–16

    Article  CAS  Google Scholar 

  • Young RC, Biggs JT et al (1978) A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry 133:429–435

    Article  CAS  PubMed  Google Scholar 

  • Zepf FD, Stadler C et al (2008a) Serotonergic functioning and trait-impulsivity in attention-deficit/hyperactivity-disordered boys (ADHD): influence of rapid tryptophan depletion. Hum Psychopharmacol 23(1):43–51

    Article  CAS  PubMed  Google Scholar 

  • Zepf FD, Wockel L et al (2008b) Diminished 5-HT functioning in CBCL pediatric bipolar disorder-profiled ADHD patients versus normal ADHD: susceptibility to rapid tryptophan depletion influences reaction time performance. Hum Psychopharmacol 23(4):291–299

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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.

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Authors and Affiliations

  1. Section of Psychiatry, Department of Clinical Neuroscience, Karolinska Institutet, 171 77, Stockholm, Sweden

    Eleonore Rydén, Christian Johansson & Mikael Landén

  2. Institute of Neuroscience and Physiology, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden

    Kaj Blennow & Mikael Landén

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  1. Eleonore Rydén
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  2. Christian Johansson
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  4. Mikael Landén
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Correspondence to Eleonore Rydén.

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Rydén, E., Johansson, C., Blennow, K. et al. Lower CSF HVA and 5-HIAA in bipolar disorder type 1 with a history of childhood ADHD. J Neural Transm 116, 1667–1674 (2009). https://doi.org/10.1007/s00702-009-0300-3

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  • DOI: https://doi.org/10.1007/s00702-009-0300-3

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