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A controlled family study of children with DSM-IV bipolar-I disorder and psychiatric co-morbidity

Published online by Cambridge University Press:  06 November 2009

J. Wozniak ,
S. V. Faraone ,
E. Mick ,
M. Monuteaux ,
A. Coville  and
J. Biederman
J. Wozniak*
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital, Boston, MA, USA Department of Psychiatry at Harvard Medical School, Boston, MA, USA
S. V. Faraone
Affiliation:
Departments of Psychiatry and Neuroscience & Physiology, SUNY Upstate Medical University, NY, USA
E. Mick
Affiliation:
Department of Psychiatry at Harvard Medical School, Boston, MA, USA
M. Monuteaux
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital, Boston, MA, USA Department of Psychiatry at Harvard Medical School, Boston, MA, USA
A. Coville
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital, Boston, MA, USA
J. Biederman
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital, Boston, MA, USA Department of Psychiatry at Harvard Medical School, Boston, MA, USA
*
*Address for correspondence: J. Wozniak, M.D., Massachusetts General Hospital, 55 Fruit St, Warren 705, Boston, MA02114, USA. (Email: [email protected])
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Abstract

Background

To estimate the spectrum of familial risk for psychopathology in first-degree relatives of children with unabridged DSM-IV bipolar-I disorder (BP-I).

Method

We conducted a blinded, controlled family study using structured diagnostic interviews of 157 children with BP-I probands (n=487 first-degree relatives), 162 attention deficit hyperactivity disorder (ADHD) (without BP-I) probands (n=511 first-degree relatives), and 136 healthy control (without ADHD or BP-I) probands (n=411 first-degree relatives).

Results

The morbid risk (MR) of BP-I disorder in relatives of BP-I probands (MR=0.18) was increased 4-fold [95% confidence interval (CI) 2.3–6.9, p<0.001] over the risk to relatives of control probands (MR=0.05) and 3.5-fold (95% CI 2.1–5.8, p<0.001) over the risk to relatives of ADHD probands (MR=0.06). In addition, relatives of children with BP-I disorder had high rates of psychosis, major depression, multiple anxiety disorders, substance use disorders, ADHD and antisocial disorders compared with relatives of control probands. Only the effect for antisocial disorders lost significance after accounted for by the corresponding diagnosis in the proband. Familial rates of ADHD did not differ between ADHD and BP-I probands.

Conclusions

Our results document an increased familial risk for BP-I disorder in relatives of pediatric probands with DSM-IV BP-I. Relatives of probands with BP-I were also at increased risk for other psychiatric disorders frequently associated with pediatric BP-I. These results support the validity of the diagnosis of BP-I in children as defined by DSM-IV. More work is needed to better understand the nature of the association between these disorders in probands and relatives.

Keywords

Bipolarchildrenfamily study
Type
Original Articles
Information
Psychological Medicine , Volume 40 , Issue 7 , July 2010 , pp. 1079 - 1088
Copyright
Copyright © Cambridge University Press 2009

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References

Asherson, P, Brookes, K, Franke, B, Chen, W, Gill, M, Ebstein, RP, Buitelaar, J, Banaschewski, T, Sonuga-Barke, E, Eisenberg, J, Manor, I, Miranda, A, Oades, RD, Roeyers, H, Rothenberger, A, Sergeant, J, Steinhausen, HC, Faraone, SV (2007). Confirmation that a specific haplotype of the dopamine transporter gene is associated with combined-type ADHD. American Journal of Psychiatry 164, 674–677.CrossRefGoogle ScholarPubMed
Biederman, J, Ball, SW, Monuteaux, MC, Mick, E, Spencer, TJ, McCreary, M, Cote, M, Faraone, SV (2008). New insights into the co-morbidity between ADHD and major depression in adolescent and young adult females. Journal of the American Academy of Child and Adolescent Psychiatry 47, 426–434.CrossRefGoogle ScholarPubMed
Biederman, J, Faraone, SV, Keenan, K, Benjamin, J, Krifcher, B, Moore, C, Sprich-Buckminster, S, Ugaglia, K, Jellinek, MS, Steingard, R, Spencer, T, Norman, D, Kolodny, R, Kraus, I, Perrin, J, Keller, MB, Tsuang, MT (1992). Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder. Patterns of comorbidity in probands and relatives in psychiatrically and pediatrically referred samples. Archives of General Psychiatry 49, 728–738.CrossRefGoogle ScholarPubMed
Biederman, J, Faraone, SV, Mick, E, Williamson, S, Wilens, TE, Spencer, TJ, Weber, W, Jetton, J, Kraus, I, Pert, J, Zallen, B (1999). Clinical correlates of ADHD in females: findings from a large group of girls ascertained from pediatric and psychiatric referral sources. Journal of the American Academy of Child and Adolescent Psychiatry 38, 966–975.CrossRefGoogle ScholarPubMed
Biederman, J, Faraone, SV, Monuteaux, MC, Feighner, JA (2000 a). Patterns of alcohol and drug use in adolescents can be predicted by parental substance use disorders. Pediatrics 106, 792–797.CrossRefGoogle ScholarPubMed
Biederman, J, Faraone, SV, Wozniak, J, Monuteaux, MC (2000 b). Parsing the association between bipolar, conduct, and substance use disorders: a familial risk analysis. Biological Psychiatry 48, 1037–1044.CrossRefGoogle ScholarPubMed
Biederman, J, Mick, E, Faraone, S (1998). Depression in attention deficit hyperactivity disorder (ADHD) children: ‘True’ depression or demoralization. Journal of Affective Disorders 47, 113–122.CrossRefGoogle ScholarPubMed
Biederman, J, Mick, E, Faraone, SV, van Patten, S, Burback, M, Wozniak, J (2004). A prospective follow up study of pediatric bipolar disorder in boys with attention deficit/hyperactivity disorder. Journal of Affective Disorders 82S, S17–S23.CrossRefGoogle Scholar
Biederman, J, Monuteaux, M, Mick, E, Spencer, T, Wilens, T, Klein, K, Price, JE, Faraone, SV (2006 a). Psychopathology in females with attention-deficit/hyperactivity disorder: a controlled, five-year prospective study. Biological Psychiatry 60, 1098–1105.CrossRefGoogle ScholarPubMed
Biederman, J, Monuteaux, M, Mick, E, Spencer, T, Wilens, T, Silva, J, Snyder, L, Faraone, SV (2006 b). Young adult outcome of attention deficit hyperactivity disorder: A controlled 10 year prospective follow-up study. Psychological Medicine 36, 167–179.CrossRefGoogle Scholar
Birmaher, B, Axelson, D, Goldstein, B, Strober, M, Gill, MK, Hunt, J, Houck, P, Ha, W, Iyengar, S, Kim, E, Yen, S, Hower, H, Esposito-Smythers, C, Goldstein, T, Ryan, N, Keller, M (2009). Four-year longitudinal course of children and adolescents with bipolar spectrum disorders: the Course and Outcome of Bipolar Youth (COBY) study. American Journal of Psychiatry 166, 795–804.CrossRefGoogle ScholarPubMed
Birmaher, B, Axelson, D, Strober, M, Gill, MK, Valeri, S, Chiappetta, L, Ryan, N, Leonard, H, Hunt, J, Iyengar, S, Keller, M (2006). Clinical course of children and adolescents with bipolar spectrum disorders. Archives of General Psychiatry 63, 175–183.CrossRefGoogle ScholarPubMed
Brookes, K, Xu, X, Chen, W, Zhou, K, Neale, B, Lowe, N, Aneey, R, Franke, B, Gill, M, Ebstein, R, Buitelaar, J, Sham, P, Campbell, D, Knight, J, Andreou, P, Altink, M, Arnold, R, Boer, F, Buschgens, C, Butler, L, Christiansen, H, Feldman, L, Fleischman, K, Fliers, E, Howe-Forbes, R, Goldfarb, A, Heise, A, Gabriels, I, Korn-Lubetzki, I, Marco, R, Medad, S, Minderaa, R, Mulas, F, Muller, U, Mulligan, A, Rabin, K, Rommelse, N, Sethna, V, Sorohan, J, Uebel, H, Psychogiou, L, Weeks, A, Barrett, R, Craig, I, Banaschewski, T, Sonuga-Barke, E, Eisenberg, J, Kuntsi, J, Manor, I, McGuffin, P, Miranda, A, Oades, RD, Plomin, R, Roeyers, H, Rothenberger, A, Sergeant, J, Steinhausen, HC, Taylor, E, Thompson, M, Faraone, SV, Asherson, P, Johansson, L (2006 a). The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes. Molecular Psychiatry 11, 934–953.CrossRefGoogle ScholarPubMed
Brookes, KJ, Mill, J, Guindalini, C, Curran, S, Xu, X, Knight, J, Chen, CK, Huang, YS, Sethna, V, Taylor, E, Chen, W, Breen, G, Asherson, P (2006 b). A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy. Archives of General Psychiatry 63, 74–81.CrossRefGoogle ScholarPubMed
Brotman, MA, Kassem, L, Reising, MM, Guyer, AE, Dickstein, DP, Rich, BA, Towbin, KE, Pine, DS, McMahon, FJ, Leibenluft, E (2007). Parental diagnoses in youth with narrow phenotype bipolar disorder or severe mood dysregulation. American Journal of Psychiatry 164, 1238–1241.CrossRefGoogle ScholarPubMed
Craddock, N, Forty, L (2006). Genetics of affective (mood) disorders. European Journal of Human Genetics 14, 660–668.CrossRefGoogle ScholarPubMed
Dwyer, J, Delong, R (1985). A family history study of twenty probands with childhood manic-depressive illness. Journal of the American Academy of Child and Adolescent Psychiatry 26, 176–180.CrossRefGoogle Scholar
Faraone, S, Glatt, S, Tsuang, M (2003). The genetics of pediatric onset bipolar disorder. Biological Psychiatry 53, 970–977.CrossRefGoogle ScholarPubMed
Faraone, SV, Biederman, J (1997). Do attention deficit hyperactivity disorder and major depression share familial risk factors? Journal of Nervous and Mental Disease 185, 533–541.CrossRefGoogle ScholarPubMed
Faraone, SV, Biederman, J, Mennin, D, Wozniak, J, Spencer, T (1997). Attention-deficit hyperactivity disorder with bipolar disorder: a familial subtype? Journal of the American Academy of Child and Adolescent Psychiatry 36, 1378–1387, discussion 1387–1390.CrossRefGoogle ScholarPubMed
Faraone, SV, Biederman, J, Monuteaux, MC (2001). Attention deficit hyperactivity disorder with bipolar disorder in girls: further evidence for a familial subtype? Journal of Affective Disorders 64, 19–26.CrossRefGoogle ScholarPubMed
Findling, RL, Gracious, BL, McNamara, NK, Youngstrom, EA, Demeter, CA, Branicky, LA, Calabrese, JR (2001). Rapid, continuous cycling and psychiatric co-morbidity in pediatric bipolar I disorder. Bipolar Disorders 3, 202–210.CrossRefGoogle ScholarPubMed
First, MB, Spitzer, RL, Gibbon, M, Williams, JBW (1997). Structured Clinical Interview for DSM-IV Axis I Disorders-Clinician Version (SCID-CV). American Psychiatric Press: Washington DC.Google Scholar
Geller, B, Bolhofner, K, Craney, JL, Williams, M, DelBello, MP, Gundersen, K (2000 a). Psychosocial functioning in a prepubertal and early adolescent bipolar disorder phenotype. Journal of the American Academy of Child and Adolescent Psychiatry 39, 1543–1548.CrossRefGoogle Scholar
Geller, B, Tillman, R, Bolhofner, K, Zimerman, B (2008). Child bipolar I disorder: prospective continuity with adult bipolar I disorder; characteristics of second and third episodes; predictors of 8-year outcome. Archives of General Psychiatry 65, 1125–1133.CrossRefGoogle ScholarPubMed
Geller, B, Tillman, R, Bolhofner, K, Zimerman, B, Strauss, NA, Kaufmann, P (2006). Controlled, blindly rated, direct-interview family study of a prepubertal and early-adolescent bipolar I disorder phenotype: morbid risk, age at onset, and comorbidity. Archives of General Psychiatry 63, 1130–1138.CrossRefGoogle ScholarPubMed
Geller, B, Zimerman, B, Williams, M, Bolhofner, K, Craney, JL, Delbello, MP, Soutullo, CA (2000 b). Diagnostic characteristics of 93 cases of a prepubertal and early adolescent bipolar disorder phenotype by gender, puberty and comorbid attention deficit hyperactivity disorder. Journal of Child and Adolescent Psychopharmacology 10, 157–164.CrossRefGoogle ScholarPubMed
Greenwood, TA, Schork, NJ, Eskin, E, Kelsoe, JR (2006). Identification of additional variants within the human dopamine transporter gene provides further evidence for an association with bipolar disorder in two independent samples. Molecular Psychiatry 11, 115, 125–133.CrossRefGoogle ScholarPubMed
Huber, PJ (1967). The behavior of maximum likelihood estimates under non-standard conditions. Proceedings of the Fifth Berkeley Symposium on Mathematical Statistics and Probability 1, 221–233.Google Scholar
Kutcher, S, Marton, P (1991). Affective disorders in first-degree relatives of adolescent onset bipolars, unipolars, and normal controls. Journal of the American Academy of Child and Adolescent Psychiatry 30, 75–78.CrossRefGoogle ScholarPubMed
Leibenluft, E, Charney, D, Towbin, K, Bhangoo, R, Pine, D (2003). Defining clinical phenotypes of juvenile mania. American Journal of Psychiatry 160, 430–437.CrossRefGoogle ScholarPubMed
Luckenbaugh, DA, Findling, RL, Leverich, GS, Pizzarello, SM, Post, RM (2009). Earliest symptoms discriminating juvenile-onset bipolar illness from ADHD. Bipolar Disorders 11, 441–451.CrossRefGoogle ScholarPubMed
Mick, E, Biederman, J, Faraone, S, Murray, K, Wozniak, J (2003). Defining a developmental subtype of bipolar disorder in a sample of non-referred adults by age-at-onset. Journal of Child and Adolescent Psychopharmacology 13, 453–462.CrossRefGoogle Scholar
Mick, E, Kim, J, Biederman, J, Wozniak, J, Wilens, T, Smoller, J, Spencer, T, McGrath, C, Sklar, P, Faraone, S (2007). Family based association study of SLC6A3 in pediatric bipolar disorder. In NIMH Collaborative Pediatric Bipolar Disorder Conference. 5U13MH064077. NIMH: Washington DC.Google Scholar
Neuman, R, Geller, B, Rice, J, Todd, R (1997). Increased prevalence and earlier onset of mood disoders among relatives of prepubertal versus adult probands. Journal of the American Academy of Child and Adolescent Psychiatry 36, 466–473.CrossRefGoogle Scholar
Orvaschel, H (1994). Schedule for Affective Disorder and Schizophrenia for School-Age Children – Epidemiologic Version. Nova Southeastern University, Center for Psychological Studies: Ft. Lauderdale.Google Scholar
Perlis, RH, Miyahara, S, Marangell, LB, Wisniewski, SR, Ostacher, M, DelBello, MP, Bowden, CL, Sachs, GS, Nierenberg, AA (2004). Long-term implications of early onset in bipolar disorder: data from the first 1000 participants in the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biological Psychiatry 55, 875–881.CrossRefGoogle ScholarPubMed
Rende, R, Birmaher, B, Axelson, D, Strober, M, Gill, MK, Valeri, S, Chiappetta, L, Ryan, N, Leonard, H, Hunt, J, Iyengar, S, Keller, M (2007). Childhood-onset bipolar disorder: Evidence for increased familial loading of psychiatric illness. Journal of the American Academy of Child and Adolescent Psychiatry 46, 197–204.CrossRefGoogle ScholarPubMed
Robins, E, Guze, SB (1970). Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia. American Journal of Psychiatry 126, 983–987.CrossRefGoogle ScholarPubMed
Rogers, W (1993). Regression standard errors in clustered samples. Stata Technical Bulletin 13, 19–23.Google Scholar
Strober, M, Morrell, W, Burroughs, J, Lampert, C, Danforth, H, Freeman, R (1988). A family study of bipolar I disorder in adolescence: Early onset of symptoms linked to increased familial loading and lithium resistance. Journal of Affective Disorders 15, 255–268.CrossRefGoogle ScholarPubMed
Tsuang, MT, Faraone, SV (1990). The Genetics of Mood Disorders. The Johns Hopkins University Press: Baltimore.Google Scholar
Wilens, T, Biederman, J, Adamson, JJ, Monuteaux, M, Henin, A, Sgambati, S, Santry, A, Faraone, SV (2007). Association of bipolar and substance use disorders in parents of adolescents with bipolar disorder. Biological Psychiatry 62, 129–134.CrossRefGoogle ScholarPubMed
Wozniak, J (2005). Recognizing and managing bipolar disorder in children. Journal of Clinical Psychiatry 66 (Suppl. 1), 18–23.Google ScholarPubMed
Wozniak, J, Biederman, J (1995). Childhood mania exists (and coexists) with ADHD. American Society of Clinical Psychopharmacology Progress Notes 6, 4–5.Google Scholar
Wozniak, J, Biederman, J, Faraone, SV, Blier, H, Monuteaux, MC (2001). Heterogeneity of childhood conduct disorder: further evidence of a subtype of conduct disorder linked to bipolar disorder. Journal of Affective Disorders 64, 121–131.CrossRefGoogle ScholarPubMed
Wozniak, J, Biederman, J, Kiely, K, Ablon, S, Faraone, S, Mundy, E, Mennin, D (1995 a). Mania-like symptoms suggestive of childhood onset bipolar disorder in clinically referred children. Journal of the American Academy of Child and Adolescent Psychiatry 34, 867–876.CrossRefGoogle ScholarPubMed
Wozniak, J, Biederman, J, Kwon, A, Mick, E, Faraone, SV, Orlovsky, K, Schnare, L, Cargol, C, Van Grondelle, A (2005). How cardinal are cardinal symptoms in pediatric bipolar disorder? An examination of clinical correlates. Biological Psychiatry 58, 583–588.CrossRefGoogle ScholarPubMed
Wozniak, J, Biederman, J, Monuteaux, MC, Richards, J, Faraone, SV (2002). Parsing the comorbidity between bipolar disorder and anxiety disorders: a familial risk analysis. Journal of Child and Adolescent Psychopharmacology 12, 101–111.CrossRefGoogle ScholarPubMed
Wozniak, J, Biederman, J, Mundy, E, Mennin, D, Faraone, SV (1995 b). A pilot family study of childhood-onset mania. Journal of the American Academy of Child and Adolescent Psychiatry 34, 1577–1583.CrossRefGoogle ScholarPubMed
Wozniak, J, Monuteaux, M, Richards, J, Lail, KE, Faraone, SV, Biederman, J (2003). Convergence between structured diagnostic interviews and clinical assessment on the diagnosis of pediatric-onset mania. Biological Psychiatry 53, 938–944.CrossRefGoogle ScholarPubMed