Skip to main content Accessibility help
×
Home

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

  • J. Wozniak (a1) (a2), S. V. Faraone (a3), E. Mick (a2), M. Monuteaux (a1) (a2), A. Coville (a1) and J. Biederman (a1) (a2)...

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.

Copyright

Corresponding author

*Address for correspondence: J. Wozniak, M.D., Massachusetts General Hospital, 55 Fruit St, Warren 705, Boston, MA 02114, USA. (Email: jwozniak@partners.org)

References

Hide All
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, 674677.
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, 426434.
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, 728738.
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, 966975.
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, 792797.
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, 10371044.
Biederman, J, Mick, E, Faraone, S (1998). Depression in attention deficit hyperactivity disorder (ADHD) children: ‘True’ depression or demoralization. Journal of Affective Disorders 47, 113122.
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, S17S23.
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, 10981105.
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, 167179.
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, 795804.
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, 175183.
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, 934953.
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, 7481.
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, 12381241.
Craddock, N, Forty, L (2006). Genetics of affective (mood) disorders. European Journal of Human Genetics 14, 660668.
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, 176180.
Faraone, S, Glatt, S, Tsuang, M (2003). The genetics of pediatric onset bipolar disorder. Biological Psychiatry 53, 970977.
Faraone, SV, Biederman, J (1997). Do attention deficit hyperactivity disorder and major depression share familial risk factors? Journal of Nervous and Mental Disease 185, 533541.
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, 13781387, discussion 13871390.
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, 1926.
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, 202210.
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.
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, 15431548.
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, 11251133.
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, 11301138.
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, 157164.
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, 125133.
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, 221233.
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, 7578.
Leibenluft, E, Charney, D, Towbin, K, Bhangoo, R, Pine, D (2003). Defining clinical phenotypes of juvenile mania. American Journal of Psychiatry 160, 430437.
Luckenbaugh, DA, Findling, RL, Leverich, GS, Pizzarello, SM, Post, RM (2009). Earliest symptoms discriminating juvenile-onset bipolar illness from ADHD. Bipolar Disorders 11, 441451.
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, 453462.
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.
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, 466473.
Orvaschel, H (1994). Schedule for Affective Disorder and Schizophrenia for School-Age Children – Epidemiologic Version. Nova Southeastern University, Center for Psychological Studies: Ft. Lauderdale.
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, 875881.
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, 197204.
Robins, E, Guze, SB (1970). Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia. American Journal of Psychiatry 126, 983987.
Rogers, W (1993). Regression standard errors in clustered samples. Stata Technical Bulletin 13, 1923.
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, 255268.
Tsuang, MT, Faraone, SV (1990). The Genetics of Mood Disorders. The Johns Hopkins University Press: Baltimore.
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, 129134.
Wozniak, J (2005). Recognizing and managing bipolar disorder in children. Journal of Clinical Psychiatry 66 (Suppl. 1), 1823.
Wozniak, J, Biederman, J (1995). Childhood mania exists (and coexists) with ADHD. American Society of Clinical Psychopharmacology Progress Notes 6, 45.
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, 121131.
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, 867876.
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, 583588.
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, 101111.
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, 15771583.
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, 938944.

Keywords

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

  • J. Wozniak (a1) (a2), S. V. Faraone (a3), E. Mick (a2), M. Monuteaux (a1) (a2), A. Coville (a1) and J. Biederman (a1) (a2)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed