Skip to main content

Advertisement

Log in

Early interventions for youths at high risk for bipolar disorder: a developmental approach

  • Review
  • Published:
European Child & Adolescent Psychiatry Aims and scope Submit manuscript

Abstract

In recent decades, ongoing research programmes on primary prevention and early identification of bipolar disorder (BD) have been developed. The aim of this article is to review the principal forms of evidence that support preventive interventions for BD in children and adolescents and the main challenges associated with these programmes. We performed a literature review of the main computerised databases (MEDLINE, PUBMED) and a manual search of the literature relevant to prospective and retrospective studies of prodromal symptoms, premorbid stages, risk factors, and early intervention programmes for BD. Genetic and environmental risk factors of BD were identified. Most of the algorithms used to measure the risk of developing BD and the early interventions programmes focused on the familial risk. The prodromal signs varied greatly and were age dependent. During adolescence, depressive episodes associated with genetic or environmental risk factors predicted the onset of hypomanic/manic episodes over subsequent years. In prepubertal children, the lack of specificity of clinical markers and difficulties in mood assessment were seen as impeding preventive interventions at these ages. Despite encouraging results, biomarkers have not thus far been sufficiently validated in youth samples to serve as screening tools for prevention. Additional longitudinal studies in youths at high risk of developing BD should include repeated measures of putative biomarkers. Staging models have been developed as an integrative approach to specify the individual level of risk based on clinical (e.g. prodromal symptoms and familial history of BD) and non-clinical (e.g. biomarkers and neuroimaging) data. However, there is still a lack of empirically validated studies that measure the benefits of using these models to design preventive intervention programmes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Lish JD, Dime-Meenan S, Whybrow PC, Price RA, Hirschfeld RM (1994) The National Depressive and Manic-Depressive Association (NDMDA) survey of bipolar members. J Affect Disord 31:281–294

    Article  CAS  PubMed  Google Scholar 

  2. 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). Biol Psychiatry 55:875–881. doi:10.1016/j.biopsych.2004.01.022

    Article  PubMed  Google Scholar 

  3. Gore FM, Bloem PJN, Patton GC, Ferguson J, Joseph V, Coffey C, Sawyer SM, Mathers CD (2011) Global burden of disease in young people aged 10–24 years: a systematic analysis. Lancet 377:2093–2102

    Article  PubMed  Google Scholar 

  4. Halfon O, Laget J, Barrie M (1995) An epidemiological and clinical approach to adolescent suicide. A comparison between suicidal and non-suicidal clinical groups in a health foundation center for French students. Eur Child Adolesc Psychiatry 4(1):32–38

    Article  CAS  PubMed  Google Scholar 

  5. Bauer M, Glenn T, Grof P, Schmid R, Pfennig A, Whybrow PC (2010) Subsyndromal mood symptoms: a useful concept for maintenance studies of bipolar disorder? Psychopathology 43:1–7

    Article  PubMed  Google Scholar 

  6. Kapczinski F, Dias VV, Kauer-Sant’Anna M, Frey BN, Grassi-Oliveira R, Colom F, Berk M (2009) Clinical implications of a staging model for bipolar disorders. Expert Rev Neurother 9:957–966

    Article  PubMed  Google Scholar 

  7. Tohen M, Waternaux CM, Tsuang MT (1990) Outcome in mania: a 4-year prospective follow-up of 75 patients utilizing survival analysis. Arch Gen Psychiatry 47:1106–1111

    Article  CAS  PubMed  Google Scholar 

  8. Post RM, Leverich GS, Kupka RW, Keck PE, McElroy SL, Altshuler LL, Frye MA, Luckenbaugh DA, Rowe M, Grunze H, Suppes T, Nolen WA (2010) Early-onset bipolar disorder and treatment delay are risk factors for poor outcome in adulthood. J Clin Psychiatry 71:864–872

    Article  PubMed  Google Scholar 

  9. Berk M, Brnabic A, Dodd S, Kelin K, Tohen M, Malhi GS, Berk L, Conus P, McGorry PD (2011) Does stage of illness impact treatment response in bipolar disorder? Empirical treatment data and their implication for the staging model and early intervention. Bipolar Disord 13:87–98. doi:10.1111/j.1399-5618.2011.00889.x

    Article  PubMed  Google Scholar 

  10. Angst J, Sellaro R (2000) Historical perspectives and natural history of bipolar disorder. Biol Psychiatry 48(6):445–457

    Article  CAS  PubMed  Google Scholar 

  11. Turvey CL, Coryell WH, Arndt S, Solomon DA, Leon AC, Endicott J, Mueller T, Keller M, Akiskal H (1999) Polarity sequence, depression, and chronicity in bipolar I disorder. J Nerv Ment Dis 187(3):181–187

    Article  CAS  PubMed  Google Scholar 

  12. Robinson LJ, Ferrier IN (2006) Evolution of cognitive impairment in bipolar disorder: a systematic review of cross-sectional evidence. Bipolar Disord 8:103–116

    Article  PubMed  Google Scholar 

  13. Torres IJ, Boudreau VG, Yatham LN (2007) Neuropsychological functioning in euthymic bipolar disorder: a meta-analysis. Acta Psychiatr Scand 434:17–26

    Article  Google Scholar 

  14. Bauer IE, Pascoe MC, Wollenhaupt-Aguiar B, Kapczinski F, Soares JC (2014) Inflammatory mediators of cognitive impairment in bipolar disorder. J Psychiatr Res 56:18–27. doi:10.1016/j.jpsychires.2014.04.017

    Article  PubMed Central  PubMed  Google Scholar 

  15. López-Jaramillo C, Lopera-Vásquez J, Gallo A, Ospina-Duque J, Bell V, Torrent C, Martínez-Arán A, Vieta E (2010) Effects of recurrence on the cognitive performance of patients with bipolar I disorder: implications for relapse prevention and treatment adherence. Bipolar Disord 12:557–567

    Article  PubMed  Google Scholar 

  16. Tohen M, Hennen J, Zarate CM Jr, Baldessarini RJ, Strakowski SM, Stoll AL, Faedda GL, Suppes T, Gebre-Medhin P, Cohen BM (2000) Two-year syndromal and functional recovery in 219 cases of first-episode major affective disorder with psychotic features. Am J Psychiatry 157:220–228

    Article  CAS  PubMed  Google Scholar 

  17. Rosa AR, Reinares M, Amann B, Popovic D, Franco C, Comes M, Torrent C, Bonnin CM, Sole B, Valenti M, Salamero M, Kapczinski F, Vieta E (2011) Six-month functional outcome of a bipolar disorder cohort in the context of a specialized-care program. Bipolar Disord 13:679–686

    Article  PubMed  Google Scholar 

  18. Malhi GS, Bargh DM, Coulston CM, Das P, Berkc M (2014) Predicting bipolar disorder on the basis of phenomenology: implications for prevention and early intervention. Bipolar Disord 16:455–470. doi:10.1111/bdi.12133

    Article  PubMed  Google Scholar 

  19. Dean BB, Gerner D, Gerner RH (2004) A systematic review evaluating health-related quality of life, work impairment and health-care costs and utilization in bipolar disorders. Curr Med Res Opin 20:139–154

    Article  PubMed  Google Scholar 

  20. Goldberg JF, Ernst CL (2002) Features associated with the delayed initiation of mood stabilizers at illness onset in bipolar disorder. J Clin Psychiatry 63:985–991

    Article  PubMed  Google Scholar 

  21. Conus P, Macneil C, McGorry PD (2014) Public health significance of bipolar disorder: implications for early intervention and prevention. Bipolar Disord 16:548–556. doi:10.1111/bdi.12137

    Article  PubMed  Google Scholar 

  22. Ketter TA, Houston JP, Adams DH, Risser RC, Meyers AL, Williamson DJ, Tohen M (2006) Differential efficacy of olanzapine and lithium in preventing manic or mixed recurrence in patients with bipolar I disorder based on number of previous manic or mixed episodes. J Clin Psychiatry 67:95–101

    Article  CAS  PubMed  Google Scholar 

  23. Berghofer A, Alda M, Adli M, Baethge C, Bauer M, Bschor T, Grof P, Muller-Oerlinghausen B, Rybakowski JK, Suwalska A, Pfennig A (2013) Stability of lithium treatment in bipolar disorder—long-term follow-up of 346 patients. Int J Bipolar Disord 1:11. doi:10.1186/2194-7511-1-11

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  24. Scott J, Paykel E, Morriss R, Bentall R, Kinderman P, Johnson T, Abbott R, Hayhurst H (2006) Cognitive-behavioural therapy for severe and recurrent bipolar disorders: randomised controlled trial. Br J Psychiatry 188:313–320

    Article  PubMed  Google Scholar 

  25. Colom F, Reinares M, Pacchiarotti I, Popovic D, Mazzarini L, Martinez AA, Torrent C, Rosa AR, Palomino-Otiniano R, Franco C, Bonnin CM, Vieta E (2010) Has number of previous episodes any effect on response to group psychoeducation in bipolar patients ? Acta Neuropsychiatrica 22:50–53

    Article  PubMed  Google Scholar 

  26. Reinares M, Sánchez-Moreno J, Fountoulakis KN (2014) Psychosocial interventions in bipolar disorder: what, for whom, and when. J Affect Disord 156:46–55. doi:10.1016/j.jad.2013.12.017

    Article  PubMed  Google Scholar 

  27. Lam DH, Burbeck R, Wright K, Pilling S (2009) Psychological therapies in bipolar disorder: the effect of illness history on relapse prevention—a systematic review. Bipolar Disord 11:474–482

    Article  PubMed  Google Scholar 

  28. Alda M (2004) The phenotypic spectra of bipolar disorder. Eur Neuropsychopharmacol 14(Suppl 2):S94–S99. doi:10.1016/j.euroneuro.2004.03.006

    Article  CAS  PubMed  Google Scholar 

  29. Grof P, Alda M, Ahrens B (1995) Clinical course of affective disorders: were Emil Kraepelin and Jules Angst wrong? Psychopathology 28(Suppl 1):73–80

    Article  PubMed  Google Scholar 

  30. Chang KD (2010) Course and impact of bipolar disorder in young patients. J Clin Psychiatry 71:e05

    Article  PubMed  CAS  Google Scholar 

  31. Brietzke E, Mansur RB, Soczynska JK, Kapczinski F, Bressan RA, McIntyre RS (2012) Towards a multifactorial approach for prediction of bipolar disorder in at risk populations. J Affect Disord 140:82–91. doi:10.1016/j.jad.2012.02.016

    Article  PubMed  Google Scholar 

  32. Hasler G, Drevets WC, Gould TD, Gottesman II, Manji HK (2006) Toward constructing an endophenotype strategy for bipolar disorders. Biol Psychiatry 60:93–105

    Article  PubMed  Google Scholar 

  33. Geller B, Craney JL, Bolhofner K, Nickelsburg MJ, Williams M, Zimerman B (2002) Two-year prospective follow-up of children with a prepubertal and early adolescent bipolar disorder phenotype. Am J Psychiatry 159(6):927–933

    Article  PubMed  Google Scholar 

  34. Green JG, McLaughlin KA, Berglund PA, Gruber MJ, Sampson NA, Zaslavsky AM, Kessler RC (2010) Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. Arch Gen Psychiatry 67(2):113–123. doi:10.1001/archgenpsychiatry.2009.186

    Article  PubMed Central  PubMed  Google Scholar 

  35. Hillegers MH, Reichart CG, Wals M, Verhulst FC, Ormel J, Nolen WA (2005) Five-year prospective outcome of psychopathology in the adolescent offspring of bipolar parents. Bipolar Disord 7(4):344–350. doi:10.1111/j.1399-5618.2005.00215.x

    Article  PubMed  Google Scholar 

  36. Duffy A, Alda M, Crawford L, Milin R, Grof P (2007) The early manifestations of bipolar disorder: a longitudinal prospective study of the offspring of bipolar parents. Bipolar Disord 9:828–838

    Article  PubMed  Google Scholar 

  37. Kessler RC, Crum RM, Warner LA, Nelson CB, Schulenberg J, Anthony JC (1997) Lifetime co-occurrence of DSM-III-R alcohol abuse dependence with other psychiatry disorders in the National Comorbidity Survey. Arch Gen Psychiatry 54:313–321

    Article  CAS  PubMed  Google Scholar 

  38. Baethge C, Hennen J, Khalsa HMK, Salvatore P, Tohen M, Baldessarini RJ (2008) Sequencing of substance use and affective morbidity in 166 first-episode bipolar I disorder patients. Bipolar Disord 10:738–741

    Article  PubMed  Google Scholar 

  39. Duffy A, Horrocks J, Doucette S, Keown-Stoneman C, McCloskey S, Grof P (2014) The developmental trajectory of bipolar disorder. Br J Psychiatry 204:122–128. doi:10.1192/bjp.bp.113.126706

    Article  PubMed  Google Scholar 

  40. Reiehart CG, Nolen WA (2004) Earlier onset of bipolar disorder in children by antidepressants or stimulants? A hypothesis. J Affect Disord 78:81–84

    Article  Google Scholar 

  41. Tillman R, Geller B (2006) Controlled study of switching from attention-deficit/hyperactivity disorder to a prepubertal and early adolescent bipolar I disorder phenotype during 6-year prospective follow-up: rate, risk, and predictors. Dev Psychopathol 18:1037–1053

    Article  PubMed  Google Scholar 

  42. Goldsmith M, Singh M, Chang K (2011) Antidepressants and psychostimulants in pediatric populations: is there an association with mania? Paediatr Drugs 13:225–243

    Article  PubMed Central  PubMed  Google Scholar 

  43. Meyer SE, Carlson GA, Wiggs EA, Ronsaville DS, Martinez PE, Klimes-Dougan B, Gold PW, Radke-Yarrow M (2006) A prospective high-risk study of the association among maternal negativity, apparent frontal lobe dysfunction, and the development of bipolar disorder. Dev Psychopathol 18:573–589

    Article  PubMed  Google Scholar 

  44. Hirschfeld RM, Lewis L, Vornik LA (2003) Perceptions and impact of bipolar disorder: how far have we really come? Results of the national depressive and manic-depressive association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry 64(2):161–174

    Article  PubMed  Google Scholar 

  45. Rucklidge JJ (2008) Retrospective parent report of psychiatric histories: do checklists reveal specific prodromal indicators for postpubertal-onset pediatric bipolar disorder? Bipolar Disord 10(1):56–66. doi:10.1111/j.1399-5618.2008.00533.x

    Article  PubMed  Google Scholar 

  46. Fergus EL, Miller RB, Luckenbaugh DA, Leverich GS, Findling RL, Speer AM, Post RM (2003) Is there progression from irritability/dyscontrol to major depressive and manic symptoms? A retrospective community survey of parents of bipolar children. J Affect Disord 77(1):71–78

    Article  PubMed  Google Scholar 

  47. Skjelstad DV, Malt UF, Holte A (2010) Symptoms and signs of the initial prodrome of bipolar disorder. A systematic review. J Affect Disord 126:1–13. doi:10.1016/j.jad.2009.10.003

    Article  PubMed  Google Scholar 

  48. 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. Arch Gen Psychiatry 63(2):175–183. doi:10.1001/archpsyc.63.2.175

    Article  PubMed Central  PubMed  Google Scholar 

  49. Axelson DA, Birmaher B, Strober MA, Goldstein BI, Ha W, Gill MK, Goldstein TR, Yen S, Hower H, Hunt JI, Liao F, Iyengar S, Dickstein D, Kim E, Ryan ND, Frankel E, Keller MB (2011) Course of subthreshold bipolar disorder in youth: diagnostic progression from bipolar disorder not otherwise specified. J Am Acad Child Adolesc Psychiatry 50:1001–1016. doi:10.1016/j.jaac

    Article  PubMed Central  PubMed  Google Scholar 

  50. Kochman FJ, Hantouche EG, Ferrari P, Lancrenon S, Bayart D, Akiskal HS (2005) Cyclothymic temperament as a prospective predictor of bipolarity and suicidality in children and adolescents with major depressive disorder. J Affect Disord 85:181–189. doi:10.1016/j.jad.2003.09.009

    Article  CAS  PubMed  Google Scholar 

  51. Akiskal HS, Maser JD, Zeller PJ, Endicott J, Coryell W, Keller M, Warshaw M, Clayton P, Goodwin F (1995) Switching from ‘unipolar’ to bipolar II: an 11-year prospective study of clinical and temperamental predictors in 559 patients. Arch Gen Psychiatry 52:114–123

    Article  CAS  PubMed  Google Scholar 

  52. Kim-Cohen J, Caspi A, Moffitt TE, Harrington H, Milne BJ, Poulton R (2003) Prior juvenile diagnoses in adults with mental disorder: developmental follow-back of a prospective-longitudinal cohort. Arch Gen Psychiatry 60(7):709–717. doi:10.1001/archpsyc.60.7.709

    Article  PubMed  Google Scholar 

  53. Costello EJ, Angold A, Burns BJ, Erkanli A, Stangl DK, Tweed DL (1996) The Great Smoky Mountains Study of Youth. Functional impairment and serious emotional disturbance. Arch Gen Psychiatry 53(12):1137–1143

    Article  CAS  PubMed  Google Scholar 

  54. Johnson JG, Cohen P, Brook JS (2000) Associations between bipolar disorder and other psychiatric disorders during adolescence and early adulthood: a community-based longitudinal investigation. Am J Psychiatry 157(10):1679–1681

    Article  CAS  PubMed  Google Scholar 

  55. Paaren A, Bohman H, von Knorring L, Olsson G, von Knorring AL, Jonsson U (2014) Early risk factors for adult bipolar disorder in adolescents with mood disorders: a 15-year follow-up of a community sample. BMC Psychiatry 14(1):363. doi:10.1186/s12888-014-0363-z

    Article  PubMed Central  PubMed  Google Scholar 

  56. Akiskal HS, Downs J, Jordan P, Watson S, Daugherty D, Pruitt DB (1985) Affective disorders in referred children and younger siblings of manic-depressives. Mode of onset and prospective course. Arch Gen Psychiatry 42(10):996–1003

    Article  CAS  PubMed  Google Scholar 

  57. Shaw JA, Egeland JA, Endicott J, Allen CR, Hostetter AM (2005) A 10-year prospective study of prodromal patterns for bipolar disorder among Amish youth. J Am Acad Child Adolesc Psychiatry 44(11):1104–1111. doi:10.1097/01.chi.0000177052.26476.e5

    Article  PubMed  Google Scholar 

  58. Egeland JA, Endicott J, Hostetter AM, Allen CR, Pauls DL, Shaw JA (2012) A 16-year prospective study of prodromal features prior to BPI onset in well Amish children. J Affect Disord 142(1–3):186–192. doi:10.1016/j.jad.2012.04.023

    Article  PubMed  Google Scholar 

  59. Axelson D, Goldstein B, Goldstein T, Monk K, Yu H, Hickey MB, Sakolsky D, Diler R, Hafeman D, Merranko J, Iyengar S, Brent D, Kupfer D, Birmaher B (2015) Diagnostic precursors to bipolar disorder in offspring of parents with bipolar disorder: a longitudinal study. Am J Psychiatry. doi:10.1176/appi.ajp.2014.14010035

    PubMed Central  PubMed  Google Scholar 

  60. Harrington R, Myatt T (2003) Is preadolescent mania the same condition as adult mania? A British perspective. Biol Psychiatry 53:961–969. doi:10.1016/S0006-3223(03)00315-9

    Article  PubMed  Google Scholar 

  61. Consoli A, Cohen D (2013) Manic-like symptoms in youths: diagnosis issues and controversies. Neuropsychiatrie de l’Enfance et de l’Adolescence 61:154–159

    Article  Google Scholar 

  62. Stringaris A, Baroni A, Haimm C, Brotman M, Lowe CH, Myers F, Rustgi E, Wheeler W, Kayser R, Towbin K, Leibenluft E (2010) Pediatric bipolar disorder versus severe mood dysregulation: risk for manic episodes on follow-up. J Am Acad Child Adolesc Psychiatry 49(4):397–405

    PubMed Central  PubMed  Google Scholar 

  63. Masi G, Perugi G, Toni C, Millepiedi S, Mucci M, Bertini N, Akiskal HS (2006) The clinical phenotypes of juvenile bipolar disorder: toward a validation of the episodic-chronic-distinction. Biol Psychiatry 59:603–610. doi:10.1016/j.biopsych.2005.08.034

    Article  PubMed  Google Scholar 

  64. Leibenluft E, Cohen P, Gorrindo T, Brook JS, Pine DS (2006) Chronic versus episodic irritability in youth: a community-based, longitudinal study of clinical and diagnostic associations. J Child Adolesc Psychopharmacol 16(4):456–466. doi:10.1089/cap.2006.16.456

    Article  PubMed  Google Scholar 

  65. Duffy A (2010) The early natural history of bipolar disorder: what we have learned from longitudinal high-risk research. Can J Psychiatry 55(8):477–485

    PubMed  Google Scholar 

  66. Hegerl U, Bottner AC, Holtschmidt-Täschner B, Born C, Seemüller F, Scheunemann W, Schütze M, Grunze H, Henkel V, Mergl R, Angst J (2008) Onset of depressive episodes is faster in patients with bipolar versus unipolar depressive disorder: evidence from a retrospective comparative study. J Clin Psychiatry 69:1075–1080

    Article  PubMed  Google Scholar 

  67. Strober M, Carlson G (1982) Bipolar illness in adolescents with major depression: clinical, genetic, and psychopharmacologic predictors in a three- to four-year prospective follow-up investigation. Arch Gen Psychiatry 39:549–555

    Article  CAS  PubMed  Google Scholar 

  68. Consoli A, Soultanian C, Tanguy ML, Laurent C, Perisse D, Luque D, Berrios G, Cohen D (2007) Cotard’s syndrome in adolescents and young adults is associated with an increased risk of bipolar disorder. Bipolar Disord 9:665–668

    Article  PubMed  Google Scholar 

  69. Birmaher B, Arbelaez C, Brent D (2002) Course and outcome of child and adolescent major depressive disorder. Child Adolesc Psychiatr Clin N Am 11:619–637

    Article  PubMed  Google Scholar 

  70. Cicchetti D, Hinshaw SP (2003) Conceptual, methodological, and statistical issues in developmental psychopathology: a special issue in honor of Paul E. Meehl Dev Psychopathol 15(3):497–499

    PubMed  Google Scholar 

  71. Fusar-Poli P, Yung AR, McGorry P, van Os J (2014) Lessons learned from the psychosis high-risk state: towards a general staging model of prodromal intervention. Psychol Med 44:17–24. doi:10.1017/S0033291713000184

    Article  CAS  PubMed  Google Scholar 

  72. Gottesman I, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645

    Article  PubMed  Google Scholar 

  73. Goldstein BI, Young LT (2013) Toward clinically applicable biomarkers in bipolar disorder: focus on BDNF, inflammatory markers, and endothelial function. Curr Psychiatry Rep 15:2–7. doi:10.1007/s11920-013-0425-9

    Article  Google Scholar 

  74. Singh MK, DelBello MP, Strakowski SM (2008) Temperament in child offspring of parents with bipolar disorder. J Child Adolesc Psychopharmacol 18(6):589–593. doi:10.1089/cap.2007.142

    Article  PubMed Central  PubMed  Google Scholar 

  75. Duffy A, Alda M, Trinneer A, Demidenko N, Grof P, Goodyer IM (2007) Temperament, life events, and psychopathology among the offspring of bipolar parents. Eur Child Adolesc Psychiatry 16(4):222–228. doi:10.1007/s00787-006-0592-x

    Article  PubMed  Google Scholar 

  76. Evans L, Akiskal HS, Keck J, McElroy SL, Sadovnick AD, Remick RA, Kelsoe JR (2005) Familiality of temperament in bipolar disorder: support for a genetic spectrum. J Affect Disord 85:153–168

    Article  PubMed  Google Scholar 

  77. Chang KD, Blasey CM, Ketter TA, Steiner H (2003) Temperament characteristics of child and adolescent bipolar offspring. J Affect Disord 77(1):11–19

    Article  PubMed  Google Scholar 

  78. Doucette S, Horrocks J, Grof P, Keown-Stoneman C, Duffy A (2013) Attachment and temperament profiles among the offspring of a parent with bipolar disorder. J Affect Disord 150(2):522–526. doi:10.1016/j.jad.2013.01.023

    Article  CAS  PubMed  Google Scholar 

  79. Ellenbogen MA, Hodgins S, Walker CD, Couture S, Adam S (2006) Daytime cortisol and stress reactivity in the offspring of parents with bipolar disorder. Psychoneuroendocrinology 31:1164–1180

    Article  CAS  PubMed  Google Scholar 

  80. Berk M, Kapczinski F, Andreazza AC, Dean OM, Giorlando F, Maes M, Yücel M, Gama CS, Dodd S, Dean B, Magalhães PV, Amminger P, McGorry P, Malhi GS (2011) Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev 35:804–817

    Article  CAS  PubMed  Google Scholar 

  81. Brown NC, Andreazza AC, Young LT (2014) An updated meta-analysis of oxidative stress markers in bipolar disorder. Psychiatry Res 218:61–68. doi:10.1016/j.psychres.2014.04.005

    Article  CAS  PubMed  Google Scholar 

  82. Andreazza AC, Kapczinski F, Kauer-Sant’Anna M, Walz JC, Bond DJ, Gonçalves CA, Young LT, Yatham LN (2009) MBBS 3-Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder. J Psychiatry Neurosci 34:263–271

    PubMed Central  PubMed  Google Scholar 

  83. Kauer-Sant’Anna M, Kapczinski FF, Andreazza AC, Bond DJ, Lam RW, Young LT, Yatham LN (2009) Brain-derived neurotrophic factor and inflammatory markers in patients with early- vs. late-stage bipolar disorder. Int J Neuropsychopharmacol 12:447–458. doi:10.1017/S1461145708009310

    Article  PubMed  CAS  Google Scholar 

  84. Fernandes BS, Gama CS, Ceresér KM, Yatham LN, Fries GR, Colpo G, de Lucena D, Kunz M, Gomes FA, Kapczinski F (2011) Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders: a systematic review and meta-regression analysis. J Psychiatr Res 45:995–1004

    Article  PubMed  Google Scholar 

  85. Grande I, Magalhães PV, Chendo I, Stertz L, Panizutti B, Colpo GD, Rosa AR, Gama CS, Kapczinski F, Vieta E (2014) Staging bipolar disorder: clinical, biochemical, and functional correlates. Acta Psychiatr Scand 129:437–444. doi:10.1111/acps.12268

    Article  CAS  PubMed  Google Scholar 

  86. Padmos RC, Hillegers MH, Knijff EM, Vonk R, Bouvy A, Staal FJT, de Ridder D, Kupka RW, Nolen WA, Drexhage HA (2008) A discriminating messenger RNA signature for bipolar disorder formed by an aberrant expression of inflammatory genes in monocytes. Arch Gen Psychiatry 65:395–407

    Article  CAS  PubMed  Google Scholar 

  87. Mesman E, Hillegers MHJ, Ambree O, Arolt V, Nolen WA, Drexhage HA (2014) Monocyte activation, brain-derived neurotrophic factor (BDNF), and S100B in bipolar offspring: a follow-up study from adolescence into adulthood. Bipolar Disord. doi:10.1111/bdi.12231

    Google Scholar 

  88. Zalla T, Joyce C, Szoke A, Schurhoff F, Pillon B, Komano O, Perez-Diaz F, Bellivier F, Alter C, Dubois B, Rouillon F, Houde O, Leboyer M (2004) Executive dysfunctions as potential markers of familial vulnerability to bipolar disorder and schizophrenia. Psychiatry Res 121:207–217

    Article  PubMed  Google Scholar 

  89. Brotman MA, Guyer AE, Lawson ES, Horsey SE, Rich BA, Dickstein DP, Pine DS, Leibenluft E (2008) Facial emotion labeling deficits in children and adolescents at risk for bipolar disorder. Am J Psychiatry 165:385–389. doi:10.1097/CHI

    Article  PubMed  Google Scholar 

  90. Schenkel LS, Marlow-O’Connor M, Moss M, Sweeney JA, Pavuluri MN (2008) Theory of mind and social inference in children and adolescents with bipolar disorder. Psychol Med 38:791–800. doi:10.1017/S0033291707002541

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. Whitney J, Howe M, Shoemaker V, Li S, Sanders EM, Dijamco C, Acquaye T, Phillips J, Singh M, Chang K (2013) Socio-emotional processing and functioning of youth at high risk for bipolar disorder. J Affect Disord 148:112–117. doi:10.1016/j.jad.2012.08.016

    Article  PubMed Central  PubMed  Google Scholar 

  92. Frey BN, Zunta-Soares GB, Caetano SC, Nicoletti MA, Hatch JP, Brambilla P, Mallinger AG, Soares JC (2008) Illness duration and total brain gray matter in bipolar disorder: evidence for neurodegeneration? Eur Neuropsychopharmacol 18:712–722

    Article  CAS  Google Scholar 

  93. Strakowski SM, Adler CM, Almeida J, Altshuler LL, Blumberg HP, Chang KD, DelBello MP, Frangou S, McIntosh A, Phillips ML, Sussman JE, Townsend JD (2012) The functional neuroanatomy of bipolar disorder: a consensus model. Bipolar Disord 14:313–325

    Article  PubMed  Google Scholar 

  94. Strakowski SM, DelBello MP, Zimmerman ME, Getz GE, Mills NP, Ret J, Shear P, Adler CM (2002) Ventricular and periventricular structural volumes in first- versus multiple-episode bipolar disorder. Am J Psychiatry 159:1841–1847

    Article  PubMed  Google Scholar 

  95. Arango C, Rapado-Castro M, Reig S, Castro-Fornieles J, Gonzalez-Pinto A, Otero S, Baeza I, Moreno C, Graell M, Janssen J, Parellada M, Moreno D, Bargallo N, Desco M (2012) Progressive brain changes in children and adolescents with first-episode psychosis. Arch Gen Psychiatry 69(1):16–26. doi:10.1001/archgenpsychiatry.2011.150

    Article  PubMed  Google Scholar 

  96. Chang K, Adleman N, Dienes K, Barnea-Goraly N, Reiss A, Ketter T (2003) Decreased N-acetylaspartate in children with familial bipolar disorder. Biol Psychiatry 53:1059–1065

    Article  CAS  PubMed  Google Scholar 

  97. Singh MK, Chang KD, Kelley RG, Saggar M, Reiss AL, Gotlib IH (2014) Early signs of anomalous neural functional connectivity in healthy offspring of parents with bipolar disorder. Bipolar Disord. doi:10.1111/bdi.12221

    Google Scholar 

  98. Pfeifer JC, Welge J, Strakowski SM, Adler CM, DelBello MP (2008) Meta-analysis of amygdala volumes in children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 47:1289–1298

    Article  PubMed  Google Scholar 

  99. Fernandes BS, Gama CS, Kauer-Sant’Anna M, Lobato MI, Belmonte-de-Abreu P, Kapczinski F (2009) Serum brain-derived neurotrophic factor in bipolar and unipolar depression: a potential adjunctive tool for differential diagnosis. J Psychiatr Res 43:100–1204. doi:10.1016/j.jpsychires.2009.04.010

    Article  Google Scholar 

  100. Correll CU, Penzner JB, Lencz T, Auther A, Smith CW, Malhotra AK, Kane JM, Cornblatt BA (2007) Early identification and high-risk strategies for bipolar disorder. Bipolar Disord 9:324–338

    Article  PubMed  Google Scholar 

  101. Pfennig A, Correll CU, Marx C, Rottmann-Wolf M, Meyer TD, Bauer M, Leopold K (2014) Psychotherapeutic interventions in individuals at risk of developing bipolar disorder: a systematic review. Early Interv Psychiatry 8:3–11. doi:10.1111/eip.12082

    Article  PubMed  Google Scholar 

  102. Nadkarni RB, Fristad MA (2010) Clinical course of children with a depressive spectrum disorder and transient manic symptoms. Bipolar Disord 12:494–503

    Article  PubMed Central  PubMed  Google Scholar 

  103. Miklowitz DJ, Chang KD, Taylor DO, George EL, Singh MK, Schneck CD, Dickinson LM, Howe ME, Garber J (2011) Early psychosocial intervention for youth at risk for bipolar I or II disorder: a one-year treatment development trial. Bipolar Disorders 13:67–75. doi:10.1111/j.1399-5618.2011.00890.x

    Article  PubMed Central  PubMed  Google Scholar 

  104. Miklowitz DJ, Schneck CD, Singh MK, Taylor DO, George EL, Cosgrove VE, Howe ME, Dickinson LM, Garber J, Chang KD (2013) Early intervention for symptomatic youth at risk for bipolar disorder: a randomized trial of family-focused therapy. J Am Acad Child Adolesc Psychiatry 52:121–131

    Article  PubMed Central  PubMed  Google Scholar 

  105. Goldstein TR, Fersch-Podrat R, Axelson DA, Gilbert A, Hlastala SA, Birmaher B, Frank E (2014) Intervention for adolescents at high risk for the development of bipolar disorder: pilot study of Interpersonal and Social Rhythm Therapy (IPSRT). Psychotherapy 51:180–189. doi:10.1037/a0034396

    Article  PubMed  Google Scholar 

  106. Pfennig A, Leopold K, Bechdolf A, Correll CU, Holtmann M, Lambert M, Marx C, Meyer TD, Pfeiffer S, Reif A, Rottmann-Wolf M, Schmitt NM, Stamm T, Juckel G, Bauer M (2014) Early specific cognitive-behavioural psychotherapy in subjects at high risk for bipolar disorders: stud protocol for a randomised controlled trial. Trials 15:161. doi:10.1186/1745-6215-15-161

    Article  PubMed Central  PubMed  Google Scholar 

  107. Consoli A, Deniau E, Huynh C, Purper D, Cohen D (2007) Treatments in child and adolescent bipolar disorders. Eur Child Adolesc Psychiatry 16:187–198

    Article  PubMed  Google Scholar 

  108. Birmaher B (2013) Bipolar disorder in children and adolescents. Child Adolesc Mental Health 18:140–148. doi:10.1111/camh.12021

    Article  Google Scholar 

  109. Geller B, Cooper TB, Zimerman B, Frazier J, Williams M, Heath J, Warner K (1998) Lithium for prepubertal depressed children with family history predictors of future bipolarity: a double-blind, placebo-controlled study. J Affect Disord 51:165–175

    Article  CAS  PubMed  Google Scholar 

  110. Findling RL, Frazier TW, Youngstrom EA, McNamara NK, Stansbrey RJ, Gracious BL, Reed MD, Demeter CA, Calabrese JR (2007) Double blind, placebo-controlled trial of divalproex monotherapy in the treatment of symptomatic youth at high risk for developing bipolar disorder. J Clin Psychiatry 68:781–788

    Article  CAS  PubMed  Google Scholar 

  111. DelBello MP, Adler CM, Whitsel RM, Stanford KE, Strakowski SM (2007) A 12-week single-blind trial of quetiapine for the treatment of mood symptoms in adolescents at high risk for developing bipolar I disorder. J Clin Psychiatry 68:789–795

    Article  CAS  PubMed  Google Scholar 

  112. Chang KD, Dienes K, Blasey C, Adleman N, Ketter T, Steiner H (2003) Divalproex monotherapy in the treatment of bipolar offspring with mood and behavioral disorders and at least mild affective symptoms. J Clin Psychiatry 64:936–942

    Article  CAS  PubMed  Google Scholar 

  113. McNamara RK, Nandagopal JJ, Strakowski SM, DelBello MP (2010) Preventative strategies for early-onset bipolar disorder: towards a clinical staging model. CNS Drugs 24:983–996

    Article  PubMed  Google Scholar 

  114. Milhiet V, Consoli A, Raffin M, Cohen D (2014) Lithium treatment in youths with bipolar disorder. Annales Médico-psychologiques, revue psychiatrique 172(3):219–228

    Article  Google Scholar 

  115. Cohen D, Bonnot O, Bodeau N, Consoli A, Laurent C (2012) Adverse effects of second-generation antipsychotics in children and adolescents: a Bayesian meta-analysis. J Clin Psychopharmacol 32(3):309–316

    Article  CAS  PubMed  Google Scholar 

  116. Grosso G, Pajak A, Marventano S, Castellano S, Galvano F, Bucolo C, Drago F, Caraci F (2014) Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS One 9(5):e96905

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  117. Sarris J, Mischoulon D, Schweitzer I (2012) Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depression. J Clin Psychiatry 73:81–86

    Article  CAS  PubMed  Google Scholar 

  118. Correll CU, Olvet DM, Auther AM, Hauser M, Kishimoto T, Carrión RE, Snyder S, Cornblatt BA (2014) The Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P): description and validation in a psychiatric sample and healthy controls. Bipolar Disord 16:505–522. doi:10.1111/bdi.12209

    Article  PubMed Central  PubMed  Google Scholar 

  119. Bechdolf A, Nelson B, Cotton SM, Chanen A, Thompson A, Kettle J, Conus P, Amminger P, Yung AR, Berk M, McGorry PD (2010) A preliminary evaluation of the validity of at-risk criteria for bipolar disorders in help-seeking adolescents and young adults. J Affect Disord 127:316–320. doi:10.1016/j.jad.2010.06.016

    Article  PubMed  Google Scholar 

  120. Bechdolf A, Ratheesh A, Cotton SM, Nelson B, Chanen AM, Betts J, Bingmann T, Yung AR, Berk M, McGorry PD (2014) The predictive validity of bipolar at-risk (prodromal) criteria in help-seeking adolescents and young adults: a prospective study. Bipolar Disord 16:493–504. doi:10.1111/bdi.12205

    Article  PubMed  Google Scholar 

  121. Leopold K, Ritter P, Correll CU, Marx C, Özgürdal S, Juckel G, Bauer M, Pfennig A (2012) Risk constellations prior to the development of bipolar disorders: rationale of a new risk assessment tool. J Affect Disord 136:1000–1010. doi:10.1016/j.jad.2011.06.043

    Article  PubMed  Google Scholar 

  122. Leopold K, Ratzer S, Correll CU, Rottmann-Wolf M, Pfeiffer S, Ritter P, Bauer M, Pfennig A (2014) Characteristics, symptomatology and naturalistic treatment in individuals at-risk for bipolar disorders: baseline results in the first 180 help-seeking individuals assessed at the dresden high-risk project. J Affect Disord 152–154:427–433. doi:10.1016/j.jad.2013.10.009

    Article  PubMed  Google Scholar 

  123. McGorry PD, Hickie IB, Yung AR, Pantelis C, Jackson HJ (2006) Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions. Aust N Z J Psychiatry 40:616–622

    Article  PubMed  Google Scholar 

  124. Berk M, Berk L, Dodd S, Cotton S, Macneil C, Daglas R, Conus P, Bechdolf A, Moylan S, Malhi G (2014) Stage managing bipolar disorder. Bipolar Disord 16:471–477. doi:10.1111/bdi.12099

    Article  PubMed Central  PubMed  Google Scholar 

  125. Reinares M, Papachristou E, Harvey P, Bonnín M, Sánchez-Moreno J, Torrent C, Ayuso-Mateos JL, Ploubidis GE, Vieta E, Frangou S (2013) Towards a clinical staging for bipolar disorder: defining patient subtypes based on functional outcome. J Affect Disord 144:65–71. doi:10.1016/j.jad.2012.06.005

    Article  PubMed  Google Scholar 

  126. Rosa AR, Magalhães PV, Czepielewski L, Sulzbach MV, Goi PD, Vieta E, Gama CS, Kapczinski F (2014) Clinical staging in bipolar disorder: focus on cognition and functioning. J Clin Psychiatry. doi:10.4088/JCP.13m08625

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xavier Benarous.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Benarous, X., Consoli, A., Milhiet, V. et al. Early interventions for youths at high risk for bipolar disorder: a developmental approach. Eur Child Adolesc Psychiatry 25, 217–233 (2016). https://doi.org/10.1007/s00787-015-0773-6

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00787-015-0773-6

Keywords

Navigation