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Treatment of Psychiatric Symptoms Among Offspring of Parents With Bipolar Disorder

  • Bipolar and Other Mood Disorders (B Goldstein and D Hafeman, Section Editors)
  • Published:
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Abstract

Purpose of review Bipolar disorder is highly familial and has a protracted and diagnostically confusing prodrome. This review critically evaluates recently published literature relevant to the treatment of psychiatric symptoms in high-risk offspring of parents with bipolar disorder.

Recent findings Non-pharmacological treatment options including psychotherapy, resilience promotion through good sleep, diet, and exercise hygiene, and omega-3 fatty acid supplementation are important first-line interventions for high-risk offspring. There has been some success in treating this population with open-label trials with mood stabilizers and atypical antipsychotics; however, these results have not been replicated in randomized controlled trails.

Summary Despite some progress in early identification of symptoms in offspring of parents with bipolar disorder, there is scarce evidence supporting the treatment of these high-risk youth to prevent psychiatric symptoms from progressing to threshold bipolar or other psychiatric disorders. There is a need for prospective and randomized trials and research that identifies reliable biomarkers to individualize treatments for these youth.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. McGuffin P, Rijsdijk F, Andrew M, Sham P, Katz R, Cardno A. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry. 2003;60:497.

    Article  PubMed  Google Scholar 

  2. Singh MK, DelBello MP, Stanford KE, Soutullo C, McDonough-Ryan P, McElroy SL, et al. Psychopathology in children of bipolar parents. J Affect Disord. 2007;102:131–6.

    Article  PubMed  Google Scholar 

  3. Henin A, Biederman J, Mick E, Sachs GS, Hirshfeld-Becker DR, Siegel RS, et al. Psychopathology in the offspring of parents with bipolar disorder: a controlled study. Biol Psychiatry. 2005;58:554–61.

    Article  PubMed  Google Scholar 

  4. Post RM. Kindling and sensitization as models for affective episode recurrence, cyclicity, and tolerance phenomena. Neurosci Biobehav Rev. 2007;31:858–73.

    Article  PubMed  Google Scholar 

  5. Paus T, Keshavan M, Giedd JN. Why do many psychiatric disorders emerge during adolescence? Nat Rev Neurosci. 2017; [Internet]. Accessed 27 Jul 2017. Available from: https://www.nature.com/doifinder/10.1038/nrn2513

  6. Goodwin F, Jamison K. Manic-depressive illness. Bipolar disorders and recurrent depression. New York: Oxford University Press; 2007.

    Google Scholar 

  7. Nusslock R, Alloy LB. Reward processing and mood-related symptoms: an RDoC and translational neuroscience perspective. J Affect Disord. 2017;216:3–16.

    Article  PubMed  Google Scholar 

  8. van Santvoort F, Hosman CMH, Janssens JMAM, van Doesum KTM, Reupert A, van Loon LMA. The impact of various parental mental disorders on children’s diagnoses: a systematic review. Clin Child Fam Psychol Rev. 2015;18:281–99.

    Article  PubMed  Google Scholar 

  9. Perlis RH, Delbello MP, Miyahara S, Wisniewski SR, Sachs GS, Nierenberg AA. Revisiting depressive-prone bipolar disorder: polarity of initial mood episode and disease course among bipolar I systematic treatment enhancement program for bipolar disorder participants. Biol Psychiatry. 2005;58:549–53.

    Article  PubMed  Google Scholar 

  10. • Diler RS, Goldstein TR, Hafeman D, Rooks BT, Sakolsky D, Goldstein BI, et al. Characteristics of depression among offspring at high and low familial risk of bipolar disorder. Bipolar Disord. [Internet]. 2017. Accessed 27 Jul 2017. Available from: https://doi.wiley.com/10.1111/bdi.12508. This study evaluated the most severe major depressive episode in offspring of a parent with bipolar disorder and community control offspring of parents with no history of Bipolar Disorder. Relative to community controls, high-risk offspring had more severe depressive symptoms, with atypical depressive features, and higher subsyndromal manic symptoms.

  11. Fritz K, Russell AMT, Allwang C, Kuiper S, Lampe L, Malhi GS. Is a delay in the diagnosis of bipolar disorder inevitable? Bipolar Disord. 2017;

  12. Mizushima J, Uchida H, Tada M, Suzuki T, Mimura M, Nio S. Early improvement of specific symptoms predicts subsequent recovery in bipolar depression: reanalysis of the systematic treatment enhancement program for bipolar disorder (STEP-BD) data. J Clin Psychiatry. 2017;78:e146–51.

    Article  PubMed  Google Scholar 

  13. Lapalme M, Hodgins S, LaRoche C. Children of parents with bipolar disorder: a metaanalysis of risk for mental disorders. Can J Psychiatr. 1997;42:623–31.

    Article  CAS  Google Scholar 

  14. Axelson D, Goldstein B, Goldstein T, Monk K, Yu H, Hickey MB, et al. Diagnostic precursors to bipolar disorder in offspring of parents with bipolar disorder: a longitudinal study. Am J Psychiatry. 2015;172:638–46.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Simpson SG, Folstein SE, Meyers DA, DePaulo JR. Assessment of lineality in bipolar I linkage studies. Am J Psychiatry. 1992;149:1660–5.

    Article  CAS  PubMed  Google Scholar 

  16. Leopold K, Ratzer S, Correll CU, Rottmann-Wolf M, Pfeiffer S, Ritter P, et al. 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. 2014;152–154:427–33.

    Article  PubMed  Google Scholar 

  17. Serra G, Koukopoulos A, De Chiara L, Koukopoulos AE, Sani G, Tondo L, et al. Early clinical predictors and correlates of long-term morbidity in bipolar disorder. Eur Psychiatry J Assoc Eur Psychiatr. 2017;43:35–43.

    Article  CAS  Google Scholar 

  18. • Hafeman DM, Merranko J, Goldstein TR, Axelson D, Goldstein BI, Monk K, et al. Assessment of a person-level risk calculator to predict new-onset bipolar spectrum disorder in youth at familial risk. JAMA Psychiatry. 2017; This study developed a risk calculator to predict the 5-year outcome of bipolar spectrum disorder in youth at familial risk for Bipolar Disorder to assist with early identification. This risk calculator can be used clinically to determine the probability of high-risk youth converting to bipolar spectrum disorder and inform clinicians of the frequency of monitoring and treatment options.

  19. Duffy A, Horrocks J, Doucette S, Keown-Stoneman C, McCloskey S, Grof P. Childhood anxiety: An early predictor of mood disorders in offspring of bipolar parents. J Affect Disord. 2013;150:363–69.

    Article  PubMed  Google Scholar 

  20. Van Meter AR, Burke C, Youngstrom EA, Faedda GL, Correll CU. The bipolar Prodrome: meta-analysis of symptom prevalence prior to initial or recurrent mood episodes. J Am Acad Child Adolesc Psychiatry. 2016;55:543–55.

    Article  PubMed  Google Scholar 

  21. Hafeman DM, Merranko J, Axelson D, Goldstein BI, Goldstein T, Monk K, et al. Toward the definition of a bipolar Prodrome: dimensional predictors of bipolar Spectrum disorders in at-risk youths. Am J Psychiatry. 2016;173:695–704.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Mesman E, Nolen WA, Keijsers L, Hillegers MHJ. Baseline dimensional psychopathology and future mood disorder onset: findings from the Dutch bipolar offspring study. Acta Psychiatr Scand. 2017;136:201–9.

    Article  CAS  PubMed  Google Scholar 

  23. Birmaher B, Axelson D, Strober M, Gill MK, Valeri S, Chiappetta L, et al. Clinical course of children and adolescents with bipolar Spectrum disorders. Arch Gen Psychiatry. 2006;63:175.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Geoffroy PA, Scott J. Prodrome or risk syndrome: what’s in a name. Int J Bipolar Disord. 2017;5:7.

    Article  PubMed  PubMed Central  Google Scholar 

  25. • Singh MK, Chang KD, Kelley RG, Saggar M, Reiss AL, Gotlib IH. Early signs of anomalous neural functional connectivity in healthy offspring of parents with bipolar disorder. Bipolar Disord. 2014;16:678–89. To better understand findings of previous studies and reviews, this article defines and differentiates “prodromes” and “risk syndromes”, both concepts critical to examining the pre-onset phase of a mental illness. The study aims to elucidate the utility of these concepts in the evolution of Bipolar Disorder to characterize the transition from risk syndrome to full-blown Bipolar Disorder as well as to guide prevention strategies and treatment planning for Bipolar Disorder.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Miklowitz DJ, Schneck CD, Singh MK, Taylor DO, George EL, Cosgrove VE, et al. Early intervention for symptomatic youth at risk for bipolar disorder: a randomized trial of family-focused therapy. J Am Acad Child Adolesc Psychiatry. 2013;52:121–31.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Garrett AS, Miklowitz DJ, Howe ME, Singh MK, Acquaye T, Hawkey C, et al. Changes in brain activation following psychotherapy for youth with mood dysregulation at familial risk for bipolar disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry (in press).

  28. • Doucette S, Levy A, Flowerdew G, Horrocks J, Grof P, Ellenbogen M, et al. Early parent-child relationships and risk of mood disorder in a Canadian sample of offspring of a parent with bipolar disorder: findings from a 16-year prospective cohort study: early predictors of mood disorder. Early Interv Psychiatry. 2016;10:381–9. This study describes specific parent-child relational factors (e.g. neglect from mother) that are significant early predictors of mood disorder in offspring at familial risk for Bipolar Disorder and may increase emotional sensitivity. The study provides specific recommendations for psychosocial support and interventions. for high-risk families that could reduce early adversity, maternal neglect, and the risk of subsequent mood disorders in high-risk offspring. Data from this study was part of a larger cohort study conducted by Duffy et al (reference 19).

    Article  PubMed  Google Scholar 

  29. Reichart CG, van der Ende J, Hillegers MHJ, Wals M, Bongers IL, Nolen WA, et al. Perceived parental rearing of bipolar offspring. Acta Psychiatr Scand. 2007;115:21–8.

    Article  CAS  PubMed  Google Scholar 

  30. Meyer SE, Carlson GA, Wiggs EA, Ronsaville DS, Martinez PE, Klimes-Dougan B, et al. A prospective high-risk study of the association among maternal negativity, apparent frontal lobe dysfunction, and the development of bipolar disorder. Dev. Psychopathol. 2006; [Internet]. Accessed 27 Jul 2017. Available from: https://www.journals.cambridge.org/abstract_S0954579406060299

  31. Goodday S, Levy A, Flowerdew G, Horrocks J, Grof P, Ellenbogen M, et al. Early exposure to parental bipolar disorder and risk of mood disorder: the Flourish Canadian prospective offspring cohort study: exposure to parental bipolar disorder. Early Interv. Psychiatry. 2015;

  32. Miklowitz DJ, Chang KD. Prevention of bipolar disorder in at-risk children: theoretical assumptions and empirical foundations. Dev Psychopathol. 2008;20:881–97.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Bauer IE, Gálvez JF, Hamilton JE, Balanzá-Martínez V, Zunta-Soares GB, Soares JC, et al. Lifestyle interventions targeting dietary habits and exercise in bipolar disorder: a systematic review. J Psychiatr Res. 2016;74:1–7.

    Article  PubMed  Google Scholar 

  34. Vancampfort D, Firth J, Schuch F, Rosenbaum S, De Hert M, Mugisha J, et al. Physical activity and sedentary behavior in people with bipolar disorder: a systematic review and meta-analysis. J Affect Disord. 2016;201:145–52.

    Article  PubMed  Google Scholar 

  35. Carter T, Morres ID, Meade O, Callaghan P. The effect of exercise on depressive symptoms in adolescents: a systematic review and meta-analysis. J Am Acad Child Adolesc Psychiatry. 2016;55:580–90.

    Article  PubMed  Google Scholar 

  36. Sebela A, Novak T, Kemlink D, Goetz M. Sleep characteristics in child and adolescent offspring of parents with bipolar disorder: a case control study. BMC Psychiatry. 2017;17:199.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Levenson JC, Soehner A, Rooks B, Goldstein TR, Diler R, Merranko J, et al. Longitudinal sleep phenotypes among offspring of bipolar parents and community controls. J Affect Disord. 2017;215:30–6.

    Article  PubMed  Google Scholar 

  38. Soehner AM, Bertocci MA, Manelis A, Bebko G, Ladouceur CD, Graur S, et al. Preliminary investigation of the relationships between sleep duration, reward circuitry function, and mood dysregulation in youth offspring of parents with bipolar disorder. J Affect Disord. 2016;205:144–53.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Blake M, Waloszek JM, Schwartz O, Raniti M, Simmons JG, Blake L, et al. The SENSE study: post intervention effects of a randomized controlled trial of a cognitive–behavioral and mindfulness-based group sleep improvement intervention among at-risk adolescents. J Consult Clin Psychol. 2016;84:1039–51.

    Article  PubMed  Google Scholar 

  40. Hiscock H, Sciberras E, Mensah F, Gerner B, Efron D, Khano S, et al. Impact of a behavioural sleep intervention on symptoms and sleep in children with attention deficit hyperactivity disorder, and parental mental health: randomised controlled trial. BMJ. 2015;h68:350.

    Google Scholar 

  41. Hall WA, Hutton E, Brant RF, Collet JP, Gregg K, Saunders R, et al. A randomized controlled trial of an intervention for infants’ behavioral sleep problems. BMC Pediatr. 2015. [Internet]. Accessed 27 Jul 2017. Available from: https://bmcpediatr.biomedcentral.com/articles/10.1186/s12887-015-0492-7

  42. Fristad MA, Young AS, Vesco AT, Nader ES, Healy KZ, Gardner W, et al. A randomized controlled trial of individual family psychoeducational psychotherapy and omega-3 fatty acids in youth with subsyndromal bipolar disorder. J Child Adolesc Psychopharmacol. 2015;25:764–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wozniak J, Faraone SV, Chan J, Tarko L, Hernandez M, Davis J, et al. A randomized clinical trial of high eicosapentaenoic acid omega-3 fatty acids and inositol as monotherapy and in combination in the treatment of pediatric bipolar spectrum disorders: a pilot study. J Clin Psychiatry. 2015;76:1548–55.

    Article  PubMed  Google Scholar 

  44. Miklowitz DJ, Chang KD, Taylor DO, George EL, Singh MK, Schneck CD, et al. Early psychosocial intervention for youth at risk for bipolar I or II disorder: a one-year treatment development trial: youth at risk for bipolar disorder. Bipolar Disord. 2011;13:67–75.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Goldstein TR, Fersch-Podrat R, Axelson DA, Gilbert A, Hlastala SA, Birmaher B, et al. Early intervention for adolescents at high risk for the development of bipolar disorder: pilot study of interpersonal and social rhythm therapy (IPSRT). Psychotherapy. 2014;51:180–9.

    Article  PubMed  Google Scholar 

  46. Goldstein TR (2017). Early-onset bipolar disorder: psychosocial treatment strategies. Paper presented at the International Society for Bipolar Disorders annual meeting, Washington, DC.

  47. Cotton S, Luberto CM, Sears RW, Strawn JR, Stahl L, Wasson RS, et al. Mindfulness-based cognitive therapy for youth with anxiety disorders at risk for bipolar disorder: a pilot trial: MBCT for youth at risk for bipolar disorder. Early Interv Psychiatry. 2016;10:426–34.

    Article  PubMed  Google Scholar 

  48. Strawn JR, Cotton S, Luberto CM, Patino LR, Stahl LA, Weber WA, et al. Neural function before and after mindfulness-based cognitive therapy in anxious adolescents at risk for developing bipolar disorder. J Child Adolesc Psychopharmacol. 2016;26:372–9.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Geller B, Cooper TB, Zimerman B, Frazier J, Williams M, Heath J, et al. Lithium for prepubertal depressed children with family history predictors of future bipolarity: a double-blind, placebo-controlled study. J Affect Disord. 1998;51:165–75.

    Article  CAS  PubMed  Google Scholar 

  50. Chang KD, Dienes K, Blasey C, Adleman N, Ketter T, Steiner H. Divalproex monotherapy in the treatment of bipolar offspring with mood and behavioral disorders and at least mild affective symptoms. J Clin Psychiatry. 2003;64:936–42.

    Article  CAS  PubMed  Google Scholar 

  51. Findling RL, Frazier TW, Youngstrom EA, McNamara NK, Stansbrey RJ, Gracious BL, et al. Double-blind, placebo-controlled trial of divalproex monotherapy in the treatment of symptomatic youth at high risk for developing bipolar disorder. J Clin Psychiatry. 2007;68:781–8.

    Article  CAS  PubMed  Google Scholar 

  52. DelBello MP, Adler CM, Whitsel RM, Stanford KE, Strakowski SM. 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. 2007;68:789–95.

    Article  CAS  PubMed  Google Scholar 

  53. Chang KD, Saxena K, Howe M, Simeonova D. Psychotropic medication exposure and age at onset of bipolar disorder in offspring of parents with bipolar disorder. J Child Adolesc Psychopharmacol. 2010;20:25–32.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Findling RL, Lingler J, Rowles BM, McNamara NK, Calabrese JRA. Pilot pharmacotherapy trial for depressed youths at high genetic risk for bipolarity. J Child Adolesc Psychopharmacol. 2008;18:615–21.

    Article  PubMed  Google Scholar 

  55. Findling RL, Rowles BM, Deeling E, Lingler J, Stansbrey RJ, McVoy M, Lytle S, Calabrese JR, McNamara NK. A Double-Blind and Placebo-Controlled Trial of Aripiprazole in Symptomatic Youths at Genetic High Risk for Bipolar Disorder. J Child Adolesc Psychopharmacol. 2017

  56. Chang K, Karchemskiy A, Kelley R, Howe M, Garrett A, Adleman N, et al. Effect of divalproex on brain morphometry, chemistry, and function in youth at high-risk for bipolar disorder: a pilot study. J Child Adolesc Psychopharmacol. 2009;19:51–9.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Joseph MF, Youngstrom EA, Soares JC. Antidepressant-coincident mania in children and adolescents treated with selective serotonin reuptake inhibitors. Future Neurol. 2009;4:87–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Baumer FM, Howe M, Gallelli K, Simeonova DI, Hallmayer J, Chang KDA. Pilot study of antidepressant-induced mania in pediatric bipolar disorder: characteristics, risk factors, and the serotonin transporter gene. Biol Psychiatry. 2006;60:1005–12.

    Article  CAS  PubMed  Google Scholar 

  59. Strawn JR, Adler CM, McNamara RK, Welge JA, Bitter SM, Mills NP, et al. Antidepressant tolerability in anxious and depressed youth at high risk for bipolar disorder: a prospective naturalistic treatment study. Bipolar Disord. 2013.

  60. Goldsmith M, Singh M, Chang K. Antidepressants and psychostimulants in pediatric populations: is there an association with mania? Paediatr Drugs. 2011;13:225–43.

    Article  PubMed  PubMed Central  Google Scholar 

  61. • Schneck CD, Chang KD, Singh MK, DelBello MP, Miklowitz DJ. A pharmacologic algorithm for youth who are at high risk for bipolar disorder. J Child Adolesc Psychopharmacol. 2017. This study describes an algorithmic approach to pharmacologic intervention in youth at high-risk for developing bipolar disorder, who were enrolled in a randomized trial of family focused therapy versus an educational control condition and followed prospectively for one year.

  62. Detke HC, DelBello MP, Landry J, Usher RW. Olanzapine/fluoxetine combination in children and adolescents with bipolar I depression: a randomized, double-blind, placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2015;54:217–24.

    Article  PubMed  Google Scholar 

  63. Findling RL, Goldman R, Chiu YY, Silva R, Jin F, Pikalov A, et al. Pharmacokinetics and tolerability of Lurasidone in children and adolescents with psychiatric disorders. Clin Ther. 2015;37(12):2788–97.

    Article  CAS  PubMed  Google Scholar 

  64. Tillman R, Geller B. 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. 2006. [Internet]. Accessed 27 Jul 2017. Available from: https://www.journals.cambridge.org/abstract_S0954579406060512

  65. Scheffer RE, Kowatch RA, Carmody T, Rush AJ. Randomized, placebo-controlled trial of mixed amphetamine salts for symptoms of comorbid ADHD in pediatric bipolar disorder after mood stabilization with divalproex sodium. Am J Psychiatry. 2005;162:58–64.

    Article  PubMed  Google Scholar 

  66. Pliszka S. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46:894–921.

    Article  PubMed  Google Scholar 

  67. Singh MK, Chang KD. The neural effects of psychotropic medications in children and adolescents. Child Adolesc Psychiatr Clin N Am. 2012;21:753–71.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Singh MK, Garrett AS, Chang KD. Using neuroimaging to evaluate and guide pharmacological and psychotherapeutic treatments for mood disorders in children. CNS Spectr. 2015;20:359–68.

    Article  PubMed  Google Scholar 

  69. Kapczinski F, Dias VV, Kauer-Sant’Anna M, Brietzke E, Vázquez GH, Vieta E, et al. The potential use of biomarkers as an adjunctive tool for staging bipolar disorder. Prog Neuro-Psychopharmacol Biol Psychiatry. 2009;33:1366–71.

    Article  CAS  Google Scholar 

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Funding

Dr. Singh receives research support from Stanford’s Child Health Research Institute, National Institute of Mental Health, Office of Research on Women’s Health, National Institute of Aging, Neuronetics, Johnson and Johnson, and the Brain and Behavior Foundation.

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Correspondence to Manpreet Kaur Singh MD MS.

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Dr. Zalpuri reports no conflicts of interest. Dr. Singh has been on the advisory board for Sunovion.

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This article is part of the Topical Collection on Bipolar and Other Mood Disorders

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Zalpuri, I., Singh, M.K. Treatment of Psychiatric Symptoms Among Offspring of Parents With Bipolar Disorder. Curr Treat Options Psych 4, 341–356 (2017). https://doi.org/10.1007/s40501-017-0126-9

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