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Preventative Strategies for Early-Onset Bipolar Disorder

Towards a Clinical Staging Model

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Abstract

Bipolar disorder is a chronic and typically recurring illness with significant psychosocial morbidity. Although the aetiological factors that contribute to the onset of mania, and by definition bipolar I disorder, are poorly understood, it most commonly occurs during the adolescent period. Putative risk factors for developing bipolar disorder include having a first-degree relative with a mood disorder, physical/sexual abuse and other psychosocial stressors, substance use disorders, psychostimulant and antidepressant medication exposure and omega-3 fatty acid deficiency. Prominent prodromal clinical features include episodic symptoms of depression, anxiety, hypomania, anger/irritability and disturbances in sleep and attention. Because prodromal mood symptoms precede the onset of mania by an average of 10 years, and there is low specificity of risk factors and prodromal features for mania, interventions initiated prior to onset of the disorder (primary prevention) or early in the course of the disorder (early or secondary prevention) must be safe and well tolerated upon long-term exposure. Indeed, antidepressant and psychostimulant medications may precipitate the onset of mania. Although mood stabilizers and atypical antipsychotic medications exhibit efficacy in youth with bipolar I disorder, their efficacy for the treatment of prodromal mood symptoms is largely unknown. Moreover, mood stabilizers and atypical antipsychotics are associated with prohibitive treatment-emergent adverse effects. In contrast, omega-3 fatty acids have neurotrophic and neuroprotective properties and have been found to be efficacious, safe and well tolerated in the treatment of manic and depressive symptoms in children and adolescents. Together, extant evidence endorses a clinical staging model in which subjects at elevated risk for developing mania are treated with safer interventions (i.e. omega-3 fatty acids, familyfocused therapy) in the prodromal phase, followed by pharmacological agents with potential adverse effects for nonresponsive cases and secondary prevention. This approach warrants evaluation in prospective longitudinal trials in youth determined to be at ultra-high risk for bipolar I disorder.

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Acknowledgements

The work was supported in part by National Institutes of Health (NIH) grants MH080973 to M.P.D., MH083924 to R.K.M. and M.P.D., and MH077138 to S.M.S. R.K.M. has received research support from Martek Biosciences Inc., Inflammation Research Foundation, Ortho-McNeil Janssen, AstraZeneca, Eli Lilly, National Alliance for Research on Schizophrenia And Depression (NARSAD), National Institute of Mental Health (NIMH) and National Institute on Aging (NIA). J.J.N. has received research support from AstraZeneca, BMS/Otsuka, Eli Lilly, GlaxoSmithKline, Pfizer, Johnson & Johnson, Shire, Abbott, Janssen, Martek Biosciences Inc., Somerset, Repligen, Sumitomo, National Institute on Drug Abuse (NIDA), NIMH, National Institute on Alcohol Abuse and Alcoholism (NIAAA) and NARSAD. S.M.S. has received research grant support from Eli Lilly, Janssen, AstraZeneca, Nutrition 21, Martek Biosciences Inc., Repligen, NIDA, NIAAA, NARSAD, NIMH and Thrasher Foundation, and is a consultant for Pfizer. M.P.D. has received research support from AstraZeneca, Eli Lilly, Martek, Johnson & Johnson, Shire, Ortho-McNeil, Janssen, Pfizer, Bristol Myers Squibb, Repligen, Somerset, Sumitomo, Thrasher Foundation, GlaxoSmithKline, NARSAD, NIMH, NIDA and NIAAA, and is a consultant for GlaxoSmithKline, Eli Lilly, France Foundation, Kappa Clinical, Pfizer, Medical Communications Media, Schering-Plough and Merck.

GlaxoSmithKline, Martek Biosciences Inc. and the Inflammation Research Foundation market omega-3 fatty acid preparations. None of these funding sources had any role in the design, implementation or writing of this manuscript.

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  1. Department of Psychiatry, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine, 260 Stetson Street, Suite 3200 ML 559, Cincinnati, Ohio, 45219, USA

    Robert K. McNamara, Jayasree J. Nandagopal, Stephen M. Strakowski &  Melissa P. DelBello

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  1. Robert K. McNamara
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  2. Jayasree J. Nandagopal
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  3. Stephen M. Strakowski
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  4. Melissa P. DelBello
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Correspondence to Melissa P. DelBello.

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McNamara, R.K., Nandagopal, J.J., Strakowski, S.M. et al. Preventative Strategies for Early-Onset Bipolar Disorder. CNS Drugs 24, 983–996 (2010). https://doi.org/10.2165/11539700-000000000-00000

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