Before Bipolar: Is There a Prodrome?

Is prevention possible? In bipolar disorder, what happens before the manic or hypomanic episode that identifies this illness? A team of specialists from the International Society for Bipolar Disorders (ISBD) undertook a rigorous literature review to address this question.¹ They asked whether there are any signs or symptoms that predict later diagnosable bipolar disorder with reasonable accuracy. If so, this would be useful for prognosis and preparation, but even more importantly, encourage efforts targeting prevention.

Led by Dr Gianni Faedda,¹ a respected child/adolescent psychiatrist, the team found 26 studies that met their tight inclusion criteria. Importantly, they looked only at studies that obtained data prospectively, to avoid the risks of recall bias in retrospective studies. Overall, they found that while acute onset of mania or depression is often reported retrospectively, chronic and gradually worsening symptoms were found in most cases.

For example, in one study that followed young adolescents for 10 years, the majority of kids who later had a full hypomanic or manic episode had previously experienced isolated hypomanic or depressive symptoms, with the number of symptoms and their persistence gradually increasing over time.² Interestingly, mood swings (“lability”) were also a strong predictor of later bipolarity.

A full episode of depression in adolescence (not just the oft-cited “early onset” age of 18 to 25 years old) was also a predictor, but much more so if the young person had been treated with an antidepressant.³ “Conversion” rates from unipolar to bipolar jumped from 3.3%, over the course of observation (which was variable among studies) to 8.2% amongst those exposed to an antidepressant. Of course this does not by itself convict the antidepressants as guilty: the adolescents who were given antidepressants may have been more depressed or in some other ways different from those not exposed, accounting for at least some of this difference in rates. But, it’s a striking difference nonetheless.

Unfortunately, this ISBD review only raises more doubt as to how to proceed when faced with a young person with mood lability or depressive symptoms. But the data support recent momentum toward preventive strategies based on lowering the wide variety of behavioral (and pro-inflammatory) factors now implicated in mood disorders: physical inactivity; low-quality diet and weight gain; insufficient sleep; low Vitamin D; and cigarette smoking. For more on this, see the masterful review by Berk Michael Berk’s Australian team.⁴ Prevention does now seem more possible.

Disclosures:

Dr Phelps is Director of the Mood Disorders Program at Samaritan Mental Health in Corvallis, Ore. He is the Bipolar Disorder Section Editor for Psychiatric Times. [full bio]

References:

1. Faedda GL, Marangoni C, Serra G, et al. Precursors of bipolar disorders: a systematic literature review of prospective studies. J Clin Psychiatry. 2015;76:614-624.
2. Tijssen MJ, van Os J, Wittchen HU, et al. Prediction of transition from common adolescent bipolar experiences to bipolar disorder: 10-year study. Br J Psychiatry. 2010;196:102-108.
3. Baldessarini RJ, Faedda GL, Offidani E, et al. Antidepressant-associated mood-switching and transition from unipolar major depression to bipolar disorder: a review. J Affect Disord. 2013;148:129-135.
4. Walker AJ, Kim Y, Price JB, et al. Stress, inflammation, and cellular vulnerability during early stages of affective disorders: biomarker strategies and opportunities for prevention and intervention. Front Psychiatry. 2014;5:34.