In October, 2011, two major studies of child bipolar disorder were published in leading psychiatry journals. The articles complement each other. Of critical interest to us, both articles are concerned with the clinical appearance of children and adolescents before bipolar disorder begins. The articles use closely related but different strategies to study the precursors of bipolar disorder in children and adolescents and arrive at different conclusions.

One of the best established findings in bipolar disorder is that it is genetic. In general, one in twenty offspring of a bipolar parent will develop bipolar disorder. These offspring are at high risk for the development of bipolar disorder over their lifetimes. A frequently employed research strategy to understand the clinical appearance of children and adolescents before they develop bipolar disorder is to follow children and adolescents from families in which one parent has bipolar disorder. John Nurnberger, Jr., M.D., and colleagues report such a study in the October, 2011 issue of the Archives of General Psychiatry.

The authors interviewed 141 offspring between the ages of twelve and twenty-one years of parents with various forms of bipolar disorder. Also, they interviewed 91 adolescents who did not have a parent with bipolar disorder or other major psychiatric disorder. The rates of psychopathology between the two groups of adolescents were compared. The authors combined bipolar disorder with major depressive disorder to create a category called major affective disorder as is often done in the research with bipolar disorder and depression. In the offspring of bipolar parents, 23.4% had an episode of a major affective disorder and only 4.4% of the offspring of the non-psychiatrically ill parents had a major affective disorder. There were only 6 cases of classic bipolar disorder BP1 (4.3%) in the bipolar offspring group and 0 cases in the non-psychiatrically ill offspring group.  Cases of major affective disorder in the bipolar offspring group were often preceded by severe behavior problems or severe anxiety disorders. They were not preceded by mild forms of mania. The behavior problems and the anxiety problems were more severe and more impairing in the offspring of bipolar families than in the offspring of non-ill families. The authors note that bipolar disorder is a disease with an onset most commonly in adolescence and early adulthood.    

The authors comment that affective disorders in children below the age of 12 often begin with an episode of depression, not mania They cite other statistics to support an estimate of the frequency of bipolar disorder in children 12 and under to be much less than 1% (.05%). The Nurnberger, et al., study is a useful corrective to excessive estimates of the rates of bipolar disorder in children (3-5%) often used to support the diagnosis of bipolar disorder in childhood. Also their view of bipolar disorder in children beginning as depression and in adolescents beginning as behavior problems or anxiety problems is consistent with other studies of children of bipolar parents, but conflicts with the picture of bipolar disorder beginning as mild mania presented below.

In the October, 2011 issue of the Journal of the American Academy of Child and Adolescent Psychiatry, David Axelson, M.D., and colleagues report a follow-up to the NIMH supported COBY (Course and Outcome of Bipolar Youth) study. In this study, children and adolescents (average age 12 years) with a diagnosis of BP-NOS were followed for at least five years to learn whether or not these youth developed more severe forms of bipolar disorder and, if so, what led to the conversion.  BP-NOS, Bipolar Disorder, Not Otherwise Specified, is a category for patients who do not meet the criteria for DSM IV bipolar disorder but who have several symptoms of the disorder. The COBY study precisely defined the criteria used to identify patients as having BP-NOS. The criteria are lengthy; I will mention a few to convey the rigor of the criteria. Elevated or irritable mood that was distinct from usual behavior; the mood had to last at least four hours per day for four days over the subjects' lifetime. Meeting these and other criteria led to a diagnosis of BP-NOS. The patients were followed up an average of five years later to learn if they developed Bipolar I (elevated mood for seven continuous days plus additional symptoms of mania) or Bipolar II (elevated or irritable mood for four continuous days, plus additional manic symptoms, plus depression).  

45% of the children and adolescents with BP-NOS converted to Bipolar I or Bipolar II. The variable that most strongly predicted this conversion was a family history of bipolar disorder.

Unexpectedly, those who received psychosocial treatments were more likely to convert to the more severe forms of bipolar disorder. It is not clear whether those who were doing poorly received more psychosocial treatment in response to their deteriorating condition or that receiving psychosocial treatment led to the patients' clinical decline. Also unexpected was the apparent failure of medication to change the progression of the illness. The receipt of antimanic pharmacologic agents had no effect on whether the offspring converted to the more severe forms of bipolar disorder. The authors end with the optimistic hope that treatment studies will be done on the problem because children and adolescents born to bipolar parents are vulnerable to developing bipolar disorder themselves. The discouraging treatment results of this study may temper premature enthusiasm over other efforts to prevent bipolar disorder with early intervention in children and adolescents.

The findings of the Axelson, et al., article are discrepant from the findings of other researchers including the findings from the article discussed at the beginning of this post. Through two methodologies, the initial symptom picture of those who go on to develop adult Bipolar Disorder are studied. In the Axelson, et al., paper, those who develop adult Bipolar Disorder present with symptoms of mania in childhood.  In the Nurnberger, et al., paper, as well as in many other studies (e.g., Meyer, et al., 2004; Egeland, et al., 2005; Duffy, 2009) manic symptoms are not found in children who later develop Bipolar Disorder. Rather, depression and anxiety symptoms are found.

36% of the BP-NOS patients in the Axelson, et al., study did not have a family history of bipolar disorder. This is a large percentage of patients with a diagnosis on a bipolar spectrum without a family history of bipolar disorder. In the Nurnberger, et al., study described in the beginning of this post, the rate of bipolar disorder in those without a family history of bipolar disorder was 0%; this reflects what is reported in other adult studies. If BP NOS were a form of bipolar disorder, a much higher rate of a family history of bipolar disorder would be expected in the Axelson, et al., study.

These two important studies offer different views of the appearance of child and adolescent patients before they develop bipolar disorder. Nurnberger and colleagues as well as other studies see these patients below the age of 12 as largely depressed before they develop bipolar disorder and during adolescence as having anxiety and behavior problems prior to developing bipolar disorder. Axelson and collegues, in contrast, view them as having  early forms of mania that narrowly miss DSM-IV criteria for the disorder. The Axelson, et al., paper more closely reflects the views of those who believe that bipolar disorder is regularly found in childhood; the Nurnberger, et al., paper more closely reflects the views of those who are skeptical of the diagnosis in childhood.

Copyright: Stuart L. Kaplan, M.D.

Stuart L. Kaplan, M.D., is the author of Your Child Does Not Have Bipolar Disorder: How Bad Science and Good Public Relations Created The Diagnosis

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