Early natural history of bipolar disorder mapped

By Joanna Lyford, senior medwireNews reporter

A longitudinal study of children of parents with bipolar disorder gives insights into the developmental trajectory of the condition, which researchers say should prove valuable in guiding future intervention and prevention efforts.

Notably, the study revealed the relatively nonspecific nature of early clinical manifestations of bipolar disorder as well as differences in disease course according to whether the parent responded to treatment with mood stabilizers.

The researchers followed-up 229 children from 113 families in which one parent had confirmed bipolar disorder (high-risk children) and 86 children from 55 families in which neither parent had a major psychiatric disorder (controls). The children were aged between 7 and 25 years at enrolment and were followed-up for approximately 6 years on average.

As expected, the high-risk children were significantly more likely than controls to develop mood disorders during the study period; the hazard ratio was 20.89 for bipolar spectrum disorders and 17.16 for major depressive disorder. They were also significantly more likely to develop non-mood disorders, with hazard ratios of 2.20 for anxiety and 28.21 for sleep disorders.

In an exploratory analysis, the high-risk children were subdivided according to whether or not their parent responded to treatment with a mood stabilizer; the parents of 96 children were responders and 133 were nonresponders.

These two groups differed in the course of mood disorder development, such that the children of responders were around eight times as likely to have an episodic clinical course with complete remissions between mood episodes. Meanwhile, the children of nonresponders had worse scores on the Global Assessment of Functioning at the last assessment. Also, all cases of schizoaffective disorder occurred in children of nonresponders.

A total of 31 high-risk children were diagnosed with a bipolar spectrum disorder during the study. In the vast majority of these individuals, the disorder began with a depressive episode at a mean age of 20.85 years; additionally, participants who had suffered a childhood anxiety disorder were significantly more likely to develop a major mood episode.

Anne Duffy (Mathison Centre for Mental Health Research, Calgary, Alberta, Canada) and fellow researchers say that their observations confirm that the children of parents with bipolar disorder are at substantially increased risk for mood disorders.

“[We] found evidence that high-risk offspring who go on to develop bipolar disorder do so in a predictable forward clinical sequence consistent with clinical staging,” they write in the British Journal of Psychiatry.

The researchers add: “[T]hese findings raise a provocative question as to the nature of the underlying pathophysiological processes and specifically why the surface clinical manifestations are relatively non-specific early in development.”

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