Bipolar Disorder in Children Is Persistent and Familial

Caroline Helwick

September 02, 2010

September 2, 2010 (Amsterdam, The Netherlands) — Two studies have clarified the characteristics and course of bipolar 1 disorder (BP1) in children, and have found a strong familial association and a high level of persistence as children mature. The studies were presented here at the 23rd European College of Neuropsychopharmacology Congress.

The first study, by Janet Wozniak, MD, and colleagues from Massachusetts General Hospital in Boston, was a 4-year prospective longitudinal study that recruited 105 youths (aged 6 to 17 years) who met the full diagnostic criteria for BP1. All subjects were comprehensively assessed with structured diagnostic interviews and neuropsychological testing for psychosocial, education, and treatment history. Batteries of neuropsychological tests were administered to assess domains of cognitive functioning, including executive function, learning, and memory. Any subjects meeting the criteria for bipolar II disorder or bipolar disorder not otherwise specified were not included.

At the 4-year assessment of the 78 people still in the study, 57 (73%) met the DSM-IV criteria for full BP1. In addition, 6.4% had subthreshold BP1, 5.1% had full or subthreshold major depressive disorder, and 9.0% were euthymic but still receiving treatment for BP1. Only 6.4% were euthymic; they were not receiving pharmacotherapy for BP1 because they did not have persistent signs of illness.

"Documenting over a 4-year period, we found that the majority of youth with BP1 continue to experience persistent disorder into their mid- to late-adolescent years. Furthermore, its persistence was associated with high levels of morbidity and disability," said coauthor Joseph Biederman, MD, director of the pediatric psychopharmacology unit at Massachusetts General Hospital and professor of neurology and psychiatry at Harvard School of Medicine in Boston, in an interview with Medscape Medical News at the meeting. "Only 6% were truly euthymic and without treatment."

Comorbid psychiatric diagnoses were prevalent at both baseline and follow-up in children, whether their illness persisted or not, but rates generally tended to be higher when the illness persisted. For instance, conduct disorder was present at baseline in 60% of persistent cases and in 40% of nonpersistent cases; at follow-up, it was observed in approximately 70% and 50%, respectively. Approximately 90% of persistent and nonpersistent cases demonstrated oppositional defiant disorder at baseline and at follow-up.

Strong Familial Link Observed

Although bipolar disorder in adults is known to be highly familial, less is known about the familiarity of pediatric bipolar disorder. In the second study, Dr. Biederman and colleagues looked for a familial association in 157 children with BP1 (probands) who had 487 first-degree relatives (parents and siblings) with bipolar disorder, 162 children with attention-deficit hyperactivity disorder (ADHD) but not BP1 who had 511 first-degree relatives with bipolar disorder, and 136 healthy control subjects (without ADHD or BP1) who had 411 first-degree relatives with bipolar disorder.

"We found that 18% of the BP1 pediatric probands had a first-degree relative with BP1 disorder," Dr. Biederman reported at the meeting.

Only 6% of the ADHD probands and 6% of the control subjects had a first-degree relative with BP1. The difference in familial association rates between the children with BP1, those with ADHD, and the control subjects was statistically significant (P < .01).

The study demonstrated the degree to which psychiatric comorbidity is observed in children with BP1. Major depression was diagnosed in 83% of the children with BP1, in 37% of the children with ADHD, and in 7% of the control subjects. Multiple anxiety disorders were seen in 64%, 27%, and 4%, respectively; oppositional defiant disorder was seen in 90%, 54%, and 6%, respectively; conduct disorder was seen in 51%, 15%, and 2%, respectively; and substance use disorder was seen in 12%, 3%, and 1%, respectively. The differences between the BP1 and ADHD probands in all these disorders were statistically significant (P < .05). The difference between the ADHD probands and control subjects was statistically significant (P < .05) for all disorders except substance use.

The relatives of children with BP1 were at increased risk for many of these additional psychiatric disorders. After correcting for socioeconomic status and race, the investigators found statistically significant increases in the relatives of the BP1 probands, compared with relatives of the ADHD probands and the control subjects, in the occurrence major depression, multiple anxiety disorders, substance use disorder, and oppositional defiant disorder. Conduct disorder/antisocial personality disorder was significantly higher in the relatives of BP1 probands than in the relatives of control subjects, but not in the relatives of the ADHD probands.

Dr. Biederman emphasized the importance of identifying BP1 at its onset. "The problem is that if these children are not diagnosed, they will not be treated and the condition will worsen and eventually be very difficult to manage," he noted. "The key to childhood diagnosis is the repertoire of aberrant moods. I am always amazed to hear that this can be hard to diagnosis, because these children behave in a manner that is totally unacceptable. They can be very agitated and behave dangerously, they tend to have a mixed state and to rapidly cycle, but they are often given other diagnoses."

Hagop Akiskal, MD, professor of psychiatry at the University of California at San Diego, and director of the International Mood Center there, commented on the topic. "The earlier the onset of bipolar illness, the more likely it is to be highly genetic. Children often have parents who are also ill. In fact, while the most heritable mental illness is autism, bipolar disorder is second. In contrast, it is almost never genetically based when diagnosed at, say, age 65. It is also true that bipolar disorder does not fully remit at any age. There is always some residual illness, as patients continue to have some oscillation of mood, and euthymia is very rare."

Dr. Wozniak is author of the book, Is Your Child Bipolar?; has been a speaker for McNeil, Primedia/MGH Psychiatry Academy; has been an advisor for Pfizer and Shire; and has received research support from McNeil, Shire, and Lilly. Dr. Biederman reports receiving research support from Alza, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen Pharmaceuticals, McNeil, Merck, Organon, Otsuka, and Shire; and receiving speakers' fees from Fundacion Areces, AstraZeneca, Celltech, Cephalon, Lilly, Esai, Forest, Glaxo, Gilatech, Janssen, McNeil, New River, Novartis, Noven, Neurosearch, Pfizer, Pharmacia, Shire, and Wyeth.

23rd European College of Neuropsychopharmacology (ECNP) Congress: Posters P.7.a.002 and P7.a.003. Presented August 31, 2010.


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