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Psychiatric Times. Vol. 24 No. 14
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Increase in Bipolar Diagnosis in Youth Prompts Debates and Calls for Research

Arline Kaplan
December 1, 2007

More research

Because of the diagnostic issues surrounding pediatric bipolar disorder, clinical psychiatrists as well as academicians and bipolar organizations are urging more research.

"The fact that the controversy over the diagnosis still exists is a good thing, as it will almost certainly drive more research into the cause, course, and treatment of children with these debilitating disorders," said James Hudziak, MD, chair of the Professional Advisory Board for the Child and Adolescent Bipolar Foundation, in a recent press statement.9

McClellan noted that research might help settle the major issue of whether there should be separate criteria established for diagnosing bipolar disorder in children.

"I think you need evidence that there actually is a discrete disorder before you start creating more new criteria," he said. "Ultimately, we need other kinds of markers like biological markers and anatomical markers to really make this work."

According to Insel, the NIMH is committed to the development of biological tests that can help validate the diagnosis of bipolar disorder in children.

"Recent research advances showed that electroencephalograms10 and magnetic resonance imaging studies of the brain11 can reveal differences between bipolar disorder and related behavioral syndromes which cause some of the same symptoms in children as bipolar disorder," he wrote in the Director's Update.

Research with MRI, according to Olfson, suggests that bipolar disorder likely involves several different brain structures, including prefrontal and subcortical regions.

"More specifically, pediatric bipolar disorder is associated with abnormalities in circuits encompassing the amygdala, striatum, and ventral prefrontal cortex," he said. "Although imaging technologies continue to improve, much more work needs to be done before neuroimaging can be used to diagnose bipolar disorder reliably in clinical practice. One of the important factors complicating identification of biomarkers is that bipolar disorder is still a fairly heterogeneous disorder. Genetic studies, for example, have proposed several candidate genes for bipolar disorder."

Research is being conducted in Europe as well that may help distinguish clinical phenotypes. Masi and colleagues12 from Italy just published results of a naturalistic study in which they addressed the clinical implications of DSM-IV subtypes for bipolar disorder in 217 referred patients, ranging in age from 8 to 18 years. Sixty-six of the patients (30.4%) were younger than 12 years. The sample included both inpatients and outpatients, and the participants were followed for 6 to 40 months (mean of 17 ± 6 months). According to the subtyping, 78 patients (35.9%) presented with a type I bipolar disorder; 97 (44.7%), type II; and 42 (19.4%), bipolar disorder not otherwise specified (NOS).

Patients with type I presented more frequently with psychotic symptoms and an elated rather than irritable mood, while those with type II had depression as the intake episode in more than half of the cases. Those with bipolar disorder NOS presented with an earlier onset of the disorder, a chronic rather than episodic course, and an irritable rather than an elated mood. Patterns of comorbidity differentiated the 3 groups, with type II having the highest rate of anxiety comorbidity, and those with bipolar disorder NOS having more frequent comorbidity with ADHD and ODD.

Assessments

While research continues on the biomarkers, experts were asked what tools and techniques they currently use to help them diagnose bipolar disorder in children and adolescents.

More than just interviewing parents and looking at reports, Mota-Castillo said that he watches closely to see how the child behaves, such as whether the child is respectful or extremely dis- respectful, and he interviews the child. He also looks carefully at the patient's history.

"I am not going to diagnose as bipolar somebody who did very well until fourth grade and had all As and all of a sudden is failing in school. I will think of other problems, such as divorce or substance abuse," he said.

As aids in assessment, Mota-Castillo uses the Incomplete Sentence instrument for children and the Bipolar Spectrum Diagnostic Scale,13 which he has adapted for use in patients aged 6 to 12 years as well as teenagers, and for use with Spanish-speaking youth. The Bipolar Spectrum Diagnostic Scale, a descriptive story that captures subtle features of bipolar illness, was developed by Ronald Pies, MD, professor of psychiatry at SUNY Upstate Medical Center, in Syracuse.

For research studies, McClellan said he uses structured interviews.

"For example, we are currently doing a lithium(Drug information on lithium) study with kids [Collaborative Lithium Trials], where we are using the K-SADS [Kiddie Schedule for Affective Disorders and Schizophrenia]; in a prior study, I used the SCID [Structured Clinical Interview for DSM-IV]," he said. "I don't think there is any magic with any of them because I can use the same tool as someone else who believes the syndrome looks different, and we will come out with a different outcome."

At present, Olfson said, clinical psychiatrists who treat youth should consider, to the extent possible, incorporating into their assessments screening tools or short bipolar assessment scales, such as the Child Mania Rating Scale; the parent version of the Mood Disorder Questionnaire; or the Conners' Abbreviated Parent Questionnaire, which is used for assessing ADHD in children and adolescents.

Beyond screening tools, Olfson said, the evaluation of a child for bipolar disorder should involve parent reports and include an assessment of all aspects of the child's life.

"Before a diagnosis of bipolar disorder is made," he said, "psychiatrists should carefully consider not only the symptom pattern over time, but the effects of the symptoms on the child's social interactions outside of the family, and his or her relationships with peers, teachers, and other individuals that are important in the child's life."

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References
1. Moreno C, Laje G, Blanco C, et al. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Arch Gen Psychiatry. 2007;64:1032-1039.
2. Blader JC, Carlson GA. Increased rates of bipolar disorder diagnoses among U.S. child, adolescent, and adult inpatients, 1996-2004. Biol Psychiatry. 2007;62:107-114.
3. Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication [published correction appears in Arch Gen Psychiatry. 2007;64:1039]. Arch Gen Psychiatry. 2007;64:543-552.
4. Wang PS, Berglund P, Olfson M, et al. Failure and delay in initial treatment contact after first onset of mental disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62:603-613.
5. McClellan J, Kowatch R, Findling RL; Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with bipolar disorder [published correction appears in J Am Acad Child Adolesc Psychiatry. 2007;46:786]. J Am Acad Child Adolesc Psychiatry. 2007;46:107-125.
6. Insel T. NIMH perspective on diagnosing and treating bipolar disorder in children. Director's Update September 3, 2007. Available at: http://www.nimh.nih.gov/about/dirupdate_NIMH_perspective_bipolar_diagnosis.cfm. Accessed October 29, 2007.
7. Mota-Castillo MR, Heath D, Pittington A. Protecting Your Child From Bad Medicine: How the ADHD Diagnosis Has Been Abused. Self-published, 2007.
8. Mota-Castillo M, Torruella A, Engels B, et al. Valproate in very young children: an open case series with a brief follow-up. J Affect Disord. 2001;67:193-197.
9. Child & Adolescent Bipolar Foundation. Families of children with bipolar disorder call for more research into this devastating illness. September 6, 2007. Available at: http://www.bpkids.org/site/PageServer?pagename=fd_pr_sept07. Accessed October 29, 2007.
10. Rich BA, Schmajuk M, Perez-Edgar KE, et al. Different psychophysiological and behavioral responses elicited by frustration in pediatric bipolar disorder and severe mood dysregulation. Am J Psychiatry. 2007;164:309-317.
11. Moore CM, Frazier JA, Glod CA, et al. Glutamine and glutamate levels in children and adolescents with bipolar disorder: a 4.0-T proton magnetic resonance spectroscopy study of the anterior cingulate cortex. J Am Acad Child Adolesc Psychiatry. 2007;46:524-534.
12. Masi G, Perugi G, Millepiedi S, et al. Clinical implications of DSM-IV subtyping of bipolar disorders in referred children and adolescents. J Am Acad Child Adolesc Psychiatry. 2007;46:1299-1306
13. Nassir Ghaemi S, Miller CJ, Bery DA, et al. Sensitivity and specificity of a new bipolar spectrum diagnostic scale. J Affect Disord. 2005;84:273-277.


 
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