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Director’s Blog: Diagnosis: Pediatric Bipolar Disorder?

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One of the more contentious issues in children’s mental health involves pediatric bipolar disorder (BD).  We now know that when BD presents in children, it tends to be a severe form of the illness.  But children who have been diagnosed with pediatric bipolar disorder (BD) may, in fact, have different illnesses requiring different treatments.  Antipsychotic and anticonvulsant medication – albeit appropriate for BD – may be used unnecessarily in children with other disorders.

The concerns are spurred by reports of a 40-fold increase of the diagnosis of child and adolescent BD between 1994-1995 and 2002-2003. It’s not clear what accounts for this apparent increase. Were children with BD mis-diagnosed before 1995 or were children with other disorders being incorrectly labeled with BD after 1995?  As many as 60 percent of children diagnosed with BD also have ADHD, including many with severe irritability.  Is this irritability a form of mania manifest in children?  Or is mania being over-diagnosed in children with ADHD?

The NIMH is committed to bringing the field together to resolve these diagnostic issues, discover the causes, and develop more effective treatments for youth with bipolar disorder and mood-related syndromes.  Achieving consensus about the boundaries of the diagnosis will lead to more reliable prevalence estimates and improve the comparability of research findings on course, causes and interventions across studies.

Since the early 1990s, the Institute has convened workshops and roundtables to sort out these issues. At the most recent such meeting, in February 2009, 24 experts from the field forged agreement on how to operationalize and gauge symptoms/criteria in studies of specific subtypes of BD in children – and on what assessment tools to use in studies.  Overall, they tightened up the technical criteria for research diagnosis. For example, they recommended that irritable mood be episodic – or if chronic, worsening at the time of the episode to qualify as a form of mania.

Dr. Ellen Leibenluft: The Warning Signs of Childhood Bipolar Spectrum Disorder video.

 

The Institute encourages researchers to adopt this common strategy for assessing and defining child and adolescent BD.  Future studies should also consider a broad range of behaviors to understand illness among those children and adolescents who do not meet stringent criteria but who are equally impaired and in need of treatment. 

Such crosscutting studies in the domain of irritability, a component of BD that overlaps with other diagnostic categories, could help clarify the boundaries of pediatric BD.  Studies might compare mania-related irritability to other forms of irritability seen in disorders like depression, examining the neural circuits known to be associated with emotion regulation.  This approach may lead to more fine-grained clinical phenotyping that links subgroups by the presence or absence of anomalous circuit function – and ultimately speeds progress toward understanding causes.

For example, children with a newly proposed depression-related syndrome called Temper Dysregulation Disorder with Dysphoria (TDD), or the similar severe mood dysregulation (SMD), present with chronic severe irritability rather than the episodic irritability and mania seen in classic BD. Yet they are as severely disabled as their BD peers and share with them features such as impaired recognition of facial emotion, poor frustration tolerance and ADHD symptoms. Children with SMD are more likely to come from families with histories of depression and to develop depression as adults, not BD.

Functional brain imaging studies are turning up circuitry differences between such seemingly overlapping disorders during emotional processing. In one recent fMRI study, while children rated their subjective fearfulness of neutral faces, the amygdala, the brain’s fear hub, over-activated in ADHD, under-activated in SMD and activated normally in BD. Similar results are emerging from studies with other techniques for measuring brain circuits, such as magnetoencephalography (MEG).  These results suggest that we may be able to use the tools of clinical neuroscience to disentangle these various syndromes to help clinicians provide children with the best care.  

We expect these approaches to evolve with the further development of an empirical base on how to define BD and related phenomenology in youth, identify youth at risk, and discover the underlying causes. Our goal is nothing less than pre-emptive interventions and cures.

References:

National trends in the outpatient diagnosis and treatment of bipolar disorder in youth.  
Moreno C, Laje G, Blanco C, Jiang H, Schmidt AB, Olfson M. Arch Gen Psychiatry. 2007 Sep;64(9):1032-9.PMID: 17768268

Amygdala activation during emotion processing of neutral faces in children with severe mood dysregulation versus ADHD or bipolar disorder.  Brotman MA, Rich BA, Guyer AE, Lunsford JR, Horsey SE, Reising MM, Thomas LA, Fromm SJ, Towbin K, Pine DS, Leibenluft E. Am J Psychiatry. 2010 Jan;167(1):61-9. Epub 2009 Nov 16.PMID: 19917597

A preliminary study of the neural mechanisms of frustration in pediatric bipolar disorder using magnetoencephalography.  Rich BA, Holroyd T, Carver FW, Onelio LM, Mendoza JK, Cornwell BR, Fox NA, Pine DS, Coppola R, Leibenluft E. Depress Anxiety. 2009 Dec 27. [Epub ahead of print] PMID: 20037920

Face emotion labeling deficits in children with bipolar disorder and severe mood dysregulation. 
Rich BA, Grimley ME, Schmajuk M, Blair KS, Blair RJ, Leibenluft E.
Dev Psychopathol. 2008 Spring;20(2):529-46. PMID: 1842309