NIMH Research Update: Pediatric Bipolar Disorder and Severe Mood Dysregulation

Chief, Unit on Affective Disorders, Pediatrics and Developmental Neuropsychiatry Branch, Mood and Anxiety Disorders Program, NIMH

First published in Psychiatry Weekly, Volume 2, Issue 43, on November 12, 2007

This interview was conducted on October 3, 2007 by Peter Cook

“Diagnosis is one of the most important issues in pediatric bipolar disorder right now,” says Dr. Ellen Leibenluft. “How do we diagnose bipolar disorder in youth? And does the illness present differently in children than in adults?” Much of the discussion has centered around whether extremely irritable children with ADHD-like symptoms should be viewed as having a form of bipolar disorder, and Dr. Leibenluft and her colleagues have employed a variety of approaches toward answering this question.

Bipolar Disorder and Severe Mood Dysregulation

“Clearly,” Dr. Leibenluft says, “some children do meet the DSM-IV criteria for bipolar disorder. However, these children are relatively rare. Far more common, perhaps as many as 3% of children in the community, are those who are extremely irritable and have ADHD-like symptoms, but don’t meet the DSM-IV criteria for bipolar disorder. A diagnosis of bipolar disorder requires distinct manic episodes, during which time one’s mood is altered, sleep and activity patterns change, and there are differences in reward-seeking behavior. More commonly, children present instead with chronic and nearly constant irritability.” Sometimes, clinicians may diagnose these irritable children with bipolar disorder based on outbursts that occur during extreme frustration, but, Dr. Leibenluft points out, these outbursts are far too short in duration to meet the necessary criteria for a manic episode.

“One of our first steps in studying this population of chronically irritable children was to define criteria so that we could reliably identify a reasonably homogeneous clinical group. We defined criteria to capture children who don’t have clear manic episodes but have very severely impairing and chronic irritability, as well as ADHD-like symptoms. We refer to them as severely mood dysregulated (SMD). Then we recruit controls and children who clearly meet the DSM-IV criteria for bipolar disorder and compare the three groups.”

Long-Term Outcomes, Familiality, and Brain Mechanisms

Dr. Leibenluft’s group’s research is still too new to have followed the SMD group into adulthood, but they have analyzed large, epidemiologic community-based data sets with a particular eye for individuals who, as children, were chronically irritable. “What we’ve found,” Dr. Leibenluft says, “is that these children are not, in general, at high risk for bipolar disorder as adults. Rather, they’re at significantly increased risk for depressions.”

Leibenluft and colleagues have also taken extensive family histories for the patients they see in their clinic. “I have to presage this by pointing out that what we’re doing is most decidedly pilot work,” she cautions. “We’ve actively recruited these children, so they are probably not representative of the population as a whole, and the sample is still relatively small. That said, while studies indicate that children with bipolar disorder are a great deal more likely than controls to have parents with bipolar disorder, we’ve found that SMD children have familial rates of bipolar disorder similar to what one finds in the general population. This suggests that SMD and bipolar disorder may not be genetically equivalent.”

Dr. Leibenluft’s lab also attempts to identify brain mechanisms that may underlie bipolar disorder and SMD. “This is really our single major focus,” she says. “We use non-invasive brain imaging such as functional and structural MRI and MEG to attempt to get at the brain mechanisms underlying psychological processes that appear to differ between children with SMD, children with bipolar disorder, and controls. We’re particularly interested in how these children process emotional stimuli.” Leibenluft and colleagues have tested their patients’ reactions to potentially frustrating games and pictures of emotional faces, and these studies have produced a number of interesting results. “Both children with bipolar disorder and children with SMD get more frustrated than our controls in comparable situations, but the brain mechanisms that are implicated in the bipolar and SMD children are different.”

Also, Dr. Leibenluft says, “children with BD or SMD have difficulty labeling facial emotion, and when we compared them to children presenting with other psychiatric disorders, including depression, anxiety disorders, and ADHD—the SMD and bipolar results were distinct. Only the SMD and bipolar groups had trouble labeling the face emotions.” Using functional MRI, Leibenluft and colleagues found that “when children with bipolar disorder look at faces that other children consider neutral, the children with bipolar disorder see the faces as angry, they are afraid of them, and they have increased amygdalar activation compared to control children. We’re currently analyzing fMRI data on the children with SMD.”

Diagnosis and Treatment

“So what conclusion can we draw from our research?” asks Dr. Leibenluft. “Are SMD and bipolar disorder on a spectrum? Are they distinct? Do they overlap? At this point, we conclude that clinicians should not be lumping SMD children without manic episodes in with bipolar children. Our data indicate significant differences between the groups in terms of long-term outcome and family history, and some differences in brain mechanisms.” Clinicians should strictly follow the DSM-IV criteria for bipolar disorder, she says, diagnosing as having bipolar disorder only children with clear manic or hypomanic episodes.

“Of course, this conclusion has treatment implications.” Dr. Leibenluft emphasizes that, prior to treatment, one must do a thorough evaluation of these patients, assessing symptoms and possible environmental stressors. It’s not uncommon for SMD children to have language or learning problems, social cognitive difficulties, and/or anxiety symptoms, all which can contribute to irritability, and some of which can be addressed through non-pharmacologic interventions. When commencing with pharmacologic treatment, one must move forward systematically and carefully.

“Since SMD is not a DSM-IV diagnosis, there aren’t controlled treatment trials in these youth, though our lab is currently investigating the efficacy of lithium. We suggest a systematic, evidence-based approach: If they have ADHD, treat that. If they have anxiety disorders, treat that, possibly with an SRI or cognitive-behavioral treatment. One needs to be very mindful that these children may become agitated on a stimulant or SRI, and so they should be treated cautiously and monitored closely. But we do not say, out of hand, that, like bipolar children, youth with SMD should not be treated with stimulants or SRI’s without first receiving antipsychotic or mood stabilizing treatment. If an SMD patient does not respond to frontline treatment, then we may switch to, or add, an antipsychotic or mood stabilizer. We also suggest that families track their child’s symptoms daily so that it’s clear whether the target symptoms are responding, and if so to which medication. These children and their condition are complicated, and clinicians should adopt a careful, systematic approach to treatment.”

Conclusion

“As we move toward the DSM-V, we’re moving toward a time when diagnosis will be based not just on clinical observation, but also on underlying brain mechanisms,” Dr. Leibenluft says. “Bipolar disorder risk is conferred by a number of different genes. Perhaps some are shared by SMD, perhaps not, we just don’t know yet. The more we know, the less we think about these illnesses as ‘yes/no.’ These illnesses are multifactorial, and as diagnostic systems and knowledge evolve, we’ll become increasingly sophisticated at identifying and classifying complex disorders.”

Dr. Leibenluft reports no affiliations with or financial interests in any organizations that may pose a conflict of interest.