Severe Childhood Mood Disorder May Be Unique Syndrome

An 11-year-old child presents with severe and chronic irritability, along with persistent sadness and anxiety, resulting in frequent emotional outbursts that have parents and others walking on eggshells.

The condition has been persistent, lasting more than a year, and resulting in disciplinary action at school and serious disruption of home life and impairment in social functioning. Hyperarousal—distractibility, insomnia, racing thoughts, and agitation—and a consistent tendency to respond to frustration in developmentally inappropriate ways are also part of the picture.

Should the child be diagnosed as bipolar and started on mood stabilizers and/or a second-generation antipsychotic? Maybe, but missing from the clinical presentation are the clearly demarcated episodes of mania that characterize bipolar disorder.

What about attention-deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder? Certainly the child's behavior and hyperarousal would qualify, yet both of these diagnoses overlook the clear evidence of mood disorder in this sad and anxious child.

The cluster of symptoms presenting in this 11-year-old has received growing attention from researchers as a troubling and severely impairing mood disorder syndrome sharing features of bipolar disorder, ADHD, and oppositional defiant disorder—but also having unique and defining characteristics with important implications for treatment.

Criteria for the syndrome—several names have been proposed but a permanent one has yet to be determined—are being tested in field trials for DSM-5.

Credit: NIMH

In a paper published in AJP in Advance on December 1, 2010, Ellen Leibenluft, M.D., outlined criteria, longitudinal data from community and clinical studies, and family history, as well as preliminary data on possible neurobiological mechanisms for the syndrome that her research group at the National Institute of Mental Health (NIMH) has termed “severe mood dysregulation” (SMD). The paper is titled “Severe Mood Dysregulation, Irritability, and the Diagnostic Boundaries of Bipolar Disorder in Youths.”

In an interview with Psychiatric News, Leibenluft said research—including treatment research—is urgently needed to learn more about a cluster of symptoms that appears to be highly prevalent and extraordinarily disabling to youngsters and their families. And she said it is a syndrome that is typically diagnosed as bipolar disorder, ADHD, or oppositional defiant disorder with treatment that may only partially address, or overlook altogether, the distinctive needs of these severely—but nonepisodically—irritable children.

“As a group, most of the children we see with SMD carry a diagnosis of bipolar disorder,” Leibenluft, who is chief of the Section on Bipolar Spectrum Disorders at NIMH and a member of the DSM-5 Childhood Disorders Work Group, told Psychiatric News. “If the clinician thinks this irritable child has bipolar disorder, he or she would likely be given a second-generation antipsychotic or possibly a mood stabilizer, and the vast majority of children with SMD have been treated with one or both of those.

“But if the clinician thinks the child has ADHD and anxiety, the treatment would be stimulants,” she said. “We don't really know exactly how to treat these children with SMD. We have done a trial with lithium, which was not effective, and we are currently doing a trial of a stimulant and an SSRI.”

Condition Is Not Rare

She added that SMD is not rare; research published in 2006 in Biological Psychiatry indicates a lifetime prevalence of 3.2 percent. “We have every reason to believe it is considerably more common than classic episodic bipolar disorder in children,” Leibenluft said.

Research criteria on SMD have been designed to capture the group of severely irritable children in whom the diagnosis of bipolar is controversial. The criteria were also designed to reflect a condition that exacts a severe toll on children and their families.

“The most prominent feature of SMD is severe irritability,” Leibenluft said. “These children have emotional outbursts when they get frustrated, if they don't succeed at something, when there is something they want to do but can't, and when they feel rejected. Commonly it's verbal, but it often manifests in kicking, screaming, hitting at property, or hurting others. These outbursts are frequent—at least three times a week—and are not developmentally appropriate.

“The phrase we commonly hear from parents is that they have to ‘walk on eggshells,’” Leibenluft said. And in between these outbursts children with SMD are angry or sad most of the time.

To qualify for the proposed diagnosis, the condition has to have started before age 12—“we didn't want to be capturing developmental adolescent irritability,” she said—and it has to be impairing in at least two of three settings: home, school, or peer relationships. And symptoms of hyperarousal have to be present.

Finally, symptoms must be chronic; research criteria require that the symptoms have been present for at least a year, but Leibenluft said children typically present to NIMH for research participation when they are about 12, and they commonly have a history dating back to approximately age 5.

“We wanted to capture the day-in-day-out nature of the syndrome,” she said.

Course Differs From Bipolar Disorder

Accurate diagnosis and treatment of mood disorders in children has been a subject of growing clinical, social, and public health concern with dramatic increases in the diagnosis of childhood bipolar disorder and use of powerful antipsychotic medications. So having criteria for precisely identifying a unique cohort of severely mood-disordered children who may not fit into existing categorical diagnoses will be crucial.

Leibenluft said longitudinal data from clinical and community samples offer the strongest evidence of the differentiation between SMD and bipolar disorder. Though children with SMD appear to be at risk for unipolar depression and anxiety as adults, their trajectory is not the same as that for children with bipolar disorder.

“What the data show is that these children with severe nonepisodic irritability do not grow up to have a particularly high risk for bipolar disorder,” she told Psychiatric News. “You would expect them to develop manic episodes, but that is not what we find.”

To be sure, children with SMD may share much with children with episodic bipolar disorder. Children with both SMD and bipolar disorder (but not those with ADHD, conduct disorder, anxiety, or major depressive disorder) showed similar deficits in tests of facial-emotion recognition.

But intriguingly, the brain mechanisms underlying those deficits may be different. In the AJP in Advance paper, Leibenluft noted that functional magnetic resonance imaging during face-emotion testing suggests that neural activity in the amygdala differs between children with SMD and those with bipolar disorder. “Youths with severe mood dysregulation exhibited lower amygdala activity while rating their subjective fear... relative to patients with bipolar disorder, nonirritable youths with ADHD, and healthy comparison subjects,” she said.

In the interview with Psychiatric News, Leibenluft emphasized that true bipolar disorder certainly exists in children. “Probably there is a spectrum, and it is not only possible but likely that there is overlapping brain dysfunction between SMD and bipolar disorder, as well as some shared genetic risk,” she said. “So it isn't a bright line.

“But the evidence leads us to believe that these children with nonepisodic irritability should not be assumed to have bipolar disorder,” she said. “At the same time, what the children with SMD have is not just ordinary grouchiness—by all kinds of standardized measures, these children are as impaired as children with bipolar disorder, and both groups of children clearly need treatment.”

“Severe Mood Dysregulation, Irritability, and the Diagnostic Boundaries of Bipolar Disorder in Youths” is posted at <http://ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2010.10050766v1>. An abstract of “Prevalence, Clinical Correlates, and Longitudinal Course of Severe Mood Dysregulation in Children” is posted at <www.ncbi.nlm.nih.gov/pubmed/17056393>.