November 2011

Getting to the Root of Irritability

By Charlotte Armstrong

At any age, occasional spells of irritability are a fact of life, a normal outcome of fatigue, discomfort or frustration. In some children, though, irritability looks different: it can be persistent and explosive, more than just a transient reaction to circumstance. Understanding what’s going on with children with severe, disruptive irritability has been a focus of research by a team of researchers at the National Institute of Mental Health (NIMH) since 2001.

During the 1990s, a team of mental health researchers led by Ellen Leibenluft, M.D.,working with children at NIMH, became interested in understanding the startling increase in the number of children being diagnosed with bipolar disorder. Previously, bipolar disorder was thought to occur rarely, if at all, in children. Bipolar disorder is a mood disorder marked by episodes of mania, during which there is a sustained period of elevated or irritable mood along with a marked speeding up of behavior and thoughts. What was going on?

Is It Bipolar Disorder?

“At the time,” says Kenneth Towbin, a psychiatrist in NIMH’s Emotion and Development Branch, “the term ‘bipolar’ was being used in cases that would not previously have been called bipolar.” The existing criteria for bipolar disorder have a central requirement that there be distinct episodes of mania, characterized by behavior different from that child’s normal day-to-day behavior. Despite this, there was a trend at the time to apply the diagnosis of bipolar disorder to children who, day after day, had severe irritability.

The NIMH team decided to study children with severe irritability to learn whether it might be a childhood form of bipolar disorder or something else altogether. Why was the question important? “The medications for bipolar disorder are potent and can have significant ill effects,” says Dr. Towbin. “Irritability in a child can be a feature of many conditions, including anxiety and attention deficit hyperactivity disorder. These conditions could be treated in other ways that would be safer and perhaps as effective. In addition, treatments for ADHD and anxiety could be hazardous for a child with true bipolar disorder, so knowing what was going on was crucial.”

They focused their study on children who had three characteristics: First, sadness and irritability had to be chronic, that is, present most of the time. Second, they had to have tantrums that were both frequent and lengthy and not in keeping with the age of the child. Third, the investigators were looking for “activated” behavior, including insomnia, distractibility, restlessness, a rush of ideas and intrusiveness. This pattern of behavior had to be present across multiple settings— at home, at school and with peers. It had to have been continuously present for at least a year, and it had to have started before the children were age 12, that is, before adolescence.

Severe Mood Dysregulation

The investigators called this set of symptoms severe mood dysregulation or SMD, and set out to find whether SMD was a childhood form of bipolar disorder or something else. If SMD is a form of bipolar disorder, then children with SMD should develop manic episodes as adults. In a study of 1,400 children in North Carolina, 3.3 percent had SMD. None of the children with SMD met the criteria for bipolar disorder; some had ADHD or oppositional defiant disorder but many did not meet criteria for any standard diagnosis. As the children were followed from age 11 until age 18, many with SMD developed depression.

The NIMH team also looked at data from a study in New York State that followed almost 800 children from the time they were 13 years old until they were in their early 30s. This study found that children who had chronic irritability had an increased risk of developing depression in adulthood. And, even when followed for 20 years, the subjects who had chronic irritability as children did not tend to develop bipolar disorder as adults.

Bipolar disorder tends to run in families. So, if SMD is a form of bipolar disorder, you would expect children with SMD to have many relatives with bipolar disorder. Investigators at NIMH studied children diagnosed with the “classic” form of bipolar disorder and another group of children with SMD. As expected, the rate of bipolar disorder in the parents of children with bipolar disorder was very high, a 10-fold increase over the rest of the population. However, in children with SMD, the rate of bipolar disorder in their parents was the same as in the general population.

Recognizing Emotions

The NIMH team has also been looking at differences in how the brains of children with bipolar disorder and SMD respond to emotional images like happy or angry faces, or to games that tap into their emotions.

These studies reveal that children with bipolar disorder and those with SMD both have problems recognizing emotions in people’s faces; for example, they are inclined to label neutral faces as angry. However, when investigators analyze what is happening in the children’s brains while they look at the faces or play games, they find differences in brain function between the SMD and bipolar youth. These results once again lead to the conclusion that SMD is not a form of bipolar disorder.

Responding to Medications

An important question for investigators is whether SMD responds to the existing medications used for bipolar disorder. Lithium is a mood stabilizing medication known to be effective for bipolar disorder. In a study at NIMH, children with SMD who were treated with lithium did no better than those on placebo, suggesting they did not respond in the same way as those with bipolar disorder.

As part of the NIH study, children were either hospitalized or in day treatment at the NIH. This carefully structured, attentive environment itself constituted a form of therapy that was quite powerful, says Dr. Towbin. Thus, while the investigators are studying whether certain medications can help children with SMD, they are also interested in developing therapies that do not use medication and might help with these children’s irritability.

Many of the SMD children showed symptoms of both ADHD and anxiety. For these children, the investigators often used stimulants, like those prescribed for ADHD, as well as the standard medications used for anxiety. Many children responded favorably; the NIMH team is now conducting a formal trial of stimulants and anti-anxiety medication in children with SMD.

Perhaps the most important take-home message, according to Dr. Towbin, is that the diagnosis of children with severe irritability needs to be made carefully. “It’s wrong to assume that severe irritability is bipolar disorder. Chronic irritability can come from a lot of things. A correct diagnosis is key; the medications used for bipolar disorder have significant side-effects and need to be used only when a diagnosis of bipolar is clear. There are safer alternatives for SMD that can be explored, including therapies that do not involve medications.”

Many Possibilities

It’s important not to jump to conclusions if a child seems to have persistent, severe irritability. Irritability can be a feature of many conditions: anxiety disorders, including generalized anxiety disorder, separation anxiety and social anxiety; ADHD; conduct disorder; and depression. The first step if you are concerned is to talk to your pediatrician. When the symptoms are present across all the domains of a child’s life, a pediatrician can suggest a mental health professional for an evaluation. A thorough evaluation may also identify other conditions that might be contributing to the picture, such as learning disabilities and auditory or other processing problems.

Charlotte Armstrong is a science writer at the National Institute of Mental Health

NIMH Free Pediatric Mood Seminar: NIH Presenter: Kenneth Towbin, M.D. Tuesday, November, 8, 2011. Understanding Severe Irritability & Bipolar Disorder in Children ages 7-17.Signs, symptoms, treatments, and research.
http://patientinfo.nimh.nih.gov/BipolarDisorderPediatric.aspx#118
RSVP by Thursday, Nov 3, 2011. 301-496-8381 | TTY: 1-866-411-1222 | Email: irritablekids@mail.nih.gov

Johns Hopkins University, Montgomery County Campus http://web.jhu.edu/MCC/directions.html

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