It wasn’t until her daughter entered preschool that Holly Provan, a nurse in Los Angeles, began to worry. Compared to other kids, including her younger sister, Anna had a harder time coping when something wasn’t going her way. When told to stop coloring or to leave the playground, she’d respond with explosive tantrums.

Between ages 5 and 9, Anna (her name has been changed) would have meltdowns several times a week, screaming, raging and crying for an hour at a time. A few times in elementary school, she ended up hitting other kids. The outbursts weren’t premeditated; Anna just couldn’t control her temper. “Seeing how bad your kid feels after they’ve come back to themselves — it’s heartbreaking,” Provan says.

At age 7, after several doctors’ visits, Anna was diagnosed with disruptive mood dysregulation disorder (DMDD), a condition in children and adolescents, typically diagnosed between ages 6 and 10, that is characterized by chronic irritability and temper outbursts. But Provan couldn’t find much information on how to help Anna. “My husband and I at the time were just like, ‘I don’t know if she’ll ever be able to live away from home or to function normally,’” Provan recalls.

Irritability — a proneness to frustration or anger — is familiar to many of us. But in children with severe irritability, a hair-trigger temper can get in the way of making friends, getting along with siblings and doing well at school. Parents often express the feeling of walking on eggshells and often refrain from asking their children to do things they don’t like in order to avoid an outburst. In the 11,000-strong Facebook support group for parents of DMDD kids that Provan helps to administrate, some parents are physically afraid of their kids.

There are few specific treatments, says clinical psychologist Melissa Brotman of the National Institute of Mental Health, who coauthored a review on the topic in the Annual Review of Clinical Psychology. But now, after years of severe irritability in children being mistaken for other mental health conditions, scientists are studying it as a condition in its own right. “We’re starting to try and understand the problem from a brain-based mechanistic perspective,” Brotman says.

Inside the irritable mind

Starting in the 1990s, many experts saw severe irritability in children — often accompanied by energetic behavior and an inability to focus — as an early manifestation of the mania experienced by adults with bipolar disorder. Bipolar diagnoses, as well as prescriptions for mood-stabilizing and antipsychotic medications, skyrocketed among adolescents and children.

But by tracking children with severe irritability over many years, Brotman found that they didn’t transition to bipolar disorder as adults; instead, they tended to develop depression and anxiety. Perhaps, then, Brotman hypothesizes, severe childhood irritability is an early manifestation of depression and anxiety-like disorders in adulthood.

As scientists furthered their understanding of irritability in children, the Diagnostic and Statistical Manual (DSM) for Mental Health Disorders created a new diagnostic category, DMDD, in its fifth iteration, in 2013. Children with DMDD often also have other conditions like attention-deficit hyperactivity disorder (ADHD) or anxiety, or have experienced bouts of depression. Severely irritable children may have more difficulty than usual coping with negative emotions like frustration, or managing when things don’t go as they expect. They may have a harder time dealing with uncertainty and changes to their routines, says clinical child psychologist Spencer Evans, who directs the University of Miami’s Child Affect and Behavior Lab.

Functional magnetic resonance imaging (fMRI) studies, which use scans to observe brain activity, have affirmed the notion that children with severe irritability respond differently to frustration. One 2019 study compared 134 children between 8 and 18 who had irritability and a diagnosis of DMDD, anxiety disorder or ADHD, with 61 non-irritable volunteers. As they lay in the MRI scanner, the children played a game, earning up to 50 cents for every target they hit — until the researchers intentionally frustrated them by deducting winnings, explains coauthor Wan-Ling Tseng, a developmental neuroscientist at Yale School of Medicine.

Though irritable and non-irritable kids reported similar levels of frustration, the brains of irritable children responded differently: They showed heightened activity in the striatum, a brain region important for processing rewards, as well as in the prefrontal cortex, key to regulating emotions and executing tasks. Some other studies have also hinted at unusual activity in the emotion-processing amygdala in frustrated kids, though Tseng’s study didn’t observe this.

To Tseng, the prefrontal cortex findings suggest that in irritable kids, prefrontal cortices need to work harder to focus. “It’s more effortful for them,” she says. (After the game, the children were given $25 to take home, in addition to their compensation for participating, so that they left with a positive experience.)

It’s unclear how children’s brains end up this way. Research suggests that many kids are genetically predisposed to developing severe irritability, says neuroscientist and child and adolescent psychiatrist Argyris Stringaris of University College London. Adverse environments that involve family conflict or violence are associated with irritability, as are patterns of acquiescence by parents when their child has tantrums, which might reinforce the behaviors. But “we don’t know whether the cause is the parent, the child that elicits the parental response, or both, or some genetic component,” Stringaris says.

New clues for therapies and treatments

DMDD diagnoses are rising, but there’s little concrete treatment guidance. A 2022 analysis of health records found that in the United States, DMDD patients between 10 and 18 were prescribed antipsychotics more often than people with bipolar disorder, and were more likely to get multiple medications. “These drugs have not been FDA-approved specifically for treating irritability or aggression among children in general,” Evans says. Antipsychotics in particular should be used cautiously in children due to their side effects (though there are two antipsychotics approved for irritability in autistic children.)

Yet the increasingly evident links between irritability, depressive episodes, anxiety and ADHD point to different kinds of medications. Stimulants like methylphenidate (Ritalin) can help to reduce irritability and anger in youth with ADHD, while the anxiety and depression medication citalopram (Celexa) in combination with Ritalin can reduce irritability in youth where stimulants alone aren’t effective.

For Anna, Ritalin had little effect, and an antidepressant caused her to hallucinate. A popular yet untested DMDD treatment protocol includes anticonvulsants, and one variety, the mood stabilizer divalproex sodium, seemed to give Anna an extra split second to think through the possible consequences before exploding into a tantrum, her mother says.

As researchers learn more about the underlying brain processes, they hope to develop better and more effective treatments. Some, meanwhile, are looking into non-pharmaceutical therapies.

Recently, Brotman adapted an established treatment for anxiety disorders that progressively exposes patients to things they fear, within the safety of a therapist’s office. Adjusting the therapy for kids with DMDD, clinicians identified the triggers of 40 children ages 8 to 17 with DMDD-type symptoms. Then they simulated anger-provoking situations — such as asking the kids to stop a video game or to do their homework, and talked the children through how to constructively cope with their frustrations.

“I was very tentative at first, because it had never been done before, and we didn’t know if it would make them more angry,” Brotman says.

The clinicians also trained parents to ignore tantrums at home and reward constructive coping behaviors — an approach called “parent management training” that tackles reinforcing cycles within families. Remarkably, irritability symptoms decreased significantly in 65 percent of the children over the 12 weeks of the study.

Most parents, including Provan, eventually settle on a combination of talk therapy and medications. While no parent wants to drug their child, Provan says medications can help make them more receptive to therapy, in Anna’s case with a psychologist. And whether it was the treatment or Anna’s growing maturity, the tantrums disappeared. Now 13, Anna is no more irritable than a regular teenager, though she is still managing anxiety and depression. Indeed, studies tracking DMDD kids suggest that irritability symptoms can taper off by late adolescence or young adulthood, while depression and anxiety can continue.

Provan says that kids with DMDD need better medical treatment options and better mental health services — as well as more awareness in general. Because Anna was judged so much for her hair-trigger temper, Provan wrote a short book — Poppy and the Overactive Amygdala — to build understanding and empathy.

Before she had Anna, she recalls, “I was that parent that was, ‘Oh, screaming toddler — can’t they control their child on an airplane?’

“So, I guess, just be nice to your fellow humans.”

This article originally appeared in Knowable Magazine, a nonprofit publication dedicated to making scientific knowledge accessible to all.