Founding Member of the Foundation Scientific Council Shares Insight from 33-year Cohort Study with Children

From The Quarterly, Spring 2012

Adolescence is a difficult time for many young people. The problems are familiar across cultures: concerns about self-image, the ability to get along with and be accepted by one’s peers, restlessness, an inclination to challenge authority.

But if ‘troubled adolescence’ is widely regarded as normal, how do we accurately identify behavior that goes over the line—conduct that is abnormal, presenting serious risks to young people, their families, and even to the larger community? This is the important question that Dr. Rachel G. Klein, a founding member of the Brain & Behavior Research Foundation Scientific Council, has devoted her career to answering.

A native of Paris who came to America during her own teen years and went on to earn a Ph.D. at Columbia University, Dr. Klein is the Fascitelli Family Professor of Child and Adolescent Psychiatry at New York University’s Child Study Center, and a pioneer in looking at pathologies in youthful behavior within the specific context of development. In numerous studies of adolescents she has uncovered crucial and often surprising facts about attention-deficit hyperactivity disorder (ADHD), major depression, anxiety disorders and schizophrenia.

In an important sense, her task as a scientist has always put her in the position of challenging popular wisdom about growing up. Take for instance the old expression, “boys will be boys.” One of the extraordinary findings Dr. Klein and colleagues have made over a period of more than 30 years is that certain behaviors which many people once chalked up to “youthful exuberance” or “garden-variety defiance” are in fact correctly understood as behavioral disorders, with biologically significant correlations and major negative impacts on life outcomes. ADHD is a case in point.

In the last year, Dr. Klein has published papers reporting on what is now a 33-year follow-up of a cohort of young people whom she began studying at the beginning of her career. Over 200 children, at the time aged 6 to 12, were admitted to the study, based initially on referral by their schools for behavior problems. The children did not have prior psychiatric diagnoses but were found upon examination to have ADHD.

Most in the group were boys, a fact that we now understand to be consistent with findings about the heightened vulnerability of boys to neurodevelopmental disorders. Dr. Klein’s persistence in following her initial cohort of 206 children with ADHD─whose mean age today is about 41 has enabled her to demonstrate some facts that are nothing short of stunning. For one thing, she and colleagues have found that children diagnosed with ADHD between ages 6 and 12 are much more likely to become convicted criminals as adults. Fully 47% of a subset of 93 New York residents among those in her study group originally diagnosed with ADHD had been arrested by age 38, according to State records, as compared with 24% of others in their peer group who were also followed over the same extended period; 42% of the group had been convicted vs. 14% of their non-ADHD peers; and 15% had spent time in jail vs. 1% of the peers.

Surprising? “Yes!” Dr. Klein says, “these figures were incredible to me. It may be true that many adolescent boys tend to get into trouble. They are prone to do foolish things. They are big risk-takers. But the rate of subsequent criminality in the ADHD group─to be twice the rate of their unaffected peers─is a very significant difference.”

Adolescence proves to be a key turning point

“We found that particularly in adolescence, the children we first assessed at ages 6-12 had a very tough time,” Dr. Klein notes. “Now, why was that? In our culture, kids have to go to school until at least age 16, and it’s in the school setting that they struggle the most because they have to conform to group expectations.” Indeed, among the defining features of ADHD are problems with self-control. “But for reasons we still don’t understand,” Dr. Klein says, “about 40% of those we diagnosed in childhood get better in late adolescence, at ages 16, 17, 18. Something kicks in that changes them and they no longer have impulsive, difficult, out-of-control behavior.”

“But those who continue to have problems have developed what we call conduct disorder. Their behavior goes against the rules. They break curfew, don’t go to school, and lie excessively. They do things that begin to expose them to the risk of being arrested, like driving with no license, disturbing the peace at night. But by far the most important problem is that a subgroup with continuing conduct problems begins to abuse drugs. Then, in adulthood, if the substance abuse continues, they often get into serious trouble: to support their habit they may sell drugs, and this makes it more likely they will be convicted of felonies. One moral for parents of kids with ADHD is: you really have to be vigilant about rule breaking and drug abuse.”

Another remarkable finding which Klein and colleagues published this past year with Dr. Xavier Castellanos as the lead author: at the 33-year follow-up, with the mean age of the study cohort then standing at 41 years, MRI brain scans revealed “significant” thinning of the cerebral cortex among those who had been diagnosed with childhood ADHD as compared with age and socioeconomically matched controls. “In addition, gray matter was significantly decreased” in the ADHD group. “The most affected brain regions underpin top-down control of attention and regulation of emotion and motivation.”

The hard data from research moves us beyond conventional wisdom

In light of these data, Dr. Klein returns to the original question. “Do people prefer to say, ‘boys will be boys’; ‘ordinary exuberance’, etc.? Of course, and that would be wonderful. I wish it were true! The problem is, if young people like those we studied did not have a real disorder, then the diagnosis of ADHD would not, over time, have successfully predicted─as it did─a specific pattern of abnormal function later in life. But we do see abnormal function. This is what the evidence has shown us.”

Gathering the evidence─and not drawing conclusions until sufficient evidence has been collected and examined─characterizes the scientific process that the Brain & Behavior Research Foundation has supported for 25 years. In 1987, Dr. Klein and other leading researchers came together under Dr. Herbert Pardes to form the Scientific Council and to steer the selection of NARSAD Grants to be funded each year.

“I think skepticism is good,” Dr. Klein says. “And it is fine to be skeptical when you don’t have the information. Indeed, this is how I became attracted to science. Like so many others who were interested in behavioral disorders, I was asking: ‘Is this for real? Does this evidence say what we think it does? I want to find out!’”

“Being able to predict what will happen later in life—we  should be able to tell parents something of the children we diagnose—has always been a strong motivation in my work,” says Dr. Klein. She was among the many doctors who compiled the Diagnostic and Statistical Manual’s 3rd edition in the 1980s. Called the DSM-III for short, it was superseded by another edition in 1994, which will soon give way to DSM-5.

“In order for an illness to be a true disorder, and not just a collection of scattered observations, it has to have a specific course.” Dr. Klein says the DSM-III was not developed with the intent of establishing “inflexible categories,” but rather as a way of helping colleagues,─psychiatrists and psychologists─recognize disorders, as an aid to successful and consistent treatment.

Dr. Klein has also played a major role in studying how best to treat young people with the disorders she studied—ADHD, major depression and anxiety. She and colleagues performed studies demonstrating the efficacy and safety of stimulants in the treatment of ADHD, for instance. “It is one of the best studied and safest class of drugs we have today,” she says.

“Each decision by a doctor to provide medication to a patient will be based on a cost-benefit calculation,” she says. “It must be remembered that the illness itself carries risks, so the question is: are these risks less than the risks associated with treatment?” In ADHD, the medication risks have been found to be negligible, “so the decision is easy. As for depression, well, if it is episodic, if it tends to come and go, then it is reasonable to observe before prescribing. But if things don’t get better, there are very significant costs to the patient in withholding treatment.”

For her work on psychopharmacology in disorders in children and adolescents, Dr. Klein was honored with the Brain & Behavior Research Foundation Ruane Prize in 2004. Dr. Klein has also demonstrated the effectiveness of preventive strategies in certain disorders. She explains: “They don’t work in ADHD, but they have been effective in treating anxiety disorders. Children who are anxious are vigilant. We can teach the children to reduce that vigilance by exposing them to the things that they think are potentially negative. If a child is prone to anxiety but you push the child into the situation he wants to avoid, he’ll get better. It doesn’t work in all children, but many do respond.“

The success of exposure therapy for anxiety indicates to Dr. Klein that “parents should not be accommodating to children who are anxious.” She admits it is hard to do, because it seems cruel. “But in the long run, you are doing the child a disservice by making sure they are protected from the situations they are anxious about and avoid.”

Rachel G. Klein, Ph.D.

Scientific Council Member

Brain & Behavior Research Foundation Ruane Prizewinner

1995 NARSAD Distinguished Investigator Grantee

Professor of Psychiatry

New York University Child Study Center