The Examined Brain

Childhood Development: ADHD and Problem Behavior

2007-11-29T10:01:00.000-08:00

Two new studies were recently published that shed light on several aspects of childhood behavioral development. The first has to do with how the brains of children with Attention Deficit / Hyperactivity Disorder (ADHD) develop differently from those of normal children. The second study, entitled "School Readiness and Later Achievement," assessed the power of early childhood social and academic skills to predict later math and reading achievement. I choose to discuss both of these studies because they are related in that they both examine aspects of childhood behavior that is often deemed unacceptable and in need of treatment. In the former case of ADHD, this treatment is often pharmaceutical. I learned about this new research from an article in the New York Times entitled “Bad Behavior Does Not Doom Pupils, Studies Say.” Although I think this headline might be a little too optimistic, both studies should be at least slightly encouraging to parents.

The ADHD brain development study involved 446 children, half of whom had been diagnosed with ADHD. Each of the children’s brains was scanned using MRI two or more times at about three year intervals between their early preschool years and young adulthood. The researchers examined the images of the brains to ascertain the thickness of over 40,000 cortex sites. Childhood brain development follows a pattern first of cortex thickening and later thinning when unused neurons are pruned away. They found that half of the cortex sites gained peak thickness about three years later, at about 10.5 years of age in the group with ADHD versus 7.5 in the control group (see picture on left). Nevertheless, the brains of children in both groups followed the same general developmental pattern. The brain’s frontal cortex was one of the areas where the children with ADHD showed the most delay in development. This area is thought to be responsible for many behaviors that are disturbed in people with ADHD, such as controlling impulses, focusing attention, and organizing complex tasks. Notably, one area of the brain, the motor cortex, actually matured faster in the children with ADHD which may explain the fidgetiness and excessive movement that sometimes characterize the hyperactive form of the disorder.

The second study set out to analyze which characteristics of preschool children would best predict their “later teacher ratings and test scores of reading and math achievement.” Among the early traits of preschool students, they found that school-entry math skills best predicted later reading and math performance, followed by early language and reading skills, and then attention skills. The most surprising result of the study was that there was no correlation between early “problem behaviors and social skills” and later math and reading achievement (see image at right). According to the New York Times article, “educators and psychologists have long feared that children entering school with behavior problems were doomed to fall behind in the upper grades.” Fundamentally, what the study says is that children who enter school being good at math and reading tend to continue to be good at math and reading regardless of whether or not they have poor social skills or act out. Put this way, the result does not seem as surprising. However, the researchers did attempt to control for the preschoolers’ cognitive ability, although they admitted that “despite our ability to control for cognitive ability … and despite our controls for concurrent reading skills in all six studies, it remains possible that our surprisingly large school-entry math coefficients overstate causal impacts.” Simply stated, the correlation between early math performance and later math and reading performance may just be the result of smart children being more likely to have early math skills than their less intellectually gifted peers. Nonetheless, just because early behavior and social skills don’t correlate with later academic achievement doesn’t mean nothing should be done to correct problem behavior, as being able to do math is of little use if a person is unable to interact with others.

Both of these studies should at the very least offer comfort to parents that are worried that any psychological or behavior problems their young children may have now will have a detrimental effect on their children’s lives forever. The ADHD brain imaging study shows that the brains of children who are diagnosed with ADHD at a young age develop in essentially the same pattern as those of normal children just a little bit later. Although it’s too early to tell, perhaps this new information will ease the pressure on parents to medicate their young children for ADHD if in many cases the disorder will go away on its own with a little patience. ADHD such as methylphenidate and amphetamine can help in some cases, but they have also been known to have serious side effects such as appetite suppression which in turn may cause stunted growth in young children. As for the second study, while it is very limited in scope, it may reassure some parents dealing with unruly children that the unruly behavior is at least an isolated problem and most likely will not affect academic performance.

Brain Surgery in the Blogosphere

2007-11-08T10:30:00.000-08:00

This week, instead of doing a regular post, I decided to explore the blogosphere. I found two posts on something many of us may not be familiar with: brain surgery. The idea of directly manipulating the brain may cause us to think of old-fashioned lobotomies, like the one preformed on the main character in One Flew Over the Cuckoo’s Nest, which rendered him mostly incapacitated. A lobotomy of this sort usually involved direct manipulation of the prefrontal cortex, either severing connections to it or removing it all together. The prefrontal cortex is thought to be the brain’s executive control center, responsible for organizing one’s thoughts and planning behavior. Lobotomies of this sort are not preformed today, at least in the United States. However, the first post I commented on was one on the blog Furious Seasons about modern-day “lobotomies” being preformed in China [as seen in the picture at right]. The second post I commented on was on the Wall Street Journal’s health blog and is about deep brain stimulation [picture below left] as a treatment for Tourette syndrome.

My Comment on "Lobotomies In China":

First of all, as an avid reader of your blog, I would like to thank you for calling attention to this important development in China. It seems to me that these brain surgeries are being preformed with little oversight and without any hard scientific evidence that they are effective. The story of the Mr. Mi in particular, is heart wrenching because of the fact that the damage to his brain is so totally irreversible. However, I am wondering if it may be a mistake to label these surgeries as lobotomies, since even the Wall Street Journal acknowledges that the “areas of the brain being targeted are more precise.” Also, isn’t the term “lobotomy” usually used in reference to manipulation of the prefrontal cortex in particular? Do we have any idea if this is also the area that Chinese surgeons are targeting? It is also interesting that Dr. Wang says “93% of respondents [to the surgery] had shown improvement.” If this figure is true, then the Wall Street Journal probably could have found one family to interview whose life had been improved by the surgery. Nevertheless, if there really are people who have improved because of this surgery, they may not have felt the need to risk getting in trouble with the government by talking to foreign reporters. Although the fact that these surgeries are so prevalent in China does at first lead me to think they are a clear-cut case of medical malpractice, it does not seem wise to me to draw conclusions about all of the patients from two interviews. Unfortunately it may not be possible in China, but I would like to see more research done on the outcomes of these surgeries before drawing conclusions.

My Comment on "Brain Stimulation Helps Tourette’s Patients":

First I would like to say thank you for posting on this new development in the treatment of Tourette syndrome. From my limited experience with people who have the disease, most of the treatments on the market now do not seem to work at a satisfactory level, so this treatment sounds very encouraging. However, I was wondering how the patients could not know if their brains were being subjected to deep brain stimulation. It would seem to me that getting a shock to the brain would be something that one would notice, but perhaps the shocks are very mild. I think it would also be interesting to see how this treatment does compare with drugs or if both drugs and DBS at the same time would yield even better results. Also, is it known how this treatment would work on a more widespread scale? Would patients undergoing treatment always have to visit a clinic once a month to have the device operated by doctors, or could patients learn to operate it by themselves? I have also heard of deep brain stimulation as a treatment for depression and other brain surgeries as treatments for obsessive-compulsive disorder. Hopefully, in the future, more direct brain treatments like this one will be as successful in treating other mental illnesses.

Marijuana: A Possible Treatment for Depression?

2007-10-29T19:33:00.000-07:00

Recently there has been debate over whether the popular recreational drug marijuana (see image at left) has legitimate medical uses. Several states, including California, have decriminalized marijuana usage for patients who have been told by their doctors that they could benefit from the drug. The main, if controversial, recognized medical use of marijuana has to do with its supposed pain-relieving effect. It is often recommended to cancer and AIDS patients to alleviate the chronic pain that often accompanies those diseases. According to the National Organization for Reforming Marijuana Laws (NORML), an organization that promotes the legalization of marijuana, it has also been recognized for “symptomatic relief for a number of medical conditions, including nausea and vomiting, stimulating appetite, promoting weight gain, and diminishing intraocular pressure from glaucoma.” However, the Drug Enforcement Agency of the United States classifies marijuana as a Schedule I drug, meaning it, among other things, “has no currently accepted medical use in treatment in the United States.” Nevertheless, a new study (the full text article requires a subscription) published in the current issue of The Journal of Neuroscience may add antidepressant to marijuana’s list of medical uses.

The new research studied the effect of tetrahydrocannabinol (THC), the active chemical in marijuana, on rats. Among other experiments, the researchers used a “Forced Swim Test” or FST to evaluate the drug’s antidepressant properties. This test involves placing the rats in water too deep to stand in and seeing how long it takes until they give up trying to swim. The basic idea is that more “depressed” rats will give up on surviving sooner. In the words of the study, “The FST is both sensitive and selective for clinically effective antidepressants, has been repeatedly validated, and is currently the most popular model for detecting antidepressant activity attributable to its simplicity, reliability, and high predictive validity.” The researchers also directly measured serotonin activity in the rats’ brains. The results showed that low doses of THC produced similar effects to SSRI (selective serotonin reuptake inhibitor) antidepressants, meaning they increased the rats’ swimming behavior in the FST (see graph below right where WIN is the THC and DIM is the SSRI used for comparison) and increased serotonin activity in their brains. On the other hand, high doses of THC did not affect the results of the FST and actually lowered serotonin activity. THC exerts its effect by activating the brain’s endocannabinoid system, which can be thought of as the brain’s stress-recovery mechanism.

I should note that this study does not necessarily translate to typical recreational marijuana use in humans. First, even though rats are often used as models for human diseases, the human brain is still infinitely more complex than the rat brain and therefore THC may influence it differently. Also, recreational marijuana is usually smoked, and this makes it difficult to control the amount of THC entering the bloodstream. As stated above, high doses of THC have detrimental effects on the brain systems thought to be responsible for mood, and therefore the researchers cautioned against attempting to use smoked marijuana as an antidepressant. In addition, marijuana and particularly smoked marijuana have other negative effects including “frequent respiratory infections, impaired memory and learning, increased heart rate, anxiety, panic attacks and tolerance,” as indicated by the White House’s fact sheet on the drug. Marijuana has also been shown in some studies to be addictive and cause physical dependence.

It would be interesting to see more research done on this subject, as today’s classes of antidepressants are by no means one hundred percent effective. Unfortunately, due to marijuana’s tight scheduling in the United States, it is difficult for American researchers to conduct quality studies on its effects. Notably, the study mentioned above was done in Canada at McGill University and the University of Montreal, both in Quebec. In order for scientists to research marijuana in this country, they must obtain it from the National Institute on Drug Abuse (NIDA). Numerous scientists have criticized this supply as being less potent than the drug that is usually found on the street. Furthermore, an article in Scientific American points out that the government is reluctant to fund studies that propose to look for health benefits of marijuana. Instead federal funding is focused on studies of its detrimental effects, perhaps because the nation's drug policy is based on the assertion that marijuana has no medical use whatsoever. I think this policy is unwise because it might limit the development of potential new treatments for depression as well as other illnesses. When possible, the government should promote open scientific inquiry, not attempt to stifle it because the findings may contradict the reasoning for its policies.

Obesity and the Brain: Is There a Gene that Makes Us Fat?

2007-10-23T09:45:00.000-07:00

A new study just published in the October issue of Behavioral Neuroscience suggests there may be a genetic component to why some people tend to eat more than others. The experiment tested 29 obese and 45 normal people for their genotype, motivation to eat, and energy consumption. The genotype that was studied has to do with the dopamine system in the brain, specifically the gene determining the amount of dopamine receptors. One of the two alleles for this gene, called the Taq1 A1 allele, “has been associated with a 30%–40% reduction in the density of the dopamine D2 receptor (DRD2).” About half the world's population carries the A1 allele. Most A1 carriers are heterozygous, meaning they carry one A1 allele and one A2 allele. The other half is homozygous for the A2 allele, meaning they have a higher number of dopamine receptors. So what does dopamine (the molecule shown on the left) have to do with eating? According to the study, “The reinforcing value of food is related to activity of the dopaminergic system. Food consumption increases brain dopamine levels in animals and humans.” It should be noted that the “reinforcing value of food” is measured by how hard someone will work to get food not how much pleasure one derives from eating food.

The study involved two behavioral experiments. In the first, the participants were given various foods and told to rate them in order of taste and personal preference. However, the rating was designed to mask the real purpose of the task, which was to see how much the subjects ate when food was freely available. The second experiment had the subjects press buttons on two different computers. Pressing buttons on one computer earned them points to eat a favorite food, whereas pressing buttons on the other earned them points to read a newspaper. This task measured how hard the participants were willing to work to get food. Based on these data, the researchers were able to divide the subjects into two groups, one low and one high on “food reinforcement.” The latter group, the ones who were willing to work hardest to earn food, consumed the most calories. In addition, the high reinforcers that were carriers of the A1 allele consumed even more calories. Yet some people with the A1 allele were also low in food reinforcement, and there was no difference among the two genotypes in that group. Instead, the A1 allele combined with high levels of food reinforcement was what made people in this group consume the most. The researchers speculated that this powerful combination could be a major risk factor for obesity.

The reason the A1 allele and its corresponding reduction in the number of dopamine receptors may increase the reinforcing value of food is similar to the way drugs act on our brains. Indeed, the study mentioned that, “Food is a powerful reinforcer that can be as reinforcing as drugs of abuse.” When dopamine receptors are stimulated (picture on the right), they produce a feeling of reward for whatever actions were taken to stimulate them. Both drugs and food can increase levels of dopamine and thus increase the feeling of reward. Having more dopamine receptors makes it easier to experience the reward, and thus less of the rewarding substance is needed to get the feeling. In contrast, to those with fewer receptors, more of the rewarding substance is needed to get the same feeling, and in some people, that substance may be food. There are many drugs that act on the dopamine system, including drugs for Parkinson’s disease and schizophrenia as well as illegal drugs like cocaine. This study leaves open the possibility that a future treatment for obesity and overeating may come from drugs that affect the dopaminergic system, especially for those individuals that have a genetic propensity for higher food reinforcement.

Depression: Two Treatments are Better than One

2007-10-02T08:52:00.001-07:00

A new study published in the October 2007 issue of the Archives of General Psychiatry has found that a combination of cognitive behavioral therapy and anti-depressant medication is the best treatment option for teens with major depressive disorder. The Treatment for Adolescents with Depress ion S tu dy followed a diverse group of 654 teens for 36 weeks. One group took the anti-depressant f l uoxetine (brand name Prozac), another group engaged in cognitive behavioral therapy with a therapist, and yet another group was given both treatments. After 18 weeks, 69 percent of the teenagers taking fluoxetine alone and 65 percent of those participating in cognitive behavioral therapy alone showed improvement. In contrast, 85 percent of those receiving both treatments showed improvement after the 18 weeks. After 36 weeks, the difference in outcome for the three treatments diminished somewhat, with 86 percent of those in the combination therapy showing improvement compared to 81 percent of those in the other single-treatment groups.

Another significant finding of the study was that combining cognitive behavioral therapy with the anti-depressant also significantly reduced the rate of suicidal thinking in the teens. Although anti-depressants have helped many people with depression, they have ironically also been blamed for increasing the rate of suicidal thoughts, especially in teens. Most SSRIs (selective serotonin reuptake inhibitors) like fluoxetine are now required to come with “black-box” labels warning of the effect, and it is for this reason many doctors are wary of prescribing this type medication to teens even though it has been shown to be effective in most people. This side-effect was seen in the study with 15 percent of the teens in the fluoxetine-only group reporting suicidal thoughts. However, only 8 percent of the teens in combination therapy reported suicidal thoughts, which was closer to the 6 percent of teens in the cognitive behavioral therapy alone. This suggested to the study’s authors that the cognitive behavioral therapy in some way mitigated the negative effects of the fluoxetine and that the two treatments complemented each other well.

One thing I am left wondering about this study is why it did not include a control group given no treatment or a placebo. It would have been interesting to see whether or not there was a large difference between teens given a placebo plus cognitive behavioral therapy differed much from the ones given the combination treatment described above. In addition, they could have given a “placebo” therapy in combination with the fluoxetine to see if it was the actual cognitive behavioral therapy that produced the changes or just the act of consistently talking with a trusted adult. Also, since many people naturally recover from depression over time, it would have been interesting to compare the results of the study with a group of teens given no treatment. However, I can see how the risk of the teens harming themselves if not treated would outweigh the benefit of including a no-treatment group.

The results of this study in some ways seem to me like common sense. Of course two treatments should be better than one. Hopefully though, it will help end the practice of psychiatrists just giving teens an anti-depressant prescription and nothing else. Although anti-depressants have greatly advanced the treatment of the physical aspects of depression, in my view they may have also made traditional methods of therapy seem less important. However, this study not only proves that cognitive behavioral therapy is basically just as effective as anti-depressants, but that the choice does not have to be between one and the other. Maybe some day in the future there will be a single miracle pill that will cure all depression, but until then it does not serve patients well to forget about lower tech methods of treatment because of new exciting drugs.

Social Phobia: Are doctors too eager to drug us?

2007-09-25T07:29:00.001-07:00

This week I ventured out into the blogosphere to see what other brain-related news people are talking about. Several blogs lead me to this op-ed in Friday’s New York Times on how psychiatrists are increasingly diagnosing social anxiety disorder in children, and consequently, prescribing anti-depressant medication as treatment. As the author points out, this is problematic because many anti-depressants have been linked to suicidal thoughts in children as well as other side effects. He then calls on psychiatrists to make the distinction between “social anxiety disorder” and “shyness” more clear cut in the upcoming edition of the Diagnostic and Statistical Manual (DSM V), which lists the standards by which mental disorders are diagnosed. I first saw this article linked to in a post titled “Shyness: Pathological or Normal Experience” in a blog authored by an anonymous academic in clinical psychology. Next, I looked at the post “Shy of a Phobia” by Jacob Sullum in Reason Magazine’s blog, Hit & Run. This blog is a little bit different in that it does not focus exclusively on neuroscience or psychology as it is part of a political magazine, but I thought Sullum’s comments on the Times piece were original and insightful.

Comment on “Shyness: Pathological or Normal Experience”

I would first like to say that I enjoyed your link to and commentary on Christopher Lane’s piece in the Times. I agree with your assertion that too many people are being diagnosed with social phobia if your figure of 13% is correct. In my opinion, a clinically significant psychiatric condition should, by definition, be something that occurs in a very small percentage of the population. Otherwise every single unfavorable aspect of human nature may one day be labeled as a disorder worthy of “treatment.” However, I partially disagree with your blaming the majority of the over diagnosis problem on drug companies. Also significant, in my view, is the fact that too many patients (and parents of patients) want something tangible to come of every doctor’s visit. The fact that these people are consulting with psychiatrists in the first place suggests that they are proactively looking for something to “cure” them. I imagine many would not be satisfied if their psychiatrist simply said there was nothing wrong with them. For many people, leaving the office with a diagnosis and a prescription makes the visit seem worthwhile. The same phenomenon can be seen in the over prescribing of antibiotics for viral illnesses that doctors know antibiotics won’t cure. Unfortunately, the side effects of psychoactive drugs are much more serious than those of common antibiotics.

Comment on “Shy of a Phobia”

I would first like to say that your take on Lane’s piece is original and insightful. It is true that in the case of psychological illnesses, there are no objective physical tests that can determine if a person has illness X or not. However, I do not think this fact excludes the DSM from being an invaluable resource for both patients and doctors. The truth is, right now the DSM is the closest thing mental health professionals have to x-rays and blood tests. Although I do think psychiatrists should have the freedom to prescribe drugs as they see fit, the DSM can help in determining if drugs are the best course of action, especially since so many psychoactive drugs have potentially harmful side effects that patients may not be aware of. The DSM has come a long way from it’s beginnings in Freudian theory of questionable scientific validity, and it would be of great value to everyone if it were to continue to be refined to reflect the growing scientific knowledge of mental illness and the brain. Maybe someday in the future a quick brain scan will tell doctors all they need to know about what mental illness a patient has, but until then the DSM is all we have.

Food Additives: Are they causing hyperactivity in children?

2007-09-20T08:53:00.000-07:00

A recent study suggests there may be a link between common food additives and hyperactive behavior in children. The idea that food additives cause hyperactivity is not new. Dr. Ben F. Feingold first introduced a diet free of food additives as a cure for attention-deficit/hyperactivity disorder (ADHD) in the 1970s. However his method never gained widespread support in the medical community and was heavily criticized by food companies involved in making or distributing food additives. The new research, financed by Britain’s Food Standards Agency and published in The Lancet, is the first double-blind placebo-controlled study of the effect of food additives on behavior.

The three-week study of over 300 children involved two different age groups: 3-year olds and 8 and 9-year olds. Each child spent one week drinking one of three fruit drinks: one containing the amount of additives found in a typical British child’s diet, another without any additives, and the last containing a lower concentration of additives than the first. All three drinks were designed to taste the same. Researchers, ignorant of which children had received which drink, then observed the behavior of the children, paying close attention to the children’s’ attention spans, fidgetiness, restlessness, hyperactivity and other behaviors associated with ADHD. The study found that children were significantly more likely to display these ADHD-like behaviors when drinking the drinks with higher levels of additives. The effect was more pronounced in the 3-year olds than the 8 and 9-year olds. In addition, there were strong individual differences between the children, meaning some did not respond at all to the additives and others responded strongly.

One limitation of the study is that the additive-containing drinks contained a variety of different additives, making it impossible to determine specifically what compound is linked to the behavioral changes. The additive-containing drinks contained a variety of artificial food colorings as well as the compound pictured on the left, sodium benzoate, a common preservative. Sodium benzoate, however, is not only found artificially in foods as a preservative. It is also found naturally in cranberries and prunes.

One obvious question the results of the study bring up is whether these kinds of food additives are causing the high number of ADHD diagnoses in the United States. No other country diagnoses the disorder in children at anywhere near the rate that we do. In addition, the United States consumes 90% of the world’s methylphenidate, a common drug used to treat ADHD, also known by the brand name Ritalin. Some psychologists have questioned whether or not the high rate of diagnoses in the United States has more to do with cultural pressure on children to perform well in school rather than a real mental disorder. The results of the food-additive study, however, suggest that there may be other non-cultural reasons for the high rates of ADHD seen in the United States. Perhaps American children consume more food additives than children in other countries. Given the sheer number of colored and processed foods seen on a regular trip to an American grocery store, this is not hard to imagine. It would be interesting to see a study on the rate of food additive consumption compared to ADHD diagnosis across different countries.

Although it is easy and interesting to speculate on whether additives cause hyperactivity and ADHD in children, it is too early to jump to these kinds of conclusions. As mentioned earlier, there was a high degree of individual difference between children in the study with some children being much more sensitive to the presence of additives than others. It may be the case that the more sensitive children are already more hyperactive or predisposed to ADHD-like symptoms and the additives just exacerbate the problem rather than additives causing ADHD to appear in children who otherwise would be completely normal.

Some scientists in the United Kingdom are already calling for the government to take a more active role in regulating food additives. Although I think the results of this most recent study do call for individuals to be more careful about what foods they and their children consume, at this point I do not think there is enough evidence for governments to make any kind of strict regulations concerning additives. The fact that the study only focused on children leaves open the possibility that additives may not affect adults at all, especially since the younger children were more affected than the older ones. In addition, the high individual differences in sensitivity to the additives calls into question the wisdom of the government regulating foods that may be perfectly harmless even for some children. At this point, I think the only role the government should play is to make sure all additives are listed in food ingredients so that consumers can make informed choices and to fund more research on the subject.