The Frontal Cortex

The Ritalin Generation

I came of age in the Ritalin generation, which meant that plenty of my classmates in elementary school went to the nurse’s office for their little dose of drug. At the time, I remember being jealous of these kids, who not only got to miss 10 minutes of instruction but got to have a real, genuine medical affliction. (I was one of those confused children who, for a brief period, thought it would be awesome to have braces and/or a big cast on my arm.)

In retrospect, I can appreciate the complexities of the ADHD debate. On the one hand, ADHD is a real syndrome, with identifiable neural correlates. For instance, in November 2007, a team of researchers from the National Institute of Mental Health and McGill University uncovered the specific deficits of the ADHD brain. The disorder turns out to be a developmental problem: the brains of kids with ADHD develop at a significantly slower pace than normal. This lag was most obvious in the prefrontal cortex, which is a brain area that’s crucial for things like directed attention and impulse control. (On average, their frontal lobes were three and a half years behind schedule.)

And yet, I often wonder about the medical treatments we’ve come to rely on for the treatment of ADHD. Ritalin (aka methylphenidate) is a potent, psychoactive drug. We prescribed it to millions of kids with little knowledge of the long-term consequences. While I know Ritalin can be effective – I’ve seen it perform wonders on my elementary school friends, not to mention all the undergraduates who juiced their attention with crushed pills – there are many uncertainties concerning its long-term application. A new PNAS paper by scientists at the National Institute for Drug Abuse (NIDA) makes this clear. I’m forced to clip from the press release, as the paper itself isn’t out yet:

Investigators funded by the National Institute on Drug Abuse (NIDA) have shown that the medication methylphenidate (Ritalin), which is commonly prescribed to treat attention-deficit hyperactivity disorder (ADHD), can cause physical changes in neurons in reward regions of mouse brains; in some cases, these effects overlapped with those of cocaine. Both methylphenidate and cocaine are in the class of drugs known as psychostimulants. While methylphenidate is widely prescribed, this study highlights the need for more research into its long-term effects on the brain. These research findings will be published February3 in Proceedings of the National Academy of Sciences.

“Studies to date suggest that prescribed use of methylphenidate in patients with ADHD does not increase their risk for subsequent addiction. However, nonmedical use of methylphenidate and other stimulant medications can lead to addiction as well as a variety of other health consequences,” said NIDA Director Dr. Nora Volkow. “This study highlights the fact that we know very little about how methylphenidate affects the structure of and communication between brain cells.”

The researchers exposed mice to 2 weeks of daily injections ofcocaine or methylphenidate, after which reward areas of the brain were examined for changes in dendritic spine formation, which is related to the formation of synapses and the communication between nerve cells; and the expression of a protein, delta Fos B, which has been implicated in the long-term actions of addictive drugs. Both drugs increased dendritic spine formation and the expression of delta Fos B; however, the precise pattern of their effects was distinct. It differed in the types of spine saffected, the cells that were affected, and the brain regions. In some cases, there was overlap between the two drugs; further, in some cases, methylphenidate produced greater effects than cocaine–for example, on protein expression in certain regions.

It’s worth noting, though, that previous studies found no link between stimulant treatment for ADHD and drug abuse. The takeaway from this latest study is NOT that Ritalin is just a fancy brand of cocaine, or that delta Fos B is a gene uniquely turned on by amphetamines or illicit drugs. (It seems to be part of the BDNF pathway, which is why its expression leads to the growth of dendritic spines.) Rather, it’s that we really don’t know how stimulants like Ritalin influence fundamental pathways in the brain.

Thanks for the tip, Dave!

Comments

  1. #1 dreikin
    February 2, 2009

    Interesting. I wonder how it compares to amphetamines? IIRC, the prescribed amphetamines also have structural effects, but I wonder how similar/different they are.

  2. #2 Matt Platte
    February 2, 2009

    “Studies to date suggest that prescribed use of methylphenidate in patients with ADHD does not increase their risk for subsequent addiction. However, nonmedical use of methylphenidate and other stimulant medications can lead to addiction as well as a variety of other health consequences

    Well yeah, sure, as long as it’s labelled “medicinal” it’s okay. Like Granny, from the Beverly Hillbillies, who kept a jug of medicine in the kitchen cabinet.

    But with the handwaving and decoys subtracted from the above:

    “Studies to date suggest that prescribed use of methylphenidate in patients with ADHD … can lead to … a variety of other health consequences”

    Which is also what we have – informally – observed in the Ritalin Generation as well as its pill-crushing parents.

  3. #3 Anne-Marie
    February 2, 2009

    Good post, I think the ADD/ADHD issue is a great example of a disorder that is affected (as far as the public’s perception and even an individual’s experience of it) just as much by sociology as medicine. The Groks Science podcast (granted, not to be cited as an authority) did an interview a few weeks ago with a doctor discussing the pros/cons to medicating adult ADHD, and she seemed to be pushing the view that there are benefits to the symptoms that shouldn’t be medicated away.

    More relevant to your post, the conclusions in the study about the risks of using Ritalin other than as prescribed should be important in light of the raging black market for the pills on college campuses.

  4. #4 Evil Rocks
    February 2, 2009

    Coffee. Coffee coffee coffee. Coffee lets me concentrate when I need to, to ignore distractions, and thankfully caffeine is much more friendly to the body than amphetamines. However dumping buckets of acid down my stomach every day won’t help in the long term…

    I’ve said it before and I’ll say it again. Messing with your neurochemistry using today’s drugs is like taking a sledgehammer to your brain (metaphorically). The kids of my generation who medicate themselves into academic excellence will probably never see the other side of negligible senescence.

  5. #5 Doc
    February 2, 2009

    Nice post! You bring a valid point about our not knowing the long term effects of these medicines. However, you failed to note what is probably the most important finding regarding ADHD and drug abuse specifically, that patients with untreated ADHD have a higher incidence of abuse than treated patients. There are long term effects of this as well, and the harm is clearer.

  6. #6 D. C. Sessions
    February 2, 2009

    It’s worth noting, though, that previous studies found no link between stimulant treatment for ADHD and drug abuse.

    Not quite true. There is a “link” — but it’s a negative correlation: ADHDers treated with stimulants have lower rates of abuse, both concurrently and subsequently.

  7. #7 OftenWrongTed
    February 2, 2009

    The use of ritalin seems from my vantage-point as untrained observer, to be largely so that the staff can rest, and not for the patient to heal.

  8. #8 D. C. Sessions
    February 2, 2009

    The use of ritalin seems from my vantage-point as untrained observer, to be largely so that the staff can rest, and not for the patient to heal.

    One of my sons’ teachers thought the same until one day …

    She told us he was working with total concentration on an in-class assignment until his pencil broke. The story of his distractions on the way to pencil repair and return to work changed her mind.

  9. #9 amybuilds
    February 2, 2009

    A couple of things to keep in mind about ADHD and drugs.

    One is that the diagnosis for ADHD is erratic at best. A LOT of things look like ADHD but aren’t, getting sound diagnostic criteria would be a true step in the right direction in the treatment of this condition. My experience is that it takes next to nothing to convince a pediatrician, psychiatrist, or a family doctor to write a script for Ritalin, Adderall, etc for a child with discipline issues.

    Number two: the side effects of these drugs are nothing to ignore or push aside. While my son could concentrate in school while on Adderall he would come home and commence (when the drug wore off) with monster tantrums. I’m not talking about the cute kind that a 2 year old has in the grocery store candy aisle either, I’m talking extreme anger that scared rational adults.

    In the end ANY person considering putting their child on ADHD medications should first, think hard and second, think of it as a trial to be re-evaluated every month or so at first and then if the drug seems to be working well re-evaluate a few times a year.

    For my son we stopped the drugs and started good old psycho-analysis. He’s a bright child and started when he was six years old. After he developed a relationship with his therapist his behavior slowly began to change. Now, six years later, we are very pleased with how things have gone. Sure it was much more labor intensive for us, going to a therapists office every week versus popping a pill was a lot more on us, his parents. But now I have a child who has worked through his issues, doesn’t exhibit any ADHD symptoms, and is drug free. Some of his cohorts still go to the office daily for their “fix.”

    For our family the psycho-therapy worked and continues to work. The more I read about what is being learned about these drugs the happier I am with our approach.

  10. #10 Texas Reader
    February 2, 2009

    Any discussion of the pros and cons of treating ADD should include 2 points: 1 – stimulants are not the only treatment, many kids and adults do very well on Concerta and 2 – the “price” to be paid for taking Ritalin in terms of changes to brain chemistry or whatever else concerns people have should be measured against the consequences of NOT treating the disorder. My nephew had TERRIBLE self esteeem before he was diagnosed because he was always being reprimanded by his teachers and he couldn’t finish tedious tasks. His parents had to work very hard with him on his self esteem after he was diagnosed and treated successfully with Concerta. Many adults who are intelligent did NOT ever get diagnosed, and carry with them serious self esteem problems even after being diagnosed and treated as adults.

    I’m tired of reading so many articles and comments implying that ADHD is rare and over-diagnosed. Who is to say what % of our population has ADD brains? I’d bet a high % of successful sales people are ADD and gravitated to jobs that their brains were capable of doing effectively.

    The tragedy is the number of kids and adults who have never been diagnosed, or were denied treatment by “drug averse” parents, and who haver suffered in their attempts to keep up with their peers in organizing their work, multi-tasking, completing tedious steps of projects, etc. etc.

  11. #11 Fertanish
    February 2, 2009

    Having grown up in the days before ADD diagnoses and subsequent medication (shut up, it wasn’t that long ago), I can certainly think back at children who were possibly suffering from its consequences. I’m not a medical expect (I’m not a medical anything, really), and I don’t know if their distraction level was truly a treatable problem or simply a reaction to social stimuli (many of these kids also came from pretty bad homes, I eventually learned).

    But I know these kids had a rough road. Many teachers had little patience for them, they were quickly labeled as “bad” by both those in authority and their peers, and they eventually acted out to the expectations of their personality without much investment towards improvement. If this was avoidable then, possibly providing a less traumatic childhood for even a fraction of these students, then it provides an argument that continuing efforts to refine and improve diagnoses and treatments is certainly worth while.

  12. #12 dreikin
    February 2, 2009

    Just a note – there are multiple forms of ADHD – three according to the DSM, one of which does NOT have a hyperactive component (ADHD – Predominantly Inattentive, or ADHD-PI). Same treatment though. A good way to think of it is that those with ADHD (hyperactive) are distracted by external stuff, while those with ADHD-PI are distracted by internal stuff.

    Actually, there are also some indications that an ADHD-PI diagnosis may be being given to those with ADHD-PI as I described it, and a possible subgroup with what’s called Sluggish Cognitive Tempo (SCT).

  13. #13 Noah
    February 3, 2009

    I think this is an excellent subject to talk about, especially considering I have ADHD. The LD and ADHD debate should talk about medication, but there are plenty of books that also stress other forms of self-medicating in healthy ways. Hallowell and Ratey’s book Delivered from Distraction is an excellent resource for people or families struggling with ADHD. Both are psychiatrists who have ADD and one focuses on the science of the brain while the other focuses on the psychological affects.

    Something else to take note of is that LD and ADHD students learn differently. It’s akin to the old analogy of sticking a square peg into a round hole. Think about the statistic that only 5% of this population is going to attend a 4 year college, and only 2.5% of that population will graduate. The number one indicator for success in school is self esteem, but how is that possible if there is only one way to succeed.

    Our school systems are geared for rote knowledge, sitting still, usually audio processing. However, that doesn’t take into account the many ways of metacognitive functioning. What about audio-visual processing, or just visual processing, or kinesthetic processing or tactile processing, or any combination of those. There is work being done to harness these alternative ways of thinking and working which may be of help.

    I think it’s important to remember that Einstein, Edison, Richard Branson, etc…all had an LD or ADHD and what would our world be without them

  14. #14 Sean
    February 3, 2009

    Let me echo the comment about the risks of NOT treating ADHD.

    My wife and I resisted medications for 4 years with our eldest son, for all the reasons that anyone here would, and for some time after two independent diagnoses. We relented and tried Ritalin (at the lowest starting dose) only after seeing his academic progress significantly affected (through being unable to stay on task) and seeing him become socially more and more isolated – clearly these things were to be devastating to his self esteem. His general behavioral discipline was also appalling but that was a lesser concern (for us rather than the school).

    Even on the lowest dose, the results were remarkable. There has been a transformation in his progress academically and socially. His melancholy of the last couple of years has lifted and he’s clearly a much happier, better adjusted and, yes, more creative kid (creative because you can actually do things when your attention is not flying from pillar to post, or being hyper-reactive to every small emotional cue). I have no doubt that the meds have given him the platform he needed to do the things he wanted to all along.

    I don’t doubt that there are serious limitations to the ablility of these drugs, the knowledge of their mechanisms and long-term effects, and that cognitive science will one day find much better and more refined ways of dealing with ADHD. I also agree that if learning environments were constructed differently, and could cater to a wider range of creative types, things would be better. But, for the moment, I have little doubt that they are the best single tool we have and clearly the lesser of the available evils.

  15. #15 Dr. Pamela Rutledge
    February 4, 2009

    As per your press release: “…nonmedical use of methylphenidate and other stimulant medications can lead to addiction as well as a variety of other health consequences.” This is true of nonmedical use of many prescription drugs. Taking a psychoactive drug for any nonmedical reasons is drug abuse, recreational or otherwise. The biggest problem with press release and others like it, is that they touches the hot buttons of worried parents and vigilantes everywhere who DON’T read the study. Already headlines for that release are appearing with a slightly different take: e.g. at PsychCentral: “ADHD Drug, Ritalin, Possibly Addictive.” In media coverage and cocktail parties there is not a big leap from there to direct causality and the promotion of more fear and less, rather than more, understanding.

  16. #16 Gustavo
    February 5, 2009

    Recently at spanish newspaper El País: one out of every three dutch kids aged 5 to 15 is under ADHD stimulant medication (www.elpais.com/articulo/salud/ninos/
    holandeses/toma/farmacos/hiperactividad/elpepusocsal/20090203elpepisal_3/Tes) while general worldwide prevalence is about 5%. Scary.

  17. #17 Baby
    February 5, 2009

    So many of my classmates at Uni used Ritalin to increase concentration. It did seem to work even though I never tried it myself. It meant they could stay out all night and still concentrate the next day at lectures.

  18. #18 Zac
    February 10, 2009

    I have this theory (as a former Ritalin user and based on what I’ve observed in friends) that drugs like Ritalin and Adderal interfere with normal right-brain function. Any thoughts on that?

  19. #19 Kateryna
    February 15, 2009

    Rats who voluntarily administer themselves cocaine demonstrate a greater degree of addiction than rats that were involuntarily given the drug, according to researchers at The University of California, San Francisco. The study suggests that our conscious choice may play greater role in the long-term alteration of our reward centers in the brain that the pharmacological effects of the drug itself. I’m willing to bet there would be a demonstrated physiological difference between kids who are prescribed Ritalin as opposed to kids who take it for recreational purposes over time.

    (http://www.universityofcalifornia.edu/news/article/18315)

  20. #20 Jamba
    May 14, 2009

    2Jonah,

    “a team of researchers from the National Institute of Mental Health and McGill University uncovered the specific deficits of the ADHD brain. The disorder turns out to be a developmental problem: the brains of kids with ADHD develop at a significantly slower pace than normal. This lag was most obvious in the prefrontal cortex, which is a brain area that’s crucial for things like directed attention and impulse control. (On average, their frontal lobes were three and a half years behind schedule.)”

    My advice to you,who seems to take this nonsens for granted..

    Type these words above in your Cell-phone and through the phone in
    a Public Garbage bin,
    In that way you’ll achieve Instant Enlightment on many levels in only 30 minutes!

    Life is a wondrous Gift,

    http://www.care-international.org/

    Best Regards

  21. #21 Jamba
    May 15, 2009

    “..behind schedule…”

    Says it all

    Not knowing pays the Rent,he Jonah

  22. #22 Jamba
    May 15, 2009

    ..and you’re still “wondering” about
    how to become the smartest amongst “them”
    ..Posting popular,contemporary Headers..

    Regards,

  23. #23 Jamba
    May 15, 2009

    Since my Frontal Cortex has been measured once in a while
    during early adolescense,
    I always felt secure about my Cortex..

    I must admit that I enjoyed the repeated and sustained Measuring Results and the Reassuring effects on my total Well-Being at that period of time..

    In the Schoolyard,youngsters like myself were trying to intimidate each other with Black and White Scans of our Frontal Cortex Scans..

    ..Those were the days, bro

  24. #24 Raquel
    November 30, 2011

    Que tal?, Estoy haciendo un estudio sobre Europa y encontré esta web, voy a mirar los otros articulos del blog, pues busco información sobre la crisis económica de Europa. Han escrito algo que me pueda servir?. Desde ya muchas gracias

  25. #25 Melany
    November 30, 2011

    Hola, Estoy haciendo un estudio sobre Europa y encontré este sitio, voy a mirar los otros articulos del blog, pues busco información sobre la crisis económica de Europa. Han escrito algo que me pueda servir?. Desde ya gracias por su ayuda

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