Depressed Dopamine Activity in Caudate and Preliminary Evidence of Limbic Involvement in Adults With Attention-Deficit/Hyperactivity Disorder
Nora D. Volkow, MD; Gene-Jack Wang, MD; Jeffrey Newcorn, MD; Frank Telang, MD; Mary V. Solanto, PhD; Joanna S. Fowler, PhD; Jean Logan, PhD; Yeming Ma, PhD; Kurt Schulz, PhD; Kith Pradhan, MS; Christopher Wong, MS; James M. Swanson, PhD
Arch Gen Psychiatry. 2007;64:932-940.
Context Attention-deficit/hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder of childhood. There is considerable evidence that brain dopamine is involved in ADHD, but it is unclear whether dopamine activity is enhanced or depressed.
Objective To test the hypotheses that striatal dopamine activity is depressed in ADHD and that this contributes to symptoms of inattention.
Design Clinical (ADHD adult) and comparison (healthy control) subjects were scanned with positron emission tomography and raclopride labeled with carbon 11 (D2/D3 receptor radioligand sensitive to competition with endogenous dopamine) after placebo and after intravenous methylphenidate hydrochloride (stimulant that increases extracellular dopamine by blocking dopamine transporters). The difference in [11C]raclopride's specific binding between placebo and methylphenidate was used as marker of dopamine release. Symptoms were quantified using the Conners Adult ADHD Rating Scales.
Setting Outpatient setting.
Participants Nineteen adults with ADHD who had never received medication and 24 healthy controls.
Results With the placebo, D2/D3 receptor availability in left caudate was lower (P < .05) in subjects with ADHD than in controls. Methylphenidate induced smaller decrements in [11C]raclopride binding in left and right caudate (blunted DA increases) (P < .05) and higher scores on self-reports of "drug liking" in ADHD than in control subjects. The blunted response to methylphenidate in caudate was associated with symptoms of inattention (P < .05) and with higher self-reports of drug liking (P < .01). Exploratory analysis using statistical parametric mapping revealed that methylphenidate also decreased [11C]raclopride binding in hippocampus and amygdala and that these decrements were smaller in subjects with ADHD (P < .001).
Conclusions This study reveals depressed dopamine activity in caudate and preliminary evidence in limbic regions in adults with ADHD that was associated with inattention and with enhanced reinforcing responses to intravenous methylphenidate. This suggests that dopamine dysfunction is involved with symptoms of inattention but may also contribute to substance abuse comorbidity in ADHD.
One of the key points in this study is that they did the brain scans on ADHD patients who had not been treated with drugs. One of the problems in studies like this is sometimes that it is hard to know if the abnormality was caused by the treatment, or by the condition. In order to get around that, you have to find patients who have not been treated. Then, you run the chance of biasing the results by selecting a nonrandom sample, but there is no easy way to avoid both problems simultaneously.
The study indicates that persons with ADHD have lower levels of dopamine in the emotional center of the brain (the limbic system).
I notice the last sentence in the abstract: "This suggests that dopamine dysfunction is involved with symptoms of inattention but may also contribute to substance abuse comorbidity in ADHD." I am not sure why the reference to substance abuse belongs there. It is true that there is an association between substance abuse and ADHD, but that is not the point of the study.
Comments
I am really glad to see this. Not that it will shut up denialists, but it is always nice to accumulate more evidence. Having grown up with rather severe ADHD and a dad who denied it, I take it very seriously.
I am not sure why the reference to substance abuse belongs there. It is true that there is an association between substance abuse and ADHD, but that is not the point of the study.
While it may not be the point of the study, it does point to a causal relationship to substance abuse. I can definitely tell you that on a baseline, I just plain don't feel right. It makes a lot of sense that someone with lower levels of dopamine would try to adjust for that, even temporarily. Using myself as an example, I have never had any serious problems with occasional use of "physically" addictive drugs, such as cocaine, methamphetimine or even heroin (not that I used the last more than a couple times). It really didn't matter what the drug was, as long as I didn't go for too long without something. Now I pretty much stick to caffeine and my music, only rarely smoking a little pot. But even now, the things that I do, theoretically boost my dopamine levels.
By the way, I tried to email you not so long ago, and gmail bounced it back, claiming your address doesn't exist. I would really like to correspond with you, as I have a couple of questions, especially after reading this post.
Posted by: DuWayne | August 10, 2007 11:22 PM
"This suggests that dopamine dysfunction is involved with symptoms of inattention but may also contribute to substance abuse comorbidity in ADHD."
Makes sense. All addictive drugs target dopamine-rich limbic structures, so people with disordered dopamine and/or serotonin pathways in the limbic system are usually going to find their way to addictive drugs as a form of self-medication. This is true with ADHD, depression, anxiety, bulimia, and Tourette's, for starters. The link between depression and smoking, for example, is rock-solid, and the three adult ADHD'ers I have known have all had on-again off-again problems with drugs, including alcohol.
Posted by: Dirkh | August 11, 2007 12:01 PM
P.S.
Nora Volkow, lead author of the study, is head of the National Institute for Drug Abuse (NIDA), which accounts for her dual interests.
Posted by: Dirkh | August 11, 2007 12:03 PM
Just to let you know, I am working on a post from this, which will repost most, possibly all of it with comments. I am providing attribution, linking your CC license and clarify that I do so without specific permission.
Thanks again for this post. I hope to see more posts about neuroscience behind neurological disorders. I will be happy to link to them as often as I see them.
I should also note that it is exciting to see research leading to a better understanding of the science behind neurological disorders. I am afraid that to a strong degree, notions of duality stemming from religion have stilted research into the physiological causes of abnormal psychology. I can only believe that with a better understanding of the root causes that define the differences between people like me and neurotypicals, can lead to better ways of dealing with the problems of neurological disorders, without throwing out the positive aspects of neurodiversity.
Posted by: DuWayne | August 11, 2007 7:14 PM
"Not that it will shut up denialists." This is what's wrong with our science these days. I agree that ADHD is legit. But calling people who doubt the science b/c it is sponsored by bigpharma and has substantial limitations "denialists" is a bully tacit akin to politics and not science. Science is never about calling those who question your position "denalists" (invoking those who deny the holocaust ever happened). We see this with the whole climate change politics and it will come to bite everyone in the ass in the years to come.
Posted by: Steve | August 12, 2007 6:07 PM
Steve -
Sorry, but I call it as I see it. If you go to the comment thread attached to Shelley's post, you will see what I mean and why I use that term. You could also go to my blog to get an idea of how such denialism effects people. I have half the posts up in a series about my own experience, living with ADHD and the denial of it. I have another post up, of someone else's experience with denial of his bipolar. In essence, for me this is not a issue of science. It is political and more than that, it's the reality of my life. There is absolutely no question that I have serious problems relating to my neurological makeup.
My own experience stems from my parent's denialism. My mother firmly believes to this day, that my ADHD, insomnia and bipolar are actually hereditary demonic activity - seriously. My dad finally accepted ADD/ADHD as legitimate, several years after it would have helped my education. The key thing to understand here, is that, as a child, I accepted both of my parents denialism. It was my dad who later convinced me that he was wrong and the doctors were right.
To give you an idea of the scope of the problem, I will explain my circumstances. To be clear, I do not blame all of my problems on the denialism, I made a lot of bad choices. But it certainly screwed up my education in a big way. By every account and batteries of testing, I am considered a genius. I learned to read when I was two, write when I was three. I started writing music when I was nine. I was successfully repairing electronics, without any training, when I was ten. I designed my first circuitry when I was thirteen, a digital thermostat that could hold an element to within a hundreth of a degree. I'm thirty-one years old, a high school dropout, finally getting back into school. My family very nearly ended up on the street this week, because I couldn't pay our rent.
The ways that denialism affected me, were many. The worse was my education. Steps were not taken that should have been, indeed, would have been, had my parents and all of my teachers accepted the problems I have. Having since seen my education file, I have learned that it was recommended that I be given preemptive substance abuse counseling, based on my being diagnosed with ADD/ADHD. My parents apparently refused, because I never had the counseling. I can't say for sure that it would have made a difference. All that I know, is that I was entirely unprepared for it, no one even warned me that people with ADHD have a strong propensity for substance abuse. Thus, I spent much of my adult life struggling with substance abuse - still do, I just use substances that are less damaging.
I could go on and on about it. Indeed, I am at my own blog. The high and the low of it, is that this is very much a denialist issue. The commenter's who put me on this tare, offered no evidence to back their assertions, not even crank evidence. They didn't even assert that the studies and science are flawed because of big pharma. They basically put their rhetorical fingers in their ears, screaming nyah, nyah, nyah, when anyone presented evidence and said everyone else was wrong. It was very much like holocaust deniers, or HIV/AIDS deniers, only they didn't even attempt to present evidence. Their basic premise was, that the whole of modern psychiatric medicine is a crock of crap, nothing more. If that is not denialism, then what exactly is it then?
Posted by: DuWayne | August 12, 2007 8:06 PM
Nora Volkow, lead author of the study
Posted by: Kız Oyunları | March 4, 2008 4:17 PM