Posted by Phillipa on September 11, 2009, at 22:00:12
Seems scanning now has evidence that reward center dopamine lacking in adult ADD ADHD Phillipa
From Medscape Medical News
Dopamine Pathway Alterations May Be Associated With Symptoms of Adult ADHD
Deborah BrauserRead more September 11, 2009 Preliminary results from a new imaging study suggest that there is an association between a reduction in the transmission of dopamine in the brain and symptoms of attention deficit hyperactivity disorder (ADHD) in adults.
"This study provides evidence in favor of the predicted disruption in the mesoaccumbens dopamine pathway in ADHD," write Nora D. Volkow, MD, director of the National Institute on Drug Abuse and Laboratory of Neuroimaging at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland, and colleagues.
In addition to finding lower postsynaptic D2/D3 receptor markers and lower presynaptic dopamine transporter (DAT) markers in those with ADHD, compared with a group of control patients, in 2 key brain regions for reward and motivation (accumbens and midbrain), the study also corroborated disruption of synaptic dopamine markers in the caudate region and provided preliminary evidence of hypothalamic involvement.
"Basically, this study showed that individuals with ADHD have a significant decrease in both of these markers in the dopamine areas associated with reward, motivation, and drive," Dr. Volkow told Medscape Psychiatry.
"We also showed that the decreases in these markers were associated with the severity of inattention. In other words, the lower the concentration of these markers in these areas of the dopamine reward pathway, the more intense the symptoms of inattention," she added.
The study was published in the September 9 issue of JAMA.
Evaluating Biological Bases
ADHD is the most prevalent childhood psychiatric disorder that persists into adulthood, affecting about 3% to 5% of the US adult population, report the authors.
Evidence from previous brain imaging studies has shown that dopamine (a neurotransmitter essential for the normal functioning of the central nervous system) transmission is disrupted in some pathways of the brain in ADHD; these deficits may underlie core symptoms of inattention and impulsivity.
In addition, there is also increased awareness that patients with ADHD may have reward and motivation deficits, typically characterized by abnormal behavior change following conditions of reward and punishment.
After they hypothesized abnormalities in the mesoaccumbens dopamine pathway (composed of dopamine cells in the midbrain and their projections to the accumbens), the investigators sought to evaluate biological bases that might underlie a reward/motivation deficit by imaging key components of this dopamine reward pathway in patients with ADHD.
Replication Required
For this study, Dr. Volkow and her team used positron emission tomography to measure both DAT and D2/D3 receptor markers in 53 nonmedicated adults with ADHD (mean age, 32 years; 51% men) and in 44 control participants without ADHD (mean age, 31 years; 68% men) between 2001 and 2009.
The investigators measured specific binding of positron emission tomography radioligands for DATs using [11C]cocaine, and for D2/D3 receptors using [11C]raclopride, quantified as binding potential (distribution volume ratio, −1). ADHD items were assessed using the Strengths and Weaknesses of ADHD-symptoms and Normal-behavior (SWAN) rating scale.
For both ligands, statistical parametric mapping at the end of the study showed that specific binding was lower for those with ADHD than in the control participants (threshold for significance set at P < .005) in regions of the dopamine reward pathway in the left side of the brain.
For the D2/D3 receptors, this included the ventral caudate, accumbens, and midbrain regions, as well as the hypothalamic region (HR).
"The fact that there was also a dopamine deficit in hypothalamic regions was surprising and not one we searched out," Dr. Volkow explained. "In the past, clinicians have noted that ADHD subjects are more likely to experience 3 symptoms that are consistent with hypothalamic pathology: obesity, sleep disturbances, and reactivity to stress. But this was a totally unexpected finding and not a priority hypothesis. Still, it is very preliminary and in need of replication."
DAT availability was also significantly lower in those with ADHD than those in the control group in the accumbens and midbrain region.
Dopamine Reward Pathway in ADHD
Left Hemisphere Controls ADHD 95% CI P Value
D2/D3 Receptors:
Accumbens 2.85 2.68 0.06 0.30 .004
Caudate 2.80 2.47 0.10 0.56 .005
Midbrain 0.28 0.18 0.02 0.17 .01
HR 0.12 0.04 0.02 0.12 .004
DAT:
Accumbens 0.71 0.63 0.03 0.13 .004
Midbrain 0.16 0.09 0.03 0.12 ≤.001In addition, the dimension of attention (from the SWAN test) was negatively correlated with D2/D3 in the accumbens region, midbrain, caudate, and hypothalamic regions and with DAT in the midbrain.
Ratings of Attention
r 95% CI P Value
D2/D3 Receptors:
Accumbens 0.35 0.15 0.52 .001
Midbrain 0.35 0.14 0.52 .001
Caudate 0.32 0.11 0.50 .003
HR 0.31 0.10 0.49 .003
DAT:
Midbrain 0.37 0.16 0.53 ≤.001ADHD Real Psychiatric Disorder
"The lower than normal D2/D3 receptor and DAT availability in the accumbens and midbrain regions supports the hypothesis of an impairment of the dopamine reward pathway in ADHD," write the study authors.
"Classically, ADHD has been thought of as a disorder where the main problem relates to the attention network," reported Dr. Volkow. "But in this imaging study, we are showing that the main deficit relates to reward pathways that are crucial for engaging attention networks. The primary deficit is not on the personal network but on the system that is required to engage it. For example, your car may work very well. But if you have no gasoline, you can not engage the engine."
She added that these findings support the need for interventions to enhance the saliency of school and work tasks to improve performance in those with ADHD.
In addition, there has been an enormous amount of conflict and debate about whether ADHD is really a disorder or just a behavioral disruption that emerges as a function of a poor education or curriculum. "By being able to clearly show biochemical and functional changes in the brain of individuals with ADHD, this study helps with the recognition of ADHD as a real psychiatric disorder," she added.
The next step for the investigative team is a study examining how genetics generate dopamine reward pathways. "We'll be asking how genetics affect the wiring of the brain, resulting in some people having these deficits and others not," Dr. Volkow concluded.
This study was supported in part by a grant from the Intramural Research Program of the National Institutes of Health and by the National Institute of Mental Health. The study authors have reported several financial relationships. The full list can be found at the end of the original article.
poster:Phillipa
thread:916581
URL: http://www.dr-bob.org/babble/20090902/msgs/916581.html