Neuroscience

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Posts tagged ADHD

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Ritalin Shows Promise in Treating Addiction

A single dose of a commonly-prescribed attention deficit hyperactivity disorder (ADHD) drug helps improve brain function in cocaine addiction, according to an imaging study conducted by researchers from the Icahn School of Medicine at Mount Sinai. Methylphenidate (brand name Ritalin®) modified connectivity in certain brain circuits that underlie self-control and craving among cocaine-addicted individuals. The research is published in the current issue of JAMA Psychiatry, a JAMA network publication.

Previous research has shown that oral methylphenidate improved brain function in cocaine users performing specific cognitive tasks such as ignoring emotionally distracting words and resolving a cognitive conflict. Similar to cocaine, methylphenidate increases dopamine (and norepinephrine) activity in the brain, but, administered orally, takes longer to reach peak effect, consistent with a lower potential for abuse. By extending dopamine’s action, the drug enhances signaling to improve several cognitive functions, including information processing and attention.

“Orally administered methylphenidate increases dopamine in the brain, similar to cocaine, but without the strong addictive properties,” said Rita Goldstein, PhD, Professor of Psychiatry at Mount Sinai, who led the research while at Brookhaven National Laboratory (BNL) in New York. “We wanted to determine whether such substitutive properties, which are helpful in other replacement therapies such as using nicotine gum instead of smoking cigarettes or methadone instead of heroin, would play a role in enhancing brain connectivity between regions of potential importance for intervention in cocaine addiction.”

Anna Konova, a doctoral candidate at Stony Brook University, who was first author on this manuscript, added, ”Using fMRI, we found that methylphenidate did indeed have a beneficial impact on the connectivity between several brain centers associated with addiction.”

Dr. Goldstein and her team recruited 18 cocaine addicted individuals, who were randomized to receive an oral dose of methylphenidate or placebo. The researchers used functional magnetic resonance imaging (fMRI) to measure the strength of connectivity in particular brain circuits known to play a role in addiction before and during peak drug effects. They also assessed each subject’s severity of addiction to see if this had any bearing on the results.

Methylphenidate decreased connectivity between areas of the brain that have been strongly implicated in the formation of habits, including compulsive drug seeking and craving. The scans also showed that methylphenidate strengthened connectivity between several brain regions involved in regulating emotions and exerting control over behaviors—connections previously reported to be disrupted in cocaine addiction.

“The benefits of methylphenidate were present after only one dose, indicating that this drug has significant potential as a treatment add-on for addiction to cocaine and possibly other stimulants,” said Dr. Goldstein. “This is a preliminary study, but the findings are exciting and warrant further exploration, particularly in conjunction with cognitive behavioral therapy or cognitive remediation.”

(Source: newswise.com)

Filed under ritalin addiction ADHD dopamine methylphenidate cocaine addiction neuroscience science

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Patience reaps rewards
Brain imaging shows how prolonged treatment of a behavioral disorder restores a normal response to rewards
Attention-deficit/hyperactivity disorder (ADHD) is characterized by abnormal behavioral traits such as inattention, impulsivity and hyperactivity. It is also associated with impaired processing of reward in the brain, meaning that patients need much greater rewards to become motivated. One of the common treatments for ADHD, methylphenidate (MPH), is known to improve reward processing in the short term, but the long-term effects have remained unclear.
Kei Mizuno from the RIKEN Center for Life Science Technologies, in collaboration with colleagues from several other Japanese research institutions, has now demonstrated that prolonged treatment with MPH brings about stable changes in brain activity that improve reward processing with a commensurate improvement in ADHD symptoms.
ADHD is thought to affect up to 5% of children worldwide, and about half of those will go on to experience symptoms of the disorder into adulthood. MPH treats the disorder by increasing the levels of the brain chemical dopamine, which is involved in reward processing.
To understand the effect of MPH on ADHD symptoms and specifically reward processing over the longer term, the researchers studied the reward response behavior of ADHD and healthy patients—all children or adolescents—before and after treatment with osmotic release oral system (OROS) MPH. They used functional magnetic resonance imaging (fMRI) to measure brain activity during a task that saw participants rewarded with payment, but in two different scenarios: a high and a low monetary reward condition.
“In the high monetary reward condition, participants earned higher than the expected reward; whereas in the low monetary condition, participants earned an average reward that was consistently lower than expected,” says Mizuno.
The brain images showed that before treatment with OROS-MPH, ADHD patients had lower than normal sensitivity to reward, as demonstrated by their abnormally low brain activity in two parts of the brain associated with reward processing—the nucleus accumbens and the thalamus—during testing under the low monetary reward scenario.
However, after three months of treatment with OROS-MPH, there was no difference in the activity of these brain areas in ADHD patients compared with the healthy controls under any of the reward conditions. Their sensitivity to reward had returned to normal, and the patients’ other ADHD symptoms also showed improvement.
Mizuno says that this study goes further than previous work. “We knew that acute MPH treatment improves reward processing in ADHD,” he explains. “Now we’ve revealed that decreased reward sensitivity and ADHD symptoms are improved by treatment for three months.”

Patience reaps rewards

Brain imaging shows how prolonged treatment of a behavioral disorder restores a normal response to rewards

Attention-deficit/hyperactivity disorder (ADHD) is characterized by abnormal behavioral traits such as inattention, impulsivity and hyperactivity. It is also associated with impaired processing of reward in the brain, meaning that patients need much greater rewards to become motivated. One of the common treatments for ADHD, methylphenidate (MPH), is known to improve reward processing in the short term, but the long-term effects have remained unclear.

Kei Mizuno from the RIKEN Center for Life Science Technologies, in collaboration with colleagues from several other Japanese research institutions, has now demonstrated that prolonged treatment with MPH brings about stable changes in brain activity that improve reward processing with a commensurate improvement in ADHD symptoms.

ADHD is thought to affect up to 5% of children worldwide, and about half of those will go on to experience symptoms of the disorder into adulthood. MPH treats the disorder by increasing the levels of the brain chemical dopamine, which is involved in reward processing.

To understand the effect of MPH on ADHD symptoms and specifically reward processing over the longer term, the researchers studied the reward response behavior of ADHD and healthy patients—all children or adolescents—before and after treatment with osmotic release oral system (OROS) MPH. They used functional magnetic resonance imaging (fMRI) to measure brain activity during a task that saw participants rewarded with payment, but in two different scenarios: a high and a low monetary reward condition.

“In the high monetary reward condition, participants earned higher than the expected reward; whereas in the low monetary condition, participants earned an average reward that was consistently lower than expected,” says Mizuno.

The brain images showed that before treatment with OROS-MPH, ADHD patients had lower than normal sensitivity to reward, as demonstrated by their abnormally low brain activity in two parts of the brain associated with reward processing—the nucleus accumbens and the thalamus—during testing under the low monetary reward scenario.

However, after three months of treatment with OROS-MPH, there was no difference in the activity of these brain areas in ADHD patients compared with the healthy controls under any of the reward conditions. Their sensitivity to reward had returned to normal, and the patients’ other ADHD symptoms also showed improvement.

Mizuno says that this study goes further than previous work. “We knew that acute MPH treatment improves reward processing in ADHD,” he explains. “Now we’ve revealed that decreased reward sensitivity and ADHD symptoms are improved by treatment for three months.”

Filed under brain activity fMRI ADHD methylphenidate dopamine osmotic release oral system neuroscience science

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Creativity Linked with Deficit in Mental Flexibility

Creative types are often seen as rather flaky — their minds leaping wildly from one bizarre idea to another, ever seeking inspiration. But a new study suggests that people who actually achieve creative success have minds that stubbornly cling to ideas, even to the point where it impairs their ability to shift focus.

In one experiment, researchers at Northwestern University in Illinois selected 34 students out of more than 300 who completed a questionnaire on creative achievement, ultimately including 19 who had outstanding achievements in music, art, science, writing or other areas and 15 of those whose scores ranked them as being among the least creative.

“We preselected people with very high and very low creative achievement,” says lead author Darya Zabelina, a graduate student at Northwestern. The research was published in Frontiers in Psychology.

During the study, participants had to shift their attention from a global level of processing to a local one, by focusing on different aspects of patterns. In some cases, they were asked to identify a large letter made up of smaller ones (for example, an “S” pattern made up of smaller “e’s”). In other instances, the correct answer was the opposite one — identifying the smaller letter.

“It’s a little counter-intuitive,” says Zabelina, “but people with high creativity actually perform badly on this test.” In fact, they made more than twice as many errors as the less creative group — and even after controlling for overall intelligence, the creative people still did less well.

A second experiment involved the same task, performed by another 39 high, moderate or low scorers in creative achievements. Again, the more creative people scored lower. And in both experiments, there was no difference in performance whether people had to shift from the “forest” focus of the larger letters to the “tree level” of the smaller ones or whether the shift was in the opposite direction. That suggests that the lower scores were not related to creative people being more focused specifically on either detail or on general patterns.

The research may help explain why autistic people, who tend to focus obsessively, can often be highly creative. Paradoxically, it may also help explain the link between attention deficit/hyperactivity disorder (ADHD) and creative success.

“The general idea is that [people with ADHD] are not able to focus on anything,” says Zabelina, “But really there are two different parts of the disorder, and one is that if they really get interested in something, they  become almost like autistic people: really focused, so much so that they are not able to practice anything else.” Indeed, between 30% and 50% of autistic people also have ADHD.

The combination of an ability to range widely from one thought to another and to focus when a good idea occurs may be the sweet spot for creative success. The trick is in the timing: to mind-wander enough when seeking ideas to hit on the best ones and then to zoom in and persist once the right solution has been found.

But the study makes clear that creative achievement may come with some trade-offs in mental flexibility, when the time comes to actually shift focus. Persistence certainly matters in creative achievement — but some creative folks may not know when to stop.

(Source: TIME)

Filed under creativity creative achievement ADHD divergent thinking psychology neuroscience science

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Research Shows How Ritalin Affects Brains of Kids With ADHD

Ritalin activates specific areas of the brain in children with attention-deficit/hyperactivity disorder (ADHD), mimicking the brain activity of children without the condition, a new review says.

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"This suggests that Ritalin does bring the brain [of a child with ADHD] back to the brain the typically developing kid has," said study author Constance Moore, associate director of the translational center for comparative neuroimaging at the University of Massachusetts Medical School.

Analyzing data from earlier studies that looked at how children’s brains were affected by doing certain tasks that are sometimes challenging for kids with ADHD, the researchers found that Ritalin (methylphenidate) was having a visible impact on three areas of the brain known to be associated with ADHD: the cortex, the cerebellum and the basal ganglia.

The study could be helpful in diagnosing and treating children with ADHD, Moore said. “It may be helpful to know that in certain children, Ritalin is having a physiological effect in the areas of the brain involved with attention and impulse control,” she said.

The research was published recently in the Harvard Review of Psychiatry.

Nine studies analyzed by the researchers used functional MRI to evaluate brain changes after children had taken a single dose of Ritalin. The children were involved in different types of tasks that tested their ability to focus and inhibit an impulse to act.

For example, to observe the brain’s reaction during a test of what is called “inhibitory control,” a child was told that every time he saw a zero show up on a screen, he should push the button on the right; every time he saw an X appear, he should push the left button. The children would then be asked to flip their responses, pushing the left button when they saw a zero.

"That’s hard to do," Moore said, "because you’ve developed the habit [of pushing the other button], so you have to suppress your impulse. If you do 20 zeros and keep pressing and then you see an X, most kids with ADHD will hit the wrong button."

In three out of five of the inhibitory control studies, Ritalin at least partially normalized brain activation in ADHD children.

To note how the brain reacted to a selective attention test, Moore said, children would first be asked, for example, what word they were seeing. The word would be “red,” and the color of the type also would be red. Then they would be shown the word “red,” but the color of the type would be green. In several studies, Ritalin affected activation in the frontal lobes during such inhibitory control tasks.

Most of the studies included in the review were performed in the United States or the United Kingdom. The majority of participants were adolescent boys, and all studies compared their results to healthy children of the same approximate age.

Because none of the studies looked at the correlation between ADHD symptoms and whether the child was taking Ritalin, there is no way to link the changes in brain activation with clinical improvement, Moore said. “It’s possible that kids who are not responsive to Ritalin may have brain changes too,” she said.

ADHD affects between 3 percent and 7 percent of school-aged children in the United States, according to the American Psychiatric Association. Boys are more likely to have ADHD than girls.

One expert was not surprised by the results.

"The review article shows there is a consensus of well-designed imaging studies showing that [Ritalin] has an impact on the frontal cortex of the brain, where we have long believed these patients have issues," said Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at the Steven & Alexandra Cohen Children’s Medical Center of New York, in New Hyde Park. Adesman wondered if Ritalin may play a role in helping the brain mature.

"Their data provides partial support for that," he said. "But if anything, the medicine seems to help the brain look more normal and doesn’t seem to do anything bad to it."

(Source: consumer.healthday.com)

Filed under ADHD ritalin brain activity neuroimaging methylphenidate cortex neuroscience science

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Sleep Promotes Consolidation of Emotional Memory in Healthy Children but Not in Children with Attention-Deficit Hyperactivity Disorder 
Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline–corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD.

Sleep Promotes Consolidation of Emotional Memory in Healthy Children but Not in Children with Attention-Deficit Hyperactivity Disorder

Fronto-limbic brain activity during sleep is believed to support the consolidation of emotional memories in healthy adults. Attention deficit-hyperactivity disorder (ADHD) is accompanied by emotional deficits coincidently caused by dysfunctional interplay of fronto-limbic circuits. This study aimed to examine the role of sleep in the consolidation of emotional memory in ADHD in the context of healthy development. 16 children with ADHD, 16 healthy children, and 20 healthy adults participated in this study. Participants completed an emotional picture recognition paradigm in sleep and wake control conditions. Each condition had an immediate (baseline) and delayed (target) retrieval session. The emotional memory bias was baseline–corrected, and groups were compared in terms of sleep-dependent memory consolidation (sleep vs. wake). We observed an increased sleep-dependent emotional memory bias in healthy children compared to children with ADHD and healthy adults. Frontal oscillatory EEG activity (slow oscillations, theta) during sleep correlated negatively with emotional memory performance in children with ADHD. When combining data of healthy children and adults, correlation coefficients were positive and differed from those in children with ADHD. Since children displayed a higher frontal EEG activity than adults these data indicate a decline in sleep-related consolidation of emotional memory in healthy development. In addition, it is suggested that deficits in sleep-related selection between emotional and non-emotional memories in ADHD exacerbate emotional problems during daytime as they are often reported in ADHD.

Filed under brain activity ADHD emotional memory memory consolidation neuroscience science

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First Long-Term Study Reveals Link Between Childhood ADHD and Obesity

A new study conducted by researchers at the Child Study Center at NYU Langone Medical Center found men diagnosed as children with attention-deficit/hyperactivity disorder (ADHD) were twice as likely to be obese in a 33-year follow-up study compared to men who were not diagnosed with the condition. The study appears in the May 20 online edition of Pediatrics.

“Few studies have focused on long-term outcomes for patients diagnosed with ADHD in childhood. In this study, we wanted to assess the health outcomes of children diagnosed with ADHD, focusing on obesity rates and Body Mass Index,” said lead author Francisco Xavier Castellanos, MD, Brooke and Daniel Neidich Professor of Child and Adolescent Psychiatry, Child Study Center at NYU Langone. “Our results found that even when you control for other factors often associated with increased obesity rates such as socioeconomic status, men diagnosed with ADHD were at a significantly higher risk to suffer from high BMI and obesity as adults.”

According to the Centers for Disease Control and Prevention, ADHD is one of the most common neurobehavioral disorders, often diagnosed in childhood and lasting into adulthood. People with ADHD typically have trouble paying attention, controlling impulsive behaviors and tend to be overly active. ADHD has an estimated worldwide prevalence of five percent, with men more likely to be diagnosed than women.

The prospective study included 207 white men diagnosed with ADHD at an average age of 8 and a comparison group of 178 men not diagnosed with childhood ADHD, who were matched for race, age, residence and social class. The average age at follow up was 41 years old. The study was designed to compare Body Mass Index (BMI) and obesity rates in grown men with and without childhood ADHD.

Results showed that, on average, men with childhood ADHD had significantly higher BMI (30.1 vs. 27.6) and obesity rates (41.1 percent vs. 21.6 percent) than men without childhood ADHD.

“The results of the study are concerning but not surprising to those who treat patients with ADHD. Lack of impulse control and poor planning skills are symptoms often associated with the condition and can lead to poor food choices and irregular eating habits,” noted Dr. Castellanos. “This study emphasizes that children diagnosed with ADHD need to be monitored for long-term risk of obesity and taught healthy eating habits as they become teenagers and adults.”

(Source: communications.med.nyu.edu)

Filed under ADHD obesity childhood body mass index adults neuroscience science

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Neurobiology of Attention Deficit/Hyperactivity Disorder
Attention deficit/hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder, has been associated with various structural and functional CNS abnormalities but findings about neurobiological mechanisms linking genes to brain phenotypes are just beginning to emerge. Despite the high heritability of the disorder and its main symptom dimensions, common individual genetic variants are likely to account for a small proportion of the phenotype’s variance. Recent findings have drawn attention to the involvement of rare genetic variants in the pathophysiology of ADHD, some being shared with other neurodevelopmental disorders. Traditionally, neurobiological research on ADHD has focused on catecholaminergic pathways, the main target of pharmacological treatments. However, more distal and basic neuronal processes in relation with cell architecture and function might also play a role, possibly accounting for the coexistence of both diffuse and specific alterations of brain structure and activation patterns. This article aims to provide an overview of recent findings in the rapidly evolving field of ADHD neurobiology with a focus on novel strategies regarding pathophysiological analyses.

Neurobiology of Attention Deficit/Hyperactivity Disorder

Attention deficit/hyperactivity disorder (ADHD), a prevalent neurodevelopmental disorder, has been associated with various structural and functional CNS abnormalities but findings about neurobiological mechanisms linking genes to brain phenotypes are just beginning to emerge. Despite the high heritability of the disorder and its main symptom dimensions, common individual genetic variants are likely to account for a small proportion of the phenotype’s variance. Recent findings have drawn attention to the involvement of rare genetic variants in the pathophysiology of ADHD, some being shared with other neurodevelopmental disorders. Traditionally, neurobiological research on ADHD has focused on catecholaminergic pathways, the main target of pharmacological treatments. However, more distal and basic neuronal processes in relation with cell architecture and function might also play a role, possibly accounting for the coexistence of both diffuse and specific alterations of brain structure and activation patterns. This article aims to provide an overview of recent findings in the rapidly evolving field of ADHD neurobiology with a focus on novel strategies regarding pathophysiological analyses.

Filed under neurodevelopmental disorders ADHD neurobiology genetics neuroscience science

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Is there a link between childhood obesity and ADHD, learning disabilities?

A University of Illinois study has established a possible link between high-fat diets and such childhood brain-based conditions as attention deficit hyperactivity disorder (ADHD) and memory-dependent learning disabilities.

“We found that a high-fat diet rapidly affected dopamine metabolism in the brains of juvenile mice, triggering anxious behaviors and learning deficiencies. Interestingly, when methylphenidate (Ritalin) was administered, the learning and memory problems went away,” said Gregory Freund, a professor in the U of I College of Medicine and a member of the university’s Division of Nutritional Sciences.

The research was published in Psychoneuroendocrinology.

Freund said that altered dopamine signaling in the brain is common to both ADHD and the overweight or obese state. “And an increase in the number of dopamine metabolites is associated with anxiety behaviors in children,” he added.

Intrigued by the recent upsurge in both child obesity and adverse childhood psychological conditions, including impulsivity, depression, and ADHD, Freund’s team examined the short-term effects of a high-fat (60% calories from fat) versus a low-fat (10% calories from fat) diet on the behavior of two groups of four-week-old mice. A typical Western diet contains from 35 to 45 percent fat, he said.

“After only one week of the high-fat diet, even before we were able to see any weight gain, the behavior of the mice in the first group began to change,” he said.

Evidence of anxiety included increased burrowing and wheel running as well a reluctance to explore open spaces. The mice also developed learning and memory deficits, including decreased ability to negotiate a maze and impaired object recognition.

Switching mice from a high-fat to a low-fat diet restored memory in one week, he noted.

In mice that continued on the high-fat diet, impaired object recognition remained three weeks after the onset of symptoms. But Freund knows from other studies that brain biochemistry normalizes after 10 weeks as the body appears to compensate for the diet. At that point, brain dopamine has returned to normal, and mice have become obese and developed diabetes.

“Although the mice grow out of these anxious behaviors and learning deficiencies, the study suggests to me that a high-fat diet could trigger anxiety and memory disorders in a child who is genetically or environmentally susceptible to them,” he said.

Because the animals adapt to the high-fat fare, the scientists also hypothesized that abruptly removing fat from the diet might negatively affect anxiety, learning, and memory.

The researchers had expected that the high-fat diet would stimulate inflammation, which is associated with obesity, but they saw no evidence of an inflammatory response in the brain after one or three weeks on the high-fat regimen.

Instead, they saw evidence that a high-fat diet initiates chemical responses that are similar to the ones seen in addiction, with dopamine, the chemical important to the addict’s pleasurable experiences, increasing in the brain.

(Source: news.aces.illinois.edu)

Filed under brain obesity ADHD dopamine learning learning disabilities neuroscience science

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ADHD medication can slow growth in teenage boys

Adolescent boys with attention deficit hyperactivity disorder (ADHD) are more likely to be shorter and slimmer than their same-age peers, according to a new study published in the Medical Journal of Australia today.

Dr Alison Poulton from the University of Sydney and her coauthors investigated the influence of stimulant medication on the growth and physical development during puberty of adolescent boys with ADHD.

The study found that prolonged treatment for more than three years with stimulant medication was associated with a slower rate of physical development during puberty.

"Our findings suggest that stimulant medication delays the rate of maturation during puberty, including the timing of the peak growth rate, but not the onset of puberty," said Dr Poulton, from Sydney Medical School.

"To maintain an adequate rate of growth during puberty we recommend that boys on ADHD stimulant medication should take the lowest dose that adequately treats their ADHD," said Dr Poulton.

The researchers recruited 65 boys aged between 12 and 16 years who had ADHD and had been on stimulant medication for more than three years. Compared with boys without ADHD, boys aged between 12 and 14 years with ADHD had significantly lower weight and body mass index, and those aged between 14 and 16 years with ADHD had significantly lower height and weight.

There was no difference in pubertal development between boys with and those without ADHD aged between 12 and 14 years, but those aged between 14 and 16 years with ADHD showed significant delay.

The study also found there was a significant inverse relationship between the dose of stimulant medication and the growth rate among boys aged between 14 and 16 years with ADHD.

The authors found that boys who had taken stimulant medication for ADHD for a minimum of three years until 14 years of age showed slower weight gain but comparable height and physical development related to puberty to boys of the same age without ADHD.

However, boys aged between 14 and 16 years with ADHD were significantly behind their peers in height and pubertal development.

(Source: sydney.edu.au)

Filed under maturation stimulant medication ADHD pubertal development science

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A DNA chip is developed to diagnose attention deficit hyperactivity disorder

Attention Deficit Hyperactivity Disorder (ADHD) is the most common childhood neuropsychiatric disorder. Yet there is currently no tool that will confirm the diagnosis of ADHD. In her thesis entitled “Development of a genotyping system to be applied in Attention Deficit Hyperactivity Disorder and its Pharmacogenetics” (“Desarrollo de un sistema de genotipado para la aplicación en el ‘trastorno por déficit de atención con hiperactividad’ y su farmacogenética”), the researcher Alaitz Molano, a graduate in biochemistry and PhD holder in Pharmacology from the UPV/EHU-University of the Basque Country, presents a tool that could improve not only the diagnosis of but also the therapeutics for this disorder.

The prevalence of ADHD is between 8% and 12% among the infant-adolescent population worldwide, and 50% continue with the symptoms into adult life. Children with ADHD have difficulty paying attention, do not complete the tasks they have been assigned and are frequently distracted. They may also display impulsive behaviour and excessive, inappropriate activity in the context they find themselves in, and experience great difficulty restraining their impulses. “All these symptoms seriously affect the social, academic and working life of the individuals, and impact greatly upon their families and milieu close to them,” says Molano.

In view of the problems existing in diagnosing ADHD patients and deciding about their treatment, this PhD thesis set out to develop and clinically validate a genotyping tool that could help to confirm the diagnosis, to predict how it will evolve, and to select the most suitable pharmacological treatment in each case.

Molano studied how genetic polymorphisms (variations in the DNA sequence between different individuals) are associated with ADHD. “We looked for all the associations that had been described previously in the literature worldwide, and did a clinical study to see whether these polymorphisms also occurred in the Spanish population; the reason is that genetic associations vary a lot between some populations and others.”

About 400 saliva samples of patients with ADHD and a further 400 samples from healthy controls without a history of psychiatric diseases were analysed. And the use of over 250 polymorphisms led to the discovery of 32 polymorphisms associated not only with the diagnosis of ADHD but also with the evolution of the disorder, with the ADHD subtype, the symptomatological severity and the presence of comorbidities.

On the basis of these results, Molano is proposing a DNA chip with these 32 polymorphisms, which could be updated with new polymorphisms, as a tool not only for diagnosing but also for calculating genetic susceptibility to different variables (responding well to drugs, normalisation of symptoms, etc.).

The study has also confirmed the existence of the 3 ADHD subtypes: lack of attention, hyperactivity, and a combination. “It can be seen that on the basis of genetics the children that belong to one subtype or another are different,” explains Molano.

By contrast, no direct associations were found between the polymorphisms analysed and the response to pharmacological treatment (atomoxetine and methylphenidate). Molano believes that this could be due to the fact that “in many cases the data on drugs we had available were not rigorous,” due to the difficulty in collecting data of this kind. Molano will in fact be pursuing her research along this line: “We want to concentrate on the drug response aspect, obtain more, better characterised samples, and monitor the variables in the taking of drugs very closely, whether they were actually being taken or not, etc.”

Molano hopes that this tool will reach the clinics: “The project was funded by Progenika Biopharma and the pharmaceutical company JUSTE SAFQ, but we also have another 10 collaborating clinics belonging to public and private centres in Spain, and it’s tricky getting them all to agree on matters like patents, marketing, etc. But our idea is that it should eventually be marketed and be welcomed.”

(Source: basqueresearch.com)

Filed under ADHD neuropsychiatric disorders diagnosis tool DNA chip science

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