̽��ֱ�� of Cambridge - ADHD

One in two children with ADHD experience emotional problems, study finds

cjb250 — Wed, 22 May 2024 08:00:15 +0000

In research published in Nature Mental Health, the team found that as many as one in two children with ADHD show signs of emotional dysregulation, and that Ritalin – the commonly-prescribed drug to help the condition – appears to be less effective at treating this symptom.

ADHD affects around one in 14 young people under the age of 18 and in around half of these cases it persists into adulthood. ̽��ֱ��condition causes problems including hyperactivity, impulsivity and a difficulty to focus attention.

It has become increasingly clear that some people with ADHD also have self-control problems, affecting their ability to regulate emotions. For example, one in 50 (2.1%) children with a diagnosis of ADHD also have a mood disorder, such as depression, while more than one in four (27.4%) have an anxiety disorder. Many also have verbal or physical outbursts due to an inability to regulate their emotions.

These problems were thought to be a result of other symptoms associated with ADHD, such as problems with cognition and motivation. But today’s study shows that emotional dysregulation occurs independently of these.

̽��ֱ��researchers examined data from the ABCD Study, a large longitudinal cohort that tracks the brain development and mental health of children from across the United States. Data on ADHD symptoms was available for just over 6,000 of these children, allowing the researchers to attribute a score to each individual indicating their likelihood of having ADHD.

A team of scientists from Fudan ̽��ֱ�� in Shanghai, China, and the ̽��ֱ�� of Cambridge identified 350 individuals within the cohort who had high symptom scores that met the clinical cut-off for ADHD. Two-thirds (65.7%) of these were male.

Parents or guardians of the children and adolescents in the cohort had previously completed a series of questionnaires, which included questions that related to emotional behaviour, for example:

When my child is upset, he/she has difficulty controlling his/her behaviours.

When my child is upset, he/she knows that he/she can find a way to eventually feel better.

When my child is upset, he/she starts to feel very bad about him/herself.

̽��ֱ��researchers found that half (51.4%) of the individuals in the high-symptom group showed signs of emotion dysregulation and this was independent of cognitive and motivational problems.

Among children with only low-ADHD symptoms at both ages 12 and 13 years, those with a high scores of emotion dysregulation at age 13 years were 2.85 times more likely to have developed high-ADHD symptoms by age 14 years compared with those with a low score of emotion dysregulation.

When the researchers examined brain imaging data available for some of the participants, they discovered a particular region of the brain known as the pars orbitalis that was smaller among children who scored highly for ADHD and emotional problems. ̽��ֱ��pars orbitalis is at the front of the brain and plays an important role in understanding and processing of emotion and communication as well as inhibitory control over behaviour, which may explain some of the behaviours seen in ADHD.

Professor Barbara Sahakian from the Department of Psychiatry at the ̽��ֱ�� of Cambridge and a Fellow of Clare Hall said: “ ̽��ֱ��pars orbitalis is a well-connected part of the brain, and if it hasn’t developed properly it might make it difficult for individuals to control their emotions and communicate with others appropriately, especially in social situations.

“Parents and teachers often say they have problems controlling children with ADHD, and it could be that when the children can’t express themselves well – when they hit emotional difficulties – they may not be able to control their emotions and have an outburst rather than communicating with the parent, teacher or the other child.”

Professor Sahakian hopes that acknowledging emotion dysregulation as a key part of ADHD will help people better understand the problems the child is experiencing. This could lead to using effective treatments for regulation of emotion, such as cognitive behavioural therapy.

̽��ֱ��findings may also point to potential ways to help the child manage their emotions, for example by using cognitive behavioural techniques to learn to stop and think before they react and to express their feelings verbally, or use techniques such as exercise or relaxation to calm themselves or alleviate symptoms of depression and anxiety.

This may be particularly important as the researchers found that Ritalin, the drug used to help manage ADHD symptoms, does not appear to fully treat symptoms of emotion dysregulation. Identifying the problem earlier would allow for alternative, more effective interventions to help the child better manage their emotions, potentially helping the individual in adulthood.

Professor Qiang Luo from Fudan ̽��ֱ�� and a Life Member at Clare Hall, Cambridge, said: “If you're having trouble controlling your emotions, this can lead to problems with social interactions, which further exacerbates any depression or anxiety that you might have. It also might mean that you're saying things or doing things that exacerbate a situation rather than calming it down. Teaching vulnerable individuals from an early age how to manage your emotions and express yourself could help them overcome such problems further down the line.”

While it is not clear exactly what causes these problems in the first place, the researchers found signs of a link to possible dysfunction of the immune system, with individuals who exhibited signs of emotion dysregulation showing higher percentages of certain types of immune cell.

Professor Sahakian added: “We already know that problems with the immune system can be linked to depression, and we’ve seen similar patterns in individuals with ADHD who experience emotion dysregulation.”

̽��ֱ��research was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Program of Shanghai Academic Research Leader and the Shanghai Municipal Science and Technology Major Project.

Reference
Hou, W et al. Emotion dysregulation and right pars orbitalis constitute a neuropsychological pathway to attention deficit hyperactivity disorder. Nature Mental Health; 13 May 2024: DOI: 10.1038/s44220-024-00251-z

Cambridge scientists have shown that problems regulating emotions – which can manifest as depression, anxiety and explosive outbursts – may be a core symptom of attention deficit hyperactivity disorder (ADHD).

When the children can’t express themselves well – when they hit emotional difficulties – they may not be able to control their emotions and have an outburst rather than communicating

Barbara Sahakian

Constantinis (Getty Images)

Teenage boys fighting on way to school

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Children with rare genetic disorders more likely to be diagnosed with developmental, behavioural and mental health problems

cjb250 — Wed, 03 Aug 2022 22:30:47 +0000

With the advent of rapid whole genome sequencing, children presenting with an intellectual disability or developmental delay are recommended to have their DNA sequenced to identify the underlying genetic cause.

To capitalise on this recent NHS development, researchers at the ̽��ֱ�� of Cambridge, ̽��ֱ�� College London and Cardiff ̽��ֱ�� established IMAGINE ID, a national UK cohort study that aims to discover how genetic changes affect children and young people’s behaviour, in order to inform better care of families and children now and in the future.

Writing in ̽��ֱ��Lancet Psychiatry today, the researchers have published the results of an analysis of data from almost 2,800 young people with rare genomic variants – changes to their DNA – that are associated with intellectual disability.

Professor Lucy Raymond from the ̽��ֱ�� of Cambridge, the study’s senior author, said: “Thanks to all the families that have taken part in our research, we’ve been able to conduct the largest study to date of the impact of rare genetic variants associated with intellectual disability. What we’ve found from parents is that these children are extremely likely to develop other neurodevelopmental or mental health conditions, which can present additional challenges both to the children and their families.”

All the participants were aged between four and 19 years. Just under three-quarters (74%) had an intellectual disability caused by a duplication or deletion of sections of DNA – a so-called copy number variant (CNV). ̽��ֱ��remaining young people had a disability caused by a single ‘spelling error’ in their DNA – a change in the A, C, G or T nucleotides – referred to as a single nucleotide variant (SNV).

Compared to the English national population, children in the study were almost 30 times as likely to have been diagnosed as autistic. In the general population, 1.2% of people are diagnosed with the condition compared to 36% of the study participants. Similarly, 22% of the study population were diagnosed with ADHD, compared to 1.6% of the general population, meaning that they were more than 13 times more likely to have the condition.

Around one in eight children (12%) had been diagnosed with oppositional defiant disorder, in which children are uncooperative, defiant, and hostile toward others – a rate 4.4 times higher than in the general population.

One in ten (11%) had an anxiety disorder, a 1.5 times increased risk. Rates of childhood depression were significantly lower, at just 0.4% compared with 2.1% of the general population, but this may increase over the next few years as some mental health disorders do not start until later adolescence or early adult life. Almost all of the children (94%) were reported to have at least one significant physical health problem, including disturbed sleep (65%), motor or movement disorders (64%) or seizures (30%).

Dr Jeanne Wolstencroft from Great Ormond Street Institute of Child Health, ̽��ֱ�� College London, said: “Routine genomic testing now allows parents to understand the genetic cause of intellectual disabilities in an increasing number of children but, because so many of these conditions are rare, we still lack information on the impact this has on their children’s future mental health.

“We already know that intellectual disabilities tend to be associated with an increased likelihood of neurodevelopmental conditions, as well as emotional and behavioural difficulties, but we found that where there is an identifiable genetic cause, the likelihood is amplified considerably. This suggests that these children should be provided with early assessment and help where appropriate.”

̽��ֱ��team has also shown for the first time that children with intellectual disability caused by a genetic variant inherited from a family member, are more likely to come from a more deprived socioeconomic background. This suggests that some parents or family members with the same variant may also have unrecognised difficulties that placed them at a social and educational disadvantage. These children were more likely to be diagnosed with a neuropsychiatric condition and were also more likely to exhibit behavioural difficulties.

Professor David Skuse from Great Ormond Street Institute of Child Health, ̽��ֱ�� College London, said: “We hope this work helps improve the targeting of assessments and interventions to support families at the earliest opportunity. We’d like to see better training for health care providers about the wider use and utility of genetic testing. We have identified its potential value in terms of prioritising children with mental health needs for child mental health services, who are currently hugely limited in the UK.”

̽��ֱ��research was funded by the Medical Research Council (part of UK Research & Innovation) and the Medical Research Foundation. Additional support was provided by the NIHR Cambridge Biomedical Resource Centre and the NIHR GOSH BRC.

Reference
Wolstencroft, J et al. Neuropsychiatric risk in children with intellectual disability of genetic origin: IMAGINE - ̽��ֱ��UK National Cohort Study. Lancet Psychiatry; 4 Aug 2022; DOI: 10.1016/PIIS2215-0366(22)00207-3

A major study of children with intellectual disabilities has highlighted the additional challenges that they often face, including a much-increased likelihood of being diagnosed as autistic, as well as Attention Deficit Hyperactivity Disorder (ADHD) and other mental health difficulties.

Thanks to all the families that have taken part in our research, we’ve been able to conduct the largest study to date of the impact of rare genetic variants associated with intellectual disability

Lucy Raymond

PhotoAlto/Laurence Mouton (Getty Images)

Toddler's hands touching tree bark

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Learning difficulties due to poor connectivity, not specific brain regions, study shows

cjb250 — Thu, 27 Feb 2020 16:00:25 +0000

Between 14-30% of children and adolescents worldwide have learning difficulties severe enough to require additional support. These difficulties are often associated with cognitive and/or behavioural problems. In some cases, children who are struggling at school receive a formal diagnosis of a specific learning difficulty or disability, such as dyslexia, dyscalculia or developmental language disorder, or of a developmental disorder such as attention deficit and hyperactivity disorder (ADHD), dyspraxia, or autism spectrum disorder.

Scientists have struggled to identify specific areas of the brain that might give rise to these difficulties, with studies implicating myriad brain regions. ADHD, for example, has been linked to the anterior cingulate cortex, caudate nucleus, pallidum, striatum, cerebellum, prefrontal cortex, the premotor cortex and most parts of the parietal lobe.

One potential explanation is that each diagnosis differs so much between one individual and the next, that each involves different combinations of brain regions. However, a more provocative explanation has been proposed by a team of scientists at the MRC Cognition and Brain Sciences Unit, ̽��ֱ�� of Cambridge: there are, in fact, no specific brain areas that cause these difficulties.

To test their hypothesis, the researchers used machine learning to map the brain differences across a group of almost 479 children, 337 of whom had been referred with learning-related cognitive problems and 142 from a comparison sample. ̽��ֱ��algorithm interpreted data taken from a large battery of cognitive, learning, and behavioural measures, as well as from brain scans taken using magnetic resonance imaging (MRI). ̽��ֱ��results are published today in Current Biology.

̽��ֱ��researchers found that the brain differences did not map onto any labels the children had been given – in other words, there were no brain regions that predicted having ASD or ADHD, for example. More surprisingly, they found that the different brain regions did not even predict specific cognitive difficulties – there was no specific brain deficit for language problems or memory difficulties, for example.

Instead, the team found that the children’s brains were organised around hubs, like an efficient traffic system or social network. Children who had well-connected brain hubs had either very specific cognitive difficulties, such as poor listening skills, or had no cognitive difficulties at all. By contrast, children with poorly connected hubs – like a train station with few or poor connections – had widespread and severe cognitive problems.

“Scientists have argued for decades that there are specific brain regions that predict having a particular learning disorder or difficulty, but we’ve shown that this isn’t the case,” said Dr Duncan Astle, senior author on the study. “In fact, it’s much more important to consider how these brain areas are connected – specifically, whether they are connected via hubs. ̽��ֱ��severity of learning difficulties was strongly associated with the connectedness of these hubs, we think because these hubs play a key role in sharing information between brain areas.”

Dr Astle said that one implication of their work is that it suggests that interventions should be less reliant on diagnostic labels.

“Receiving a diagnosis is important for families. It can give professional recognition for a child’s difficulties and open the door to specialist support. But in terms of specific interventions, for example from the child’s teachers, they can be a distraction.

“It’s better to look at their areas of cognitive difficulties and how these can be supported, for example using specific interventions to improve listening skills or language competencies, or at interventions that would be good for the whole class, like how to how to reduce working memory demands during learning.”

̽��ֱ��findings may explain why drugs treatments have not proven effective for developmental disorders. Methylphenidate (Ritalin), for example, which is used to treat ADHD, appears to reduce hyperactivity, but does not remediate cognitive difficulties or improve educational progress. Drugs tend to target specific types of nerve cells, but would have little impact on a ‘hub-based’ organisation that has emerged over many years.

While this is the first time that hubs and their connections have been shown to play a key role in learning difficulties and developmental disorders, their importance in brain disorders is becoming increasingly clear in recent years. Cambridge researchers have previously shown that they also play an important role in mental health disorders that begin to emerge during adolescence, such as schizophrenia.

̽��ֱ��study was funded by the Medical Research Council.

Reference
Siugzdaite, R et al. Transdiagnostic brain mapping in developmental disorders. Current Biology; 27 Feb 2020; DOI: 10.1016/j.cub.2020.01.078

Different learning difficulties do not correspond to specific regions of the brain, as previously thought, say researchers at the ̽��ֱ�� of Cambridge. Instead poor connectivity between ‘hubs’ within the brain is much more strongly related to children’s difficulties.

Roma Siugzdaite

Brain map showing examples of networks and hubs

Researcher profile: Dr Roma Siugzdaite

Matematika – tai proto gimnastika

Dr Roma Siugzdaite describes her mother, Marijona Siugzdiene, as the best maths teacher in her school in Kaisiadorys, Lithuania. This phrase was written on the wall in her classroom: it means ‘Mathematics is a gymnastics to your mind’.

“Looking back, it seems like it was my destiny written on that wall,” says Roma. “My background studies in mathematics brought me to study the brains and minds of children and people with certain diseases and disorders.”

Nowadays, Roma is based at the MRC Cognition and Brain Sciences Unit at Cambridge, which means she can impress people at parties by describing herself as a brain scientist. “I am fascinated by the complexity of the brain,” she says.

Her research is aimed at helping children to overcome learning difficulties, but to achieve this she must first understand what happens in the brains of these children.

“Every time I have a hypothesis I need to get some data to test it, whether that’s by old-fashioned, pen and paper tests, using iPads or – as it mostly is – using magnetic resonance imaging (MRI). That’s when the fun part begins – data analysis. I love it: it feels like searching for an order in a chaos.”

Fortunately, Cambridge is the ideal place to be doing research on children with learning difficulties, Roma says, in part because of the huge dataset held by the Centre for Attention, Learning and Memory (CALM) at her Unit, but also because of the Unit’s expertise working with MRI data.

Outside of the Unit, Roma – together with her family – will most likely be seen playing basketball. “I’ve been playing basketball my whole life. My husband is a basketball coach and now my daughter is playing basketball, too. We love the game!”

Yes

Differences in brain structure and memory suggest adolescents may not ‘grow out of’ ADHD

cjb250 — Thu, 27 Aug 2015 10:37:33 +0000

̽��ֱ��findings, published today in the journal European Child Adolescent Psychiatry, suggest that aspects of ADHD may persist into adulthood, even when current diagnostic criteria fail to identify the disorder.

ADHD is a disorder characterised by short attention span, restlessness and impulsivity, and is usually diagnosed in childhood or adolescence. Estimates suggest that more than three in every 100 boys and just under one in every 100 girls has ADHD. Less is known about the extent to which the disorder persists into adulthood, with estimates suggesting that between 10-50% of children still have ADHD in adulthood. Diagnosis in adulthood is currently reliant on meeting symptom checklists (such as the American Psychiatric Association’s Diagnostic and Statistical Manual).

Some have speculated that as the brain develops in adulthood, children may grow out of ADHD, but until now there has been little rigorous evidence to support this. So far, most of the research that has followed up children and adolescents with ADHD into adulthood has focused on interview-based assessments, leaving questions of brain structure and function unanswered.

Now, researchers at Cambridge and Oulu have followed up 49 adolescents diagnosed with ADHD at age 16, to examine their brain structure and memory function in young adulthood, aged between 20-24 years old, compared to a control group of 34 young adults. ̽��ֱ��research was based within the Northern Finland Birth Cohort 1986, which has followed up thousands of children born in 1986 from gestation and birth into adulthood. ̽��ֱ��results showed that the group diagnosed in adolescence still had problems in terms of reduced brain volume and poorer memory function, irrespective of whether or not they still met diagnostic checklist criteria for ADHD.

By analysing the structural magnetic resonance imaging (MRI) brain scans and comparing them to the controls, the researchers found that the adolescents with ADHD had reduced grey matter in a region deep within the brain known as the caudate nucleus, a key brain region that integrates information across different parts of the brain, and supports important cognitive functions, including memory.

To investigate whether or not these grey matter deficits were of any importance, the researchers conducted a functional MRI experiment (fMRI), which measured brain activity whilst 21 of the individuals previously diagnosed with ADHD and 23 of the controls undertook a test of working memory inside the scanner.

One third of the adolescents with ADHD failed the memory test compared to less than one in twenty of the control group (an accuracy of less than 75% was classed as a fail). Even amongst the adolescent ADHD sample who passed the memory test, the scores were on average 6 percentage points less than controls. ̽��ֱ��poor memory scores seemed to relate to a lack of responsiveness in the activity of the caudate nucleus: in the controls, when the memory questions became more difficult, the caudate nucleus became more active, and this appeared to help the control group perform well; in the adolescent ADHD group, the caudate nucleus kept the same level of activity throughout the test.

There were no differences in brain structure or memory test scores between those young adults previously diagnosed with ADHD who still met the diagnostic criteria and those who no longer met them.

Dr Graham Murray from the Department of Psychiatry, ̽��ֱ�� of Cambridge, who led the study, says: “In the controls, when the test got harder, the caudate nucleus went up a gear in its activity, and this is likely to have helped solve the memory problems. But in the group with adolescent ADHD, this region of the brain is smaller and doesn’t seem to be able to respond to increasing memory demands, with the result that memory performance suffers.

“We know that good memory function supports a variety of other mental processes, and memory problems can certainly hold people back in terms of success in education and the workplace. ̽��ֱ��next step in our research will be to examine whether these differences in brain structure and memory function are linked to difficulties in everyday life, and, crucially, see if they respond to treatment.”

̽��ֱ��fact that the study was set in Finland, where medication is rarely used to treat ADHD, meant that only one of the 49 ADHD adolescents had been treated with medication. This meant the researchers could confidently rule out medication as a confounding factor.

To date, ‘recovery’ in ADHD has focused on whether people do or do not continue to meet symptom checklist criteria for diagnosis. However, this research indicates that objective measures of brain structure and function may continue to be abnormal even if diagnostic criteria are no longer met. ̽��ֱ��results therefore emphasize the importance of taking a wider perspective on ADHD outcomes than simply whether or not a particular patient meets diagnostic criteria at any given point in time.

̽��ֱ��research was funded in part by the Medical Research Council, with additional support from the Wellcome Trust and the NIHR Cambridge Biomedical Research Centre.

Reference
Roman-Urrestarazu, A et al. Brain structural deficits and working memory fMRI dysfunction in young adults who were diagnosed with ADHD in adolescence. European Child Adolescent Psychiatry; 27 Aug 2015

Young adults diagnosed with attention deficit/hyperactivity disorder (ADHD) in adolescence show differences in brain structure and perform poorly in memory tests compared to their peers, according to new research from the ̽��ֱ�� of Cambridge, UK, and the ̽��ֱ�� of Oulu, Finland.

Good memory function supports a variety of other mental processes, and memory problems can certainly hold people back in terms of success in education and the workplace

Graham Murray

mararie

ADHD

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Imaging study shows dopamine dysfunction is not the main cause of Attention Deficit Hyperactivity Disorder (ADHD)

gm349 — Mon, 28 Oct 2013 11:38:27 +0000

A new Cambridge study questions previous suggestions that attention deficit hyperactivity disorder (ADHD) is the result of fundamental abnormalities in dopamine transmission, and suggests that the main cause of the disorder may lie instead in structural differences in the grey matter in the brain. This landmark study, published in Brain, could significantly improve understanding of how ADHD is caused and help inform the development of treatments in the future.

̽��ֱ��double-blind study, which was carried out by researchers at the ̽��ֱ�� of Cambridge MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute (BCNI) and funded by the Medical Research Council (MRC), found that administering methylphenidate (more commonly known as Ritalin) to healthy adult volunteers as well as those who exhibit symptoms of ADHD as adults, led to similar increases of the chemical dopamine in their brain. Both groups also had equivalent level of improvements as a result of the drug when tested on their ability to concentrate and pay attention.

Dopamine is a crucial chemical for concentration or sustained attention, working memory and motivational processes in the brain and acting as a chemical transmitter between brain cells by combining with specialised receptors on nerve cells. Ritalin works by increasing the levels of dopamine which binds to the receptors and increases the flow of communication between these cells.

By using positron emission tomography (PET) imaging techniques to measure dopamine receptors, the researchers were able to measure how Ritalin affects dopamine in patients with ADHD and people unaffected by the condition. In both groups, volunteers were given either a dose of Ritalin or a placebo pill. Researchers then analysed the results of tasks done by the volunteers which tested their ability to concentrate and pay attention over a period of time.

Patients with ADHD, who had significant loss of grey matter in the brain, as measured by magnetic resonance imaging, showed significant impairments in attentional performance compared with healthy individuals. Consistent with its therapeutic use in ADHD, Ritalin improved sustained attention performance in the patients. However, dopamine receptor levels in an area of the brain called the striatum were similar in the patients and healthy individuals. Ritalin also increased dopamine levels in the striatum to a similar degree, importantly suggesting that there was no underlying deficiency in dopamine function in the ADHD patients. Interestingly, Ritalin also improved sustained attention performance in some healthy individuals as well, and this overall ability of the drug to improve performance (with or without ADHD) was related to the increases in dopamine levels in the striatum caused by Ritalin.

Professor Barbara Sahakian who led the study at the BCNI said: “We feel these results are extremely important since they show that people who have poor concentration improve with methylphenidate (Ritalin) treatment whether they have a diagnosis of adult ADHD or not. These new findings demonstrate that poor performers, including healthy volunteers, were helped by the treatment and this improvement was related to increases in dopamine in the brain.”

Professor Trevor Robbins, co-author of the study and Director of the BCNI, said: “These findings question the previously accepted view that major abnormalities in dopamine function are the main cause of ADHD in adult patients. While the results show that Ritalin has a 'therapeutic' effect to improve performance, it does not appear to be related to fundamental underlying impairments in the dopamine system in ADHD.”

Research suggests that the main cause of the disorder may lie instead in structural differences in the grey matter in the brain.

These findings question the previously accepted view that major abnormalities in dopamine function are the main cause of ADHD in adult patients.

Professor Trevor Robbins

̽��ֱ��journal Brain.

Cluster of greatest grey matter volume reduction in patients with ADHD compared with control subjects located in the left middle frontal gyrus, overlaid on a rendered standardized brain template.

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