Pain killer Paracetamol (Acetaminophen) use in pregnancy linked to ADHD

Acetaminophen, also known as Paracetamol in UK or Tylenol in US, a common pain reliever considered safe for pregnant women, has been linked for the first time to an increased risk of attention deficit and hyperactivity disorder in children, said a study, published Monday.

More studies are needed to confirm the findings, but experts said the research points to a new potential cause for the worldwide rise in cases of ADHD, a neuro-behavioural condition which has no known cause and affects as many as five percent of US children.

Women who took acetaminophen, also known as Paracetamol, while pregnant had a 37 percent higher risk of having a child who would be later given a hospital diagnosis of hyperkinetic disorder, a particularly severe form of ADHD, said the study in February 24 edition of the Journal of the American Medical Association (JAMA) Pediatrics: doi:10.1001/jamapediatrics.2013.4914.

Compared to women who did not take Acetaminophen while pregnant, women who did also had a 29 percent higher chance of having children who were later prescribed medications for attention deficit hyperactivity disorder, and a 13 percent higher chance of exhibiting ADHD-like behaviours by age seven.

Previous research has suggested that Acetaminophen can interfere with normal hormone function and may affect the developing fetal brain.

The painkiller has also been linked to a slightly increased risk in boys of cryptorchidism, a condition in which the testicles do not descend.

The latest research was based on survey data on more than 64,000 Danish women from 1996 to 2002.

More than half said they took Acetaminophen at least once during pregnancy.

Peer group experts cautioned that; 'The observational findings do not prove that taking Paracetamol or Tylenol-like pain relievers causes ADHD, only that a preliminary link between the two has appeared and would need to be confirmed by further research.'

Miriam Cooper

"Findings from this study should be interpreted cautiously and should not change practice," said an accompanying editorial in JAMA Pediatrics by Miriam Cooper and colleagues at the Cardiff University Institute of Psychological Medicine and Clinical Neurosciences.

"However, they underline the importance of not taking a drug's safety for granted, especially during pregnancy."

The reasons the women took the painkillers could have also had a confounding effect on the outcome, they added.

The study was led by Zeyan Liew, of the University of California, Los Angeles, and was co-authored by Jorn Olsen of the University of Aarhus in Denmark.

Chindren with Autism: EphB Link through Family Genes

Harvard Medical School researchers at McLean Hospital have found that a gene family linked to autism, EphB, is essential for proper brain wiring during development.

The findings suggest that the abnormal brain wiring that results from mutations in this gene family could contribute to autism symptoms.

"Using animal models, we were able to see that EphB is required for normal brain development. Mutations in EphB that compromise its function led to abnormal connections between key brain regions involved in processing of sensory information," said Christopher Cowan, HMS associate professor of psychiatry at McLean Hospital.

The findings were reported by McLean Hospital researchers and collaborators in the Proceedings of the National Academy of Sciences on Jan. 22, 2014.

Christopher Cowan

Recent genetic analysis had revealed an EphB gene as a new candidate risk factor for human autism, so investigators targeted the gene in animals to assess its role in the proper development of communication networks between the thalamus and the cortex, the regions of the brain responsible for processing information from the senses, such as touch and hearing.

"Some individuals with autism show abnormalities in sensory perception and processing, including touch, sound and vision," Cowan explained.

Investigators, from left: Yuhong Guo, Jesse Kumar, Laura Smith, Chris Cowan, Adam Harrington, Maria Carreira, Makoto Taniguchi and Rachel Penrod-Martin. 

Not pictured: Carly Hale and Mike Robichaux. 

Image: Patrick O'Connor.

"We found that EphB genes are essential for normal wiring of at least two key parts of the brain that process sensory information, particularly regions involved in touch and sound," Cowan said.

"Our findings suggest that defects in early brain wiring might underlie at least some of the sensory-associated symptoms found in individuals with autism spectrum disorders."

Future work, supported in part by the Simons Foundation Autism Research Initiative, seeks to extend these findings to better understand the relationship between EphB genes and the risk for developing autism.

Understanding the underlying causes of autism may help in the development of effective treatments.

More information: "EphB receptor forward signaling regulates area-specific reciprocal thalamic and cortical axon pathfinding." Robichaux MA, Chenaux G, Ho HY, Soskis MJ, Dravis C, Kwan KY, Sestan N, Greenberg ME, Henkemeyer M, Cowan CW. Proc Natl Acad Sci U.S.A.. 2014 Jan 22. 

Scientist find Gene linked to Asperger Syndrome and empathy

Scientists have confirmed that variations in a particular gene play a key role in the autism spectrum condition known as Asperger Syndrome.

They have also found that variations in the same gene are also linked to differences in empathy levels in the general population.

A study to be published later this month in the journal Molecular Autism confirms previous research that people with Asperger Syndrome (AS) are more likely to carry specific variations in a particular gene.

More strikingly, the study supports existing findings that the same gene is also linked to how much empathy typically shown by individuals in the general population.

The research was carried out by a team of researchers led by Professor Baron-Cohen at the Autism Research Centre at Cambridge University.

Asperger Syndrome is an autism spectrum condition. The researchers looked for sequence variations (called single nucleotide polymorphisms, SNPs) in the gene known as GABRB3 in a total of 530 adults - 118 people diagnosed with AS and 412 people without a diagnosis.

The team found that certain SNPs in GABRB3 were significantly more common in people with AS.

They also discovered that additional genetic variations in the same gene were linked to scores on an empathy measure called the Empathy Quotient in the general population.

AS is diagnosed when a person struggles with social relationships and communication, and shows unusually narrow interests and resistance to change, but has good intelligence and language skills.

Most genetic studies of autistic spectrum conditions treat autism as if they are all very similar, whereas in reality there is considerable variation (e.g., in language level and intellectual ability).

Rather than studying people on the autistic condition spectrum, this new study looked only people with AS, as a well-defined subgroup of individuals within this range.

The researchers examined the gene GABRB3 which regulates the functioning of a neurotransmitter called gamma-aminobutyric acid (GABA) and which contains a number of SNPs that vary across the population.

The volunteers were tested for 45 SNPs within this key gene. The team had previously found that SNPs in this gene were more common in adults with AS and also showed a relationship with empathy levels and tactile sensitivity (how sensitive people are to being touched) in the general population.

Testing a new sample of volunteers who had not taken part in previous studies, the researchers found that three of the SNPs were again more common in adults with AS, and two different SNPs in the same gene were again related to empathy levels in the general population, confirming that the gene is involved in autism spectrum conditions.

Professor Baron-Cohen said: "We are excited that this study confirms that variation in GABRB3 is linked not just to AS but to individual differences in empathy in the population.

Many candidate genes do not replicate across studies and across different samples, but this genetic finding seems to be a solid result.

Research now needs to focus on where this gene is expressed in the brain in autism, and how it interacts with other genetic and non-genetic factors that cause AS."

The team was co-led by Dr Bhismadev Chakrabarti from the Department of Psychology at Reading University. He commented: "Genes play an important role in autism and Asperger Syndrome."

"This new study adds to evidence that GABRB3 is a key gene underlying these conditions."

"This gene is involved in the functioning of a neurotransmitter that regulates excitation and inhibition of nerve cell activity so the research gives us vital additional information about how the brain may develop differently in people with Asperger Syndrome."

Varun Warrier, who carried out the study as part of his graduate research at Cambridge University, added: "The most important aspect of this research is that it points to common genetic variants in GABRB3 being involved in both AS and in empathy as a dimensional trait."

"Although GABRB3 is not the only gene to be involved in this condition and in empathy levels, we are confident that we have identified one of the key players."

"We are following this up by testing how much protein GABRB3 produces in the brain in autism, since a genetic finding of this kind becomes more explanatory when we can also measure its function."

More information: "Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism." Varun Warrier, Simon Baron-Cohen and Bhismadev Chakrabarti. Molecular Autism 2013, 4:48 DOI: 10.1186/2040-2392-4-48

Breaking the link between ADHD and addiction

Dr Melanie White

Adult sufferers of ADHD are two to three times more likely to experience substance abuse or dependence, but a research project which will map the genetic markers of the condition will help sever ties with addiction and could lead to customised treatments.

Dr Melanie White from QUT's Institute of Health and Biomedical Innovation (IHBI) said testing for specific genes associated with actions of the reward centre of the brain involving dopamine - a neurotransmitter which plays a major role in reward-motivated behaviour - would give a better understanding of how the brain works in those with ADHD (Attention Deficit Hyperactivity Disorder).

"I'm looking at genetic markers of symptoms of ADHD in adulthood as well as whether people have used a range of different types of substances, and the interaction between these genetic markers and aspects of the environment," Dr White said.

"Given ADHD medication is typically a stimulant, I'll be investigating whether it improves their symptoms in the short term and the role of this medication in future substance use or symptoms."

Dr White, who was awarded a Churchill Fellowship to progress her research, said most children diagnosed with the neurodevelopmental disorder carried it into adulthood.

While symptoms, which include restlessness in work and relationships and impulsivity, can be adapted to fit in with the demands of life, the link between ADHD and substance abuse is impossible to ignore.

"One theory is that people are using substances to redress the chemical imbalance in their brain, or that the reward centre and dopamine activity is wired differently in those with ADHD versus the rest of the population," Dr White said.

"However, the theory I'll be investigating is whether early stimulant medication use when the brain is still developing, results in the brain responding differently when exposed to substance use later in life.

"There are diagnostic differences in terms of whether your symptoms are predominantly inattentive or hyperactive-impulsive, but I have no doubt there are several different genes that might lead to susceptibility to substance abuse on top of the risk for these ADHD symptoms."

Dr White carried out research at the Federal University of Rio Grande do Sul in Brazil, which has studied the largest group of adults with ADHD in the world.

However, she is looking for expressions of interest from Australian adults with ADHD for future studies.

"Hopefully in the future, this type of information will enable us to make customised plans based on people's specific genetic profile amongst other characteristics, often called 'personalised medicine'," she said.

"We hope to be able to effectively say 'this medication would be more effective for you because of your genetic makeup', or conversely 'we don't believe this medication would be a good idea because it may increase some risks for you down the track'."

Soft Fizzy Drinks Linked to Obesity and Behavioural Problems in Children

Americans buy more soft drinks per capita than people in any other country. 

These drinks are consumed by individuals of all ages, including very young children. 

Image Credit: © sfmthd / Fotolia

Although soft drink consumption is associated with aggression, depression, and suicidal thoughts in adolescents, the relationship had not been evaluated in younger children.

A new study scheduled for publication in the Journal of Pediatrics finds that aggression, attention problems, and withdrawal behaviour are all associated with soft drink consumption in young children.

Shakira Suglia, ScD, and colleagues from Columbia University's Mailman School of Public Health, University of Vermont, and Harvard School of Public Health assessed approximately 3,000 5-year-old children enrolled in the Fragile Families and Child Wellbeing Study, a prospective birth cohort that follows mother-child pairs from 20 large U.S. cities.

Shakira Suglia

Mothers reported their child's soft drink consumption and completed the Child Behaviour Checklist based on their child's behaviour during the previous two months.

The researchers found that 43% of the children consumed at least 1 serving of soft drinks per day, and 4% consumed 4 or more.

Aggression, withdrawal, and attention problems were associated with soda consumption.

Even after adjusting for socio-demographic factors, maternal depression, intimate partner violence, and paternal incarceration, any soft drink consumption was associated with increased aggressive behavior.

Children who drank 4 or more soft drinks per day were more than twice as likely to destroy things belonging to others, get into fights, and physically attack people.

They also had increased attention problems and withdrawal behaviour compared with those who did not consume soft drinks.

According to Dr. Suglia, "We found that the child's aggressive behaviour score increased with every increase in soft drinks servings per day."

Although this study cannot identify the exact nature of the association between soft drink consumption and problem behaviors, limiting or eliminating a child's soft drink consumption may reduce behavioural problems.

Journal Reference: Shakira F. Suglia, Sara Solnick, and David Hemenway. Soft Drinks Consumption Is Associated with Behavior Problems in 5-Year-Olds. The Journal of Pediatrics, 2013 DOI: 10.1016/j.jpeds.2013.06.023

Autism: Link to increased genetic change in regions of genome instability

These microscopic images were taken as part of research to explore rearrangements of DNA in one of the "hotspots" of the human genome, where deletions and duplications occur at higher rates. 

Credit: Betsy Hirsch/University of Minnesota and Scott Selleck /Penn State University

Children with autism have increased levels of genetic change in regions of the genome prone to DNA rearrangements, so called "hotspots," according to a research discovery to be published in the print edition of the journal Human Molecular Genetics.

The research indicates that these genetic changes come in the form of an excess of duplicated DNA segments in hotspot regions and may affect the chances that a child will develop Autism—a behavioural disorder that affects about 1 of every 88 children in the US, according to the Centers for Disease Control (CDC).

Earlier work had identified, in children with Autism, a greater frequency of rare DNA deletions or duplications, known as DNA copy number changes.

These rare and harmful events are found in approximately 5 to 10 percent of cases, raising the question as to what other genetic changes might contribute to the disorders known as autism spectrum disorders.

The new research shows that children with autism have—in addition to these rare events—an excess of duplicated DNA including more common variants not exclusively found in children with autism, but are found at elevated levels compared to typically developing children.

The investigators also found that the balance of DNA duplications and deletions in children with autism was different from that found in more severe developmental disorders, such as intellectual disability or multiple congenital anomalies, where the levels of both deletions and duplications are increased compared to controls, and are even higher than in children with autism.

They also found that children who had more difficulty with daily living skills also had the greatest level of copy number change throughout their genome.

Scott Selleck

"These measures of adaptive behaviour provide an indication of the severity of the impairment in the children with autism. These behaviours were significantly correlated with the amount of DNA copy number change," Selleck said, emphasizing that the research revealed "clear and graded effects of the genetic change."

"These results beg the question as to the origin of this genetic change," Selleck said. "The increased levels of both rare and common variants suggests the possibility that these individuals are predisposed to genetic alteration."

The research collaboration includes groups led at Penn State by Scott Selleck; at the University of California Davis /MIND Institute by Isaac Pessah, Irva Hertz-Picciotto, Flora Tassone, and Robin Hansen; and at the University of Washington by Evan Eichler.

CHARGE
The University of California Davis /MIND Institute group directs a large population-based case-control study of autism called CHARGE (Childhood Autism Risks from Genetics and Environment).

In this multiyear study, clinical history, environmental, nutritional, family, and medical data are collected from the families of children with autism and other developmental disorders, as well as from randomly selected control children from the general population.

The research took advantage of the CHARGE study, supported by the National Institute of Environmental Health Sciences and the Environmental Protection Agency.

"The CHARGE study is a true population-based case-control cohort for the study of autism, the only one of its kind that I am aware of " says Selleck, and allows for comparisons between the children with autism and controls matched for geographical location and time of birth.

The research team plans to continue its collaboration to further characterize the more common genetic variants found to be associated with autism and to explore the relationship between genome variation and environmental exposures.

Reference
Global increases in both common and rare copy number load associated with autism;  hmg.ddt136.abstract

Signaling Pathway Linked to Fetal Alcohol Risk

Fetal alcohol syndrome is the leading preventable cause of developmental disorders in developed countries and fetal alcohol spectrum disorder (FASD), a range of alcohol-related birth defects that includes fetal alcohol syndrome, is thought to affect as many as 1 in 100 children born in the United States.

Any amount of alcohol consumed by the mother during pregnancy poses a risk of FASD, a condition that can include the distinct pattern of facial features and growth retardation associated with fetal alcohol syndrome as well as intellectual disabilities, speech and language delays, and poor social skills. But drinking can have radically different outcomes for different women and their babies.

While twin studies have suggested a genetic component to susceptibility to FASD, researchers have had little success identifying who is at greatest risk or what genes are at play.

Research from Harvard Medical School and Veterans Affairs Boston Healthcare System sheds new light on this question, identifying for the first time a signaling pathway that might determine genetic susceptibility for the development of FASD.

The study was published online Feb. 19 in the journal Proceedings of the National Academy of Sciences.

"Our work points to candidate genes for FASD susceptibility and identifies a path for the rational development of drugs that prevent ethanol neurotoxicity," said Michael Charness, chief of staff at VA Boston Healthcare System and HMS professor of neurology.

"And importantly, identifying those mothers whose fetuses are most at risk could help providers better target intensive efforts at reducing drinking during pregnancy."

Reference
Mitogen-activated protein kinase modulates ethanol inhibition of cell adhesion mediated by the L1 neural cell adhesion molecule.Proceedings of the National Academy of Sciences, 2013; DOI: 10.1073/pnas.1221386110

Western diet link to ADHD - Australian study

Leader of Nutrition studies at the Institute, Associate Professor Wendy Oddy, said the study examined the dietary patterns of 1800 adolescents from the long-term Raine Study and classified diets into ‘Healthy’ or ‘Western’ patterns.

“We found a diet high in the Western pattern of foods was associated with more than double the risk of having an ADHD diagnosis compared with a diet low in the Western pattern, after adjusting for numerous other social and family influences,” Dr Oddy said.

“We looked at the dietary patterns amongst the adolescents and compared the diet information against whether or not the adolescent had received a diagnosis of ADHD by the age of 14 years. In our study, 115 adolescents had been diagnosed with ADHD, 91 boys and 24 girls.”

A “healthy” pattern is a diet high in fresh fruit and vegetables, whole grains and fish. It tends to be higher in omega-3 fatty acids, folate and fibre. A “Western” pattern is a diet with a trend towards takeaway foods, confectionary, processed, fried and refined foods. These diets tend to be higher in total fat, saturated fat, refined sugar and sodium.

“When we looked at specific foods, having an ADHD diagnosis was associated with a diet high in takeaway foods, processed meats, red meat, high fat dairy products and confectionary,” Dr Oddy said.

“We suggest that a Western dietary pattern may indicate the adolescent has a less optimal fatty acid profile, whereas a diet higher in omega-3 fatty acids is thought to hold benefits for mental health and optimal brain function.

“It also may be that the Western dietary pattern doesn’t provide enough essential micronutrients that are needed for brain function, particularly attention and concentration, or that a Western diet might contain more colours, flavours and additives that have been linked to an increase in ADHD symptoms. It may also be that impulsivity, which is a characteristic of ADHD, leads to poor dietary choices such as quick snacks when hungry.”

Dr Oddy said that whilst this study suggests that diet may be implicated in ADHD, more research is needed to determine the nature of the relationship.

“This is a cross-sectional study so we cannot be sure whether a poor diet leads to ADHD or whether ADHD leads to poor dietary choices and cravings,” Dr Oddy said.

ADHD is the most commonly diagnosed childhood mental health disorder and has a prevalence of approximately 5%. ADHD is known to be more common in boys.