Language and attention gene variations in those with ADHD

A study shows that in those with ADHD, gene variations are seen specifically in language and attention.

Are deficits in attention limited to those with attention-deficit/hyperactivity disorder (ADHD) or is there a spectrum of attention function in the general population? The answer to this question has implications for psychiatric diagnoses and perhaps for society, broadly.

A new study published in the current issue of Biological Psychiatry, by researchers at Cardiff University School of Medicine and the University of Bristol, suggests that there is a spectrum of attention, hyperactivity/impulsiveness and language function in society, with varying degrees of these impairments associated with clusters of genes linked with the risk for ADHD.

Viewing these functions as dimensions or spectrums contrasts with a traditional view of ADHD as a disease category.

To answer this question, researchers led by senior author Dr. Anita Thapar used genetic data from patients with ADHD as well as data from the Avon Longitudinal Study of Parents and Children (ALSPAC). The ALSPAC is based in England and is a large, ongoing study of parents and children followed since birth in the early '90s.

They created polygenic risk scores -- a 'composite' score of genetic effects that forms an index of genetic risk -- of ADHD for 8,229 ALSPAC participants.

They found that polygenic risk for ADHD was positively associated with higher levels of traits of hyperactivity/impulsiveness and attention at ages 7 and 10 in the general population. It was also negatively associated with pragmatic language abilities, e.g., the ability to appropriately use language in social settings.

"Our research finds that a set of genetic risks identified from UK patients with a clinical diagnosis of childhood ADHD also predicted higher levels of developmental difficulties in children from a UK population cohort, the ALSPAC," said Thapar.

First author Joanna Martin added, "Our results provide support at a genetic level for the suggestion that ADHD diagnosis represents the extreme of a spectrum of difficulties. The results are also important as they suggest that the same sets of genetic risks contribute to different aspects of child development which are characteristic features of neurodevelopmental disorders such as ADHD and autism spectrum disorder."

"It may be the case that at some point polygenic risk scores may, in conjunction with other clinical information, help to identify children who will struggle in school and other demanding contexts due to attention difficulties," said Dr. John Krystal, Editor of Biological Psychiatry. "The objective of this type of early identification would be to provide children who are at risk for difficulties with support so that problems at school may be prevented."

Read more here

Study: Brain miswires could contribute to ADHD

A study looks into brain miswires that could contribute ADHD.

Neuroscientists at Mayo Clinic in Florida and at Aarhus University in Denmark have shed light on why neurons in the brain's reward system can be miswired, potentially contributing to disorders such as attention deficit hyperactivity disorder (ADHD).

They say findings from their study, published online today in Neuron, may increase the understanding of underlying causes of ADHD, potentially facilitating the development of more individualized treatment strategies.

The scientists looked at dopaminergic neurons, which regulate pleasure, motivation, reward, and cognition, and have been implicated in development of ADHD.

They uncovered a receptor system that is critical, during embryonic development, for correct wiring of the dopaminergic brain area. But they also discovered that after brain maturation, a cut in the same receptor, SorCS2, produces a two-chain receptor that induces cell death following damage to the peripheral nervous system.

The researchers report that the SorCS2 receptor functions as a molecular switch between apparently opposing effects in proBDNF. ProBDNF is a neuronal growth factor that helps select cells that are most beneficial to the nervous system, while eliminating those that are less favorable in order to create a finely tuned neuronal network.

They found that some cells in mice deficient in SorCS2 are unresponsive to proBDNF and have dysfunctional contacts between dopaminergic neurons.

"This miswiring of dopaminergic neurons in mice results in hyperactivity and attention deficits," says the study's senior investigator, Anders Nykjaer, M.D., Ph.D., a neuroscientist at Mayo Clinic in Florida and at Aarhus University in Denmark.

"A number of studies have reported that ADHD patients commonly exhibit miswiring in this brain area, accompanied by altered dopaminergic function. We may now have an explanation as to why ADHD risk genes have been linked to regulation of neuronal growth," he says.

"SorCS2 is produced as a single-chain protein -- one long row of amino acids -- but it can be cut into two chains to perform a different function. While the single-chain receptor is essential to tell the neuron that it is time to stop growing, the two-chain form tells cells that support neurons in the developing peripheral nervous system to die when they should," says Dr. Nykjaer.

Unfortunately, if damage occurs to a nerve in the peripheral nervous system, these cells that wrap around and nourish the neurons will die, preventing efficient regeneration, he says. "Our finding suggests that it may be possible to develop drug therapy to prevent this deadly cut of SorCS2 and treat acute nerve injury," Dr. Nykjaer says.

Other Danish and German researchers contributed to the research. The study was funded by the Lundbeck Foundation and the Danish Medical Research Council.

Read more here

Study: ADHD in children linked to tylenol use in pregnancy

A recent study claims that women who took tylenol (acetaminophen) while pregnant may have a higher chance of having a child with ADHD.

If you were pregnant, did you ever take a Tylenol?

If not, you have unreal levels of tolerance for discomfort but if you did, and you think your child is hyperactive, a new study may have some answers. Not 'why' answers, just a 'perhaps' answer. But look for mainstream media to declare that Tylenol causes attention-deficit/hyperactivity disorder (ADHD) in kids.

Acetaminophen is the most commonly used medication for pain and fever during pregnancy. But some studies have suggested that acetaminophen has effects on sex and other hormones, which can in turn affect neurodevelopment and cause behavioral dysfunction. The authors of a new paper in JAMA Pediatrics studied 64,322 children and mothers in the Danish National Birth Cohort (1996-2002). Parents reported behavioral problems on a questionnaire, and hyperkinetic disorders (HKDs, a severe form of ADHD) diagnoses and ADHD medication prescriptions were collected from Danish registries.

They found that more than half of the mothers reported using acetaminophen while pregnant. No surprise there. But then they also found that the use of acetaminophen during pregnancy appeared to be associated with a higher risk of HKD diagnosis, of using ADHD medications or of having ADHD-like behaviors at age 7 years. The risk increased when mothers used acetaminophen more than one trimester during pregnancy.

“Maternal acetaminophen use during pregnancy is associated with a higher risk for HKDs and ADHD-like behaviors in children. Because the exposure and outcomes are frequent, these results are of public health relevance but further investigations are needed,” they conclude.

In an accompanying editorial (JAMA Pediatr doi:10.1001/jamapediatrics.2013.5292), Miriam Cooper, M.R.C.Psych, M.Sc., of Cardiff University School of Medicine, and colleagues write, “Indeed, causation cannot be inferred from the present observed associations, and Liew et al are right to point out that a replication of their study is needed. 

“In summary, findings from this study should be interpreted cautiously and should not change practice. However, they underline the importance of not taking a drug’s safety during pregnancy for granted, and they provide a platform from which to conduct further related analyses exploring a potential relationship between acetaminophen use and altered neurodevelopment.”

Read more here

Brain Development Determines ADHD Recovery

Studies show that around 50% of children with ADHD grow out of the condition while the rest become adults with ADHD. This article claims that the pattern of a child's brain development could determine if a child grows out of their ADHD or not.

Some people grow out of their childhood attention-deficit/hyperactivity disorder (ADHD) and some don't. In fact, around 50% of individuals diagnosed as children continue to suffer from ADHD as adults.

Researchers are trying to understand the reasons why, and relatedly, whether there are any differences that distinguish the two groups. Gender, ethnicity, socioeconomic class, and symptom severity have already been ruled out as potentials. So, perhaps there is a distinguishing variable in the brain? Dr. Philip Shaw at the National Human Genome Research Institute and his colleagues conducted a study to find out.

They already knew from prior work that cortical structure is thinner in adults with ADHD, particularly in regions of the brain that play important roles in cognitive functioning and attention. However, that work was cross-sectional, meaning it was conducted at a single point in time, so any changes over time weren't captured. Thus, they focused on those same regions in this study, but conducted a longitudinal study so they could link trajectories of symptoms with trajectories of brain development, particularly the structure of cortical regions that control attention.

They recruited 92 children with ADHD, with a mean age of 11, who underwent repeated structural imaging scans and clinical assessments over the years, including as adults at a mean age of 24 years. For comparison, they also scanned 184 volunteers without ADHD.

They found that ADHD continued into adulthood in 37 (40%) of the participants diagnosed with childhood ADHD, and these individuals showed increased rates of thinning. In contrast, the cortical thickness of individuals who achieved remission of their ADHD developed toward the normal range.

"We find that differences in patterns of brain growth are linked with differences in the adult outcome of childhood ADHD. Differences in these regions -- specifically a thinner cortex -- are found in childhood ADHD," Shaw further explained. "However, for the group whose ADHD improved with age, these differences tend to resolve and by adulthood, these regions did not differ significantly from individuals who never had ADHD. By contrast, for the group with persistent ADHD, childhood differences persisted in the 'attention' regions of the brain."

These findings seem to suggest that the trajectory of cortex development differentiates people who recover from childhood ADHD from people whose disorder continues into adulthood.

"The development of the cortex seems to be a critical factor influencing the recovery from childhood ADHD. However, there is much that we do not understand about this relationship," commented Dr. John Krystal, Editor of Biological Psychiatry. "Cortical thinning may be related to the pruning of connections in the brain, in this case, connections with the prefrontal cortex. The current data would seem to suggest that excessive trimming of connections is a risk factor for the persistence of ADHD into adulthood. But we do not yet understand which connections are being trimmed, why these connections disappear, and how this loss of connections contributes to ADHD symptoms."

More work will be necessary to answer these questions, but Shaw concludes that "understanding how differences in brain development are tied to the course of ADHD is the first step in developing tools to help us predict the outcome of childhood ADHD."

Read more here

Study: Breastfed children less likely to develop ADHD

A study from Tel Aviv University shows that breastfeeding may be protective against a child developing ADHD later in life.

We know that breastfeeding has a positive impact on child development and health -- including protection against illness. Now researchers from Tel Aviv University have shown that breastfeeding may also help protect against Attention Deficit/Hyperactivity Disorder (ADHD), the most commonly diagnosed neurobehavioral disorder in children and adolescents.

Seeking to determine if the development of ADHD was associated with lower rates of breastfeeding, Dr. Aviva Mimouni-Bloch, of Tel Aviv University's Sackler Faculty of Medicine and Head of the Child Neurodevelopmental Center in Loewenstein Hospital, and her fellow researchers completed a retrospective study on the breastfeeding habits of parents of three groups of children: a group that had been diagnosed with ADHD; siblings of those diagnosed with ADHD; and a control group of children without ADHD and lacking any genetic ties to the disorder.

The researchers found a clear link between rates of breastfeeding and the likelihood of developing ADHD, even when typical risk factors were taken into consideration. Children who were bottle-fed at three months of age were found to be three times more likely to have ADHD than those who were breastfed during the same period. These results have been published in Breastfeeding Medicine.

Understanding genetics and environment

In their study, the researchers compared breastfeeding histories of children from six to 12 years of age at Schneider's Children Medical Center in Israel. The ADHD group was composed of children that had been diagnosed at the hospital, the second group included the siblings of the ADHD patients, and the control group included children without neurobehavioral issues who had been treated at the clinics for unrelated complaints.

In addition to describing their breastfeeding habits during the first year of their child's life, parents answered a detailed questionnaire on medical and demographic data that might also have an impact on the development of ADHD, including marital status and education of the parents, problems during pregnancy such as hypertension or diabetes, birth weight of the child, and genetic links to ADHD.

Taking all risk factors into account, researchers found that children with ADHD were far less likely to be breastfed in their first year of life than the children in the other groups. At three months, only 43 percent of children in the ADHD group were breastfed compared to 69 percent of the sibling group and 73 percent of the control group. At six months, 29 percent of the ADHD group was breastfed, compared to 50 percent of the sibling group and 57 percent of the control group.

One of the unique elements of the study was the inclusion of the sibling group, says Dr. Mimouni-Bloch. Although a mother will often make the same breastfeeding choices for all her children, this is not always the case. Some children's temperaments might be more difficult than their siblings', making it hard for the mother to breastfeed, she suggests.

Added protection

While researchers do not yet know why breastfeeding has an impact on the future development of ADHD -- it could be due to the breast milk itself, or the special bond formed between mother and baby during breastfeeding, for example -- they believe this research shows that breastfeeding can have a protective effect against the development of the disorder, and can be counted as an additional biological advantage for breastfeeding.

Dr. Mimouni-Bloch hopes to conduct a further study on breastfeeding and ADHD, examining children who are at high risk for ADHD from birth and following up in six-month intervals until six years of age, to obtain more data on the phenomenon.

Read more here

Risk of ADHD higher in children whose parents are depressed or violent

A study shows that young children whose parents are depressed or are involved in partner violence are more likely to develop ADHD by age 6.

Preschoolers whose parents reportdepression and intimate partner violence may be more likely to develop attention-deficit/hyperactivity disorder (ADHD) by the age of 6, new research suggests.

And young children with depressed moms may be more likely to receive prescription drugs to treat behavioral and mental health issues down the road.

"Our study indicates that preschoolers who are diagnosed with ADHD are more likely to have been exposed to both intimate partner violence and parental depression within the first three years of life than their peers not exposed to either risk factor," said study author Dr. Nerissa Bauer, an assistant professor of pediatrics at Indiana University School of Medicine, in Indianapolis.

"There has been increasing awareness that certain psychosocial risk factors can impact the behavioral presentation of children at very young ages," she said. Still, not all children who are exposed to maternal depression and intimate partner violence will develop ADHD, she noted.

"There are other factors that can be associated with a child's higher likelihood of being diagnosed with ADHD, including a family history of ADHD," Bauer explained.

ADHD symptoms can include impulsiveness, hyperactivity and difficulty focusing.Kids with ADHD may have difficulty in school, holding down jobs and sustaining relationships. They are also at greater risk for alcohol or substance abuse, depression and anxiety disorders. Treatment typically involves medication and behavioral modifications.

"Pediatricians and family practitioners know to routinely screen for the presence of these psychosocial risk factors because of the potential negative effects on the child," Bauer said. "Families who experience intimate partner violence will need help, not only to make sure the victims stay safe from physical harm, but there [are] also psychological effects."

The study, which appeared online Feb. 4 in the journal JAMA Pediatrics, included more than 2,400 children who were 3 years old. Parents who brought them to four different pediatric community clinics filled out questionnaires regarding their personal history of depression and domestic violence while in the pediatricians' waiting room.

Fifty-eight caregivers reported a history of intimate partner violence and depression before their child turned 3. In addition, 69 reported a history of intimate partner violence and 704 had symptoms of depression during this time frame. Close to 66 percent of the parents reported neither depression nor intimate partner violence. Children who were exposed to intimate partner violence and/or parental depression were four times more likely to be diagnosed with ADHD by the age of 6.

What's more, 2.9 percent of kids whose parents reported depression received prescription drugs to treat behavioral and mental health issues, compared with 1.6 percent of children whose parents did not report a history of depression. Medications included those that treat anxiety, depression and sleep problems.

While the study showed an association, it did not prove a cause-and-effect link between intimate partner violence and/or maternal depression and likelihood of anADHD diagnosis.

Experts said the findings make sense, but more study is needed.

"This study adds to the already robust literature revealing that early life experiences can have profound effects on brain development," said Dr. Michael Duchowny, a pediatric neurologist at Miami Children's Hospital. "While heredity is known to play a strong role in the expression of ADHD symptoms, the study further suggests that additional environmental factors operating during the formative years of brain maturation are also significant."

New York City-based child psychoanalyst Dr. Leon Hoffman said the new findings make sense. "Unquestionably, intimate partner violence and maternal depression have a profound effect on children," he said.

Exactly how to deal with this is another story, said Hoffman, who is the co-director of the New York Psychoanalytic Society's Pacella Parent Child Center. "This is a public health problem that needs a lot of funds if reasonably effective programs are to be developed," he noted.

Dr. Rachel Klein, professor of child and adolescent psychiatry at NYU Langone Medical Center in New York City, said the study shows an association based on how parents answered certain questions, but it can't say how, or even if, maternal depression and intimate partner violence predict a child's risk of ADHD.

"If parents are worried, ask the pediatrician to evaluate your child for possible ADHD or refer the child to a mental health professional," she added.

Read more here