Yi-Chia Ku1,2, Chih-Hsin Muo3, Chin-Shein Ku4, Chao-Huei Chen1, Wen-Yuan Lee5,6, Ein-Yiao Shen2,5, Yen-Jung Chang3,7, Chia-Hung Kao6,8

 

 

Published Online First 4 December 2013

Abstract

Objective In this study, we obtained relevant data from a nationwide cohort database to investigate the risk of attention deficit-hyperactivity disorder (ADHD) in children with a history of febrile seizures (FS).

 

Methods We identified 1081 children with FS as the case cohort, and the date of diagnosis was used as an index date. Four controls were matched randomly with each case based on age, sex, urbanisation level, parents’ occupation, and index date. We applied Cox's proportional hazards regression to estimate the HR and CI of FS-associated ADHD.

 

Results After 11 years of follow-up, the incidence of ADHD for the FS and control cohorts is 7.83 and 4.72 per 1000 person-years, respectively. The FS cohort was 1.66 times more at risk of ADHD occurrence (95% CI 1.27 to 2.18) than the control cohort. The risk of developing ADHD increased in conjunction with the frequency of FS-related visits.

 

Conclusions FS may increase the risk of subsequent ADHD occurrence in children. Children who visited physicians for FS more than twice had a significantly higher cumulative incidence of ADHD.

 

 

 

​One of the most common pediatric psychiatric disorders is attention-deficit/hyperactivity disorder (ADHD), and the most common therapy for ADHD is stimulant medication. In the past few decades, concerns have been raised about a possible link between ADHD and the rapid increase in obesity rates among children.

 

In the April 2014 Pediatrics study, “Attention Deficit Disorder, Stimulant Use, and Childhood Body Mass Index Trajectory,” (published online March 17), researchers studied electronic health record data from the Geisinger Health System on 163,820 children aged 3 to 18 years of age in Pennsylvania.

 

Models were used to determine BMI trajectories in relation to ADHD diagnosis, age when first using stimulants, and duration of stimulant use. Researchers found that children with untreated ADHD or ADHD treated without stimulants had faster BMI growth than those without ADHD. Conversely, children who had ADHD treated with stimulants demonstrated slower BMI growth early in childhood, but they rebounded later in adolescence to higher BMIs -- higher than children without a history of ADHD or stimulant use. The earlier stimulants were started and the longer they were used, the stronger were these effects.

 

Study authors concluded their findings support the idea that children with ADHD are at an increased risk for obesity. However, they concluded that stimulant use and the impressive rebound in BMI growth later in childhood and adolescence -- rather than ADHD itself -- was most responsible for these observations. Clinicians should be aware of the obesity risk of ADHD and particularly stimulant use. Further research is needed to develop appropriate obesity prevention interventions for children with ADHD.

 

Editor’s Note: A related study, “Attention-Deficit/Hyperactivity Disorder in Young Children: Predictors of Diagnostic Stability,” will also be published online on March 17 in Pediatrics.

 

 

 

 

 

 

 

 

Da https://medicalxpress.com/news/2014-03-childhood-adhd-autism-schizophrenia-tied.html

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by Stuart Mason Dambrot feature

Childhood's end: ADHD, autism and schizophrenia tied to stronger inhibitory interactions in adolescent prefrontal cortex

Images of the monkey brain around the time of puberty, with the prefrontal cortex highlighted. Credit: Courtesy of Xin Zhou

(Medical Xpress)—Key cognitive functions such as working memory (which combines temporary storage and manipulation of information) and executive function (a set of mental processes that helps connect past experience with present action) are associated with the brain's prefrontal cortex. Unlike other brain regions, the prefrontal cortex does not mature until early adulthood, with the most pronounced changes being seen between its peripubertal (onset of puberty) and postpubertal developmental states. Moreover, this maturation period is correlated with cognitive maturation – but the physical neuronal changes during this transition have remained for the most part unknown. Recently, however, scientists at the Wake Forest School of Medicine in Winston-Salem, NC recorded and compared prefrontal cortical activity peripubertal and adult monkeys.

 

 

The researchers found that compared with adults, peripubertal monkeys showed lower connectivity due to stronger inhibitory interactions, suggesting that intrinsic (or resting state) inhibitory connections – that is, inhibitory neural connections that are active in the absence of any particular task – decline with maturation. The scientists then concluded that prefrontal intrinsic connectivity changes are a possible substrate for cognitive maturation.

Prof. Christos Constantinidis discusses the paper that he, Dr. Xin Zhou and their co-authors published in Proceedings of the National Academy of Sciences. When comparing the functional connectivity between pairs of neurons in neuronal activity recorded from the prefrontal cortex of peripubertal and adult monkeys and evaluating the developmental stage of peripubertal rhesus monkeys with a series of morphometric, hormonal, and radiographic measures, Constantinidis tells Medical Xpress that a major challenge was to obtain neural activity from the brain of monkeys around the time of puberty. "We needed to make ourselves experts in the developmental trajectories of monkeys and conduct experiments just at the right time relative to the onset of puberty," he explains.

Furthermore, he continues, identifying changes in intrinsic connectivity between prefrontal neurons as a possible substrate for peri- and postpubertal cognitive maturation carried challenges as well. "To address a potential difference in connectivity between neurons within the prefrontal cortex – that is, intrinsic connectivity – we needed to obtain a large sample of neuronal recordings from multiple neurons simultaneously. We inferred the strength of connections using a mathematical analysis of the time course of neuronal activity in each neuron – but this indirect measure is very noisy." For this reason, their conclusions needed to be based on hundreds of recording sessions.

Childhood's end: ADHD, autism and schizophrenia tied to stronger inhibitory interactions in adolescent prefrontal cortex

Intrinsic connectivity in the monkey prefrontal cortex. (A) The ellipse indicates the recording areas in the dorsolateral prefrontal cortex. AS, arcuate sulcus; PS, principal sulcus. (B) Predictor-corrected average (and SE) of …more

Another challenge in these experiments was encountered in conducting behavioral and neurophysiological tests. "As the monkeys performed working memory tasks," Constantinidis says, "the young monkeys were rather temperamental and impulsive, and could not focus for very long time at the cognitive tasks we used – not unlike children of equivalent ages." The scientists therefore had to devise simplified versions of the tasks and optimize data collection to be as fast as possible."

 

 

In their paper, the scientists also acknowledge that their conclusions carry a number of caveats:

the study relied exclusively on male monkeys

it wasn't practical to obtain neurophysiological recordings from a greater number of animals

while effective connectivity allows statistical comparisons at the level of neuronal populations, this represents a functional rather than anatomical measure of connectivity

Regarding their findings, Constantinidis says "When we quantified the strength of connections between neurons in the prefrontal cortex, we observed that the average overall strength of connections was lower in the young monkeys than in the adults. Considering that there are two types of connections between neurons – excitatory and inhibitory – this difference could imply that excitatory connections were weaker, or inhibitory connections were stronger. We were surprised," he adds, "to find that the latter was the case." A corollary of this observation,

Constantinidis points out, is that maturation of neuronal connections between neurons must result in a decrease in inhibitory connections as the animals mature from the adolescent to the adult stage.

"The differences in the strength of connections we observed occur at the stage in development when cognitive capacities including working memory, impulsivity and executive function, are still not fully mature," Constantinidis continues. "Our conjecture therefore is that changes in intrinsic connectivity are ultimately responsible for the maturation of these cognitive functions, at least in part. A number of neuropsychiatric conditions – most notably, schizophrenia – also appear during the time period of transition between adolescence and adulthood. Our results raise the possibility that connections within the prefrontal cortex follow an abnormal developmental trajectory in this condition."

While their results do not speak directly to the treatment for ADHD, autism and schizophrenia, Constantinidis notes, they do provide some working hypotheses about the mechanisms through which treatment works. "In recent years," he illustrates, "computerized training in working memory tasks has shown promise in the treatment of conditions including ADHD and schizophrenia. We hypothesize that such training can alter the strength of connections between neurons in the prefrontal cortex."

Another recent study1,2 finding that a microglia deficit in mice lacking a given gene impairs functional neural connectivity and thereby leads to autism-associated behavior, Constantinidis says, "is a fascinating finding, pointing that maturation of connections between the prefrontal cortex and other brain areas is also a factor in the development of social behavior, in agreement with prior human studies. Together these studies and ours outline the range of connectivity changes that occur in cognitive development."

When it comes to next steps in their research, Constantinidis notes that the researchers are currently in the process of analyzing neural activity in the prefrontal cortex in monkeys during the execution of a variety of cognitive tasks as they progress from adolescence to adulthood. "Our long term goal is to understand the critical parameters of neuronal activity that characterize mature from immature cognitive behavior, and the structural substrates that mediate them in the prefrontal cortex."

Constantinidis tells Medical Xpress that other areas of research might also benefit from their paper. "We hope our findings will guide further research on functional and structural changes between cortical neurons. Such changes may be responsible for other types of long-term cortical reorganization as a result of normal development and experience. Moreover," he concludes, "our research may ultimately benefit clinical applications for treatment of conditions such as autism, ADHD and schizophrenia. New drugs, training in cognitive tasks and other types of interventions may be evaluated based on their potential to modify the strength of connections between neurons in the prefrontal cortex."

 Explore further: Altered brain activity responsible for cognitive symptoms of schizophrenia

More information: Age-dependent changes in prefrontal intrinsic connectivity, Proceedings of the National Academy of Sciences, Published online before print on February 24, doi:10.1073/pnas.1316594111

Related

1Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior, Nature Neuroscience published online 02 February 2014, doi:10.1038/nn.3641 

2When less is more: Microglia deficit impairs functional neural connectivity, leads to autism-associated behaviors, Medical Xpress February 13, 2014

 

 

 

 

 

 

 

 

Megan Brooks

March 13, 2014

 

Roughly 30% of adults with attention-deficit disorder (ADD) or attention-deficit/hyperactivity disorder (ADHD) were physically abused as children, new research shows.

 

Investigators from the University of Toronto in Canada found that the likelihood of ADD/ADHD was about 7 times higher in those who reported a history of physical abuse before age 18 years.

 

"Only 7.2% of those without ADD/ADHD reported childhood physical abuse, in sharp contrast to 29.6% of those with ADD/ADHD," the researchers, led by Esme Fuller-Thomson, PhD, report.

 

"This strong association between abuse and ADD/ADHD was not explained by differences in demographic characteristics or other early adversities experienced by those who had been abused," Dr. Fuller-Thomson said in a statement.

 

The study was published online March 3 in the Journal of Aggression, Maltreatment and Trauma.

 

Strong Independent Link

 

The researchers analyzed data from the 2005 Canadian Community Health Survey on a representative sample of 13,054 adults aged 18 years and older. The group included 1020 who reported childhood physical abuse and 64 who reported being diagnosed by a health professional with either ADD or ADHD.

 

Adjusted analysis revealed that the odds of ADD/ADHD were more than 6 times higher for those reporting childhood physical abuse relative to their nonabused peers (odds ratio [OR], 6.56; 95% confidence interval [CI], 4.00 - 10.74).

 

When further adjusted for other adverse childhood experiences such as parental divorce, addictions, and long-term unemployment, the odds of ADD/ADHD were more than 7-fold higher for those reporting abuse (OR, 7.64; 95%, CI 4.38 - 13.33).

 

"This study underlines the importance of ADD/ADHD as a marker of abuse," coauthor Angela Valeo, PhD, from Ryerson University in Toronto, said in a statement. "With 30% of adults with ADD/ADHD reporting childhood abuse, it is important that health professionals working with children with these disorders screen them for physical abuse."

 

"Our data do not allow us to know the direction of the association," added coauthor Rukshan Mehta, a graduate of the University of Toronto's Masters of Social Work program.

 

"It is possible that the behaviors of children with ADD/ADHD increase parental stress and the likelihood of abuse. Alternatively, some new literature suggests early childhood abuse may result in and/or exacerbate the risk of ADD/ADHD."

 

Complex Relationship

 

Commenting on the study for Medscape Medical News, Julian D. Ford, PhD, director of the Center for Trauma Recovery and Juvenile Justice, University of Connecticut Health Center in Farmington, who was not involved in the study, said it is "an interesting extension of smaller clinical studies."

 

He cautioned, however, that it is hard to tell whether the real link is between childhood abuse and ADHD or a variety of related psychological and behavioral problems.

 

Dr. Ford noted that the "strongest link to date has been between childhood maltreatment and problems associated with ADHD but not ADHD itself ― so called oppositional-defiant disorder, problems with anger, frustration, and difficulties in relationships, which are common (but by no means universal) for people who have attentional and hyperactivity problems."

 

"It's important not to take the results as definite evidence that abuse leads to ADHD (or that ADHD leads to abuse)," Dr. Ford said. "There probably is a relationship, but it’s very complicated, and all of the risks that this study assessed may be involved in the adverse outcomes (which extend well beyond ADHD, unfortunately) of childhood abuse in very unique ways for each individual," he added.

 

The authors and Dr. Ford report no relevant financial relationships.

 

J Aggress Maltreat Trauma. 2014;23:188-198. Abstract