Tag Archive for: post-traumatic stress disorder

Paper cutout of head with brainwaves

Lifesaving ICDs can cause anxiety, stress, PTSD for parents and kids

Paper cutout of head with brainwaves

Research shows that children with implantable cardioverter-defibrillators, and their parents, are at risk for anxiety, post-traumatic stress disorder and other psychological distress.

Recent advances in design and efficiency of implantable cardioverter-defibrillators (ICDs) have led to their increased use in younger patients, protecting more children with congenital heart disease from sudden cardiac arrest and sudden cardiac death, says a commentary in the journal Heart Rhythm. However, living longer with these devices and the day-to-day worry that they may have to deliver a lifesaving shock in the blink of an eye, may cause unusually high rates of anxiety, stress and other psychosocial distress for children with ICDs and their families.

Commentary authors Vicki Freedenberg, Ph.D., RN, electrophysiology nurse scientist, and Charles Berul, M.D., chief of cardiology, both from Children’s National Hospital, note that current available research shows both children with these ICDs and their parents are at risk for anxiety, post-traumatic stress disorder (PTSD) and other psychological distress. They highlight a new study published in the same journal that reports data related to prevalence and factors associated with PTSD in children with ICDs and their parents as a good start to better understanding these impacts.

Why it matters

Freedenberg and Berul say that the new study adds important information to an area without a lot of previous research. They also point out that understanding the long-term impacts of life with these devices is critical to ensuring the overall long-term health and wellbeing of both the children with these devices and their families.

What’s been the hold-up in the field?

The development of devices that work for younger children with congenital heart disease, including advances in ICDs and pacemakers, has increased in the last decade. In this time, studies of how these devices work for children have focused predominantly on clinical outcomes and questions related to clinical care.

As survival rates for children have increased, research needs to shift from the study of mortality and clinical outcomes toward understanding the full spectrum of how these devices impact daily life for these children and their families.

Moving the field forward

According to Freedenberg and Berul, the new study importantly includes both patient and parent perspectives, which is a first in this research area. They also offer recommendations for future studies, including the use of comparison groups to allow for generalization of findings. Researchers might also ask research questions to determine whether the device itself or the medical and non-medical factors that often occur simultaneously are more important to predicting mental health and wellbeing.

However, the commentary concludes with the most important takeaway: More research, with specific parameters focused on the impact of clinical interventions, is desperately needed to truly understand all the ways that children and their families are affected throughout life by the clinical care and support they receive.

Read the full commentary, Potential for shock leads to potential for stress, in the journal Heart Rhythm.

DNA moleucle

PAC1R mutation may be linked to severity of social deficits in autism

DNA moleucle

A mutation of the gene PAC1R may be linked to the severity of social deficits experienced by kids with autism spectrum disorder (ASD), finds a study from a multi-institutional research team led by Children’s National faculty. If the pilot findings are corroborated in larger, multi-center studies, the research published online Dec. 17, 2018, in Autism Research represents the first step toward identifying a potential novel biomarker to guide interventions and better predict outcomes for children with autism.

As many as 1 in 40 children are affected by ASD. Symptoms of the disorder – such as not making eye contact, not responding to one’s name when called, an inability to follow a conversation of more than one speaker or incessantly repeating certain words or phrases – usually crop up by the time a child turns 3.

The developmental disorder is believed to be linked, in part, to disrupted circuitry within the amygdala, a brain structure integral for processing social-emotional information. This study reveals that PAC1R is expressed during key periods of brain development when the amygdala – an almond-shaped cluster of neurons – develops and matures. A properly functioning amygdala, along with brain structures like the prefrontal cortex and cerebellum, are crucial to neurotypical social-emotional processing.

“Our study suggests that an individual with autism who is carrying a mutation in PAC1R may have a greater chance of more severe social problems and disrupted functional brain connectivity with the amygdala,” says Joshua G. Corbin, Ph.D., interim director of the Center for Neuroscience Research at Children’s National Health System and the study’s co-senior author. “Our study is one important step along the pathway to developing new biomarkers for autism spectrum disorder and, hopefully, predicting patients’ outcomes.”

The research team’s insights came through investigating multiple lines of evidence:

  • They looked at gene expression in the brains of an experimental model at days 13.5 and 18.5 of fetal development and day 7 of life, dates that correspond with early, mid and late amygdala development. They confirmed that Pac1r is expressed in the experimental model at a critical time frame for brain development that coincides with the timing for altered brain trajectories with ASD.
  • They looked at gene expression in the human brain by mining publicly available genome-wide transcriptome data, plotting median PAC1R expression values for key brain regions. They found high levels of PAC1R expression at multiple ages with higher PAC1R expression in male brains during the fetal period and higher PAC1R expression in female brains during childhood and early adulthood.
  • One hundred twenty-nine patients with ASD aged 6 to 14 were recruited for behavioral assessment. Of the 48 patients who also participated in neuroimaging, 20 were able to stay awake for five minutes without too much movement as the resting state functional magnetic resonance images were captured. Children who were carriers of the high-risk genotype had higher resting-state connectivity between the amygdala and right posterior temporal gyrus. Connectivity alterations in a region of the brain involved in processing visual motion may influence how kids with ASD perceive socially meaningful information, the authors write.
  • Each child also submitted a saliva sample for DNA genotyping. Previously published research finds that a G to C single nucleotide polymorphism, a single swap in the nucleotides that make up DNA, in PAC1R is associated with higher risk for post traumatic stress disorder in girls. In this behavioral assessment, the research team found children with autism who carried the homozygous CC genotype had higher scores as measured through a validated tool, meaning they had greater social deficits than kids with the heterozygous genotype.

All told, the project is the fruit of six years of painstaking research and data collection, say the researchers. That includes banking patients’ saliva samples collected during clinical visits for future retrospective analyses to determine which genetic mutations were correlated with behavioral and functional brain deficits, Corbin adds.

“Lauren Kenworthy, who directs our Center for Autism Spectrum Disorders, and I have been talking over the years about how we could bring our programs together. We homed in on this project to look at about a dozen genes to assess correlations and brought in experts from genetics and genomics at Children’s National to sequence genes of interest,” he adds. “Linking the bench to bedside is especially difficult in neuroscience. It takes a huge amount of effort and dozens of discussions, and it’s very rare. It’s an exemplar of what we strive for.”

In addition to Corbin, study co-authors include Lead Author Meredith Goodrich and Maria Jesus Herrero, post-doctoral fellow, Children’s Center for Neuroscience Research; Anna Chelsea Armour and co-Senior Author Lauren Kenworthy, Ph.D., Children’s Center for Autism Spectrum Disorders; Karuna Panchapakesan, Joseph Devaney and Susan Knoblach, Ph.D., Children’s Center for Genetic Medicine Research; Xiaozhen You and Chandan J. Vaidya, Georgetown University; and Catherine A.W. Sullivan and Abha R. Gupta, Yale School of Medicine.

Financial support for the research described in this report was provided by DC-IDDRC under awards HD040677-07 and 1U54HD090257, the Clinical and Translational Science Institute at Children’s National, The Isidore and Bertha Gudelsky Family Foundation and the National Institutes of Health under awards MH083053-01A2 and MH084961.