Posts Tagged ‘trauma’

Exposure to early life trauma can lead to poor physical and mental health in some individuals, which can be passed on to their children. Studies in mice show that at least some of the effects of stress can be transmitted to offspring via environmentally-induced changes in sperm miRNA levels.

A new epigenetics study raises the possibility that the same is true in humans. It shows for the first time that the levels of the same two sperm miRNAs change in both men and mice exposed to early life stress. In mice, the negative effects of stress are transmitted to offspring. The study is published On May 23rd in Translational Psychiatry.

“The study raises the possibility that some of the vulnerability of children is due to Lamarckian type inheritance derived from their parents’ experiences,” said Larry Feig, Ph.D., professor of Developmental, Molecular and Chemical Biology at Tufts University School of Medicine and member of the Cell, Molecular and Developmental Biology and Neuroscience programs at the Sackler School of Graduate Biomedical Sciences at Tufts.

The human part of the study utilized the Adverse Childhood Experiences (ACE) questionnaire as an indicator of men’s early life trauma. The ACE Study questionnaire includes 10 yes or no questions about one’s experiences until the age of 18, including physical, verbal, or sexual abuse, and physical or emotional neglect. Other questions relate to one’s family members. Four or more yes answers put one at significantly increased risk for future mental and physical health problems. According to a ChildTrends research brief published in 2014, a remarkably high percentage (~10 percent) of the population report scores at or above this cutoff.

miRNAs constitute a newly appreciated type of gene regulator, where each miRNA controls a distinct set of genes. Until recently, sperm from fathers were thought to contribute only DNA to the mother’s egg upon fertilization, but new data in mice indicate that sperm also contribute miRNAs that influence the next generation. Sperm miRNA expression in humans is known to be affected by environmental factors, such as smoking and obesity, but no human study to date has documented the effects of stress.

The new study found that among 28 Caucasian male volunteers, the expression of two highly related sperm miRNAs, miR-449 and miR-34, were inversely proportional to the men’s ACE scores. Men with the most extensive early abuse (highest ACE scores) had as much as a 300-fold reduction in the two sperm miRNAs compared to men with the least abuse.

The idea that these changes can affect the next generation is supported by additional findings in the study, e.g.:

the same sperm miRNA changes that take place in men with high ACE scores also occur in mice exposed to early life social instability stress, which Feig’s lab has shown previously leads to anxiety and sociability defects in female offspring of stressed males for at least three generations;
these two sets of miRNAs are known to work together in mice to allow proper development of the brain and sperm;
in humans, miR-34c has been implicated in promoting early embryo development;
the mouse studies showed that the decline in these sperm miRNA levels is transmitted to the next generation; and
when these embryos mature, these miRNAs are also reduced in the sperm of their male offspring who pass on stress behaviors to their female offspring.
“This is the first study to show that stress is associated with altered levels of sperm miRNAs in humans. We are currently setting up a new, larger study in men, and additional experiments in mice that could yield further support for the idea that changes in these sperm miRNAs do, in fact, contribute to an elevation of stress-related disorders across generations,” said David Dickson, an M.D./Ph.D. student at Tufts and first author of the study.

“Looking to the future, we may be able to figure out a way to restore the low miRNA levels found in men exposed to extreme trauma, because epigenetic changes, such as stress-induced decreases in sperm miRNA expression, are reversible, unlike genetic changes that alter the DNA sequence,” Dickson added.

For example, obesity has been shown to alter specific sperm miRNA levels in men, while bariatric surgery and subsequent weight loss can reverse the changes. In addition, Isabelle Mansuy’s lab has reversed some of the negative effects of stress in mice across generations by exposing mice to an “enriched environment” that involves extensive social interactions, exercise and opportunities to explore their surroundings.

Feig pointed out that in addition to focusing on the potential transgenerational effects of stress, there is a growing appreciation that physicians should collect information on childhood trauma for the sake of the patients who are experiencing this early trauma.

This is because “childhood abuse, trauma and dysfunction adds to the risk of future physical and psychiatric maladies, and significant exposure to abusive and/or dysfunctional families is remarkably common. Moreover, sensitivity to PTSD has been shown to correlate with ACE score, implying the ACE questionnaire could be used as a screening tool to identify people who should take extra precaution to avoid potentially traumatic experiences,” he said.

“However, some people may not answer the ACE survey accurately due to inaccurate recall or because of the sensitive nature of many of the questions, particularly in settings that do not allow anonymity and/or where their answers could affect their future. Thus, discovery of unbiased markers for early trauma, like specific sperm miRNA content, could complement ACE surveys in some clinical settings to bolster preventative medicine,” he concluded.

The authors note that the relatively small sample size limits their ability to more deeply explore the association between ACE scores and miRNA expression. In addition, a longitudinal study with information on behavioral and psychological factors throughout adulthood, with repeated measurements of sperm miRNA content, could allow for further exploration on the effect of cumulative exposure to childhood trauma on miRNA.

Additional authors are Jessica Paulus, Sc.D., Tufts Medical Center as well as Tufts University School of Medicine and the Sackler School; Virginia Mensah, M.D., formerly in Feig’s lab with Women & Infants Hospital and the Warren Alpert Medical School at Brown University and now with the Reproductive Science Center of New Jersey; Janis Lem, Ph.D., Tufts Medical Center; Lorena Saavedra-Rodriguez, Ph.D., formerly a postdoctoral fellow in Feig’s laboratory at Tufts and now with a biopharmaceutical company; and Adrienne Gentry, D.O. and Kelly Pagidas, M.D., University of Louisville School of Medicine.

This study was supported by awards from the National Institute of Mental Health of the National Institutes of Health (R01MH107536), as well as the Tufts Center for Neuroscience Research (National Institute of Neurological Disorders and Stroke of the NIH, P30NS047243). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or other funders.

Dickson, D.A., Paulus, J.K., Mensah, V., Lem, J., Saavedra-Rodriguez, L., Gentry, A., Pagidas, K., and Feig, L. A. (2018). Reduced levels of miRNAs 449 and 34 in sperm of mice and men exposed to early life stress. Translational Psychiatry. https://doi.org/10.1038/s41398-018-0146-2

https://now.tufts.edu/news-releases/early-life-trauma-men-associated-reduced-levels-sperm-micrornas

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Researchers reported on Monday in the journal JAMA Neurology that dementia was a possible complication following concussion even if the patient did not lose consciousness.

Scientists from the University of California, San Francisco (UCSF) tracked more than one-third of a million American veterans, and found that the likelihood of dementia more than doubled following concussion.

After adjusting for age, sex, race, education and other health conditions, they found that concussion without loss of consciousness led to 2.36 times the risk for dementia.

According to the study, these risks were slightly elevated for those in the loss-of-consciousness bracket (2.51 times) and were nearly four times higher (3.77 times) for those with the more serious moderate-to-severe traumatic brain injury.

In the total of 357,558 participants, whose average age was 49, half had been diagnosed with traumatic brain injury, of which 54 percent had concussion. The study followed participants for an average of 4.2 years, and 91 percent were male and 72 percent were white.

“There are several mechanisms that may explain the association between traumatic brain injury and dementia,” said the study’s senior author Kristine Yaffe, professor with the UCSF departments of neurology, psychiatry, and epidemiology and biostatistics.

“There’s something about trauma that may hasten the development of neurodegenerative conditions. One theory is that brain injury induces or accelerates the accumulation of abnormal proteins that lead to neuronal death associated with conditions like Alzheimer’s disease,” said Yaffe.

“It’s also possible that trauma leaves the brain more vulnerable to other injuries or aging processes,” said Yaffe, “but we need more work in this area.”

http://www.xinhuanet.com/english/2018-05/08/c_137162226.htm

by Tori Rodriguez, MA, LPC

While the top risk factor for completed suicide is a history of previous attempts, childhood trauma and impulsivity have also been found to increase the risk of suicidality in adults (1,2). However, there have been few investigations into whether these 2 variables influence each other in their association with suicidal ideation and attempts.

Prior research has linked childhood trauma with increased frequency of a range of psychiatric disorders, such as depression, posttraumatic stress disorder, eating disorders, panic disorder, and substance abuse.1 Additionally, a correlation between impulsivity and risky behaviors — including suicidality — has been found, and research published in 2014 discovered higher levels of impulsivity among patients with a self-reported history of at least 1 suicide attempt, compared to those with no reported previous attempts (3).

“People with histories of childhood trauma often develop difficulties with managing negative emotion, coping with stress, and maintaining optimism in the face of life stressors,” Lisa Cohen, PhD, a professor of psychiatry at Icahn School of Medicine at Mount Sinai Beth Israel in New York, told Psychiatry Advisor. “Impulsivity is a risk factor for all types of reckless behavior, including suicidal behavior,” she added.

Dr Cohen and others, including lead author Laura DeRubeis, a doctoral student at Adelphi University in New York, recently sought to determine whether impulsivity mediates the relationship between childhood trauma and suicidality in a sample of 113 adult inpatients (4). They hypothesized that after impulsivity was controlled for, childhood trauma would no longer predict suicidality at a statistically significant level.

As part of a larger investigation, participants were administered several questionnaires: the Childhood Trauma Questionnaire (CTQ), a Likert-type scale that measures emotional, physical, and sexual abuse, as well as emotional and physical neglect; the Barratt Impulsiveness Scale (BIS-11) and the Behavioral Activation Scale (BAS) of the Behavioral Inhibition and Activation Scales (collectively known as BIS/BAS, not to be confused with the BIS-11); and select items from the Columbia Suicide Severity Rating Scale (C-SSRS) to assess ideation and attempts.

According to the results, which were presented at the 2016 Annual Meeting of the American Psychiatric (APA) in Atlanta, Georgia, both childhood trauma and impulsivity had independent effects on suicidal ideation. However, childhood trauma was found to have an independent association with suicide attempts, while impulsivity was not. “We expected childhood trauma to influence suicidal ideation and attempts through a pathway of impulsivity, so that trauma leads to impulsivity which then leads to suicidal ideation and attempts,” explains Dr Cohen. Instead, they found that impulsivity was only related to suicidal ideation, and when childhood trauma was controlled for, impulsivity no longer predicted attempts.

Though these findings are in line with previous data on the correlation between childhood trauma, impulsivity, and suicidal ideation, they contradict the hypothesis of the current study as well as results of other studies suggesting that impulsivity is a risk factor for suicide attempts. “Childhood trauma seems to have a potent independent effect on both suicidal ideation and suicidal attempts,” the authors concluded in their paper.

References

1. O’Brien BS, Sher L. Child sexual abuse and the pathophysiology of suicide in adolescents and adults. Int J Adolesc Med Health. 2013;25(3):201-205.

2. Wedig MM, Silverman MH, Frankenburg FR, Reich DB, Fitzmaurice G, Zanarini MC. Predictors of suicide attempts in patients with borderline personality disorder over 16 years of prospective follow-up. Psychol Med. 2012;42(11):2395-2404.

3. Mccullumsmith CB, Williamson DJ, May RS, A, Bruer EH, Sheehan DV, Alphs LD. Simple measures of hopelessness and impulsivity are associated with acute suicidal ideation and attempts in patients in psychiatric crisis. Innov Clin Neurosci. 2014;11(9-10): 47-53.

4. DeRubeis L, Kim KHS, Ardalan F, Tanis T, Galynker I, Cohen L. The relationship between childhood trauma, impulsivity, and suicidality in an inpatient sample. Poster presentation at: 2016 Annual Meeting of the American Psychiatric Association; May 14-18, 2016; Atlanta, GA. Young Investigators’ New Research 1–017.

http://www.psychiatryadvisor.com/apa-2016-coverage/apa-2016-research-found-impulsivity-without-childhood-trauma-did-not-predict-suicide-attempts/article/497331/

Our brain’s ability to process information and adapt effectively is dependent on a number of factors, including genes, nutrition, and life experiences. These life experiences wield particular influence over the brain during a few sensitive periods when our most important muscle is most likely to undergo physical, chemical, and functional remodeling.

According to Tara Swart, a neuroscientist and senior lecturer at MIT, your “terrible twos” and those turbulent teen years are when the brain’s wiring is most malleable. As a result, traumatic experiences that occur during these time periods can alter brain activity and ultimately change gene expressions—sometimes for good.

Throughout the first two years of life, the brain develops at a rapid pace. However, around the second year, something important happens—babies begin to speak.

“We start to understand speech first, then we start to articulate speech ourselves and that’s a really complex thing that goes on in the brain,” Swart, who conducts ongoing research on the brain and how it affects how we become leaders, told Quartz. “Additionally, children start to walk—so from a physical point of view, that’s also a huge achievement for the brain.

Learning and understanding a new language forces your brain to work in new ways, connecting neurons and forming new pathways. This is a mentally taxing process, which is why learning a new language or musical instrument often feels exhausting.

With so many important changes happening to the brain in such a short period of time, physical or emotional trauma can cause potentially momentous interruptions to neurological development. Even though you won’t have any memories of the interruptions (most people can’t remember much before age five), any kind of traumatic event—whether it’s abuse, neglect, ill health, or separation from your loved ones—can lead to lasting behavioral and cognitive deficits later in life, warns Swart.

To make her point, Swart points to numerous studies on orphans in Romania during the 1980s and 1990s. After the nation’s communist regime collapsed, an economic decline swept throughout the region and 100,000 children found themselves in harsh, overcrowded government institutions.

“[The children] were perfectly well fed, clothed, washed, but for several reasons—one being that people didn’t want to spread germs—they were never cuddled or played with,” explains Swart. “There was a lot of evidence that these children grew up with some mental health problems and difficulty holding down jobs and staying in relationships.”

Swart continues: “When brain scanning became possible, they scanned the brains of these children who had grown up into adults and showed that they had issues in the limbic system, the part of the brain [that controls basic emotions].”

In short, your ability to maintain proper social skills and develop a sense of empathy is largely dependent on the physical affection, eye contact, and playtime of those early years. Even something as simple as observing facial expressions and understanding what those expressions mean is tied to your wellbeing as a toddler.

The research also found that the brains of the Romanian orphans had lower observable brain activity and were physically smaller than average. As a result, researchers concluded that children adopted into loving homes by age two have a much better chance of recovering from severe emotional trauma or disturbances.

The teenage years

By the time you hit your teenage years, the brain has typically reached its adult weight of about three pounds. Around this same time, the brain is starting to eliminate, or “prune” fragile connections and unused neural pathways. The process is similar to how one would prune a garden—cutting back the deadwood allows other plants to thrive.

During this period, the brain’s frontal lobes, especially the prefrontal cortex, experience increased activity and, for the first time, the brain is capable of comparing and analyzing several complex concepts at once. Similar to a baby learning how to speak, this period in an adolescent’s life is marked by a need for increasingly advanced communication skills and emotional maturity.

“At that age, they’re starting to become more understanding of social relationships and politics. It’s really sophisticated,” Swart noted. All of this brain activity is also a major reason why teenagers need so much sleep.

Swart’s research dovetails with the efforts of many other scientists who have spent decades attempting to understand how the brain develops, and when. The advent of MRIs and other brain-scanning technology has helped speed along this research, but scientists are still working to figure out what exactly the different parts of the brain do.

What is becoming more certain, however, is the importance of stability and safety in human development, and that such stability is tied to cognitive function. At any point in time, a single major interruption has the ability to throw off the intricate workings of our brain. We may not really understand how these events affect our lives until much later.

http://qz.com/470751/your-brain-is-particularly-vulnerable-to-trauma-at-two-distinct-ages/