Early puberty in girls may be 'big bang theory' for migraine
July 11, 2019
Science Daily/University of Cincinnati
Adolescent girls who reach puberty at an earlier age may also have a greater chance of developing migraine headaches, according to new research from investigators at the University of Cincinnati (UC) College of Medicine.
"We know that the percentage of girls and boys who have migraine is pretty much the same until menstruation begins," says Vincent Martin, MD, professor in the Division of General Internal Medicine and director of the Headache and Facial Pain Center at the UC Gardner Neuroscience Institute. "When the menstrual period starts in girls, the prevalence goes way up, but what our data suggests is that it occurs even before that."
The findings will be presented by Martin at the American Headache Society 61st Annual Scientific Meeting Saturday, July 13, in Philadelphia.
Nationally, about 10 percent of school age children suffer from migraine, according to the Migraine Research Foundation (MRF). As adolescence approaches, the incidence of migraine increases rapidly in girls, and by age 17, about 8 percent of boys and 23 percent of girls have experienced migraine, the MRF reports.
Martin and a team of researchers were part of a longitudinal study looking at 761 adolescent girls from sites in Cincinnati, New York and the San Francisco Bay area. The girls ranged in age from 8 to 20 and study took place over a 10-year period beginning in 2004. Girls enrolled in the study at age 8-10 were examined during study visit every six to 12 months. Researchers determined when they showed initial signs of thelarche (breast development), pubarche (pubic hair growth) and menarche (start of menstrual periods).
Girls answered a headache questionnaire to find out if they suffered from migraine headache, no migraine or probable migraine -- the latter is defined as meeting all the diagnostic criteria for migraine except one. The average age at which they completed the survey was 16.
Of those surveyed, 85 girls (11 percent) were diagnosed with migraine headache while 53 (7%) had probable migraine and 623 (82%) had no migraine, according to Martin, also a UC Health physician specializing in migraine.
Researchers found that girls with migraine had an earlier age of thelarche (breast development) and the onset of menarche (menstrual periods) than those with no migraine. On average breast development occurred four months earlier in those with migraine while menstruation started five months earlier. There was no difference in the age of pubarche (pubic hair development) between those with migraine and no migraine.
"There was a 25 percent increase in the chance of having migraine for each year earlier that a girl experienced either thelarche or menarche," says Susan Pinney, PhD, professor in the UC Department of Environmental Health and lead investigator on the study. "This suggests a strong relationship between early puberty and the development of migraine in adolescent girls."
The age of onset of thelarche, pubarche or menarche did not differ between those with probable migraine and no migraine, says Pinney.
Previous research suggests that migraine often starts with the onset of menstrual cycles during menarche in adolescent girls. But this study looks at earlier stages of puberty such as thelarche and pubarche, explains Martin.
"To suggest the origins of migraine may occur actually before menstrual periods begin is pretty novel," says Martin. "At each of these stages, different hormones are starting to appear in girls. During pubarche, testosterone and androgens are present, and during thelarche, there is the very first exposure to estrogen. Menarche is when a more mature hormonal pattern emerges. Our study implies that the very first exposure to estrogen could be the starting point for migraine in some adolescent girls. It may be the Big Bang Theory of migraine."
So is there anything that one can do to prevent an early puberty?
"Studies suggest that childhood obesity is associated with early puberty," says Martin, who is also president of the National Headache Foundation. "Keeping your weight down might prevent the early onset of puberty. Future studies will need to be done to determine if strategy will decrease also the likelihood of developing migraine."
https://www.sciencedaily.com/releases/2019/07/190711122700.htm
Childhood adversity linked to early puberty, premature brain development and mental illness
Penn study details effects of poverty and trauma on youth brain and behavior
May 31, 2019
Science Daily/University of Pennsylvania School of Medicine
Growing up in poverty and experiencing traumatic events like a bad accident or sexual assault can impact brain development and behavior in children and young adults. Low socioeconomic status (L-SES) and the experience of traumatic stressful events (TSEs) were linked to accelerated puberty and brain maturation, abnormal brain development, and greater mental health disorders, such as depression, anxiety, and psychosis, according to a new study published this week in JAMA Psychiatry. The research was conducted by a team from Perelman School of Medicine at the University of Pennsylvania and Children's Hospital of Philadelphia (CHOP) through the Lifespan Brain Institute (LiBI).
"The findings underscore the need to pay attention to the environment in which the child grows. Poverty and trauma have strong associations with behavior and brain development, and the effects are much more pervasive than previously believed," said the study's lead author Raquel E. Gur, MD, PhD, a professor of Psychiatry, Neurology, and Radiology at the Perelman School of Medicine at the University of Pennsylvania, and director of the Lifespan Brain Institute.
Parents and educators are split into opposing camps with regard to the question of how childhood adversity affects development into mature, healthy adulthood. Views differ from "spare the rod and spoil the child" to concerns that any stressful condition such as bullying will have a harmful and lasting effects. Psychologists and social scientists have documented lasting effects of growing up in poverty on cognitive functioning, and clinicians observed effects of childhood trauma on several disorders, though mostly in the context of post-traumatic stress disorders (PTSD). There are also anecdotal observations, supported by some research, that adversity accelerates maturation -- children become young adults faster, physically and mentally. Neuroscientists, who are aware of the complexity of changes that the brain must undergo as it transitions from childhood to young adulthood, suspected, and more recently documented that childhood adversity affects important measures of brain structure and function. But this study was the first to compare the effects of poverty (L-SES) to those who experienced TSEs in the same sample set.
The researchers analyzed data from the Philadelphia Neurodevelopmental Cohort, which included 9,498 participants aged 8 to 21 years for the study. The racially and economically diverse cohort includes data on SES, TSEs, neurocognitive performance, and in a subsample, multimodal neuroimaging taken via MRI.
The researchers found specific associations of SES and TSE with psychiatric symptoms, cognitive performance, and several brain structure abnormalities.
The findings revealed that poverty was associated with small elevation in severity of psychiatric symptoms, including mood/anxiety, phobias, externalizing behavior (oppositional-defiant, conduct disorder, ADHD), and psychosis, as compared to individuals who did not experience poverty. The magnitude of the effects of TSEs on psychiatric symptom severity was unexpectedly large. TSEs were mostly associated with PTSD, but here the authors found that even a single TSE was associated with a moderate increase in severity for all psychiatric symptoms analyzed, and two or more TSEs showed large effect sizes, especially in mood/anxiety and in psychosis. Additionally, these effects were larger in females than in males.
With neurocognitive functioning, the case was reversed; poverty was found to be associated with moderate to large cognitive deficits, especially in executive functioning -- abstraction and mental flexibility, attention, working memory -- and in complex reasoning. TSEs were found to have very subtle effects, with individuals who experienced two or more TSEs showing a mild deficit in complex cognition, but demonstrating slightly better memory performance.
Both poverty and TSEs were associated with abnormalities across measures of brain anatomy, physiology, and connectivity. Poverty associations were widespread, whereas TSEs were associated with more focused differences in the limbic and fronto-parietal regions of the brain, which processes emotions, memory, executive functions and complex reasoning.
The researchers also found evidence that adversity is associated with earlier onset of puberty. Both poverty and experiencing TSEs are associated with the child physically maturing at an earlier age. The researchers also found the same effects on the brain, with findings revealing that a higher proportion of children who experienced adversity had characteristics of adult brains. This affects development, as the careful layering of the structural and functional connectivity in the brain requires time, and early maturity could prevent the necessary honing of skills.
"Altogether our study shows no evidence to support the 'spare the rod' approach, to the contrary we have seen unexpectedly strong effects of TSEs on psychiatric symptoms and of poverty on neurocognitive functioning, and both are associated with brain abnormalities," Gur said. "The study suggests that it makes sense for parents and anyone involved in raising a child to try and shield or protect the child from exposure to adversity. And for those dealing with children who were already exposed to adversity -- as is sadly the case today with refugees around the world -- expect an increase in symptoms and consider cognitive remediation, a type of rehabilitation treatment which aims to improve attention, memory, and other cognitive functions."
"Traumas that happen to young children can have lifelong consequences," said the study's senior author Ruben C. Gur, PhD, a professor of Psychiatry, Radiology, and Neurology, and director of the Brain Behavior Laboratory. "Obviously it would be best if we could ameliorate poverty and prevent traumatic events from occurring. Short of that, the study calls for paying more attention to a child's socioeconomic background and to effects of trauma exposure. Parents and educators should become more aware of the special needs of children who are exposed to either adversity. Additionally, mental health professionals should be particularly on notice that traumatic events are associated not only with PTSD, but with elevations across domains including mood, anxiety, and psychosis."
https://www.sciencedaily.com/releases/2019/05/190531085404.htm
Early puberty linked with increased risk of obesity for women
March 15, 2018
Science Daily/Imperial College London
Girls who start puberty earlier are more likely to be overweight as adults, finds new research
The researchers say their findings, published today in the International Journal of Obesity, strengthen existing evidence of a link between the onset of puberty and a woman's body mass in adulthood.
Previous studies have established a link between obesity and puberty, with increased bodyweight known to be a risk factor for girls starting puberty earlier.
However, these observational findings can be influenced by situational factors, such as ethnicity, economic background, education level, and diet, making it difficult to determine whether early puberty or these other factors are the cause.
But now this latest research shows that early puberty is itself a risk factor for being overweight, with girls who have their first period earlier more likely to have a higher Body Mass Index (BMI).
According to the authors of the study, their findings help to untangle these complex external factors and add insight into an underlying causal link, showing that early puberty has a significant impact on a woman's risk of obesity.
Dr Dipender Gill, a Wellcome Trust Clinical Research Fellow in the School of Public Health and first author of the study, said: "Previous studies have shown there is an association, but we didn't know whether early puberty caused obesity in adulthood, or was simply associated with it. In our latest study we've generated evidence to support that it is a causal effect."
In order to get around the effects of confounding factors, the Imperial team used genetic variants as a tool to look at the effect of the onset of puberty (known as age at menarche), measured as the age of a girl's first period.
The genes in every cell of our bodies are randomly gifted to us from our parents when their sperm and egg cells fuse, with the outcome of this random jumble being the genetic basis of the embryo -- influencing everything from hair colour to risk of disease for the rest of your life.
But single 'letter' changes to the DNA sequence of a gene can alter its function. In terms of disease risk, these single letter variants (called single-nucleotide polymorphisms, or SNPs) can result in a small increase or decrease in risk. The combination of variants of more than 20,000 genes contribute towards our cumulative genetic risk.
In the latest study, researchers employed a statistical technique called Mendelian Randomization which uses these genetic variants as a tool to show the causal relationship between earlier puberty and increased BMI.
Using data from 182,416 women they identified 122 genetic variants that were strongly associated with the onset of puberty -- with the women's age at first period obtained via questionnaire.
The team then looked at data from the UK Biobank, which holds biomedical information on hundreds of thousands of people, incorporating physiological measurement data with genetic sequence data and questionnaire responses. Specifically, they looked for the effect of the genetic variants related to age at menarche with BMI in a second set of 80,465 women from the UK Biobank, for whom they also had measurements for BMI.
Initial analysis revealed a link between these genetic variants and BMI, with those women who had variants associated with earlier puberty having an increased BMI. The researchers then tested for this same association in a third group 70,962 women, finding the same association.
Dr Gill, added: "Some of these genetic variants are associated with earlier puberty and some with later onset, so by taking advantage of this we were able to investigate any association of age at menarche with BMI in adulthood.
"We're not saying that it's a genetic effect, but rather that by using these genetic variants as a proxy for earlier puberty, we are able to show the effect of earlier puberty without the impact of external factors that might confound our analysis. We performed a range of statistical sensitivity analyses to test the robustness of our findings and they remained strong through this, so within the limitations of the study design, we are confident of findings."
Previous research from the group has used the same technique to show that low iron levels are associated with an increased risk of heart disease, as well as showing that girls who start puberty earlier are likely to spend less time in education.
Future studies will use the same Mendelian Randomization approach to look at genetic variants in relation to drug targets for cardiovascular disease and stroke.
The technique is not without its limitations, and it is possible that these genetic variants could be influencing bodyweight independently of age at menarche, such as through altering metabolism or fat production. However, even after the team had removed any genetic variants that were also associated with childhood obesity (12 in total), they came to the same finding.
According to the researchers, it remains unclear how maturing earlier has a direct impact on bodyweight, but they indicate that differences between physical and emotional maturity may play a role. It could be that young women who mature earlier than their peers are treated differently or have different societal pressures than girls of the same age who have not started puberty.
Another explanation could be the physical effects of hormonal changes during puberty, such as increased fat deposition in breast tissue, which when established earlier may move them to a higher risk profile for higher BMI or obesity in later life.
"It is difficult to say that changing someone's age of puberty will affect their adult risk of obesity and whether it is something that we can clinically apply -- as it would unlikely be ethically appropriate to accelerate or delay the rate of puberty to affect BMI," added Dr Gill. "But it is useful for us to be aware that it's a causal factor- girls who reach puberty earlier may be more likely to be overweight when they are older."
https://www.sciencedaily.com/releases/2018/03/180315203819.htm