Teenage girls exposed to more stressors that increase depression risk

Adolescence is often a turbulent time, and it is marked by substantially increased rates of depressive symptoms, especially among girls. New research indicates that this gender difference may be the result of girls' greater exposure to stressful interpersonal events, making them more likely to ruminate, and contributing to their risk of depression.

The findings are published in Clinical Psychological Science, a journal of the Association for Psychological Science.
"These findings draw our focus to the important role of stress as a potential causal factor in the development of vulnerabilities to depression, particularly among girls, and could change the way that we target risk for adolescent depression," says psychology researcher and lead author on the study, Jessica Hamilton of Temple University.

"Although there is a range of other vulnerabilities that contribute to the emergence of girls' higher rates of depression during adolescence, our study highlights an important malleable pathway that explains girls' greater risk of depression."

Research has shown that cognitive vulnerabilities associated with depression, such as negative cognitive style and rumination, emerge during adolescence. Teens who tend to interpret events in negative ways (negative cognitive style) and who tend to focus on their depressed mood following such events (rumination) are at greater risk of depression.

Hamilton, a doctoral student in the Mood and Cognition Laboratory of Lauren Alloy at Temple University, hypothesized that life stressors, especially those related to adolescents' interpersonal relationships and that adolescents themselves contribute to (such as a fight with a family member or friend), would facilitate these vulnerabilities and, ultimately, increase teens' risk of depression.

The researchers examined data from 382 Caucasian and African American adolescents participating in an ongoing longitudinal study. The adolescents completed self-report measures evaluating cognitive vulnerabilities and depressive symptoms at an initial assessment, and then completed three follow-up assessments, each spaced about 7 months apart.
As expected, teens who reported higher levels of interpersonal dependent stress showed higher levels of negative cognitive style and rumination at later assessments, even after the researchers took initial levels of the cognitive vulnerabilities, depressive symptoms, and sex into account.

Girls tended to show more depressive symptoms at follow-up assessments than did boys -- while boys' symptoms seemed to decline from the initial assessment to follow-up, girls' symptoms did not.

Girls also were exposed to a greater number of interpersonal dependent stressors during that time, and analyses suggest that it is this exposure to stressors that maintained girls' higher levels of rumination and, thus, their risk for depression over time.
The researchers emphasize that the link is not driven by reactivity to stress -- girls were not any more reactive to the stressors that they experienced than were boys.

"Simply put, if boys and girls had been exposed to the same number of stressors, both would have been likely to develop rumination and negative cognitive styles," Hamilton explains.

Importantly, other types of stress -- including interpersonal stress that is not dependent on the teen (such as a death in the family) and achievement-related stress -- were not associated with later levels of rumination or negative cognitive style.

"Parents, educators, and clinicians should understand that girls' greater exposure to interpersonal stressors places them at risk for vulnerability to depression and ultimately, depression itself," says Hamilton. "Thus, finding ways to reduce exposure to these stressors or developing more effective ways of responding to these stressors may be beneficial for adolescents, especially girls."

According to Hamilton, the next step will be to figure out why girls are exposed to more interpersonal stressors: "Is it something specific to adolescent female relationships? Is it the societal expectations for young adolescent girls or the way in which young girls are socialized that places them at risk for interpersonal stressors? These are questions to which we need to find answers!"
 

Journal Reference:

1. J. L. Hamilton, J. P. Stange, L. Y. Abramson, L. B. Alloy. Stress and the Development of Cognitive Vulnerabilities to Depression Explain Sex Differences in Depressive Symptoms During Adolescence. Clinical Psychological Science, 2014; DOI: 10.1177/2167702614545479

 Courtesy: ScienceDaily

Drug used for another disease slows progression of Parkinson's

A new study from UCLA found that a drug being evaluated to treat an entirely different disorder helped slow the progression of Parkinson's disease in mice.

The study, published in the October edition of the journal Neurotherapeutics, found that the drug, AT2101, which has also been studied for Gaucher disease, improved motor function, stopped inflammation in the brain and reduced levels of alpha-synuclein, a protein critically involved in Parkinson's.
though the exact cause of Parkinson's is unknown, evidence points to an accumulation of alpha-synuclein, which has been found to be common to all people with the disorder. The protein is thought to destroy the neurons in the brain that make dopamine, a neurotransmitter that helps regulate a number of functions, including movement and coordination. Dopamine deficiency is associated with Parkinson's disease.
Gaucher disease is a rare genetic disorder in which the body cannot produce enough of an enzyme called β-glucocerebrosidase, or GCase. Researchers seeking genetic factors that increase people's risk for developing Parkinson's have determined that there may be a close relationship between Gaucher and Parkinson's due to a GCase gene. Mutation of this gene, which leads to decreased GCase activity in the brain, has been found to be a genetic risk factor for Parkinson's, although the majority of patients with Parkinson's do not carry mutations in the Gaucher gene.
"This is the first time a compound targeting Gaucher disease has been tested in a mouse model of Parkinson's disease and was shown to be effective," said the study's senior author, Marie-Francoise Chesselet, the Charles H. Markham Professor of Neurology at UCLA and director of the UCLA Center for the Study of Parkinson's Disease. "The promising findings in this study suggest that further investigation of this compound in Parkinson's disease is warranted."
In the study, the researchers used mice that were genetically engineered to make too much alpha-synuclein which, over time, led the animals to develop deficits similar to those observed in humans with Parkinson's. The researchers found that the mice's symptoms improved after they received AT2101 for four months.
The researchers also observed that AT2101 was effective in treating Parkinson's in mice even though they did not carry a mutant version of the Gaucher gene, suggesting that the compound may have a clinical effect in the broader Parkinson's population.
AT2101 is a first-generation "pharmacological chaperone" -- a drug that can bind malfunctioning, mutated enzymes and lead them through the cell to their normal location, which allows the enzymes to carry on with their normal work. This was the first time that a pharmacological chaperone showed promise in a model of Parkinson's, according to Chesselet.
Parkinson's disease affects as many as 1 million Americans, and 60,000 new cases are diagnosed each year. The disorder continues to puzzle scientists. There is no cure and researchers have been unable to pin down its cause and no drug has been proven to stop the progression of the disease, which causes tremors, stiffness and other debilitating symptoms. Current Parkinson's treatments only address its symptoms.

Journal Reference:

1. Franziska Richter, Sheila M. Fleming, Melanie Watson, Vincent Lemesre, Lee Pellegrino, Brian Ranes, Chunni Zhu, Farzad Mortazavi, Caitlin K. Mulligan, Pedrom C. Sioshansi, Sindalana Hean, Krystal De La Rosa, Richie Khanna, John Flanagan, David J. Lockhart, Brandon A. Wustman, Sean W. Clark, Marie-Françoise Chesselet. A GCase Chaperone Improves Motor Function in a Mouse Model of Synucleinopathy. Neurotherapeutics, 2014; DOI: 10.1007/s13311-014-0294-x

 Courtesy: ScienceDaily

Non-coding half of human genome unlocked with novel sequencing technique

An obscure swatch of human DNA once thought to be nothing more than biological trash may actually offer a treasure trove of insight into complex genetic-related diseases such as cancer and diabetes, thanks to a novel sequencing technique developed by biologists at Texas A&M University.

Texas A&M University biology doctoral student John C. Aldrich (left), working with associate professor of biology Dr. Keith A. Maggert (right), has developed an inexpensive, fluorescent-dye-based sequencing technique to monitor DNA-related dyanmics in heterochromatin -- a game-changing discovery that lays the groundwork to study the non-coding half of the human genome.

The game-changing discovery was part of a study led by Texas A&M biology doctoral candidate John C. Aldrich and Dr. Keith A. Maggert, an associate professor in the Department of Biology, to measure variation in heterochromatin. This mysterious, tightly packed section of the vast, non-coding section of the human genome, widely dismissed by geneticists as "junk," previously was thought by scientists to have no discernable function at all.

In the course of his otherwise routine analysis of DNA in fruit flies, Aldrich was able to monitor dynamics of the heterochromatic sequence by modifying a technique called quantitative polymerase chain reaction (QPCR), a process used to amplify specific DNA sequences from a relatively small amount of starting material. He then added a fluorescent dye, allowing him to monitor the fruit-fly DNA changes and to observe any variations.

Aldrich's findings, published today in the online edition of the journal PLOS ONE, showed that differences in the heterochromatin exist, confirming that the junk DNA is not stagnant as researchers originally had believed and that mutations which could affect other parts of the genome are capable of occurring.

"We know that there is hidden variation there, like disease proclivities or things that are evolutionarily important, but we never knew how to study it," Maggert said. "We couldn't even do the simplest things because we didn't know if there was a little DNA or a lot of it.

"This work opens up the other non-coding half of the genome."

Maggert explains that chromosomes are located in the nuclei of all human cells, and the DNA material in these chromosomes is made up of coding and non-coding regions. The coding regions, known as genes, contain the information necessary for a cell to make proteins, but far less is known about the non-coding regions, beyond the fact that they are not directly related to making proteins.

"Believe it or not, people still get into arguments over the definition of a gene," Maggert said. "In my opinion, there are about 30,000 protein-coding genes. The rest of the DNA -- greater than 90 percent -- either controls those genes and therefore is technically part of them, or is within this mush that we study and, thanks to John, can now measure. The heterochromatin that we study definitely has effects, but it's not possible to think of it as discrete genes. So, we prefer to think of it as 30,000 protein-coding genes plus this one big, complex one that can orchestrate the other 30,000."

Although other methods of measuring DNA are technically available, Aldrich notes that, as of yet, none has proven to be as cost-effective nor time-efficient as his modified-QPCR-fluorescence technique.

"There's some sequencing technology that can also be used to do this, but it costs tens of thousands of dollars," Aldrich said. "This enables us to answer a very specific question right here in the lab."

The uncharted genome sequences have been a point of contention in scientific circles for more than a decade, according to Maggert, a Texas A&M faculty member since 2004. It had long been believed that the human genome -- the blueprint for humanity, individually and as a whole -- would be packed with complex genes with the potential to answer some of the most pressing questions in medical biology.

When human DNA was finally sequenced with the completion of the Human Genome Project in 2003, he says that perception changed. Based on those initial reports, researchers determined that only two percent of the genome (about 21,000 genes) represented coding DNA. Since then, numerous other studies have emerged debating the functionality, or lack thereof, of non-coding, so-called "junk DNA."

Now, thanks to Aldrich's and Maggert's investigation of heterochromatin, the groundwork has been laid to study the rest of the genome. Once all of it is understood, scientists may finally find the root causes and possibly treatments for many genetic ailments.

"There is so much talk about understanding the connection between genetics and disease and finding personalized therapies," Maggert said. "However, this topic is incomplete unless biologists can look at the entire genome. We still can't -- yet -- but at least now, we're a step closer."

Journal Reference:

1. John C. Aldrich, Keith A. Maggert. Simple Quantitative PCR Approach to Reveal Naturally Occurring and Mutation-Induced Repetitive Sequence Variation on the Drosophila Y Chromosome. PLoS ONE, 2014; 9 (10): e109906 DOI: 10.1371/journal.pone.0109906 

Courtesy: ScienceDaily