Neurobiologists find chronic stress in early life causes anxiety, aggression in adulthood

Cold Spring Harbor, NY -- In recent years, behavioral neuroscientists have debated the meaning and significance of a plethora of independently conducted experiments seeking to establish the impact of chronic, early-life stress upon behavior – both at the time that stress is experienced, and upon the same individuals later in life, during adulthood. These experiments, typically conducted in rodents, have on the one hand clearly indicated a link between certain kinds of early stress and dysfunction in the neuroendocrine system, particularly in the so-called HPA axis (hypothalamic-pituitary-adrenal), which regulates the endocrine glands and stress hormones including corticotropin and glucocorticoid. Yet the evidence is by no means unequivocal. Stress studies in rodents have also clearly identified a native capacity, stronger in some individuals than others, and seemingly weak or absent in still others, to bounce back from chronic early-life stress. Some rodents subjected to early life stress have no apparent behavioral consequences in adulthood – they are disposed neither to anxiety nor depression, the classic pathologies understood to be induced by stress in certain individuals. Today, a research team led by Associate Professor Grigori Enikolopov of Cold Spring Harbor Laboratory (CSHL) reports online in the journal PlOS One the results of experiments designed to assess the impacts of social stress upon adolescent mice, both at the time they are experienced and during adulthood. Involving many different kinds of stress tests and means of measuring their impacts, the research indicates that a "hostile environment in adolescence disturbs psychoemotional state and social behaviors of animals in adult life," the team says. The tests began with 1-month-old male mice – the equivalent, in human terms of adolescents -- each placed for 2 weeks in a cage shared with an aggressive adult male. The animals were separated by a transparent perforated partition, but the young males were exposed daily to short attacks by the adult males. This kind of chronic activity produces what neurobiologists call social-defeat stress in the young mice. These mice were then studied in a range of behavioral tests. "The tests assessed levels of anxiety, depression, and capacity to socialize and communicate with an unfamiliar partner," explains Enikolopov. These experiments showed that in young mice chronic social defeat induced high levels of anxiety helplessness, diminished social interaction, and diminished ability to communicate with other young animals. Stressed mice also had less new nerve-cell growth (neurogenesis) in a portion of the hippocampus known to be affected in depression: the subgranular zone of the dentate gyrus. Another group of young mice was also exposed to social stress, but was then placed for several weeks in an unstressful environment. Following this "rest" period, these mice, now old enough to be considered adults, were tested in the same manner as the other cohort. In this second, now-adult group, most of the behaviors impacted by social defeat returned to normal, as did neurogenesis, which retuned to a level seen in healthy controls. "This shows that young mice, exposed to adult aggressors, were largely resilient biologically and behaviorally," says Dr. Enikolopov. However, in these resilient mice, the team measured two latent impacts on behavior. As adults they were abnormally anxious, and were observed to be more aggressive in their social interactions. "The exposure to a hostile environment during their adolescence had profound consequences in terms of emotional state and the ability to interact with peers," Dr. Enikolopov observes. ### The research described in this release was supported by the Russian Foundation for Basic Research and by the National Institute of Mental Health. "Extended Effect of Chronic Social Defeat Stress in Childhood on Behaviors in Adulthood" appears online in PlOS One Tuesday, March 25, 2014. The authors are: Irina L. Kovalenko, Anna G. Galyamina, Dmitry A. Smagin, Tatyana V. Michurina, Natalia N. Kudryavtseva and Grigori Enikolopov. About Cold Spring Harbor Laboratory Founded in 1890, Cold Spring Harbor Laboratory (CSHL) has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. CSHL is ranked number one in the world by Thomson Reuters for the impact of its research in molecular biology and genetics. The Laboratory has been home to eight Nobel Prize winners. Today, CSHL's multidisciplinary scientific community is more than 600 researchers and technicians strong and its Meetings & Courses program hosts more than 12,000 scientists from around the world each year to its Long Island campus and its China center LCSW Continuing Education

Autism Spectrum Disorder: Uncovering Clues to a Complicated Condition

Autism Spectrum Disorder Uncovering Clues to a Complicated Condition Autism is a complex brain disorder that first appears during early childhood. It affects how a person behaves and interacts with others. People with autism might not look you in the eye when talking. They may spend a lot of time lining up toys or other objects. Or they may say the same sentence over and over. The disorder is so variable—affecting each person in very different ways—that it can be difficult to diagnose and treat. This variability is why autism is called a “spectrum” disorder. It spans the spectrum from mild to severe and includes a wide range of symptoms. NIH-funded scientists have been working to uncover the secrets of autism. They’ve identified genes that may boost the risk for autism. They’ve developed therapies that can help many of those affected. And they’ve found that starting treatment as early as possible can lead to better outcomes. Still, there’s much more we need to learn about this complicated condition. About 1 in 88 children may have autism spectrum disorder, according to the U.S. Centers for Disease Control and Prevention. The number of affected children has been growing in recent years. Many researchers believe this increase is due to better diagnosis and awareness. Others suspect that yet-unknown factors may be partly to blame. Although the exact causes of autism are unclear, research suggests that both genes and the environment play important roles. Autism affects a child’s development in different ways, and so it’s known as a developmental disorder. Parents are often the first to suspect that something may not be quite right with their child’s development. They may notice their baby doesn’t make eye contact, becomes overly focused on certain objects or isn’t “babbling” like other children the same age. “A parent may first have concerns when a child is under 2 years of age,” says Dr. Connie Kasari, a child development expert at the University of California, Los Angeles. “A more certain diagnosis can usually be made by age 2, but some cases might not be clear until much later.” There are no direct tests, like blood tests or brain scans, that can identify autism. Instead, the condition is diagnosed by looking at a child’s behaviors and development. “All affected children have some sort of social impairment, but symptoms vary along a continuum,” Kasari says. “Impairment can range from kids who are in their ‘own world’ and seemingly unaware of others to high-functioning individuals who are just awkward and seem to miss the point of social interactions.” In May 2013, the American Psychiatric Association updated an important book that’s used to diagnose and classify mental disorders. The DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) includes an updated definition for autism spectrum disorder. The condition is now identified by looking for 2 broad categories of symptoms: problems with social communication and the presence of “stereotyped” behaviors, such as walking in certain patterns or insisting on specific or unusual routines. To be diagnosed with autism, these symptoms must arise during early childhood, even if they’re not noticed until later, when social demands increase. “The new DSM-5 definition moves all the disorders into a single spectrum, rather than the 4 separate autistic disorders described in the past,” says NIH pediatrician and neuroscientist Dr. Susan Swedo. She chaired the expert panel that updated the DSM-5 definition of autism spectrum disorders. “The new criteria are also more inclusive of minorities, adolescents and young adults with autism than the previous edition, which focused more on boys ages 4 to 9.” Getting diagnosed as early as possible is crucial. “Autism is treatable even though it’s not curable,” says Dr. David Mandell, an expert in autism and health services at the University of Pennsylvania. “If we intervene early enough with appropriate and intensive care, we can reduce a lot of impairments for many kids who have autism.” Research has shown that therapies focusing on behavior and communication can be helpful. Some drugs can also reduce certain related symptoms, but no medications have been approved by the U.S. Food and Drug Administration specifically for treating the main symptoms of autism. “Because autism is such a complicated disorder, no one therapy fits everyone,” Kasari explains. Kasari and her colleagues developed and tested several treatments that focus on improving social skills and communication. In one study, preschoolers with autism received intense training in basic skills such as playing and sharing attention. Five years later, these children tended to have stronger vocabularies and better communication skills than children who received standard therapy. “We’ve found that if we can improve these basic skills, we can also improve language learning for these kids,” Kasari says. “We’re now studying 2 potential therapies in at-risk babies, ages 12- to 21-months old, to see if we can push language development along faster for the children.” Scientists are also looking for ways to predict likely outcomes for children with autism. One NIH-funded team found that the brain waves of some 2-year-olds with autism can have a distinctive pattern when they listen to familiar words. The children with more severe social symptoms didn’t have a typical focused response in the brain region that processes language. Follow-up studies showed that these brain responses predicted the children’s developmental abilities 2 and 4 years later. “In the future, we’d like to be able to assess a child based on brain function or their genetic profile and then identify the intervention that might be best for that particular kid,” Mandell says. A growing number of studies are looking at autism in older age groups. “While we think about autism as a disorder of childhood, it actually continues through adolescence and into adulthood,” Mandell says. “Some adults with autism have been misdiagnosed, and they can find themselves being treated for other conditions. We’d like to develop better screening tools and ultimately provide these adults with skills and supports to help them become happy and productive citizens.” While research is ongoing, it’s clear that early diagnosis and treatment can improve outcomes for those with autism. If you’re concerned about your child’s social communication and behaviors, don’t wait. Talk with your child’s doctor. You may be referred to a specialist who can do a thorough evaluation. The earlier autism is diagnosed, the sooner specific therapy can begin Social Worker Continuing Education