Earthquakes and Mental Health

Impact on Children and Families

Because earthquakes are unexpected and can be very destructive, being in one can be terrifying. People fear they will be injured or killed. They may be separated from family, with hours passing before knowing if their loved ones are safe. They may see collapsed buildings or other destruction and experience the horror of seeing severely injured people or even dead bodies. As they assess the damage, people may find that a relative or close friend has been killed or that their home has been destroyed. Earthquakes are particularly difficult physically and emotionally for people who are disabled or have special needs ceus for social workers

In the aftermath, people may continue to encounter sights, sounds, smells, sensations, and inner feelings that remind them-even years after-of the earthquake. These traumatic reminders can bring on distressing mental images, thoughts, and emotional/physical reactions. Common reminders include aftershocks, cracks in the wall, rumbling noises, destroyed buildings, smells of fire and smoke, the place where they experienced the earthquake, seeing people with disabilities, funerals, anniversaries of the date, and television or radio news about earthquakes.

An earthquake may serve as a reminder of prior trauma and loss, making the current reactions even worse. Post-earthquake problems with living conditions, food, water, electricity, transportation, school, work, and daily routines may make living very difficult for weeks or even months. Efforts to contend with these adversities may significantly reduce a person's coping and emotional resources, and in turn interfere with their ability to recover

Post-earthquake studies of children and adults from around the world have found that:
•Those with the most severe earthquake-related experiences and losses have the most severe and persistent posttraumatic stress and grief reactions.
•There can be widespread separation-anxiety in children and adolescents following the event.
•Depression, associated with posttraumatic stress reactions and disruption to living circumstances, often occurs after major earthquakes.
•Ongoing problems may include: marital discord; substance abuse; delinquent, aggressive or withdrawn behavior; and complaints about physical health, including headaches, stomachaches, rapid heartbeat, tightness in the chest, and appetite and digestive problems.
•Children and adolescents lose trust in the safety and security of the world, and in the ability of adults to protect them.
•Specialized trauma- or grief-focused mental health services can help children and adolescents recover from the psychological consequences of an earthquake.

Recovery: After an Earthquake



Most families will recover over time, particularly with the support of family, friends, and organizations. The length of recovery will depend, in part, upon how frightening the earthquake was, whether evacuation from home was necessary, and the extent of the damage and loss. Some families will be able to return to their normal routines rather quickly, while others will have to contend with repairing damage to their home and possessions, finding medical care, and facing financial hardship. Some families will have lost a loved one or a pet. Others will need to deal with school closings or changes in school schedules.

Children's functioning and recovery will be influenced by how their parents and caregivers cope during and after the earthquake. Children often turn to adults for information, comfort, and help. Children do best when parents and teachers remain (or at least appear) calm, answer children's questions honestly, and respond as best they can to requests.

What You Should Know About Tornadoes

A tornado is a rapidly rotating column of air that extends from the cloud base to the ground. Tornadoes generally travel from west/southwest to east/northeast, but they can travel in any direction and can change their course suddenly. Sometimes tornadoes are preceded by heavy rain, wind, and hail; other times they seem to arise out of relatively clear conditions. Sometimes people hear a loud roar or trainlike sound when a tornado approaches. While tornadoes have occurred in all fifty states, the Midwestern and Southern states have the greatest number. The most violent tornadoes tend to be in the spring, but they can occur any time of the year.

Advances in weather prediction have resulted in fewer tornado-related injuries and fatalities. Unfortunately, these advances have led to a false sense of security. If a tornado watch (when atmospheric conditions are favorable for forming a tornado) should become a tornado warning (when a tornado has formed), families should seek shelter quickly. The National Oceanographic and Atmospheric Administration's Storm Prediction Center has a Tornado FAQ with more information about tornadoes.

Impact on Children and Families

A tornado threatens the usual assumptions of safety. The winds and flying debris can disrupt telephone lines and other utilities, breaking down communication. A powerful storm can blow off the roofs of houses, break windows, blow open doors, split trees in two, and destroy entire homes. Leaving shelter is dangerous, as windblown items such as shards of glass, parts of houses, and uprooted trees can cause sudden injury or death.

Tornadoes are unusual storms, as their path is often erratic. In the same neighborhood, some houses may be leveled completely while others sustain little damage. While scattered destruction can be easier on the community than that of a flood or a hurricane—in that not all community resources may be used up—the inconsistent pattern of damage can cause feelings of guilt in those spared or unfairness in those recovering. Children may develop unusual ideas or myths about why a tornado did or did not hit their home.

Children may see anxiety and fear in parents and caregivers who are usually confident. They may lose their homes and cherished pets, memorabilia, and toys. They may see collapsed or damaged buildings—including their schools or familiar community landmarks. They may encounter rubble, debris, or other wreckage, and experience the horror of seeing severely injured people or dead bodies.

As with other natural disasters, there may be a spectrum of psychological casualties. Individuals with preexisting emotional and behavioral problems may get worse if their support systems fail, they run out of medications, and/or their routine destabilizes. Others may develop chronic emotional and behavioral problems following exposure to pervasive stresses, such as the loss of community infrastructure, home or employment, or family or friends. In addition, emotional and physical exhaustion may affect individuals or families' ability to recover counselor ceus

Children and adults frequently experience traumatic reminders, during which they suddenly relive and reexperience the emotions, fears, thoughts, and perceptions, they experienced at the time of the tornado. Typical traumatic reminders include tornado watches and warnings, thunderstorms, dark clouds, high winds, and hail.

Common emotional reactions of children and family members exposed to a tornado include:
•Feelings of insecurity, unfairness, anxiety, fear, anger, sadness, despair, and worries about the future
•Fear that another tornado will occur
•Believing myths or folklore as to the cause of the tornado
•Disruptive behaviors, irritability, temper tantrums, agitation, or hyperactivity
•Clinging/dependent behaviors or avoidant and phobic symptoms
•Physical symptoms, such as stomachaches, headaches, loss of appetite, nightmares, or sleep problems
•Increased concerns regarding the safety of family members, friends, and loved ones
•School-based problems, with decreased motivation and school performance

Adolescents may differ from younger children in how they respond to a tornado or other natural disaster. Some believe they will not live long and may exhibit:

•Socially withdrawn, angry, or irritable
•Risky behavior
•Conflict with authority

Many School-aged Children with ASD in South Korea Go Undiagnosed

Total population study points to possible higher rates of ASDs when screening the general population and the growing worldwide concern for screening, diagnosis, and services

Source: Getty
The prevalence of autism spectrum disorder (ASD) among children in South Korea appears to be much higher than the range of estimates previously reported in other countries, according to a study partly funded by NIMH. The researchers found that two-thirds of ASD cases occurred in children attending mainstream schools; these children had not been previously diagnosed and had never received treatment for the disorder. The study was published online ahead of print on May 9, 2011, in the American Journal of Psychiatry CEUs for counselors

Background
Recent reports of increased prevalence of ASD have raised concerns among parents, researchers, and policymakers. However, it is still unclear whether these estimates reflect a true rise in ASD occurrence or improved rates of detection and diagnosis. And because different studies use different designs and methods, they may not be truly comparable. There are also limited data on the prevalence of ASD in countries outside of North America and Europe.

To address these issues, Young Shin Kim, M.D., Ph.D., of Yale School of Medicine, and colleagues targeted all children ages 7-12 in a South Korean community representative of the country's general population. The researchers asked parents and teachers about the children's social interactions, and whether they had communication problems or restricted and repetitive behaviors.

The researchers then evaluated 286 children suspected as having ASD based on the answers given. Of these children, 114 attended special education schools, had a history of mental health service use, or were listed in the local disability registry. For study purposes, the researchers considered these children to have a high probability of having ASD. The other 172 children attended regular schools, had never received special education or mental health services, and were not listed in the disability registry.

The study incorporated multiple measures to address potential cultural issues. For example, board-certified Korean child psychiatrists trained in both Korea and the United States conducted the diagnostic assessments using screening and diagnostic tools validated for Korean children. An anthropologist on the research team also organized focus groups with local parents and teachers to identify beliefs that may influence symptom reporting and to address stigma related to ASD.

Results of the Study
Based on diagnostic assessments, the prevalence of ASD among the total study population was 2.64 percent. Among the children attending regular schools, the prevalence was 1.89 percent and boys were 2.5 times more likely to have ASD than girls. Among the high-probability group the prevalence of ASD was 0.75 percent and boys were 5 times more likely to have ASD than girls.

Of the 2.64 percent of all ASD cases, 0.94 percent met diagnostic criteria for autism and 1.7 percent met criteria for other types of ASD, including Asperger's disorder and pervasive developmental disorder not otherwise specified.

Significance
Unlike previous studies that analyzed health records and registries, the researchers attempted to look at each child in every school in a particular community, even children who did not have a record of any special education need. According to the researchers, this method unmasked cases that could have gone unnoticed if they had relied solely on health records. As a result, this study's estimate of ASD prevalence is higher than previously reported estimates, which range from 0.6 percent to 1.8 percent.

However, according to the researchers, the prevalence in the high probability group is similar to reports in other studies that have focused on the same target populations. The major difference in this study was that two-thirds of ASD cases were identified in the general population among children who never had contact with care systems. This particular finding highlights the importance of screening mainstream school populations as well as clinical populations in future studies. The researchers also suggest that the highly structured educational system in South Korea may allow children with less severe ASD symptoms to manage in general education settings, despite their impairments.

What's Next
More research is needed to find out whether these results can be repeated in other populations in Korea and other countries. The researchers note that more rigorous ASD screening may provide a more accurate estimate of the number of people with ASD, and that this number may exceed previous prevalence estimates. Additionally, this study only addressed ASD prevalence, or the current number of people with the disorder. Incidence studies—those that focus on the numbers of new cases—are essential to examine possible environmental and other potential causes of the rising ASD prevalence.

Reference
Kim YS, Leventhal BL, Koh YJ, Fombonne E, Laska E, Lim EC, Cheon KA, Kim SJ, Kim YK, Lee HK, Song DH, Grinker RR. Prevalence of Autism Spectrum Disorders in a Total Population Sample. Am J Psychiatr.

Depressed Teens with History of Abuse Less Likely to Respond to Combination Treatment

Adolescents with treatment-resistant depression who have a history of abuse—especially physical abuse—are less likely to respond to combination treatment than to medication alone, according to data from the NIMH-funded Treatment of Resistant Depression in Adolescents (TORDIA) study. The new study was published in the March 2011 issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

Background
Although the relationship between childhood abuse and risk for depression or other mental disorder is well-established, few studies have examined whether a history of abuse may affect response to treatment, especially among adolescents. Some studies have suggested that a history of abuse is associated with a lower response to cognitive behavioral therapy (CBT), a type of psychotherapy that emphasizes problem-solving and behavior change social worker ceus

In the Treatment of Resistant Depression in Adolescents (TORDIA) study, teens whose depression had not improved after an initial course of selective serotonin reuptake inhibitor (SSRI) antidepressant treatment were randomly assigned to one of four interventions for 12 weeks:

Switch to another SSRI—paroxetine (Paxil), citalopram (Celexa) or fluoxetine (Prozac)
Switch to a different SSRI plus CBT
Switch to venlafaxine (Effexor), a different type of antidepressant called a serotonin and norepinephrine reuptake inhibitor (SNRI)
Switch to venlafaxine plus CBT
As reported in May 2010, about 40 percent of those who completed 24 weeks of treatment achieved remission, regardless of the treatment to which they had initially been assigned. The risk for relapse remained high, however.

About 13 percent of TORDIA participants had a history of physical abuse, 17 percent had a history of sexual abuse, and 5 percent had a history of both. In this most recent study, Wael Shamseddeen, M.D., MPH, of Rosalind Franklin University of Medicine and Sciences in North Chicago, and colleagues examined the association between having a history of physical or sexual abuse and response to combination treatment among TORDIA participants.

Results of the Study
The researchers found that teens without a history of abuse had a higher response rate to combination therapy compared to medication-only therapy (63 percent vs. 37.6 percent). Those with a history of sexual abuse responded similarly to combination and medication-only therapy (48 percent vs. 42 percent). However, those with a history of physical abuse had a much lower response rate to combination therapy (18.4 percent) compared to medication-only (52.4 percent).

Significance
The researchers were unable to identify the specific mechanism that might affect response to combination therapy among teens with a history of physical abuse. They suggest that because abuse can affect a child's brain development, abused youth may need psychotherapeutic approaches that target trauma before engaging in traditional CBT designed to treat depression. The researchers also suggest that abused youth may have a tendency to avoid unpleasant emotions, and therefore may have been averse to CBT. It is possible that therapeutic approaches that focus more on behavior and do not rely heavily on the processing of negative thoughts and emotions may be more acceptable and effective for these youth.

What's Next
The researchers concluded that more research is needed into the ways in which abuse history can confer treatment resistance among teens with hard-to-treat depression, and in developing alternative treatment approaches that are more effective.

Reference
Shamseddeen W, Asarnow JR, Clarke G, Vitiello B, Wagner KD, Birmaher B, Keller MB, Emslie G, Iyengar S, Ryan ND, McCracken JT, Porta G, Mayes T, Brent D. Impact of physical and sexual abuse on treatment response in the Treatment of Resistant Depression in Adolescents Study (TORDIA). Journal of the American Academy of Child and Adolescent Psychiatry. 2011 March. 50(3):293-301.

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5-minute Screen Identifies Subtle Signs Of Autism in 1-year Olds

NIH-funded Study Demonstrates Feasibility and Effectiveness of Conducting Systematic Screening During Well-Baby Check-Ups

A five-minute checklist that parents can fill out in pediatrician waiting rooms may someday help in the early diagnosis of autism spectrum disorder (ASD) , according to a study funded by the National Institutes of Health. Published today in the Journal of Pediatrics, the study's design also provides a model for developing a network of pediatricians to adopt such a change to their practice. Continuing education for counselors

"Beyond this exciting proof of concept, such a screening program would answer parents' concerns about their child's possible ASD symptoms earlier and with more confidence than has ever been done before," noted Thomas R. Insel, M.D., director of the National Institute of Mental Health (NIMH), part of NIH.

Identifying autism at an early age allows children to start treatment sooner, which can greatly improve their later development and learning. However, many studies show a significant delay between the time parents first report concerns about their child's behavior and the eventual ASD diagnosis, with some children not receiving a diagnosis until well after they've started school.

Recognizing the need to improve early ASD screening, Karen Pierce, Ph.D., of the University of California, San Diego, and colleagues established a network of 137 pediatricians across San Diego County. Following an hour-long educational seminar, the pediatricians screened all infants at their 1-year, well-baby check-up using the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist, a brief questionnaire that detects ASD, language delay, and developmental delay. The questionnaire asks caregivers about a child's use of eye gaze, sounds, words, gestures, objects and other forms of age-appropriate communication. Any child who failed the screen was referred for further testing and was re-evaluated every six months until age 3.

Out of 10,479 infants screened, 32 were identified as having ASD. After excluding for late onset and regression cases, this is consistent with current rates that would be expected at 12 months, according to the researchers. When including those identified as having language delay, developmental delay, or some other form of delay, the brief screen provided an accurate diagnosis 75 percent of the time.

Following the screen, all toddlers diagnosed with ASD or developmental delay and 89 percent of those with language delay were referred for behavioral therapy. On average, these children were referred for treatment around age 17 months. For comparison, a 2009 study using data from the Centers for Disease Control and Prevention found that, on average, children currently receive an ASD diagnosis around 5.7 years (68.4 months) of age, with treatment beginning sometime later.

In addition to tracking infant outcomes, the researchers also surveyed the participating pediatricians. Prior to the study, few of the doctors had been screening infants systematically for ASD. After the study, 96 percent of the pediatricians rated the program positively, and 100 percent of the practices have continued using the screening tool.

"In the context of a virtual lack of universal screening at 12 months, this program is one that could be adopted by any pediatric office, at virtually no cost, and can aid in the identification of children with true developmental delays," said Dr. Pierce.

The researchers note that future studies should seek to further validate and refine this screening tool, track children until a much older age, and assess barriers to treatment follow up.

This study was also supported by an NIMH Autism Center of Excellence grant as well as Autism Speaks and the Organization for Autism Research.

Reference
Pierce K, Carter C, Weinfeld M, Desmond J, Hazin R, Bjork R, Gallagher N. Catching, Studying, and Treating Autism Early: The 1-Yr Well-Baby Check-Up Approach. J Pediatr. 2011 Apr. [Epub ahead of print]

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The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

Light Switches Brain Pathway On-and-Off to Dissect How Anxiety Works

Turns Cowering Mice into Instant Adventurers
Scientists, for the first time, have switched anxiety on-and-off in active animals by shining light at a brain pathway. Instinctively reclusive mice suddenly began exploring normally forbidding open spaces when a blue laser activated the pathway – and retreated into a protected area when it dimmed. By contrast, anxiety-like behaviors increased when an amber laser inhibited the same pathway. Researchers, supported in part by NIMH, used a virus, genetic engineering and fiber-optics to control the pathway in the brain's fear center with millisecond precision. CEUs for Social Workers

"Our findings reveal how balanced antagonistic brain pathways are continuously regulating anxiety," explained Karl Deisseroth, M.D., Ph.D., of Stanford University, a practicing psychiatrist as well as a neuroscientist. "We have pinpointed an anxiety-quelling pathway and demonstrated a way to control it that may hold promise for new types of anti-anxiety treatments."

NIMH grantees Deisseroth, Kay M. Tye, Ph.D., and colleagues, report on their findings March 17, 2011 in the journal Nature.

Optogenetic alchemy
Anxiety disorders are the most common type of psychiatric illness, affecting more than 1 in 4 people at some time during their lives. To understand the neural basis of these disorders, researchers are studying the workings of circuitry in the fear center, called the amygdala, in rodents.

Deisseroth's team has pioneered a method, called optogenetics, of experimentally activating brain activity with light. They incorporate a protein borrowed from light-reactive organisms to make brain tissue similarly light-responsive. Previously, they used this tool to activate particular types of neurons. The new study is the first to use it to reversibly manipulate a specific projection of a neuron (see picture below). It's also the first time the technique has been used to study anxiety as opposed to fear – a generalized state versus a transient reaction to an immediate threat.

The researchers borrowed a gene that codes for a light-sensitive protein from algae and delivered it to the amygdala pathway via a virus. In the algae, the protein's function is to activate a pathway that causes the organism to swim toward blue spectrum light. Hence a blue light now activated the amygdala pathway. When they wanted to inhibit the pathway in response to light, they similarly borrowed a gene from a light-responsive bacterium that codes for a protein that inhibits a pathway in response to a particular spectrum of light — in this case amber — and infected the amygdala pathway with that gene.

When the researchers optogenetically activated whole neuronal cell bodies in the amygdala, it increased anxiety-like behavior: mice hunkered down in a protected corner of a maze and wouldn't venture into more exposed areas. These and related findings led the researchers to hypothesize that they would get the same effect if they narrowed the focus of the activation to just a specific neuronal projection (see picture below).

A post-doc's eureka! moment
But it turned out that the opposite was true.

When they activated the projection with the blue laser, the engineered mice suddenly seemed to summon the courage to explore the more exposed parts of the maze that they would normally avoid (see video below).

"I was quite surprised. We did not see aversion. We did not see fear. We did not see any of these things I expected to see," said Tye, whose post-doctoral study is supported by a NIMH-funded training grant. "I suddenly got this huge, dramatic effect of reduction in anxiety-related behaviors and I had to follow it up. So I pretty much dropped my original ideas of what I was going to study during my fellowship and started pursuing this."

When the researchers blocked activity in the projection with the amber laser, the animals showed even more anxiety-like behavior than they usually do. The experiments hint at how the brain is able to regulate anxiety levels — on a millisecond timescale — by dialing activity up and down in such antagonistic amygdala pathways.

Futuristic anxiety treatment?
Tye said she and Deisseroth plan to follow up with further dissection of anxiety pathways. She also hopes to examine whether such optogenetic manipulations, sustained over hours or days, might induce long-lasting adaptations — perhaps for weeks –– in the set-points of anxiety pathways.

A future anxiety disorder treatment that might similarly target such specific pathways could, theoretically, quell anxiety instantly without producing unwanted side effects, such as drowsiness, often experienced with current anti-anxiety medications. For patients with severely debilitating anxiety, a treatment something like deep brain stimulation for depression, but more precisely targeted at a specific pathway, might someday be feasible, she suggested."Everything else in your brain should be unperturbed, because the manipulation would be so specific," explained Tye.

Video shows a mouse under "optogenetic" control while in an anxiety-producing situation. Being in elevated, open spaces makes mice anxious. So, in this "elevated-plus maze," the mouse normally stays in the arms with high walls; it normally won't venture into arms with low walls. However, this mouse has been genetically engineered to have an anxiety-quelling pathway in its fear hub activate when a blue laser shines on it via the fiber-optic cable. At those times (when the blue text appears), the animal gains courage and ventures into the normally scary places. Video speeds up a 15 minute session 10-fold.

Researchers were surprised to discover that activating the whole cell body of an amygdala neuron increased anxiety in mice, while activating just one of its projections had the opposite effect. So unraveling the secrets of how anxiety works might require dissecting the action of each such pathway individually, say the researchers.

Reference
Amygdala circuitry mediating reversible and bidirectional control of anxiety. Tye KM, Prakash R, Kim SY, Fenno LE, Grosenick L, Zarabi H, Thompson KR, Gradinaru V, Ramakrishnan C, Deisseroth K. Nature. 2011 Mar 17;471(7338):358-62. Epub 2011 Mar 9. PMID: 21389985

Tired Neurons Caught Nodding Off in Sleep-deprived Rats

Performance Decline Belies Seeming Wakefulness – NIH-funded Study
A new study in rats is shedding light on how sleep-deprived lifestyles might impair functioning without people realizing it. The more rats are sleep-deprived, the more some of their neurons take catnaps — with consequent declines in task performance. Even though the animals are awake and active, brainwave measures reveal that scattered groups of neurons in the thinking part of their brain, or cortex, are briefly falling asleep, scientists funded by the National Institutes of Health have discovered CEUs for counselors

"Such tired neurons in an awake brain may be responsible for the attention lapses, poor judgment, mistake-proneness and irritability that we experience when we haven't had enough sleep, yet don't feel particularly sleepy," explained Giulio Tononi, M.D., Ph.D., of the University of Wisconsin-Madison. "Strikingly, in the sleep-deprived brain, subsets of neurons go offline in one cortex area but not in another — or even in one part of an area and not in another."

Tononi and colleagues report their findings online in the April 28, 2011 issue of the journal Nature. Their study was funded in part by the NIH's National Institute of Mental health and a NIH Director's Pioneer Award, supported through the Common Fund, and administered by NIMH and the National Institute on Neurological Disorders and Stroke.

Previous studies had hinted at such local snoozing with prolonged wakefulness. Yet little was known about how underlying neuronal activity might be changing.

To learn more, the researchers tracked electrical activity at multiple sites in the cortex as they kept rats awake for several hours. They put novel objects into their cages — colorful balls, boxes, tubes and odorous nesting material from other rats. The sleepier the rats got, more subsets of cortex neurons switched off, seemingly randomly, in various localities. These tired neurons' electrical profiles resembled those of neurons throughout the cortex during NREM or slow wave sleep. Yet, the rats' overall EEG, a measure of brain electrical activity at the scalp, confirmed that they were awake, as did their behavior. So neuronal tiredness differs from more overt "microsleep" — 3-15-second lapses with eyes closing and sleep-like EEG - that is sometimes experienced with prolonged wakefulness. It is more analogous to local lapses seen in some forms of epilepsy, suggest the researchers.

However subtle, having tired neurons did interfere with task performance. If neurons switched off in the motor cortex within a split second before a rat tried to reach for a sugar pellet, it decreased its likelihood of success by 37.5 percent. And the overall number of such misses increased significantly with prolonged wakefulness. This suggests that tired neurons, and accompanying increases in slow wave activity, might help to account for the impaired performance of sleep-deprived people who may seem behaviorally and subjectively awake.

Subsets of neurons going offline with longer wakefulness is, in many ways, the mirror image of progressive changes that occur during recovery sleep following a period of sleep deprivation. Tononi suggests that both serve to maintain equilibrium — part of the compensatory mechanisms that regulate sleep need. Just as sleep deprivation produces a brain-wide state of instability, it may also trigger local instability in the cortex, possibly by depleting levels of brain chemical messengers. So, tired neurons might nod off as part of an energy-saving or restorative process for overloaded neuronal connections.

"Research suggests that sleep deprivation during adolescence may have adverse emotional and cognitive consequences that could affect brain development," noted NIMH Director Thomas R. Insel, M.D. "The broader line of studies to which this belongs, are, in part, considering changes in sleep patterns of the developing brain as a potential index to the health of neural connections that can begin to go awry during the critical transition from childhood to the teen years."

Source: Giulio Tononi, M.D., Ph.D., University of Wisconsin-Madison

Reference
Local sleep in awake rats. Vyazovskiy VV, Olcese U, Hanlon EC, Nir Y, Cirelli C, Tononi G. Nature. 2011 April 28.

Novel Model of Depression from Social Defeat Shows Restorative Power of Exercise

New Neurons Pinpointed as Central to Exercise Benefit

In a study in a mouse model that mimics the contribution of social stress to human depression, an environment that promotes exercise and exploration alleviated depressive behavior in the mice. The beneficial effect of activity depended on the growth of new neurons in the adult brain Continuing Education for Counselors

Background
In the 1990s scientists established that new neurons grow in the adult as well as the immature brain. The functions of neurogenesis, or new neuronal growth, are still being explored, but it is known that stress slows this growth in the hippocampus―a brain center involved in the formation of new memories―and that antidepressant treatment promotes it.

Previous research in animal models has also demonstrated that environmental enrichment―the addition of features in an animal's cage that provide opportunities for exercise and investigation―fosters resilience to stress and can alleviate the depression-like behavior that results from uncontrollable stress. Environmental enrichment has also been shown to promote hippocampal neurogenesis in animals.

This Study
This work, by Michael Lehmann and Robert Schloesser and colleagues in NIMH's intramural research program, focused on the ability of environmental enrichment to reverse depressive behaviors caused by social defeat, a situation paralleling the social stresses that can trigger human depression. Past work in animal models has often used physical stressors such as electric shock, restraint, or forced exercise to create depressive behaviors. In addition, the scientists inserted a gene in mice that made it possible to selectively interrupt the growth of new neurons at a specific time and in a specific population of cells in the hippocampus, avoiding any spillover effects to other tissues.

More on Mouse Behavior
Although "dominant and aggressive" may not sound like descriptors that apply to mice, male mice in the wild live apart from other males and they are intensely aggressive if housed together. In this study, male mice were allowed to interact directly for no more than five minutes at a time and were supervised to make sure one mouse did not injure or kill the other.
Mice naturally cover territory in the wild; if furnished with running wheels in a cage, they will, on their own, run the equivalent of as much as 6 to 10 kilometers in one day.
Stress―in this case social defeat stress―has unmistakable effects on the behavior of mice. Researchers use a variety of tests to describe changes in behavioral tendencies, including observing how boldly the mice explore an unfamiliar cage; how much time they will choose to spend in a dark (safe) vs. light (risky) compartment; and the extent to which they'll indulge their taste for something pleasant like sweetened water. Mice who have been the losers of repeated social defeats are visibly cautious and subdued, even in the judgment of observers who do not know whether they were winners or losers in a conflict.
Test mice in this study were housed across a partition in the home cage of a dominant, aggressor mouse. For 5 minutes per day, the partition was removed, allowing the "intruder" and dominant mouse to interact directly. After 2 weeks, the test mice consistently behaved submissively. The test mice were then divided and placed in either a spare environment, or one enriched with running wheels, and tubes of various shapes and sizes. Some of the mice assigned to either environment were a standard laboratory strain. Others had an inserted gene targeted to a population of hippocampal cells that give rise to new neurons; in mice with this transgene, the antibiotic valganciclovir is toxic to dividing cells so neurogenesis is prevented when the drug was added to the animals' feed.

The nontransgenic test mice in the enriched environment, but not those in the more spartan cages, recovered from the submissive behavior seen after social defeat. The transgenic mice, in which neurogenesis was stopped, remained submissive, resembling the mice housed in the impoverished environment.

In tests to probe affect, or mood, the transgenic mice housed in the enriched environment also resembled mice housed in the impoverished environment in that they showed the same reduced inclination to explore, greater anxiety, and a less than normal interest in sweet solutions which mice usually prefer. Interruption of neurogenesis had no effects on the baseline health and behavior of the animals, so the lack of new neurons did not cause depression, but interfered with recovery.

Significance
This study demonstrates that psychosocial stress in mice can cause behavior resembling human depression, which environmental enrichment can ameliorate as long as neurogenesis is intact.

Key elements of this study included its use of a social stressor, more analogous to the social experiences that can contribute to human depression than the physical stressors often used in research. In addition, the use of the transgene in test animals enabled the scientists to control the interruption of neurogenesis with precision with respect to both timing and location and with no effects on neighboring cells.

According to author Michael Lehmann, "There are multiple avenues through which environmental enrichment can have a positive impact on depression. In this model we use a natural psychosocial stressor with relevance to social stress in humans, to induce depressive-like behaviors. We show that environmental enrichment can facilitate the recovery from social stress, and that adult neurogenesis is a requirement for the rehabilitating effects of enrichment."

The authors suggest that neurogenesis may be central to the ability of an animal to update emotional information upon exposure to a novel environment. With neurogenesis impaired, they may be unable to integrate information on the features of a new, changed environment. The resulting cognitive distortions may trigger symptoms of major depression.

Research suggests that one important consequence of environmental enrichment is its impact on the function of the body's stress response system. Animals in these enriched environments show positive effects on the physiology of stress resilience. In humans, successful antidepressant treatment is reflected in similar beneficial changes. Prior research has also linked neurogenesis with positive changes in the stress response system.

The authors also point out that in humans, physical exercise and positive psychosocial activity have beneficial effects on depression and stress resilience. Forms of entertainment that encourage mental activity, according to Lehmann, such as reading, video games, exercise and outdoor recreation could have longer lasting changes for many suffering from mild depressive symptoms than pharmacologic treatment, without the accompanying side effects.

Reference
Schloesser, R.J., Lehmann, M., Martinowich, K., Manji, H.K., and Herkenham, M. Environmental enrichment requires adult neurogenesis to facilitate recovery from psychosocial stress. Molecular Psychiatry 2010 Dec;15(12):1152-1163. Epub 2010 March 23.

Combination Antidepressant Therapy May Not Improve Odds of Remission Among Chronically Depressed

A combination of two antidepressants may not be any more effective in treating chronic major depression than a single antidepressant, according to an NIMH-funded study published online ahead of print May 2, 2011, in the American Journal of Psychiatry CEUs for Counselora

Background
When treating depression, doctors sometimes prescribe a second antidepressant medication if a patient does not improve after several weeks. Because some antidepressants work for some people and not others, the hope is that adding another one will increase the odds of remission. However, treatment guidelines generally do not recommend adding another medication until it is evident the first one is not working.

Madhukar H. Trivedi, M.D., at the University of Texas Southwestern, and colleagues aimed to determine if combination antidepressant therapy as a first treatment step might produce a higher remission rate among people with chronic major depression. In the Combining Medications to Enhance Depression Outcomes (CO-MED) trial, 665 adult participants from several sites around the country were randomly assigned to one of three antidepressant combinations:

Escitalopram plus placebo
Bupropion sustained release plus escitalopram
Venlafaxine plus mirtazapine
Although participants did not know which treatments they were receiving, clinicians were aware of their patients' treatment assignments so that they could adjust doses as necessary to manage symptoms and side effects. The measurement of primary outcome was based on a self-reporting scale called the Quick Inventory of Depressive Symptoms.

Results of the Study
After three months, remission rates among the three groups all were around 38 percent. After seven months, remission rates continued to be similar among the three treatment groups and averaged around 45 percent. However, the venlafaxine plus mirtazapine combination was associated with a higher risk for side effects and serious adverse events compared to the other treatment options.

Significance
Despite other research suggesting combination antidepressant treatment may work better than a single medication, neither of the combination therapies in this trial appeared to be more effective than the single medication plus placebo. The researchers suggest that the chronic nature of participants' major depression may be associated with lower remission rates. They also noted that dosage differences may account for the difference in outcomes compared to other studies.

What's Next
Further evaluation is needed to determine if other drug combinations may affect remission rates differently. Results also highlight the need to evaluate biological markers as a means of personalizing treatment and possibly improving remission rates in major depression.

Reference
Rush AJ, Trivedi MH, Stewart JW, Nierenberg AA, Fava M, Kurian BT, Warden D, Morris DW, Luther JF, Husain MM, Cook IA, Shelton RC, Lesser IM, Kornstein SG, Wisniewski SR. Combining medications to enhance depression outcomes (CO-MED): Acute and long-term outcomes: a single-blind randomized study. Journal of American Psychiatry. online ahead of print May 2, 2011.

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Study Reveals New Clues to How Depression May Develop

Activating neurons in a brain structure linked to disappointment increased depression-like behaviors in rats, while suppressing the neurons' activity reduced the behaviors, according to an NIMH-funded study. The findings help to explain previous research linking this brain structure to depression in humans and highlight a cellular process that hadn't been previously explored in mood disorders research. The study was published in the February 24, 2011, issue of Nature.

Background
Depression is one of the most studied mental disorders, with research honing in on brain structures, circuits, and biochemical processes critical to the development of the disorder. Yet many questions remain about how changes in the brain result in the observable symptoms and behaviors associated with depression. Counselor continuing education
To advance the science in this area, Bo Li, Ph.D., of Cold Spring Harbor Laboratory in New York, and colleagues, explored the role and connectivity of neurons in the lateral habenula (LHb) in rats that showed learned helplessness, a set of behaviors similar to symptoms of depression in people. The LHb is associated with how humans and animals experience disappointment or anticipate negative outcomes.

Results of the Study
The researchers found that LHb neurons receive input from many different brain regions involved in responding to stress. LHb neurons also connect out to many brain regions, such as the ventral tegmental area (VTA). The VTA helps to control reward-seeking behavior and may have a role in depression and other mood disorders.

LHb neurons in helpless rats were more responsive, such that communication signals to the VTA were more likely to be transmitted in the helpless rats than in control rats. In an attempt to moderate this phenomenon, the researchers tested the effects of deep brain stimulation (DBS), a surgical procedure currently being tested in humans for treatment-resistant depression. Applying continuous electrical stimulation directly to the LHb resulted in greatly reduced transmission to the VTA and a marked reduction in helpless behavior. The effects on transmission lasted only as long as the stimulation lasted. More intense stimulation resulted in stronger behavioral effects.

Significance
Although LHb activity was previously unstudied in the context of mood disorders, these findings suggest that this brain structure may actually play a central role in the development of depression.

What's Next
Further studies focusing on the molecular processes and signals underlying LHb activity in depression may reveal new targets for treatment development, according to the researchers. Such new treatments also may be able to reverse some forms of depressive disorders.

This study was supported in part by a Biobehavioral Research Award for Innovative New Scientists (BRAINS) from NIMH. Dr. Li was one of 12 researchers to receive this award in 2010.