Autism Risk in Younger Siblings May be Higher Than Previously Thought

Autism Risk in Younger Siblings May be Higher Than Previously Thought

Parents of a child with autism spectrum disorder (ASD) face about a 19 percent chance that subsequent children will also develop ASD, according to a study partially funded by NIMH. This estimate is much higher than previous reports but may also be more accurate due to the study's size and design, according to the researchers. Their study was published August 15, 2011, online ahead of print in the journal Pediatrics ceus for social workers

Background

A few previous studies have explored the recurrence rate of ASD, or the likelihood of later-born siblings of children with ASD to also develop ASD. However, few studies addressed factors likely to influence risk estimates, such as:
Stoppage—the tendency for families to choose not to have more children after one child is diagnosed with ASD. Such families would not be included in research on ASD recurrence.
Overreporting—an error that can occur when researchers rely solely on parent reports or health records, which have been shown to inflate estimates.
Ascertainment bias—an example is overselection, which can occur when parents with one child who has ASD pay very close attention to a later child's development. They may be more likely to take part in ASD recurrence studies than other parents.

Taking a different approach, Sally Ozonoff, Ph.D., of the University of California-Davis, and colleagues evaluated data on 664 infants who were tested at 12 sites across the United States and Canada. All sites were members of the Baby Siblings Research Consortium (BSRC), an international network supported by the U.S. advocacy group Autism Speaks. All BSRC members contribute data to a centralized database that allows infant-sibling researchers to pool data across many sites and answer questions that require very large and geographically diverse samples to address.

The average age of the infant participants at the start of the study was 8 months, an age when signs of ASD are not usually present; two-thirds of the total study population were enrolled before age 6 months. All had at least one older sibling diagnosed with ASD, which was confirmed by a consortium doctor. The participants were themselves assessed for ASD multiple times in their first three years of life.

Results of the Study

Out of the total study sample, 18.7 percent of participants were diagnosed with ASD by age 3. Boys were nearly three times as likely as girls to be diagnosed with ASD. Participants who had more than one older sibling with ASD were about twice as likely to also be diagnosed with ASD, compared to participants who had only one older sibling with ASD.

Unlike some previous studies, the gender or IQ of the older sibling with ASD did not affect the later sibling's risk in the present study.

Significance

The findings indicate that ASD recurrence is 18 percent or higher, compared to 3-14 percent estimated in earlier studies. The researchers note that their study's size and design minimized the effects of stoppage, overreporting, and ascertainment bias.

Despite the strengths of their study, the researchers emphasize that recurrence estimates cannot provide information on an individual's risk. They highlight the need for careful and extensive counseling and thorough genetic work-ups for concerned parents, as well as close monitoring, especially of high-risk children, and prompt referrals for intervention by primary care providers.

What’s Next

According to the researchers, larger, population-based studies that include families of children with ASD who are not listed in the Baby Siblings Research Consortium may help to further refine recurrence estimates. Future studies will examine DNA collected from participants to examine genetic factors that may be associated with recurrence.

Reference

Ozonoff S, Young GS, Carter A, Messinger D, Yirmiya N, Zwaigenbaum L, Bryson S, Carver LJ, Constantino JN, Dobkins K, Hutman T, Iverson JM, Landa R, Rogers SJ, Sigman M, Stone WL. Recurrence Risk for Autism Spectrum Disorders: A Baby Siblings Research Consortium Study. Pediatrics. 2011 Aug 15. [Epub ahead of print] PubMed PMID: 21844053.

Biology, Not Just Society, May Increase Risk of Binge Eating During Puberty

Source: Kelly Klump, Ph.D., Michigan State University

Biological changes associated with puberty may influence the development of binge eating and related eating disorders, according to a recent study on female rats conducted by NIMH-funded researchers. After puberty, the rats showed binge eating patterns that resemble those in humans, supporting the role of biological factors, since rats do not experience pressures to be thin or other psychosocial risk factors commonly associated with human eating disorders. The study was published online ahead of print on May 16, 2011, in the Journal of Abnormal Psychology.

Background
Among girls, symptoms of binge eating or bulimia nervosa often arise around puberty. Past research has largely focused on psychosocial roots for this association, but biological changes that occur during and after puberty are likely to have an effect as well.

Kelly Klump, Ph.D., of Michigan State University, and colleagues tested this theory in an animal model since animals do not experience psychological risk factors during puberty. They used a rat model that can distinguish between rats that are resistant to binge eating (BER) from those prone to binge eating (BEP), based on their individual eating habits.

For this study, the researchers studied binge eating risk from pre-puberty to adulthood in 66 female rats. In addition to their standard food, the rats were provided intermittent access to cake frosting, a highly enjoyable but nutritionally empty and high fat food.

Results
Over the course of development, all rats ate more frosting as they matured. However, a difference in frosting intake between BER and BEP rats emerged during puberty—no differences in frosting intake were observed in pre-puberty, but large differences were observed in puberty and adulthood (see Figure 1)

The researchers noted that rats in the BER and BEP groups ate similar amounts of the standard food and were similar in body weight. This suggests that the BEP rats were not overeaters generally, but were instead, prone to binge eat on high-fat foods only.

Significance
The findings reveal dramatic increases in binge eating proneness during puberty, suggesting that increases in binge eating and similar eating disorders during and after puberty in girls may be partially due to biological factors ceus for counselors

Similar to binge eating in humans, BEP rats ate much more of the high-fat food but did not increase their consumption of the standard food. Also, all rats preferred the high-fat food, regardless of developmental stage, which is similar to behaviors seen in girls; for example, girls tend to prefer candy over healthier treats at all ages. In both rats and humans, this behavior begins to diverge during puberty, with some consuming much more of the high-fat food than others.

Unlike humans, however, the percentage of binge eating rats (30 percent) was much higher than estimates in humans (3.5–19 percent). According to the researchers, this difference may indicate that binge eating in rats is a “pure” form of binge eating that is unmodified by psychosocial factors—such as social disapproval or guilt—that tends to decrease binge eating rates in humans.

What’s Next
More research is needed to develop and validate animal models of the cognitive and behavioral symptoms of eating disorders. Studies exploring the mechanisms underlying developmental changes that occur during puberty, for example the action of ovarian hormones, may also inform research on eating disorders.

Reference
Klump KL, Suisman JL, Culbert KM, Kashy DA, Sisk CL. Binge eating proneness emerges during puberty in female rats: A longitudinal study. J Abnorm Psychol. 2011 May 16. [Epub ahead of print] PubMed PMID: 21574664.

Source: Kelly Klump, Ph.D., Michigan State University

Adapted with permission from APA

For Minor Depression, Study Shows No Benefit Over Placebo from St. John’s Wort, Citalopram

An extract of the herb St. John's Wort and a standard antidepressant medication both failed to outdo a placebo in relieving symptoms of minor depression in a clinical trial comparing the three. The results of this study, consistent with earlier research, do not support the use of medications for mild depression counselor ceus

Background
St. John's Wort is a plant whose yellow flowers have been the source of extracts used medicinally for centuries. It is widely used to treat depression, as a nutritional supplement in the United States, and as a prescription medication in Europe. Evidence from clinical trials of St. John's Wort has failed to show effectiveness for treatment of major depression; but research has raised the question as to whether the herb might offer benefit for people with less severe depression.

This Study
This study, focusing specifically on minor depression, was conducted by Mark Hyman Rapaport and colleagues at the Cedars-Sinai Medical Center and David Geffen School of Medicine in Los Angeles; the Massachusetts General Hospital, in Boston; and the University of Pittsburgh. Participants in the study had minor depression, defined as the presence of two to four symptoms used to diagnose major depression, with at least one symptom being depressed mood or anhedonia, a lack of pleasure in activities usually found enjoyable. Symptoms had to have been present for six months to two years. Subjects were randomly assigned to receive St. John's Wort, the antidepressant medication citalopram, or a placebo. Neither participants, nor the staff treating them, knew what treatment they took. Seventy-three subjects completed the trial.

Results from the trial showed that no treatment relieved depression more than any other; patients in all three of the treatment groups showed improvements in symptoms over the course of the study, and in measures of quality of life and psychological well-being.

Patients in all three treatment groups—including placebo—also frequently reported side effects. In addition, before treatment began in this study, more than half of participants responded positively when they were asked if they had any of a broad list of physical or psychological complaints. This finding suggests that it's important to assess both physical and psychological symptoms even before treatment begins; otherwise, many of these symptoms might be interpreted as medication-related.

Significance
While minor depression is by definition a milder condition than major depression, research suggests it has consequences for health and well-being that go beyond the symptoms themselves, including lost work days, social difficulties, and possibly a higher risk of developing future major depression.

The authors are careful to point out that the reason that there was no difference in benefit between St. John's Wort, citalopram, and placebo was not because the study was too small to detect a difference, but because participants taking placebo experienced substantial improvement in measures of depression and well-being—participation in the study had positive effects. In addition, participants taking all three treatments—even those on placebo—experienced side-effects. Fewer of the subjects taking St. John's Wort reported that side effects were distressing (40 vs. 60 percent); but St. John's Wort recipients reported more gastrointestinal and sleep problems than those receiving placebo.

Identifying effective and safe ways to treat minor depression remains an important goal; further research on non-pharmacologic treatment is needed to identify the optimal psychotherapies for minor depression.

This study was funded by the National Institute of Mental Health and the National Center for Complementary and Alternative Medicine, National Institutes of Health.

Reference
Rapaport, M.H., Nierenberg, A.A., Howland, R., Dording, C., Schettler, P.J., and Mischoulon, D. The treatment of minor depression with St. John's Wort or citalopram: Failure to show benefit over placebo. Journal of Psychiatric Research 45:931-941, 2011.

Thinking Globally to Improve Mental Health

Source: NASA Jet Propulsion Laboratory (NASA-JPL)
Mental health experts are calling for a greater world focus on improving access to care and treatment for mental, neurological, and substance use (MNS) disorders, as well as increasing discoveries in research that will enable this goal to be met.

The Grand Challenges in Global Mental Health Initiative, led by the National Institutes of Health and the Global Alliance for Chronic Diseases, has identified the top 40 barriers to better mental health around the world. Similar to past grand challenges, which focused on infectious diseases and chronic, noncommunicable diseases, this initiative seeks to build a community of funders dedicated to supporting research that will significantly improve the lives of people living with MNS disorders within the next 10 years.

Twenty-five of the specific challenges and the process used to derive them are described in an article that will be published on July 7, 2011, in the journal Nature.

"Participating in global mental health research is an enormous opportunity, a means to accelerate advances in mental health care for the diverse U.S. population, as well as an extension of our vision of a world where mental illnesses are prevented and cured," said Thomas R. Insel, M.D., director of the National Institute of Mental Health (NIMH), the NIH institute heading this effort.

According to the paper's authors, the disorders targeted by the Grand Challenges in Global Mental Health—for example, schizophrenia, depression, epilepsy, dementia, and alcohol dependence—collectively account for more years of life lost to poor health, disability, or early death than either cardiovascular disease or cancer. Yet, compared to illnesses like cardiovascular disease and cancer, there are far fewer effective treatments or preventive methods. In addition, interventions are not widely available to those who need them most.

In recognizing the need to address this imbalance, Pamela Collins, M.D., M.P.H., of the NIMH Office for Research on Disparities and Global Mental Health, and colleagues assembled an international panel of experts to identify research priorities using the Delphi method, a widely accepted consensus-building tool. The panel consisted of 422 experts in fields such as neuroscience, basic behavioral science, mental health services, and epidemiology, and represented more than 60 countries social worker ceus

Over the course of two months, NIMH staff pared the panel's initial list of 1,565 challenges down to 154, with input from a scientific advisory board. From this list, the expert panel selected the top 40, of which the top five challenges identified after the third and final round of ranking are:

Integrate screening and core packages of services into routine primary health care
Reduce the cost and improve the supply of effective medications
Improve children's access to evidence-based care by trained health providers in low- and middle-income countries
Provide effective and affordable community-based care and rehabilitation
Strengthen the mental health component in the training of all health care personnel.
These top five challenges were ranked according to the ability to reduce the burden of disease, ability to reduce inequalities in health and health care, length of time until results can be observed, and the ability for the topic to be researched effectively.

"Addressing these challenges could have far-reaching effects, including increasing access to services and ultimately, reducing the treatment gap associated with these disorders," said Dr. Collins.

The Grand Challenges in Global Mental Health Initiative is led by NIMH and the Global Alliance for Chronic Diseases, in partnership with the Wellcome Trust, the McLaughlin-Rotman Centre for Global Health, and the London School of Hygiene and Tropical Medicine. Other NIH components participating in the Grand Challenges in Global Mental Health include the Fogarty International Center; the National Heart, Lung, and Blood Institute; and the National Institute of Neurological Disorders and Stroke.

Reference
Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar A, on behalf of the Grand Challenges in Global Mental Health Scientific Advisory Board and Executive Committee. Grand Challenges in Global Mental Health. Nature. 2011 July 7. 474(7354):pp.

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.

Support Program Can Help Caregivers Cope with Relative’s Mental Illness

A free, nationally available program can significantly improve a family's ability to cope with an ill relative's mental disorder, according to an NIMH-funded study published June 2011 in Psychiatric Services, a journal of the American Psychiatric Association.

Background
The Family-to-Family (FTF) education and support program is a free, 12-week course offered by the National Alliance on Mental Illness (NAMI). FTF is offered throughout the United States, in two Canadian provinces and in three regions in Mexico. With more than 3,500 volunteer teachers, it is supported by local donations or municipal funds. Since 1991, 250,000 family members have participated in the program. It is the most widely available education and support program for family members of individuals with mental illnesses.

Two previous studies suggested that FTF reduces caregivers' stress and helps them gain a sense of empowerment over their situation. For this most recent evaluation of the program, Lisa Dixon, M.D., M.P.H., of the University of Maryland, and colleagues aimed to determine its effectiveness using a randomized controlled trial. Half of the 318 participants were assigned to the program immediately after enrolling in the study, while the other half were waitlisted for the program for at least three months (control condition). Those who were waitlisted were free to seek assistance from other sources.

Participants were interviewed at the beginning of the three-month program and again three months later. They were asked about their problem-solving and coping skills, their overall distress level and worries about their ill relative's situation. They were also asked about their sense of empowerment to manage challenges within the family, the mental health system, and the community. They were also tested regarding their factual knowledge about mental illness.

Results of the Study
Compared to the waitlisted control group, FTF participants showed significantly greater improvements in coping with their ill relative's condition by learning more about the illness and gaining a sense of empowerment in the family, service system and community. FTF participants also showed increased acceptance of their family member's illness as well as improved problem-solving skills, compared to those who were waitlisted. Results also suggested that FTF participants' overall sense of emotional distress eased.

Significance
The researchers concluded that FTF effectively enhances coping skills among families of people with mental illness. These results echo those found in the previous qualitative studies. The researchers suggest the program can positively influence how family members solve problems and "navigate emotional difficulties" surrounding their loved one's illness.

What's Next
Additional research is needed to conclusively determine if the positive effects of FTF can improve the outcomes of the individuals with mental illness for whom the family members were taking the class.

Citation
Dixon LB, Lucksted A, Medoff DR, Burland J, Stewart B, Lehman AF, Fang LJ, Sturm V, Brown C, Murray-Swank A. Outcomes of a randomized study of a peer-taught family-to-family education program for mental illness. Psychiatric Services. 2011 June. 62(6):591-597.

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Drug Boosts Growth Factor to Jumpstart Rapid Antidepressant Response

Little-known Enzyme Pivotal, Mouse Study Reveals
A study in mice has pinpointed a pivotal new player in triggering the rapid antidepressant response produced by ketamine. By deactivating a little-known enzyme, the drug takes the brakes off rapid synthesis of a key growth factor thought to lift depression, say NIMH-funded researchers LPCC Continuing Education

"Other agents that work through this pathway and block the enzyme may also similarly induce anti-depressant-like effects and hold promise for development of new treatments," said Lisa Monteggia, Ph.D., of the University of Texas Southwestern Medical Center, Dallas.

Monteggia, Ege Kavalali, Ph.D., and colleagues reported their findings online June 15, 2011 in the journal Nature.

Unlike currently available antidepressants that take weeks to work, ketamine can lift mood within hours. Yet adverse side effects preclude it from becoming a practical treatment. So, researchers have been studying its mechanism of action, in hopes of developing safer alternatives that work the same way.

Earlier studies had shown that the growth factor, called brain-derived neurotrophic factor (BDNF), produces antidepressant-like effects. To find out if BDNF is involved in ketamine's action, the researchers gave the drug to mice genetically engineered to lack BDNF. Unlike in control mice, ketamine failed to produce a fast-acting antidepressant-like response in such BDNF knockout mice exposed to experimental situations that trigger depression-like behaviors. This and other tests confirmed that ketamine's rapid antidepressant effects depend on rapid synthesis of BDNF in the brain's memory center, or hippocampus.

The researchers determined that this happens so quickly — within 30 minutes — because it only requires the translation of BDNF mRNA into protein, rather than transcription, which involves new gene expression and takes much longer.

Ketamine achieves this boost in BDNF levels by first blocking a protein on neurons (brain cells) called the NMDA receptor. The Texas team discovered that this blockade, in turn, deactivates an enzyme called eukaryotic elongation factor 2 (eEF2) kinase, that restrains BDNF synthesis. So, ketamine (and presumably other agents that similarly turn off the enzyme) effectively takes the brakes off of this antidepressant mechanism.

"Selectively inhibiting the eEF2 kinase was sufficient to trigger a rapidly acting antidepressant response in control mice but not in mice lacking BDNF," explained Monteggia.

The researchers discovered that the boost in BDNF occurs while neurons are in their default mode — not doing anything in particular. But the cells continue communicating via a low level of background chatter, spontaneously releasing chemical messengers that bind to receptors. So, when ketamine blocks NMDA receptors, it prevents their naturally-occurring messenger chemical, glutamate, from binding to them.

"Interference with such spontaneous neurotransmission to trigger production of a protein represents a novel mode of drug action," Monteggia noted. "It may also hold clues to what goes awry in the brain in disorders like depression."

Although BDNF levels fall off sharply following the transient increase triggered by ketamine, she says evidence may also support a role for BDNF in the drug's longer-term antidepressant effects. The exact role of another enzyme implicated in ketamine's antidepressant action remains to be determined, in light of the new findings. Yale researchers reported last Fall that the drug triggered increased connections between neurons via effects on the enzyme, called mTOR.

"This discovery of a novel pathway involved in mediating fast-acting antidepressant action holds hope for development of new rapid-acting medications," said Monteggia.

When in their default state, neurons that mediate ketamine's action engage in the brain's equivalent of background chatter. They spontaneously spray out (orange) the chemical messenger glutamate (green circles), which binds to NMDA receptors (black ovals) on adjoining neurons. This activates the enzyme eEF2 kinase, which suppresses synthesis of BDNF, a growth factor that has antidepressant effects. Treatment with ketamine blocks the binding of the neurotransmitter to the receptors (blue dots on black ovals), which inactivates the enzyme, taking the brakes off translation of BDNF into protein. This jumpstarts a fast-acting antidepressant effect.

Source: Lisa Monteggia, Ph.D., University of Texas Southwestern Medical Center

Reference
NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, Kavalali ET, Monteggia LM. Nature. 2011 Jun 15. doi: 10.1038/nature10130. [Epub ahead of print] PMID:21677641

Focusing on School Attendance Reduces HIV Risk Among Orphaned Teens

Source: iStock
A comprehensive school support program effectively reduced risk factors associated with infection with HIV among teens who had lost one or both parents, according to early results from a pilot study funded by NIMH. The paper was published online ahead of print on February 17, 2011, in the Journal of Adolescent Health LPCC Continuing Education

Background
Current statistics estimate there are more than 11 million children living in sub-Saharan Africa who have lost one or both parents to HIV/AIDS. These children are at increased risk of dropping out of school, which in turn increases their risk for unprotected sexual behavior. Some research suggests that interventions that aim to change a person's living conditions, such as methods designed to help them stay in school, may be effective in reducing or preventing HIV infection among these at-risk children.

To further explore this idea, Hyunsan Cho, Ph.D., of the Pacific Institute for Research and Evaluation in Chapel Hill, N.C., and colleagues recruited 105 students, ages 12-14, from a rural area in Kenya with high HIV prevalence who had lost one or both parents to any cause. All participants received supportive household supplies (e.g., mosquito nets, blankets, food supplements) every two weeks. Participants randomly assigned to the test group also received school uniforms and money to pay school fees. A local woman, designated as a "community visitor," was assigned for every 10 teens in the test group to visit their homes at least monthly. She also visited the teens' schools weekly to monitor their school attendance and address problems that may lead to absenteeism.

Results
After one year, teens in the test group were less likely to have:

Dropped out of school (4 percent vs 12 percent of the control group)
Begun having sex (19 percent vs 33 percent control)
Reported attitudes supporting initiation of sexual relationships at a young age
Teens in the test group were also more likely to perceive that adults in the family liked or cared about them, and were generally less likely to endorse attitudes accepting of husbands beating their wives.

Significance
According to the researchers, these findings support previous research suggesting that comprehensive, community-based school support can help reduce multiple HIV risk factors among orphaned teens. The researchers also found evidence that school support enhances social bonding and positive attitudes toward gender equity.

What's Next
Given that these findings resulted from an experimental pilot study, the researchers emphasized that future studies should include more participants and focus on methods for generalizing this approach to broader populations.

Reference
Cho H, Hallfors DD, Mbai II, Itindi J, Milimo BW, Halpern CT, Iritani BJ. Keeping Adolescent Orphans in School to Prevent Human Immunodeficiency Virus Infection : Evidence From a Randomized Controlled Trial in Kenya. J Adolesc Health. 2011 Feb 17. [online ahead of print]