Background

Stimulant medications, such as methylphenidate (Ritalin and Concerta) and amphetamines (Adderall), are used to treat ADHD in children. These medications may increase the risk for sudden cardiac deaths (SCD) in some children with certain underlying heart conditions. Peter Denchev, Ph.D., of NIMH and colleagues at NIMH and the National Heart, Lung and Blood Institute developed a model to compare the cost-effectiveness of three strategies for screening for the risk of heart disease and SCD among children being treated with stimulants.

The three strategies are:

1. conducting a history and physical exam (H&P) and referral to a cardiologist if the exam showed anything abnormal (considered usual standard of care),
2. H&P plus an ECG and referral to cardiologist if either showed abnormal results,
3. H&P plus ECG and referral to cardiologist only if the ECG showed abnormal results.

Results of the Study

The authors measured the cost-effectiveness of each strategy by estimating its cost per quality-adjusted life year (QALY). A QALY is a type of outcome measure that takes both length and quality of life into account. Denchev and colleagues found that compared to strategy 1, strategy 2 would cost $39,300 per additional QALY, and strategy 3 would cost $27,200 per additional QALY. According to the modeling data, both strategy 2 and 3 would likely prevent 13 SCDs per 400,000 children seeking stimulant treatment for ADHD over a 10-year period. Assuming that society would be willing to pay up to $50,000 per (QALY), the authors conclude that ECG screening for heart conditions in children with ADHD is borderline cost-effective.

Significance

The authors conclude that adding ECG to the current standard of care may identify more children at risk for SCD prior to starting them on stimulants for treating ADHD. It also would afford an opportunity to discourage at-risk children from playing competitive sports, which could bring on a cardiac event. However, adding ECG as a matter of course is borderline cost-effective.

What’s Next

The authors caution that the economic analysis is meant only to provide information to decision-makers, not affect diagnostic or treatment recommendations. The American Heart Association currently recommends that doctors consider obtaining an ECG prior to prescribing stimulants if they believe it is warranted.

Reference

Denchev P, Kaltman J, Schoenbaum M, Vitiello B. A modeled economic evaluation of alternative strategies to reduce sudden cardiac death among children treated for attention deficit/hyperactivity disorder. Circulation: Journal of the American Heart Association. Online ahead of print March 8, 2010.

All 170 patients also received cognitive-behavioral therapy, and the four treatment groups all showed clinical reductions in depressive symptoms over the 14-week study, which was conducted by Helen Pettinati, Ph.D., and colleagues of the University of Pennsylvania.
In addition to a higher abstinence rate, the group receiving combination treatment had a longer interval before resumption of drinking: a median of 61 days compared with 15 days for the other groups combined. Serious adverse events were actually less frequent in the group receiving both medications, since the most common serious event was hospitalization for detoxification or rehabilitation.
“When depression and alcohol dependence occur together, each condition has a negative influence on the outcome of the other, so not only does this pairing of illnesses affect a lot of patients, it also makes the individual disorders worse,” Dr. Pettinati stated. “Combining sertraline and naltrexone could be a practical approach for these patients because both have FDA approval.”
The study will appear on March 15 at AJP in Advance, the online advance edition of The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association. Funding for this study was received from the National Institute on Alcohol Abuse and Alcoholism. Pfizer Pharmaceuticals donated sertraline and a matching placebo.
The American Journal of Psychiatry is the oldest continuously published medical specialty journal in the United States and was recently named one of the “Most Influential Journals in Biology & Medicine of the Last 100 Years.” Statements in this press release or the articles in the Journal are not official policy statements of the American Psychiatric Association.
About the American Psychiatric Association:
The American Psychiatric Association is a national medical specialty society whose physician members specialize in the diagnosis, treatment, prevention and research of mental illnesses, including substance use disorders. Visit the APA at www.psych.org and www.HealthyMinds.org.

WASHINGTON — Scientists are beginning to find out why people with Parkinson’s disease often feel socially awkward. Parkinson’s patients find it harder to recognize expressions of emotion in other people’s faces and voices, report two studies published by the American Psychological Association.

One of the studies raises questions about how deep brain stimulation, the best available treatment for patients who no longer respond to medication, more strongly affects the recognition of fear and sadness.

A neurodegenerative disorder, Parkinson’s causes tremors, stiffness and balance problems, as well as fairly frequent depression and dementia.

In the March issue of Neuropsychology, Heather Gray, PhD, and Linda Tickle-Degnen, PhD, report that people with Parkinson’s disease, compared with matched controls, often have difficulty discerning how others are feeling.

Their meta-analysis of 34 different studies using data from 1,295 participants shows a robust link between Parkinson’s and specific deficits in recognizing emotions, especially negative emotions, across different types of stimuli and tasks.

The meta-analysis, conducted at Harvard Medical School and Tufts University, found that patients typically had some degree of problem identifying emotion from faces and voices.

Further clarification is provided in a second study that showed that deep-brain stimulation, compared with medication, caused a consistently large deficit in the recognition of fear and sadness – two key facial expressions that, when understood, aid survival. That study is published in the January issue of Neuropsychology.

Researchers led by Julie Péron, PhD, at the Centre Hospitalier Universitaire de Rennes in France, compared the ability of people with Parkinson’s in three different groups to recognize facial emotions: 24 advanced patients implanted with deep-brain stimulators after they didn’t respond or were sensitive to oral levodopa (the usual drug for the disease); 20 advanced patients given apomorphine hydrochloride by injection or infusion pump while they waited an implant; and 30 healthy controls.

Researchers tested all participants using standard photographs of facial expression before and three months after they were treated. Before implantation of the stimulators, all participants read facial expressions equally well.

Patients in the surgical group were implanted with stimulators, electrical devices that prod the brain’s subthalamic nucleus, a small, lens-shaped structure, to normalize the nerve signals that control movement. This nucleus is part of the basal ganglia system, which is thought to integrate movement, cognition and emotion.

Three months after treatment, only the patients with stimulators – not the drug-treated patients or the healthy controls – were significantly worse at recognizing fear and sadness. Patients with stimulators confused those expressions with others, such as surprise, or even no emotion. Medicated patients and healthy controls were either accurate about fear and sadness or occasionally mistook them for other negative emotions, such as disgust.

“Having Parkinson’s predisposes an individual to errors in emotion recognition,” said Gray. “The research in France, along with previous studies, indicates that deep-brain stimulation produces an even more severe deficit.”

Why would treating a movement disorder affect the perception of emotions? Implants affect a part of the brain that reaches across functions, so the authors suggested that the same electrical stimulation that calms over-excited motor activity may also somehow inhibit emotional processing.

Although the impact of Parkinson’s and deep-brain stimulation varies by patient, it’s important to understand. “The first step is to educate patients and their close associates about the potential for emotion recognition difficulties, so they can learn to manage some of the social consequences, such as misunderstanding and frustration,” said Gray and Tickle-Degnen. The next step might be training in emotion recognition, which they said has shown promise.

According to the National Institutes of Health, deep-brain stimulation is used to treat a variety of disabling neurological symptoms, including Parkinson’s and essential tremor, a common neurological movement disorder.

At present, the procedure is used only for patients whose symptoms cannot be adequately controlled with medications. According to Péron, about 15 percent of Parkinson’s disease patients are thought capable of benefiting from the surgery.

Article: “Subthalamic Nucleus Stimulation Affects Fear and Sadness Recognition in Parkinson’s Disease,” Julie Péron, PhD, Isabelle Biseul, PhD, and Emmanuelle Leray, PhD, Centre Hospitalier Universitaire de Rennes and Centre Eugène Marquis; Siobhan Vicente, PhD, Centre Hospitalier Universitaire de Rennes and Centre Hospitalier Guillaume Régnier; Florence Le Jeune, MD, PhD, Centre Hospitalier Universitaire de Rennes and Centre Eugène Marquis; Sophie Drapier, MD, Centre Hospitalier Universitaire de Rennes; Dominique Drapier, MD, PhD, Centre Hospitalier Universitaire de Rennes and Centre Hospitalier Guillaume Régnier; Paul Sauleau, MD, PhD, Claire Haegelen, MD, and Marc Vérin, MD, PhD, Centre Hospitalier Universitaire de Rennes; Neuropsychology, Vol. 24, No. 1.

Julie Péron can be reached by e-mail or at 0041 (0)794 54 13 88 (Swiss Centre for Affective Sciences, Geneva University) or 00 33 (0)6 88 31 30 43 (permanent number in France).

Article: “A Meta-Analysis of Performance on Emotion Recognition Tasks in Parkinson’s Disease,” Heather M. Gray, PhD, Cambridge Health Alliance, Harvard Medical School, and Linda Tickle-Degnen, PhD, Tufts University; Neuropsychology, Vol. 24, No. 2.

Heather Gray can be reached by e-mail (Division on Addictions, Cambridge Health Alliance, Harvard Medical School) or by phone at (781) 306-8611.

Background

Vulnerability to mental health disorders as well as tendencies toward certain behaviors are associated with variations in the numerous genes involved in shaping brain function. Brain-derived neurotrophic factor (BDNF) is a protein that supports the development of neurons and is involved in learning and memory. Previous research has suggested that a pinpoint variation in the gene for BDNF, found only in humans, is associated with some disorders of mental health, including anxiety-based disorders. (The variation—a single nucleotide polymorphism or SNP—is a substitution of a single link in the chemical chain that makes up genes. It results in a change in the protein’s activity.) The variant has been designated Val66Met.

This Study

In this study, scientists Fatima Soliman, Francis Lee, B.J. Casey and colleagues at Weill Cornell Medical College in New York City, and Stanford University in California, conducted parallel studies in humans and mice on the impact of the Val66Met variant on fear learning and extinction of fearful memories. The Val66Met substitution occurs naturally only in human populations. In this study, the scientists determined which of the human subjects in the study carried the variant vs. the more common form of the gene. They used genetic techniques to introduce the human Val66Met variant into mice.

Following a classic fear learning procedure, the investigators exposed mice and humans repeatedly to a neutral stimulus (for the mice a sound; for the humans, colored squares) simultaneously with an unpleasant one (for mice a foot shock; for humans, a loud noise). Eventually both mice and humans reacted to the neutral stimulus with an anxiety response, even if there was no accompanying unpleasant stimulus. Afterwards, mice and humans repeatedly exposed to the neutral stimulus alone eventually lost the fear association, a process known as fear extinction. In both humans and mice, however, carriers of the Val66Met variant took longer to lose the fear association than noncarriers.

The investigators also used functional brain imaging in the human subjects to monitor areas of the brain known to be involved in fear extinction. The results paralleled the behavioral responses; the area of the cortex that is engaged during fear extinction showed less activity during extinction in the carriers of the Val66Met variant. In contrast, an area of the brain involved in emotional responses—the amygdala—showed continued activity during extinction in Val66Met carriers relative to what was seen in subjects without the substitution. In these individuals, then, the activity of the amygdala—a reflection of emotional arousal—remained elevated, instead of subsiding as it would normally if the level of fear were decreasing.

Significance

The change in behavior observed in this study was not the result of a general increase in anxiety or level of fear arousal, but an effect on a specific brain circuit involved in the extinction of fear memory in both humans and mice. Treatment for anxiety-based disorders and phobias sometimes involves exposing patients—in a safe environment—to the objects or situations they fear. The ability to test for the presence of genetic variants, like the BDNF Val66Met substitution in patients, could provide useful information to therapists on what to expect in terms of responses to treatment in different individuals.

Evidence suggests that disorders of mental health are genetically complex, with many genes contributing to risk, each one having a small, sometimes difficult to measure, effect. Teasing out the effects of individual genes and gene variants on specific facets of behavior can help provide information on the contributions of these genes to personality and to risk of mental illness.

Reference

Soliman, F., Glatt, C.E., Bath, K.G., Levita, L., Jones, R.M., Pattwell, S.S., Jing, D., Tottenham, N., Amso, D., Somerville, L., Voss, H.U., Glover, G., Ballon, D.J., Liston, C., Teslovich, T., Van Kempen, T., Lee., F.S., Casey, B.J. A genetic variant BDNF polymorphism alters extinction learning in both mouse and human. Science. 2010 Feb. 12;327(5967):863-6.

Background

Research has shown that depression is commonly associated with diabetes. People who have both diabetes and depression tend to have more severe symptoms of both diseases, higher rates of work disability and use more medical services than those who only have diabetes alone.

Elizabeth Lin M.D., MPH, Michael Von Korff, Sc.D., and colleagues from Group Health Research Institute in Seattle, WA, and Wayne Katon M.D., and colleagues from the University of Washington, examined the association between type 2 diabetes and depression among 4,623 patients enrolled in Group Health, a health plan serving residents of Washington state. They first interviewed the participants between 2000 and 2002, and then conducted follow-up interviews between 2005 and 2007. They tracked the participants’ rates of microvascular complications (e.g., blindness, end-stage kidney disease, amputations and kidney failure deaths) and macrovascular complications (e.g., heart attack, stroke, cardiovascular procedures and deaths).

Results of the Study

At the follow-up interview, 14 percent of the participants had developed a clinically advanced microvascular complication, and 24 percent had developed a severe macrovascular complication. Over the five-year follow-up period, those with major depression had a 36 percent higher risk of developing microvascular complications and a 25 percent higher risk of developing macrovascular complications compared with patients without major depression.

Significance

Those with type 2 diabetes and coexisting major depression are more likely to experience life-threatening complications than those without coexisting major depression. To reduce the risk of diabetes complications, better interventions are needed that not only treat the diabetes but address any accompanying depression as well.

What’s Next

More research is needed to identify the underlying mechanisms for the association between depression and diabetes complications, and to develop interventions that treat both diabetes and accompanying major depression. In addition, better screening is needed to help identify those patients with diabetes who are at higher risk for developing major depression and other life-threatening complications.

More information about diabetes is available from the National Diabetes Education Program.

Reference

Lin EHB, Rutter CM, Katon W, Heckbert SR, Ciechanowski P, Oliver MM, Ludman EJ, Young BA, Williams LH, McCulloch DK, Von Korff M. Depression and advanced complications of diabetes. Diabetes Care. 2010 Feb. 33(2): 264-269.

This is the first study to describe the prevalence of depression among low-income urban mothers, who were attending well-child care visits, through the use of a diagnostic interview. It also is the first study of this population group to test the accuracy of three depression screening tools routinely used by physicians.

The screening tools have high accuracy in identifying depression, the researchers concluded, but cutoff scores may need to be altered to identify depression more accurately among low-income urban mothers.

The study involved 198 mothers who were 18 years of age or older and whose children were no older than 14 months. The mothers attended well-child visits at the outpatient pediatric clinic at Golisano Children’s Hospital at the Medical Center.

The researchers found that 56 percent of the mothers, after a diagnostic interview, met the criteria for a diagnosis of a major or minor depressive disorder.

“This is an unexpected, very high proportion to meet diagnostic criteria for depression,” said Linda H. Chaudron, M.D., associate professor of Psychology, Pediatrics and of Obstetrics and Gynecology. “This may be a group at high risk for depression. The message of this study is that pediatricians and other clinicians who work with low-income urban mothers have multiple screening tools that are easy to use and accurate. These tools can help clinicians identify mothers with depression so they can be referred for help.”

Many women experience the so-called “baby blues.” When the feelings persist or worsen it may be clinical depression. The symptoms include insomnia, persistent sadness, lack of interest in nearly all activity, anxiety, change in appetite, persistent feelings of guilt, and thoughts of harming oneself or the baby. Postpartum depression affects up to 14 percent of new mothers in the United States, with higher rates among poor and minority women.

The researchers evaluated three screening tools, the Edinburgh Postnatal Depression Scale, the Beck Depression Inventory II and the Postpartum Depression Screening Scale, using the diagnostic interviews for validation.

The three screening tools have been evaluated in many populations, but one of the reasons the study was done was to test the tools with a group for whom there is not much data — low-income women, especially African-American women, Chaudron said. The researchers also evaluated the validity of the screening tools at various times during the postpartum year.

“The screening tools are valid when used anytime during the postpartum year,” Chaudron said.

Use of traditional cutoff scores may not be as accurate as previously thought. Clinicians should be aware that scores two or three points below traditional cutoff scores may indicate a need for further evaluation, the researchers concluded.

The study was funded by a grant from the National Institute of Mental Health.

Background

Most studies on HIV/AIDS have focused on conditions in U.S. inner cities and sub-Saharan Africa. Despite this lack of research attention, the AIDS epidemic in China and other Asian countries is rapidly growing.

Led by Xiaoming Li, Ph.D., of Wayne State University, researchers in China and the United States collaborated on a study to better understand the impact of parental HIV/AIDS on the emotional well-being of children. The researchers assessed 1,625 children, ages 6-18, living in two rural counties in central China, where many residents had been infected with HIV through unsafe blood collection practices.

Among the participants, 755 children had lost one or both parents to AIDS and 466 “vulnerable” children lived with HIV-infected parents. A comparison group of 404 children from the same community who did not have a HIV/AIDS-related illness or death in their immediate families were also included.

Results of the Study

As a group, children orphaned or made vulnerable by parental HIV/AIDS scored significantly higher on measures of depression and loneliness, and significantly lower on self-esteem, positive future expectations, hopefulness about the future, and perceived control over the future, than children in the comparison group. HIV/AIDS orphans were more likely to be depressed than vulnerable children, but the latter reported greater loneliness and lower self-esteem.

Children who lost one parent to HIV/AIDS showed similar rates of mental health problems as those who lost both parents, suggesting that having a surviving parent may not provide a significant protective effect on the emotional costs of losing a parent to HIV/AIDS.

Among HIV/AIDS orphans, the type of care setting—living in an orphanage, group home, or with kin—also affected their psychosocial adjustment. Group homes in China are managed by local adults serving the role of house parents for four to six orphans who refer to each other as siblings and the house parents as mother and father. HIV/AIDS orphans living in small group homes reported less depression and higher perceived control over their futures, but greater loneliness and lower self-esteem than those living in orphanages or with kin. Those living in orphanages showed greater hopefulness and expectations for the future compared with children in kinship care.

Significance

In one of the first efforts to assess the psychological well-being of Chinese children orphaned or made vulnerable by parental HIV/AIDS, the study shows that parental illness or death due to HIV/AIDS causes considerable psychosocial stress. Having a surviving parent does not appear to reduce this stress, but a child’s care setting may help moderate it.

The findings also suggest a range of factors that may affect the emotional well-being of Chinese children orphaned by HIV/AIDS. For example, unlike orphanages or kinship care, group homes seem to provide a more family-like atmosphere in the children’s own community, which may be more supportive of their mental health needs. Also, children in kinship care may have faced greater hardships than they’d previously experienced, due to increased financial strain on kinship households. These distinctions likely vary by culture—for example, HIV/AIDS orphans in African countries are predominantly cared for by kin or in community-based orphan care.

Though parental death is clearly a risk factor for emotional adjustment issues, some orphans in this study did not show higher levels of mental health problems compared with children living with an HIV-infected parent or those with no HIV/AIDS-related illness in their families. According to the researchers, this finding may demonstrate children’s natural resilience to highly stressful situations, as suggested by many past studies.

The researchers also caution that their findings may not apply to different populations within China or elsewhere. Factors such as cultural, ethnic, or socioeconomic background, or more common modes of HIV infection, such as unsafe sex or intravenous drug use, may affect a child’s psychosocial adjustment to parental death.

What’s Next

Further studies can help identify protective factors that promote better psychosocial adjustment in the face of living with or losing a parent to HIV/AIDS. Additional studies in this field may also improve scientists’ understanding of factors that influence the experience of bereavement and grief among children in China and other Asian countries. The researchers also emphasized the need to develop culturally appropriate measures and interventions for this diverse population.

Reference

Fang X, Li X, Stanton B, Hong Y, Zhang L, Zhao G, Zhao J, Lin X, Lin D. Parental HIV/AIDS and psychosocial adjustment among rural Chinese children. J Pediatr Psychol. 2009 Nov-Dec;34(10):1053-62. Epub 2009 Feb 10. PubMed PMID: 19208701; PubMed Central PMCID: PMC2782251.

Background

The very behaviors that put young women at risk for pregnancy also put them at risk for STIs. Since they are no longer trying to prevent pregnancy, young, pregnant women are less likely to use condoms than their non-pregnant peers. This, in turn, puts them at high risk for contracting HIV and other STIs during and shortly after pregnancy. However, few HIV interventions have been developed to address the specific needs of young, pregnant women.

For their study, Jeanette Ickovics, Ph.D., of Yale University, and colleagues recruited 1,047 teens and young women (ages 14-25). All participants were in their second trimester of pregnancy and receiving prenatal care at one of two clinical sites during 2001-2004. The researchers randomly assigned the study participants to one of three care groups:

• Standard CenteringPregnancy group prenatal care
• CenteringPregnancy group prenatal care + HIV prevention components
• Standard individual prenatal care

CenteringPregnancy consisted of 10 two-hour sessions led by a midwife or obstetrician. During the sessions, women receive their prenatal care, engage in self-care activities (such as documenting their own weight and blood pressure), and attend a group discussion of important issues related to prenatal care, childbirth preparation, and postpartum care.

“CenteringPregnancy Plus” offered the same general content and structure of CenteringPregnancy, but three of the 10 sessions included 40 minutes of content related to preventing HIV. The HIV prevention components addressed the participants’ perception of HIV risk, personal goals for safer sex behaviors during and after pregnancy, and skills for communicating about safer sex behaviors with sexual partners.

Study participants receiving standard individual prenatal care met with their health care providers on the same schedule and the same number of times as women in the other two care groups, but they only spent about 10-15 minutes with their prenatal care provider per appointment, as is considered standard.

After the initial assessment, the researchers conducted follow-up interviews for all participants during the third trimester, and at six and 12 months after postpartum.

Results of the Study

Participants who received CenteringPregnancy Plus were 51 percent less likely to become pregnant again within six months of giving birth, compared with women in the two other care groups. The CenteringPregnancy Plus program also increased condom use and safe sex communication between partners, and reduced incidences of unprotected sex, compared with the other study treatments.

Teens (ages 14-19) who received CenteringPregnancy Plus had significantly fewer new STIs than teens in the other study conditions (9 percent vs. 12.5 percent of teens in the CenteringPregnancy group and 20 percent in the standard care group). There were no differences in infection rates among young adults (ages 20-25) in the study.

Significance

According to the researchers, CenteringPregnancy Plus differs from other HIV interventions by integrating sexual risk prevention into the existing structure of prenatal care, drawing on women’s motivations for a healthy pregnancy and their frequent contact with care providers.

Offering an HIV prevention program within the context of prenatal care may help to reduce the spread of HIV and other sexually transmitted infections by reaching an at-risk population that may not otherwise have had access to such programs. The researchers noted that the added time needed to deliver the HIV prevention did not come at the expense of prenatal care. However, they further cautioned that while the program was effective, the differences between groups were modest.

Past research has shown that among teenagers, repeat pregnancy shortly after giving birth increases parenting-related stress and negative parenting behaviors. Thus, by reducing or preventing repeat pregnancies, CenteringPregnancy Plus may help to improve the quality of life of young mothers and their children. The researchers suggest booster sessions of the program may prolong this effect beyond six months postpartum.

What’s Next

The researchers note that pregnancy may be an important window of opportunity to promote changes in behavior and improve the health of women. This study demonstrates the possibility of creating integrated programs that positively influence a wide range of health problems, rather than dealing with each problem separately. Such research may impact the design and delivery of future prenatal care services.

Dr. Ickovics and co-author Trace Kershaw, Ph.D., are conducting a follow-up study, also funded by NIMH, to test the “real-world” effectiveness of CenteringPregnancy Plus when provided through 14 New York City community hospitals and health centers.

Reference

Kershaw TS, Magriples U, Westdahl C, Rising SS, Ickovics J. Pregnancy as a window of opportunity for HIV prevention: effects of an HIV intervention delivered within prenatal care. Am J Public Health. 2009 Nov;99(11):2079-86. Epub 2009 Sep 17. PubMed PMID: 19762662.