The Mental Health Social Worker

Obtaining an electrocardiogram (ECG) to screen for heart conditions in children prior to prescribing stimulant medication to treat attention deficit hyperactivity disorder (ADHD) may save some lives but it is borderline cost-effective, according to an NIH study published online ahead of print March 8, 2010, in Circulation: Journal of the American Heart Association.

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.

Both humans and mice carrying a variant of a gene that plays a role in memory were slow to learn to forget a fear-based memory. The parallels in gene effects observed in mice and humans in this work means that investigation using the mouse model can provide insights into effects in humans; results may inform treatment approaches to anxiety disorders such as post-traumatic stress disorder.

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.

People with type 2 diabetes and coexisting major depression are more likely to experience life-threatening diabetes-related complications, according to a recent NIMH-funded study published in the February 2010 issue of Diabetes Care.

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.

ScienceDaily (Feb. 20, 2010) — More than half of low-income urban mothers met the criteria for a diagnosis of depression at some point between two weeks and 14 months after giving birth, according to a study led by University of Rochester Medical Center researchers and published online by the journal Pediatrics.

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.

Having a parent with HIV/AIDS or losing one or both parents to the illness leads to poorer mental health among children in China, according to a recent study funded in part by NIMH. Published in the November-December 2009 issue of the Journal of Pediatric Psychology, the study also emphasizes the need to develop culturally and developmentally appropriate measures and interventions for diverse populations.

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.

An HIV-prevention program targeted at women receiving prenatal care may effectively reduce risks for HIV, sexually transmitted infections (STIs), and unplanned future pregnancies, according to NIMH-funded researchers. Bundling such interventions into existing health care models, like prenatal care, also may be more accessible to those who may not have the time, interest, or resources to attend a stand-alone HIV prevention program. Changing the way prenatal care is provided also may create sustainable advantages in reproductive health for all at-risk women. The study was published in the November 2009 issue of the American Journal of Public Health.

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.

A new NIMH-funded grant aims to increase suicide detection and prevention efforts among patients who present with suicide risk factors in hospital emergency departments.

The Emergency Department Safety Assessment and Follow-up Evaluation (EDSAFE) trial will be coordinated by the Emergency Medicine Network (EMNet), which is based at Massachusetts General Hospital. The team of researchers will be led by Edwin D. Boudreaux, Ph.D., of the University of Massachusetts, Carlos A. Camargo, Jr., M.D., DrPH, of Massachusetts General Hospital and Harvard Medical School, and Ivan Miller, Ph.D., of Butler Hospital in Providence, RI. The project is expected to enroll nearly 1,420 participants over five years.

EDSAFE will be conducted in three phases. The first phase will assess treatment as usual (TAU) for patients. TAU typically consists of evaluating suicidal risk only among those emergency department patients who have psychiatric risk factors such as depression, suicidal thinking or behavior (ideation), or substance abuse. Often these patients are put under observation while at the hospital and are evaluated by a mental health provider. They also may be referred to a mental health professional outside the hospital, but few receive adequate follow-up care after they are discharged. During the second phase, a universal screening process will be tested in which all patients, regardless of whether they exhibit typical risk factors for suicide, will be screened for suicidal ideation. The researchers will compare universal screening with TAU to determine how well each detects suicidal patients.

During the third phase, a more intensive intervention that includes screening, brief counseling, an evaluation by a mental health provider, referral to outpatient care and other components will be implemented. Patients will then receive follow-up phone counseling. The intensive intervention will be compared to TAU and to universal screening.

The study will be conducted at eight sites throughout the nation and is set to begin in June 2010.

Gender Gaps Linked to Status of Women, According to New Analysis

WASHINGTON – Girls around the world are not worse at math than boys, even though boys are more confident in their math abilities, and girls from countries where gender equity is more prevalent are more likely to perform better on mathematics assessment tests, according to a new analysis of international research.

“Stereotypes about female inferiority in mathematics are a distinct contrast to the actual scientific data,” said Nicole Else-Quest, PhD, a psychology professor at Villanova University, and lead author of the meta-analysis. “These results show that girls will perform at the same level as the boys when they are given the right educational tools and have visible female role models excelling in mathematics.”

The results are reported in the latest issue of Psychological Bulletin, published by the American Psychological Association. The finding that girls around the world appear to have less confidence in their mathematical abilities could help explain why young girls are less likely than boys to pursue careers in science, technology, engineering and mathematics.

Else-Quest and her fellow researchers examined data from the Trends in International Mathematics and Science Study and the Programme for International Student Assessment, representing 493,495 students ages 14-16 from 69 countries. Both studies’ results were released in 2003, and not all countries participated in both assessments. The TIMSS focuses on basic math knowledge, while the PISA test assesses students’ ability to use their math skills in the real world. The researchers felt these two tests offered a good sampling of students’ math abilities.

While these measures tested different math abilities, there were only small gender differences for each, on average. However, from nation to nation, the size of the gender differences varied a great deal.

The two studies also assessed students’ level of confidence in their math abilities and how important they felt it was to do well in math in order to have a successful career. Despite overall similarities in math skills, boys felt significantly more confident in their abilities than girls did and were more motivated to do well.

The researchers also looked at different measures of women’s education, political involvement, welfare and income in each country. There was some variability among countries when it came to gender differences in math and how it related to the status and welfare of women. For example, if certain countries had more women in research-related positions, the girls in that country were more likely to do better in math and feel more confident of those skills.

‘This meta-analysis shows us that while the quality of instruction and curriculum affects children’s learning, so do the value that schools, teachers and families place on girls’ learning math. Girls are likely to perform as well as boys when they are encouraged to succeed,” said Else-Quest.

Article: “Cross-National Patterns of Gender Differences in Mathematics: A Meta-Analysis,” Nicole M. Else-Quest, PhD, Villanova University; Janet Shibley Hyde, PhD, University of Wisconsin-Madison; Marcia C. Linn, PhD, University of California, Berkeley. Psychological Bulletin, Vol. 136, No. 1.

Contact Dr. Nicole Else-Quest by e-mail or at (610) 519-4758.

Translational Experiments in Rats, Humans Suggest New Medication Target

A study has linked panic disorder to a wayward hormone in a brain circuit that regulates vigilance. While too little of the hormone, called orexin, is known to underlie narcolepsy, the new study suggests that too much of it may lead to panic attacks that afflict 6 million American adults.

“Targeting the brain’s orexin system may hold promise for a new generation of anti-anxiety treatments,” said Thomas R. Insel, M.D., Director of the National Institute of Mental Health (NIMH), part of the National Institutes of Health. “This is a good example of how translational experiments in rats and humans can potentially yield clinical benefits.”

NIMH grantee Anantha Shekhar, M.B., Ph.D., and colleagues at Indiana University and Lund University, report on their findings online Dec. 27, 2009 in the journal Nature Medicine. They showed that blocking orexin gene expression or its receptor prevented panic attack-like responses in rats. The study also revealed that panic disorder patients have excess levels of the hormone.

Background

Orexin, also called hypocretin, is secreted exclusively in a circuit emanating from the brain’s hypothalamus, known to regulate arousal, wakefulness and reward.

Panic attacks can be experimentally-induced by infusing susceptible humans with a normally innocuous salt called sodium lactate. The salt similarly triggers panic-like anxiety behaviors in susceptible rat strains, suggesting that something is altered in their arousal circuit. Since sodium lactate activated orexin-secreting neurons in panic-prone rats but not in control rats, the researchers hypothesized that something might be orexin.

Results of This Study

The investigators first discovered that increased gene expression in orexin-secreting neurons correlated with increases in anxiety-like behavior in panic-prone rats following sodium lactate infusions. Using a technique called RNA interference, they then protected the panic-prone rats from developing anxiety behaviors following the infusions by first injecting them with a genetically-engineered agent that prevented orexin genes from turning on. Blocking orexin receptors with a drug that specifically binds to it also blocked the anxiety like behavior following the infusions. This mirrored effects, seen in both rats and humans, of benzodiazepine medications used to treat panic disorder.

The excess sleepiness of narcolepsy, traced a decade ago to loss of orexin-secreting neurons in the arousal circuit, might seem to be an opposite state of a panic attack. However, the researchers demonstrated in rats that such sedation could not account for orexin’s effects on anxiety. Also in rats, they traced orexin neurons to their end target to pinpoint the specific brain site that accounts for the anxiety effects, disentangled from cardio-respiratory components of the panic response.

Finally, by measuring orexin in cerebrospinal fluid of 53 patients, the researchers showed that those with just panic disorder had higher levels of orexin than those with both panic disorder and depression.

Significance

Taken together, these results and other evidence suggest a critical role for an overactive orexin system in producing panic attacks, say the researchers.

What’s Next?

Medications that block the orexin receptor may provide a new therapeutic approach for the treatment of panic disorder, they add.

The research was also supported, in part, by NIH’s National Center for Research Resources.

Reference

A key role for orexin in panic anxiety. Johnson PL, Truitt W, Fitz SD, Kelley PE, Dietrich A, Sanghani S, Traskman-Bendz L, Goddard AW, Brundin, L, Shekhar A. Nature Medicine. Epub 2009 Dec 27.

Depressed teens who report low levels of impairment related to drug or alcohol use tended to respond better to depression treatment than depressed teens with higher levels substance-related impairment, according to an analysis of data from the NIMH-funded Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study. However, it is unclear whether less substance-related impairment allowed for better response to depression treatment, or if better treatment response led to less substance-related impairment. The study was published in the December 2009 issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

Background

Substance use is more common among teens with depression than among those without depression. Researchers have also found that depression can inhibit teens’ response to treatment of substance abuse, and substance abuse is associated with a poorer response to treatment of depression. Still, few trials have examined how coexisting depression and substance use among teens may affect treatment outcomes for both.

In the TORDIA study, 334 teens who did not respond to a type of antidepressant called a selective serotonin reuptake inhibitor (SSRI) before the trial were randomly assigned to one of four treatments for 12 weeks:

• Switch to another SSRI
• Switch to venlafaxine (Effexor), a different type of antidepressant
• Switch to another SSRI and add cognitive behavioral therapy (CBT), a type of psychotherapy
• Switch to venlafaxine and add CBT

Results of the trial were previously reported in February 2008. They showed that teens who received combination therapy, with either type of antidepressant, were more likely to improve than those on medication alone.

In this new analysis, Benjamin Goldstein, M.D., of the University of Toronto, and colleagues examined TORDIA data to determine the relationship, if any, between substance use, major depression and response to depression treatment. Substance use was defined as using alcohol or drugs without meeting criteria for having a full-blown substance abuse disorder. Teens who were diagnosed with a substance abuse disorder were excluded from the TORDIA study.

Results of the Study

Substance use was fairly common among TORDIA participants. At baseline, about 28 percent reported experimenting with drugs or alcohol. Those who showed more substance -related impairment were older, felt more hopeless, had greater family conflict, developed depression at an earlier age, were more likely to have a history of physical or sexual abuse, and were more likely to have coexisting oppositional defiant disorder (ODD) or conduct disorder (CD). Substance-related impairment included certain attitudes and behaviors such as craving the substance, feeling hooked on it, accidentally hurting oneself or others while using it, and other similar effects.

Participants with low levels of substance use and substance-related impairment throughout the study tended to respond better to depression treatment than those who showed persistently high or increasing levels of substance-related impairment. There were no significant differences in rates of substance use and impairment among the treatment groups.

Significance

This study is one of the first to examine the association between substance use and depression treatment among depressed teens. The findings are consistent with other studies that found depression severity to be associated with a history of physical or sexual abuse, coexisting ODD or CD, and substance-related impairment. However, the direction of the association is uncertain. The data could not determine whether low substance-related impairment facilitates improvement in depression symptoms, or whether improvement in depressed mood leads to a decrease in substance-related impairment.

What’s Next

The authors caution that the study does not provide definitive conclusions about depression treatment and substance use. However, they do suggest that clinicians treating teens for depression screen for signs of substance use and address those issues as well, even if the teen does not meet criteria for a full-blown substance abuse disorder.

Reference

Goldstein BI, Shamseddeen W, Spirito A, Emslie G, Clarke G, Wagner KD, Asarnow JR, Vitiello B, Ryan N, Birmaher B, Mayes T, Onorato M, Zelazny J, Brent D. Substance use and the treatment of resistant depression in adolescents. Journal of the American Academy of Child and Adolescent Psychiatry. 2009 Dec. 48(12):1182-1192.

Children with autism who receive a high intensity developmental behavioral intervention starting by age 18-30 months show major improvements in IQ, language, adaptive behavior, and severity of their diagnosis, according to an NIMH-funded study.

Background

Current guidelines by the American Academy of Pediatrics recommend screening children for autism spectrum disorder (ASD) by age 18 months. However, no randomized clinical trials of intensive interventions for this age group had been conducted.

To address this gap, Geraldine Dawson, Ph.D., who was at the University of Washington at the time of the study, and colleagues randomly assigned 48 children, ages 18-30 months, to one of two intervention groups:

• Early Start Denver Model (ESDM), a comprehensive, developmental behavioral intervention designed for toddlers with ASD as young as 12 months old. ESDM combines aspects of applied behavioral analysis (ABA) with developmental and relationship-based approaches.
• Assess and Monitor (A/M), the comparison group intervention in which parents received recommendations on ASD interventions for their children, as well as referrals to local community providers of the interventions. A/M represents typical community-based care.

Children in the ESDM group were provided 20 hours per week of therapy from study clinicians, while their parents received related training to use ESDM strategies for at least five additional hours per week during their daily activities. Parents of all study participants were also free to receive other community services they thought appropriate.

All children in the study had been diagnosed with autism or a milder form of ASD called pervasive developmental disorder not otherwise specified (PDD-NOS). They were assessed yearly for two years or until the child turned four years old, whichever was longer.

Results of the Study

By the first- year assessment, children in the ESDM group gained 15.4 IQ points on average, while children in the A/M group gained an average of 4.4 points.

Over the two-year study period, children in the ESDM group consistently improved on measures of communication skills. They also showed improvements in motor skills, daily living skills, and other adaptive behaviors.

While children in the ESDM group were significantly delayed in their adaptive behaviors compared to typically developing children, they showed similar rates of improvement. In contrast, children in the A/M group fell further and further behind over time.

By the end of the study, more children who had received ESDM received improved diagnoses than children in the A/M group—seven children initially diagnosed with autistic disorder had their diagnosis change to PDD-NOS after receiving ESDM (30 percent), compared to only one child in the A/M group (5 percent).

Significance

According to the researchers, this is the first randomized controlled trial to study a potentially useful intensive intervention for very young children with ASD.

The study’s findings suggest that ESDM can help children with ASD achieve better outcomes in terms of IQ, language, and behavioral skills, and in severity of their ASD diagnosis, than if they receive community-based care. Compared to research on other, similar interventions, this study showed greater differences between groups, suggesting that ESDM, delivered at a very young age, may be more effective than other approaches. The researchers noted that parents’ use of ESDM strategies at home may have been key to this intervention’s effectiveness.

What’s Next

The University of Washington research team has been funded through the NIH Autism Centers of Excellence (ACE) program to follow this study’s participants to determine whether the effects of ESDM can be sustained over time. In addition, Dr. Sally Rogers, Ph.D., a co-author on the study and co-developer with Dr. Dawson of the ESDM model, is leading a multi-site, randomized clinical trial of ESDM, also funded through the NIH ACE program. With a larger sample size, the investigators hope to better understand factors that predict level of response to the ESDM intervention.

Reference

Dawson G, Rogers S, Munson J, Smith M, Winter J, Greenson J, Donaldson A, Varley J. Randomized, Controlled Trial of an Intervention for Toddlers With Autism: The Early Start Denver Model. Pediatrics. 2009 Nov 30. [Epub ahead of print] PubMed PMID: 19948568.

Alcoholic ‘energy’ drinks could raise risks from intoxication

WASHINGTON, DC—People who drink may want to know that coffee won’t sober them up, according to new laboratory research. Instead, a cup of coffee may make it harder for people to realize they’re drunk.

What’s more, popular caffeinated “alcohol-energy” drinks don’t neutralize alcohol intoxication, suggest the findings from a mouse study reported in the journal Behavioral Neuroscience, which is published by the American Psychological Association.

“The myth about coffee’s sobering powers is particularly important to debunk because the co-use of caffeine and alcohol could actually lead to poor decisions with disastrous outcomes,” said co-author Thomas Gould, PhD, of Temple University, in extending the research to what it means for humans.

“People who have consumed only alcohol, who feel tired and intoxicated, may be more likely to acknowledge that they are drunk,” he added. “Conversely, people who have consumed both alcohol and caffeine may feel awake and competent enough to handle potentially harmful situations, such as driving while intoxicated or placing themselves in dangerous social situations.”

In the laboratory, caffeine made mice more alert but did not reverse the learning problems caused by alcohol, including their ability to avoid things they should have known could hurt them, according to the study.

Scientists gave groups of young adult mice various doses, both separately and together, of caffeine and of ethanol (pure alcohol) at levels known to induce intoxication. The doses of caffeine were the equivalent of one up to six or eight cups of coffee for humans. Control mice were given saline solution.

Gould and co-author Danielle Gulick, PhD, then tested three key aspects of behavior: the ability to learn which part of a maze to avoid after exposure to a bright light or loud sound; anxiety, reflected by time spent exploring the maze’s open areas; and general locomotion.

Ethanol, as expected, increased locomotion and reduced anxiety and learning in proportion to the dose given. In other words, intoxicated animals were more relaxed and moved around more but learned significantly less well than control mice to avoid the part of the maze with the unpleasant stimuli.

By itself, caffeine increased anxiety and reduced both learning and locomotion. Compared to the control animals, mice given caffeine were significantly more inhibited, less mobile and less savvy about avoiding the unpleasant stimuli.

When the drugs were given together, ethanol blocked caffeine’s ability to make the mice more anxious. Conversely, caffeine did not reverse ethanol’s negative effect on learning. As a result, alcohol calmed the caffeine jitters, leaving an animal more relaxed but less able to avoid threats – a combination that the authors speculated could make people more likely to believe they are not drunk or not impaired enough to have problems functioning.

“The alcohol-energy drink combinations have skyrocketed in popularity,” Gould noted. He cited other evidence that these drinks produce deficits in general cognitive ability and raise the odds of alcohol-related problems such as drunken-driving citations, sexual misconduct, and needing medical assistance.

“The bottom line is that, despite the appeal of being able to stay up all night and drink, all evidence points to serious risks associated with caffeine-alcohol combinations,” he concluded.

The Food and Drug Administration is looking into the safety and legality of combination alcohol-caffeine beverages. In November, it sent letters to 30 manufacturers asking for evidence that such drinks are safe and legal under FDA regulations. To date, the FDA has only approved caffeine as an additive in soft drinks at concentrations less than 200 parts per million and has not approved adding caffeine at any level to alcoholic beverages. Under the Federal Food, Drug and Cosmetic Act, a substance added intentionally to food (such as caffeine in alcoholic beverages) is deemed unsafe and is unlawful unless its particular use has been approved by FDA regulation or is generally recognized as safe.

Article: “Effects of Ethanol and Caffeine on Behavior in C57BL/6 Mice in the Plus-Maze Discriminative Avoidance Task,” Danielle Gulick, PhD, and Thomas J. Gould, PhD, Temple University; Behavioral Neuroscience, Vol. 123, No. 6.

(Full text of the article is available from the APA Public Affairs Office)

Thomas Gould can be reached by e-mail or at (215) 204-7495.

The American Psychological Association, in Washington, D.C., is the largest scientific and professional organization representing psychology in the United States and is the world’s largest association of psychologists. APA’s membership includes more than 150,000 researchers, educators, clinicians, consultants and students. Through its divisions in 54 subfields of psychology and affiliations with 60 state, territorial and Canadian provincial associations, APA works to advance psychology as a science, as a profession and as a means of promoting health, education and human welfare.

Epigenetic Mark in Blood Could Serve as Biomarker for Disorder

For the first time, inherited disruption of gene expression in a brain system for social behavior has been implicated in autism. NIMH grantee Margaret Pericak-Vance, Ph.D., at the University of Miami and Simon Gregory, Ph.D., at Duke University, and a multinational team of researchers found evidence for such epigenetic effects on the gene for the oxytocin receptor –– part of a brain system that mediates social behaviors disturbed in autism. The findings suggest a potential genetic biomarker for the disorder.

The researchers report on their findings online October 22, 2009 in BMC Medicine.

Background

Environmentally-influenced and heritable chemical tags called epigenetic marks regulate the mix of proteins needed to build each tissue of the body. These alterations do not change a person’s DNA, or genetic blueprint. However, epigenetic changes that occur from the moment sperm meets egg can alter when and where genes get turned on.

Researchers are testing oxytocin as a possible treatment for social behavior disturbances in autism. Oxytocin is a hormone produced in the brain, which works through the oxytocin receptor. Previous studies had hinted at oxytocin receptor abnormalities in autism, but not at an epigenetic mechanism.

The researchers first used high-tech, genome-wide techniques to search for deletions or duplications of genes in 119 people with autism from families that had multiple children with the disorder and 54 healthy controls. They then searched in brain tissue and blood samples from affected and unaffected individuals for a common type of epigenetic mark created by methylation. In this process, molecules called methyl groups attach to DNA in response to an environmental trigger, preventing a gene’s expression.

Findings of This Study

The researchers found a deletion in the oxytocin receptor gene in a person with autism and his mother, who had obsessive compulsive disorder (OCD). OCD shares with autism symptoms of repetitive behaviors. Oxytocin receptor genes were similarly silenced –– but by methylation — in a sibling with autism who lacked the deletion. That is, two separate mechanisms of gene expression regulation resulted in the same outcome — loss of oxytocin receptor expression — in the same family.

Following up in blood cells and temporal cortex brain tissue of people with autism, the researchers pinpointed higher levels of methylation — about 70 percent vs. the normal 40 percent –– at an epigenomic site known to regulate the oxytocin receptor. They also found decreased expression of the receptor in the temporal cortex tissue, an area previously linked to autism.

Significance

Excess methylation of the oxytocin receptor could render people with autism less sensitive to the social hormone’s effects. Gene expression most likely became altered in very early gestation (between fertilization and implantation), suggest the researchers. This could increase vulnerability of the oxytocin receptor gene to environmental insults during the first few weeks of pregnancy, they say. The results suggest that such epigenetic misregulation of the oxytocin receptor gene may be an important factor in the development of autism.

What’s Next?

Since evidence of excess methylation of the oxytocin receptor gene in temporal cortex was also found in blood cells, the researchers suggest that the blood measure may be a marker, more generally, of the methylation status of the temporal cortex. So measuring the methylation status of the oxytocin receptor in blood could potentially serve as a biomarker for autism that might be used in conjunction with traditional diagnostic criteria. Drugs that target methylation might also hold promise for treatment.

Reference

Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. Gregory SG, Connelly JJ, Towers AJ, Johnson J, Biscocho D, Markunas CA, Lintas C, Abramson RK, Wright HH, Ellis P, Langford CF, Worley G, Delong GR, Murphy SK, Cuccaro ML, Persico A, Pericak-Vance MA. BMC Med. 2009 Oct 22;7(1):62. [Epub ahead of print]PMID: 19845972.

Other Subtypes May Affect Disease Outcomes Too

In a study of HIV-related cognitive impairment in Uganda, people with HIV subtype D were more likely than those with the other subtypes to have HIV-associated dementia (HAD), according to NIMH-funded researchers. This study, published in the September 1, 2009, issue of Clinical Infectious Diseases, is the first to show that HIV subtype may affect a person’s risk for developing HAD.

Background

HIV-associated dementia is a common symptom of advanced HIV infection, affecting a person’s central nervous system and cognitive skills. While the subtype of HIV has been shown to affect the progression of HIV to AIDS, the effect on HAD risk has been unknown.

To explore this relationship, Ned Sacktor, M.D., of Johns Hopkins Bayview Medical Center, and colleagues conducted a study in Uganda of 60 people at risk of developing HAD. The wide variety of HIV subtypes in Uganda and other sub-Saharan countries, along with studies suggesting a relatively high prevalence of HAD and other HIV-related neurological complications in these regions, makes them ideal locations for studying the effects of HIV subtypes on various disease outcomes.

All participants in Sacktor’s study had advanced HIV infection but had not previously received highly active antiretroviral treatment (HAART), the current standard of care for HIV. The researchers assessed participants’ neurological, neuropsychological, and functional status, as well as their HIV subtype.

Results of the Study

Of the 60 study participants:

• 33 were infected with subtype A
• 2 were infected with subtype C
• 9 were infected with subtype D
• 16 were infected with a subtype that had characteristics of both subtype A and subtype D.

Participants with HIV subtype D were more likely to have HAD (89 percent with dementia) than those with subtype A (24 percent with dementia). The two other HIV subtypes observed in the study did not show a significant association with HAD.

Significance

The results suggest that among people with advanced HIV infection, those with subtype D are more likely to have HAD than those with other subtypes. According to the researchers, these findings are the first to show that HIV subtypes may play a role in causing HAD.

What’s Next

More studies are needed to confirm whether the relationship between HIV subtype D and increased HAD risk exists among the broader HIV-infected community, instead of just those who had not previously received HAART. Additional research should also focus on how subtype D may lead to increased risk of HAD, and whether other subtypes may also influence risk for this and other HIV-related neurological complications.

Reference

Sacktor N, Nakasujja N, Skolasky RL, Rezapour M, Robertson K, Musisi S, Katabira E, Ronald A, Clifford DB, Laeyendecker O, Quinn TC. HIV subtype D is associated with dementia, compared with subtype A, in immunosuppressed individuals at risk of cognitive impairment in Kampala, Uganda. Clin Infect Dis. 2009 Sep 1;49(5):780-6. PubMed PMID: 19622045.

Long-term treatment of adolescents with major depression is associated with continuous and persistent improvement of depression symptoms in most cases, according to the most recent analysis of follow-up data from the NIMH-funded Treatment of Adolescents with Depression Study (TADS). The report, along with a commentary compiling the take-home messages of the study, was published in the October 2009 issue of the American Journal of Psychiatry.

Background

The TADS team randomly assigned 439 adolescents aged 12 to 17 to one of four treatment strategies for 36 weeks—the antidepressant fluoxetine (Prozac) only, cognitive behavioral therapy (CBT) only, the combination of the two, or placebo (inactive or “sugar” pill). After the first 12 weeks, the placebo group was discontinued, while the participants assigned to the active interventions continued treatment for another six months. Overall, the combination therapy was found to be the most effective in speeding up remission. Visit the NIMH website for more information about TADS results.

After the trial ended, the teens who had been assigned to the active treatments were assessed up to four times during the following year to determine if improvements were sustained over time. TADS treatments were no longer offered, but participants were encouraged to continue to seek treatment within their communities.

Participants who had been assigned to the placebo group received open treatment during the one-year follow-up period and were not included in this follow-up assessment. About 66 percent of TADS subjects (not including those who had been in the placebo group) participated in at least one assessment during the follow-up year.

Results of the Study

By the end of the 36-week trial, 82 percent of participants had improved and 59 percent had reached full remission. During the follow-up year, most participants maintained their improvements, and the remission rate climbed to 68 percent. However, about 30 percent of the participants who were in remission at week 36 became depressed again during the following year.

In addition, while 91 percent of participants showed no evidence of suicidal thinking or behavior at the end of the trial, 6 percent developed suicidal thinking during the follow-up year, with no statistically significant differences among the treatment groups.

Significance

The longer-term treatment of TADS, regardless of treatment strategy, was associated with lasting benefits for the majority of participants. However, a significant number of those who had recovered worsened during the follow-up period, indicating a need for continuous clinical monitoring and further improvement in long-term treatment of youth with major depression.

What’s Next?

The final results of TADS suggest that for most teens with depression, long-term, evidence-based treatments are effective and sustainable. But future research should concentrate on improving treatment strategies to reduce the rate of depression relapse or deterioration. The authors suggest that a randomized maintenance therapy trial would help determine how long active treatment should last to ensure the effects of treatment will endure over time.

References

TADS Team. The Treatment for Adolescents with Depression Study (TADS): Outcomes over one year of naturalistic follow-up. American Journal of Psychiatry. 2009 Oct. 166(10): 1141-1149.

March JS and Vitiello B. Take home messages from the Treatment for Adolescents with Depression Study (TADS). American Journal of Psychiatry. 2009 Oct.166(10):1118-1123.

Numerous studies have suggested that depression runs in families. Children of depressed parents are 2–3 times as likely to develop depression as compared to children who do not have a family history of the disorder.¹ Other studies have shown that remission of depression in mothers is associated with improvements in psychiatric symptoms in their children.² Despite all signs encouraging mothers to prioritize their own mental health, many suffer from untreated depression while managing treatment for their children’s emotional or behavioral problems.³

An NIH Challenge grant was awarded on behalf of NIMH to Judy Garber, Ph.D., of Vanderbilt University, to develop and test a method encouraging depressed mothers to follow treatment recommendations. For this study, Garber is recruiting 200 mothers of children receiving psychiatric treatment at a community mental health center.

All study participants will receive a referral for treatment and an information pamphlet describing the symptoms of depression and anxiety, possible effects of depression on children, and different types of treatments. Randomly assigned participants will also receive a brief, one-session Enhanced Motivation Intervention (EMI). EMI uses special interviewing techniques to identify and resolve a person’s concerns about and practical barriers to treatment.

The researchers anticipate that EMI will result in more participants getting treatment for mental disorders compared with the control group. If successful, such interventions would not only benefit the depressed individual, but may improve the well-being of her children as well.

The NIH Challenge Grants in Health and Science Research program is a new initiative funded through the American Recovery and Reinvestment Act of 2009 (Recovery Act). This program supports research on 15 broad Challenge Areas that address specific scientific and health research challenges in biomedical and behavioral research that will benefit from an influx of significant two-year funds to quickly advance the area.

Within these Challenge Areas, NIMH identified 35 topics of particular funding interest that advance the Institute’s mission and the objectives outlined in the NIMH Strategic Plan, the Trans-NIH Plan for HIV-Related Research, and the National Advisory Mental Health Council report on research training. These topics can be found at NIMH’s Challenge Grant web page.

Citations

¹Weissman MM, Wickramaratne P, Nomura Y, Warner V, Pilowsky D, Verdeli H. Offspring of depressed parents: 20 years later. Am J Psychiatry. 2006 Jun;163(6):1001-8. PubMed PMID: 16741200.

²Pilowsky DJ, Wickramaratne P, Talati A, Tang M, Hughes CW, Garber J, Malloy E, King C, Cerda G, Sood AB, Alpert JE, Trivedi MH, Fava M, Rush AJ, Wisniewski S, Weissman MM. Children of depressed mothers 1 year after the initiation of maternal treatment: findings from the STAR*D-Child Study. Am J Psychiatry. 2008 Sep;165(9):1136-47. Epub 2008 Jun 16. PubMed PMID: 18558646.

³Verdeli H, Ferro T, Wickramaratne P, Greenwald S, Blanco C, Weissman MM. Treatment of depressed mothers of depressed children: pilot study of feasibility. Depress Anxiety. 2004;19(1):51-8. PubMed PMID: 14978786.

ARLINGTON, Va. (Nov. 16, 2009) – Persons convicted of serious crimes by age 23 did not have the normal heightened response to cues associated with loud, unpleasant noise when they were tested at 3 years of age, according to a new study published in The American Journal of Psychiatry.

The finding strengthens evidence that early brain dysfunction increases the risk for criminal offending, since learning to associate a cue with a frightening outcome, known as fear conditioning, relies on the amygdala and prefrontal cortex.

Nearly 1,800 children were studied over 20 years by Yu Gao, Ph.D., and colleagues in the United States and the United Kingdom. When subjects were 3 years of age, fear conditioning was assessed by measuring electrical activity of the skin after presentation of two types of long auditory tones. One tone was usually followed by a short, loud, unpleasant sound, conditioning the child’s reaction to this tone due to anticipation of the unpleasant noise. The other tone served as a control tone, which was deeper in pitch and had no unpleasant association. Skin conductance measures the nervous system’s control over sweat secretion that is part of the body’s fear response.

Normal fear conditioning would result in greater skin responses to the conditioned tone than to the control tone. According to the authors, poor fear conditioning is hypothesized to predispose to crime because “individuals who lack fear are less likely to avoid situations, contexts, and events that are associated with future punishment—resulting in a lack of conscience.”

By age 23, 137 subjects had convictions for serious crimes. These individuals showed a lack of fear conditioning at age 3 whereas noncriminal subjects with similar characteristics, including social adversity, exhibited normal fear conditioning.

The report will appear online on November 16 at AJP in Advance, the online advance edition of The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association. Data collection was supported by the Medical Research Council (U.K.), Wellcome Trust (U.K.), and National Institute of Mental Health.

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.

The American Psychiatric Association is a national medical specialty society whose more than 38,000 physician members specialize in diagnosis, treatment, prevention and research of mental illnesses including substance use disorders. Visit the APA at www.psych.org and www.HealthyMinds.org.

WASHINGTON—The belief that healthy older brains are substantially smaller than younger brains may stem from studies that did not screen out people whose undetected, slowly developing brain disease was killing off cells in key areas, according to new research. As a result, previous findings may have overestimated atrophy and underestimated normal size for the older brain.

The new study tested participants in Holland’s long-term Maastricht Aging Study who were free of neurological problems such as dementia, Parkinson’s disease or stroke. Once participants were deemed otherwise healthy, they took neuropsychological tests, including a screening test for dementia, at baseline and every three years afterward for nine years.

According to the report in the September Neuropsychology, published by the American Psychological Association, participants were also given MRI scans at Year 3 to measure seven different parts of the brain, including the memory-laden hippocampus, the areas around it, and the frontal and cingulate areas of the cognitively critical cortex.

After examining behavioral data collected from 1994 to 2005 (with scans taken between 1997 and 1999 depending on when people entered the study), the researchers divided participants into two groups: one group with 35 cognitively healthy people who stayed free of dementia (average starting age 69.1 years), and the other group with 30 people who showed substantial cognitive decline but were still dementia-free (average starting age 69.2 years).

That cognitive decline was measured by drops of at least 30 percent on two or more of six core tests of verbal learning and fluency, recall, processing speed, and complex information processing, and/or drops of 3 or more points, or scores of 24 or lower (raising suspicion for cognitive impairment), on the Mini-Mental State Examination screening tool for dementia.

In contrast to the 35 people who stayed healthy, the 30 people who declined cognitively over nine years showed a significant effect for age in the hippocampus and parahippocampal areas, and in the frontal and cingulate cortices. In short, among the people whose cognition got worse, older participants had smaller brain areas than younger participants.

Thus, the seeming age-related atrophy in gray matter more likely reflected pathological changes in the brain that underlie significant cognitive decline than aging itself, the authors wrote. As long as people stay cognitively healthy, the researchers believe that the gray matter of areas supporting cognition might not shrink much at all. “If future longitudinal studies find similar results, our conception of ‘normal’ brain aging may become more optimistic,” said lead author Saartje Burgmans, who is due to receive her PhD later this year.

The findings should caution scientists about drawing conclusions from brain studies that don’t screen participants over time, using precise and objective definitions, the authors added.

Article: “The Prevalence of Cortical Gray Matter Atrophy May Be Overestimated In the Healthy Aging Brain,” Saartje Burgmans, PhD student, Martin P. J. van Boxtel, PhD, MD, Eric F. P. M. Vuurman, PhD, Floortje Smeets, PhD student, and Ed H. B. M. Gronenschild, PhD, Maastricht University; Harry B. M. Uylings, PhD, Maastricht University and VU University Medical Center Amsterdam; and Jelle Jolles, PhD, Maastricht University; Neuropsychology, Vol. 23, No. 5.

Full text of the article is also available from the APA Public Affairs Office.

Saartje Burgmans can be reached by email or at (+31) 43 3881942.

WASHINGTON, DC—Although exercise is good for your health, extreme exercise may be physically addicting. Rats given a drug that produces withdrawal in heroin addicts went into withdrawal after running excessively in exercise wheels, according to new research. Rats that ran the hardest had the most severe withdrawal symptoms.

The scientists who conducted the study reason that if excessive exercise is addicting, then maybe, to feel good, addicts could take moderate exercise instead of drugs. The findings also shed light on the potentially fatal eating disorder called anorexia athletica, in which exercise undertaken to shed pounds becomes as compulsive as taking drugs, resulting in even greater weight loss.

“Excessive running shares similarities with drug-taking behavior,” the researchers wrote in the August issue of Behavioral Neuroscience, published by the American Psychological Association.

For those looking for an excuse to hit the couch, however, this study looked at excessive, not moderate, exercise. “As with food intake and other parts of life, moderation seems to be the key. Exercise, as long as it doesn’t interfere with other aspects of one’s life, is a good thing with respect to both physical and mental health,” said lead author Robin Kanarek, PhD, of Tufts University.

For several weeks, 44 male and 40 female rats were allowed to either run in exercise wheels or remain inactive. To simulate anorexia athletica, the researchers divided the active and inactive rats into groups whose members were either given food for one hour a day or around the clock. Rats in all four groups were then given naloxone, a medicine for heroin overdose that produces immediate withdrawal symptoms.

Active and inactive rats responded very differently to naloxone, which was given in proportion to their weight. The active rats showed withdrawal symptoms like those seen in narcotics addicts: trembling, writhing, teeth chattering, and drooping eyelids.

The active rats who had access to food for only one hour a day both ran the most and displayed the most severe withdrawal symptoms. Like people with anorexia athletica, they ran so much that they lost significant amounts of weight. Additionally, the more a given rat had run, the worse its withdrawal symptoms after naloxone. In contrast, regardless of how much they ate, inactive rats responded very little to the drug.

Because of the way the active rats responded to naloxone, they seemed to have undergone the same changes in the brain’s reward system as rats addicted to drugs. “Exercise, like drugs of abuse, leads to the release of neurotransmitters such as endorphins and dopamine, which are involved with a sense of reward,” noted Kanarek.

Insights into behaviors that trigger the release of the brain’s “reward” chemicals may lead to addiction treatments that incorporate moderate exercise, according to the researchers. The findings also suggest that active rats given limited food may make a good experimental model for studying and developing treatments for anorexia athletica, added Kanarek.

Because rats and humans share many nervous-system traits, researchers frequently carry laboratory findings like these out into the real world.

Article: “Running and Addiction: Precipitated Withdrawal in a Rat Model of Activity-Based Anorexia,” Robin B. Kanarek, PhD, Kristen E. D’Anci, PhD, Nicole Jurdak, MS, and Wendy Foulds Mathes, PhD, Tufts University; Behavioral Neuroscience, Vol. 123, No. 4.

(Full text of the article is available from the APA Public Affairs Office and at http://www.apa.org/journals/releases/bne1234905.pdf)

Robin Kanarek can be reached at e-mail. Her office number is (617) 627-5902. During the first two weeks of August, she can be reached by cell phone at (978) 835-9132.

A combination of an atypical antipsychotic medication and an antidepressant known as a selective serotonin reuptake inhibitor (SSRI) may be more effective in treating psychotic depression than an atypical antipsychotic alone, according to results from an NIMH-funded clinical study.

Background

Psychotic depression is characterized by major depression accompanied by symptoms such as hallucinations, delusions, and breaks with reality. A person with psychotic depression may be unwilling or unable to care for him or herself and often is admitted to the hospital. Typically, psychotic depression is treated with electroconvulsive therapy (ECT), known to be effective but not always acceptable to patients and their families. It is less commonly treated with an antipsychotic or an antipsychotic plus an antidepressant.

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