The Mental Health Social Worker

Nearly 40 percent of people with major depression may also have subthreshold hypomania, a form of mania that does not fully meet current diagnostic criteria for bipolar disorder, according to a new NIMH-funded study. The study was published online ahead of print August 15, 2010, in the American Journal of Psychiatry.

Background

Mania is a symptom of bipolar disorder. According to the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV), it is generally defined as a discrete period of increased energy, activity, euphoria or irritability that leads to marked impairment in one’s daily life. The DSM-IV states that a manic episode lasts for one week or more, and may sometimes require hospitalization.  Hypomania is defined as a milder form of mania that lasts for four days at a time, but does not interfere with one’s daily activities. The majority of people diagnosed with bipolar disorder experience repeated episodes of hypomania rather than mania.

For this new study, Kathleen Merikangas, PhD., of NIMH, and colleagues aimed to characterize the full spectrum of mania by identifying hypomanic episodes that last less than four days among those diagnosed with major depression. They described this type of hypomania as subthreshold hypomania. Merikangas and colleagues used data from 5,692 respondents of the National Comorbidity Survey Replication (NCS-R), a nationally representative survey of American adults ages 18 and older.

Results of the Study

The researchers found that nearly 40 percent of those identified as having major depression also had symptoms of subthreshold hypomania. Compared to those with major depression alone, those with depression plus subthreshold hypomania tended to be younger at age of onset and to have had more coexisting health problems, more episodes of depression and more suicide attempts.  They also found that among those with subthreshold hypomania, a family history of mania was just as common as it was among people with bipolar disorder.

Significance

According to the researchers, the findings indicate that many adults with major depression may in fact have mild but clinically significant symptoms of bipolar disorder.  In addition, because many with subthreshold hypomania had a family history of mania, the researchers suggest that subthreshold hypomania may be predictive of future hypomania or mania. Previous research has indicated that young people with subthreshold hypomania symptoms are more likely to develop bipolar disorder over time, compared to those without subthreshold hypomania, said the authors.

What’s Next

The researchers suggest that depression and mania may be defined as dimensions, rather than as discrete diagnostic categories. Clinicians should be aware that patients who report repeated episodes of subthreshold hypomania may have a risk of developing mania, the researcher concluded.

Reference

Angst J, Cui L, Swendsen J, Rothen S, Cravchik A, Kessler R, Merikangas K. Major depressive disorder with sub-threshold bipolarity in the National Comorbidity Survey Replication. American Journal of Psychiatry. Online ahead of print August 15, 2010.

Socioeconomic status plays important role

People with treatment-resistant bipolar disorder experienced relief from symptoms of depression in as little as 40 minutes after an intravenous dose of the anesthetic medication ketamine in a preliminary study; while the patient group was small, this work adds to evidence that compounds in the class to which ketamine belongs have potential as rapid and effective medications for depression, including bipolar depression. The potential for side-effects makes ketamine an impractical drug for standard use, but it provides a way to test this approach for developing novel treatments that act more rapidly than existing ones.

Background

Bipolar disorder (BD) is a potentially debilitating illness marked by severe swings in mood, energy, and behavior. Episodes of depression alternate with spells of mania but depressive episodes tend to be more frequent and longer-lasting and the depression is difficult to treat. BD is usually treated with mood stabilizing medications such as lithium, valproate, carbamazepine or other medications with the goal of preventing mood episode relapse. Antidepressant medications are often used in addition to a mood stabilizer for depressive episodes, but antidepressants typically take weeks to have an effect and many patients do not respond adequately to existing medications.

Previous research has suggested that a disruption of signaling between neurons involving the neurotransmitter glutamate is likely to play a role in depression. The anesthetic medication ketamine shuts down one class of receptor for glutamate (NMDA receptors).

This Study

Eighteen people with BD participated in this study of ketamine. All received maintenance treatment with a mood stabilizer medication during the study. All had previously been unsuccessfully treated with at least one antidepressant medication and a mood stabilizer; the average number of medications they had tried unsuccessfully was seven.

In the first phase of the study, each person was randomly assigned to receive a single dose of either intravenous ketamine or placebo (saline). After two weeks, treatment was switched, so those initially receiving ketamine received placebo, and vice versa. Neither patients nor those treating them were told whether they were receiving ketamine or placebo. Investigators used standard surveys of depression symptoms to assess the effect of medication.

Within 40 minutes, 9 of 16 (56 percent) patients receiving ketamine had at least a 50 percent reduction in symptoms, and 2 of 16 (13 percent) became nearly symptom-free. The response to ketamine lasted an average of about a week. By contrast, no patients receiving placebo had declines in symptoms close to the magnitude seen with ketamine within the first 3 days.

Significance

In this study, carried out by scientists Nancy Diazgranados, Carlos Zarate, Jr., and colleagues at the Experimental Therapeutics & Pathophysiology Branch of NIMH’s intramural research program, a single intravenous dose of ketamine brought relief from depression in severely treatment resistant patients with BD, in over half of them within 40 minutes. This study supports a previous one by the same group in which they also found a rapid antidepressant effect in patients with treatment-resistant major depression (unipolar). (NIMH press release, August 7, 2006). The authors note that the rapid antidepressant response observed in these two different disorders (major depressive disorder and bipolar disorder) highlights the importance of the NMDA receptor in developing treatments with a rapid onset of action.

The work adds to the evidence of the potential of medications targeting the glutamate system for rapid relief from depression, even in cases of people who have failed to respond to other existing therapies. Rapid and effective treatment of depression is an urgent public health need. BD can be disabling—nearly all the patients in this study were unemployed as a result of the severity of their illness. BD is among the psychiatric disorders with the highest risk of suicide.

Continuing research is focusing on developing NMDA-targeting medications that are suitable for clinical use; and investigating the use of this class of drugs for long-term maintenance of the rapid antidepressant effect seen in this study.

Reference

Diazgranados, N., Ibrahim, L., Brutsche, N.E., Newberg, A., Kronstein, P., Khalife, S., Kammerer, W. A., Quezado, Z., Luckenbaugh, D.A., Salvadore, G., Machado-Vieira, R., Manji, H.K., and Zarate, C. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Archives of General Psychiatry 2010;67(8):793-802.

For information on this study and other research conducted at NIMH please see http://patientinfo.nimh.nih.gov/ or email: nimhcore@mail.nih.gov, telephone 301-496-5645.

NIH Grantees Eye Neuroprotective Mechanism for Alzheimer’s

Scientists have discovered a compound that restores the capacity to form new memories in aging rats, likely by improving the survival of newborn neurons in the brain’s memory hub. The research, funded in part by the National Institutes of Health, has turned up clues to a neuroprotective mechanism that could lead to a treatment for Alzheimer’s disease.

“This neuroprotective compound, called P7C3, holds special promise because of its medication-friendly properties,” explained Steven McKnight, Ph.D., who co-led the research with Andrew Pieper, M.D., Ph.D., both of University of Texas Southwestern Medical Center, Dallas. “It can be taken orally, crosses the blood-brain barrier with long-lasting effects, and is safely tolerated by mice during many stages of development.”

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By Faith H. Robinson, CNN

(CNN) — Every Friday morning, students walk into an art class in Atlanta, Georgia. Some look dazed, uncertain in their environment, as if it’s vaguely familiar but they can’t fully recognize where they are — until they sit down and begin to draw.

The moment their brushes hit the paper, their faces light up. Using bright colors — yellows, oranges, greens, purples — they begin to transfer the images from their minds. Sometimes they paint what they want and sometimes they draw the highlighted centerpiece of the day. One week it’s vegetables, another week it’s hats. As their artworks progress, they look happy, smiling and glancing at their teachers for approval. They’re not the only ones who are pleased.

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By Elizabeth Landau
CNN.com Health Writer/Producer

Some guys sound tough – and according to a new study, that may a good way of predicting whether they really are.

Results  in the current Proceedings of the Royal Society B found that people can accurately evaluate the upper-body strength based on men’s voices from four different populations and language groups. The voice samples came from the Tsimane of Bolivia, Andean herder-horticulturalists from Argentina, and college students from the United States and Romania.

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Up to 14 percent of soldiers returning from Iraq suffer Post-Traumatic Stress Disorder (PTSD) or depression that is severe enough to disrupt their daily lives, new research finds. Between 8.5 percent and 14 percent of soldiers reported mental health issues that caused difficulties in work or private life, according to the report published in the Archives of General Psychiatry. After 12 months, there was a sharp increase among Guard members with self-reported depression and PTSD. Researchers speculate these men and women experience stress of going back to work and have less access to medical care. The regular Army soldiers may also suppress symptoms because they know they will be rotated back to duty. (HealthDay News, 6/07/10)

Older veterans with Post-Traumatic Stress Disorder (PTSD) are more likely to develop dementia than fellow vets who don’t have PTSD, new research finds. Researchers followed more than 180,000 veterans aged 55 and older for seven years. All were free from dementia at the study’s outset, while about 30 percent had PTSD. Nearly 11 percent of the vets with PTSD developed dementia during follow-up, compared to only about 7 percent of those who didn’t have PTSD. Once the researchers, whose findings are reported in the Archives of General Psychiatry, took into account factors such as other physical or mental health problems, they found that vets with PTSD were still nearly twice as likely to develop dementia. (Reuters, 6/07/10)

Secondhand smoke may place individuals at greater risk for mental health problems, new research asserts. In a study of 8,155 men and women in the Scottish Health survey, published in the Archives of General Psychiatry, researchers found non-smokers exposed to a lot of secondhand smoke were 50 percent more likely to suffer from psychological distress than those not exposed to other people’s smoke. Their risk of being admitted to a psychiatric hospital over the next six years nearly tripled. Previous studies had suggested a link between smoking and mood disorders, and nicotine exposure in animals is known to trigger depressive symptoms, stress, anxiety and a dampening of feelings of reward and satisfaction. (Reuters, 6/08/10)

Bad effects depend on certain personality traits; games can offer learning opportunities for others.

WASHINGTON – Playing violent video games can make some adolescents more hostile, particularly those who are less agreeable, less conscientious and easily angered. But for others, it may offer opportunities to learn new skills and improve social networking.

In a special issue of the journal Review of General Psychology, published in June by the American Psychological Association, researchers looked at several studies that examined the potential uses of video games as a way to improve visual/spatial skills, as a health aid to help manage diabetes or pain and as a tool to complement psychotherapy. One study examined the negative effects of violent video games on some people.

“Much of the attention to video game research has been negative, focusing on potential harm related to addiction, aggression and lowered school performance,” said Christopher J. Ferguson, PhD, of Texas A&M International University and guest editor of the issue. “Recent research has shown that as video games have become more popular, children in the United States and Europe are having fewer behavior problems, are less violent and score better on standardized tests. Violent video games have not created the generation of problem youth so often feared.”

In contrast, one study in the special issue shows that video game violence can increase aggression in some individuals, depending on their personalities.

In his research, Patrick Markey, PhD, determined that a certain combination of personality traits can help predict which young people will be more adversely affected by violent video games. “Previous research has shown us that personality traits like psychoticism and aggressiveness intensify the negative effects of violent video games and we wanted to find out why,” said Markey.

Markey used the most popular psychological model of personality traits, called the Five-Factor Model, to examine these effects. The model scientifically classifies five personality traits: neuroticism, extraversion, openness to experience, agreeableness and conscientiousness.

Analysis of the model showed a “perfect storm” of traits for children who are most likely to become hostile after playing violent video games, according to Markey. Those traits are: high neuroticism (e.g., easily upset, angry, depressed, emotional, etc.), low agreeableness (e.g., little concern for others, indifferent to others feelings, cold, etc.) and low conscientiousness (e.g., break rules, don’t keep promises, act without thinking, etc.).

Markey then created his own model, focusing on these three traits, and used it to help predict the effects of violent video games in a sample of 118 teenagers. Each participant played a violent or a non-violent video game and had his or her hostility levels assessed. The teenagers who were highly neurotic, less agreeable and less conscientious tended to be most adversely affected by violent video games, whereas participants who did not possess these personality characteristics were either unaffected or only slightly negatively affected by violent video games.

“These results suggest that it is the simultaneous combination of these personality traits which yield a more powerful predictor of violent video games,” said Markey. “Those who are negatively affected have pre-existing dispositions, which make them susceptible to such violent media.”

“Violent video games are like peanut butter,” said Ferguson. “They are harmless for the vast majority of kids but are harmful to a small minority with pre-existing personality or mental health problems.”

The special issue also features articles on the positives of video game play, including as a learning tool. For example:

• Video games serve a wide range of emotional, social and intellectual needs, according to a survey of 1,254 seventh and eighth graders. The study’s author, Cheryl Olson, PhD, also offers tips to parents on how to minimize potential harm from video games (i.e., supervised play, asking kids why they play certain games, playing video games with their children).
• Commercial video games have been shown to help engage and treat patients, especially children, in healthcare settings, according to a research review by Pamela Kato, PhD. For example, some specially tailored video games can help patients with pain management, diabetes treatment and prevention of asthma attacks.
• Video games in mental health care settings may help young patients become more cooperative and enthusiastic about psychotherapy. T. Atilla Ceranoglu, M.D., found in his research review that video games can complement the psychological assessment of youth by evaluating cognitive skills and help clarify conflicts during the therapy process.

Contact Dr. Christopher Ferguson by e-mail or by phone at (956) 326-2636 or (407) 384-8874 during June 1 – June 15.

Contact Dr. Patrick Markey by e-mail or by phone at (610) 519-4743.

Differences in brain growth patterns between preschool-aged boys with Fragile X syndrome (FXS), the most common cause of inherited intellectual disability, and their healthy peers suggest that the disorder may affect brain development both before and after birth, according to NIMH-funded researchers. In addition, their findings indicate ages 1-5 are an important window for better understanding the effects of FXS on brain development. The study was published May 18, 2010, in the Proceedings of the National Academy of Sciences.

Background

In addition to its association with intellectual disability, FXS is the most common known specific genetic risk factor for autism spectrum disorders (ASD). FXS results from mutations on a gene that creates a protein called FMRP. The mutations, in effect, turn off the gene. Relatively little is known about how these mutations affect brain development in early childhood.

Allan Reiss, M.D., of Stanford University, in collaboration with colleagues from Stanford and the University of North Carolina, used magnetic resonance imaging (MRI) to examine changes in brain volumes in 69 boys, first assessed at ages 1-3 and then again an average of two years later at ages 3-5. Of the participants, 41 had FXS, 21 had typical development, and seven had some form of developmental delay.

Results of the Study

The researchers found that some brain regions were similar between the boys with FXS and those without FXS at both times they underwent MRI. Other regions were abnormal among those with FXS at the first time point and remained that way at the second time point, suggesting that the gene mutations responsible for FXS begin to alter brain development early in life, possibly even before birth.

Furthermore, some brain regions were similar among all the participants at the start of the study but showed major differences by the second MRI at ages 3-5.

“This third category is the most interesting because it suggests that we have captured a critical development window of brain development that is significantly affected by fragile X,” said Reiss.

Significance

The same mutations that cause FXS are also strongly linked to ASD. Thus, FXS is considered a model condition for informing research on ASD.

This study provides greater insight into how FXS mutations affect early brain development, which may one day serve as targets for the development and evaluation of new interventions for FXS and related disorders.

What’s Next

The researchers note that their study provides only preliminary information and that it will be crucial to follow the study participants as they enter their school age years, a time when the greatest number and severity of ASD behaviors tend to appear.

Future studies should include larger control samples, track development from an earlier age, and follow participants for a longer period of time. Studies comparing FXS population with those affected by other specific genetic risk factors, such as those occurring in Williams syndrome, may be useful as well.

Reference

Hoeft F, Carter JC, Lightbody AA, Cody Hazlett H, Piven J, Reiss AL. Region-specific alterations in brain development in one- to three-year-old boys with fragile X syndrome. Proc Natl Acad Sci U S A. 2010 2010 May 18;107(20):9335-9. Epub 2010 May 3. PubMed PMID: 20439717.

An early response to second-course treatment is associated with greater likelihood of remission among teens with hard-to-treat depression, according to recent data from an NIMH-funded study published online ahead of print May 17, 2010, in the American Journal of Psychiatry.

“These results suggest that early treatment decisions are probably the most crucial to the recovery of teens with hard-to-treat depression,” said NIMH Director Thomas R. Insel, M.D.

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

• Switch to another SSRI-paroxetine (Paxil), citalopram (Celexa) or fluoxetine (Prozac)
• Switch to a different SSRI plus cognitive behavioral therapy (CBT), a type of psychotherapy that emphasizes problem-solving and behavior change
• Switch to venlafaxine (Effexor), another type of antidepressant called a serotonin and norepinephrine reuptake inhibitor (SNRI)
• Switch to venlafaxine plus CBT

As reported in February 2008, after 12 weeks, about 55 percent of those who switched to either type of medication and added CBT responded, while 41 percent of those who switched to another medication alone responded.

For the most recent findings, Graham Emslie, M.D., of the University of Texas Southwestern Medical Center at Dallas, and colleagues measured the teens’ rate of remission after 24 weeks of treatment. Among the 334 TORDIA participants, 78 percent completed the 24-week assessment. The researchers found that nearly 40 percent of those who completed 24 weeks of treatment achieved remission, regardless of which treatment to which they had initially been assigned. However, those who achieved remission were more likely to have responded to treatment early—during the first 12 weeks.

Those who had very severe depression at baseline, a sense of hopelessness, anxiety and family conflict were less likely to achieve remission. Those who were taking an additional mood stabilizing medication, such as an antipsychotic or anti-anxiety medication, or who were receiving CBT, were more likely to achieve remission, but ONLY if the teens received these additional treatments in the first 12 weeks.

Moreover, those who achieved remission tended to have responded to treatment by six weeks into treatment compared to those who had not achieved remission by 24 weeks, underscoring the importance of early treatment decisions.

The authors suggest that the current clinical guidelines, which recommend staying with a treatment for at least eight to twelve weeks before trying another, may need to be revisited. More research is needed to clarify when is the optimal time to change a treatment strategy among treatment-resistant teens with depression, they concluded.

Reference

Emslie GJ, Mayes T, Porta G, Vitiello B, Clarke G, Wagner KD,Asarnow JR, Spirito A, Birmaher B, Ryan N, Kennard B, DeBar L, McCracken J, Strober M, Onorato M, Zalazny J, Keller M, Iyengar S, Brent D. Treatment of resistant depression in adolescents (TORDIA): week 24 outcomes. American Journal of Psychiatry. Online ahead of print May 17, 2010.

A coordinated, multi-component treatment approach was more effective in treating anxiety disorders than usual care found in primary care settings, according to an NIMH-funded study published May 19, 2010, in a special issue of the Journal of the American Medical Association devoted to mental health.

Background

Research has found that a collaborative care approach, in which one care manager coordinates a team of treatment providers, is effective in treating depression. However, research is limited on whether the same type of approach could work to treat anxiety disorders, which are commonly treated in primary care settings.

In response, Peter Roy-Byrne, M.D., of the University of Washington Seattle, and colleagues designed a flexible collaborative treatment model for anxiety disorders—Coordinated Anxiety Learning and Management (CALM)—and compared it to usual care. CALM included cognitive behavioral therapy (CBT) that was tailored to any one of four anxiety disorders—panic disorder, generalized anxiety disorder, social anxiety disorder or post traumatic stress disorder. It also included strategies to improve medication delivery and adherence. Of the 1,004 participants recruited from 17 primary care clinics in four U.S. cities, half were randomized to CALM and were allowed to choose whether they received CBT, medication, or both. The other participants were referred to usual care which could include medication, brief counseling with a physician, or referral to a mental health specialist. All participants were diagnosed with at least one of the four anxiety disorders addressed in the CBT program.

CALM participants received their initial treatment for 10 to 12 weeks. Those who still had symptoms after 12 weeks could receive additional CBT or medication, or both. They then received monthly follow-up phone calls to reinforce CBT skills or medication management advice for up to a year.

CALM relied on a computerized program to help train care managers in CBT techniques and ensure consistency of care. The computer program employed CBT principles common to all anxiety disorders, but included specific techniques designed to address the four anxiety disorders in the study, thus allowing for personalized treatment.

Care managers also encouraged participants to stay in treatment and monitored their reactions to medication, relaying any observations and suggestions for changes to the primary care provider. CALM tracked participants’ progress and outcomes through a web-based monitoring system as well.

Results of the Study

Participants in the CALM group showed significantly greater symptom improvement than those receiving usual care. After 12 months, about 63.6 percent receiving CALM had responded to treatment compared to 44.7 percent in usual care, and 51.5 percent receiving CALM had remitted compared to 33 percent in usual care.

CBT appeared to be the most popular treatment choice among those in the CALM group—57 percent chose CBT and medication combination treatment, and 34 percent chose CBT-only treatment, while 9 percent chose medication-only treatment. This preference is consistent with research that finds those with anxiety disorders tend to favor psychosocial treatment approaches over medication to treat their illness, said the researchers.

Significance

Because CALM included flexible treatment options, targeted multiple anxiety disorders, and was effective across a range of patients and clinics, it is broadly applicable in primary care settings. It could serve as a model for developing effective collaborative care of people with anxiety disorders as well as those with coexisting psychiatric disorders like depression, a situation commonly found in clinical settings.

What’s Next

Research is needed to determine how the strategy could best be implemented in primary care settings. In addition, a cost analysis of CALM is needed to determine whether it is a financially feasible option for payers and clinical settings.

Reference

Roy-Byrne P, Craske MG, Sullivan G, Rose RD, Edlund MJ, Lang AJ, Bystritsky A, Welch SS, Chavira DA, Golinelli D, Campbell-Sills, L, Sherbourne CD, Stein MB. Delivery of evidence-based treatment for multiple anxiety disorders in primary care: a randomized controlled trial. Journal of the American Medical Association. 19 May 2010. 303(19).

A comprehensive behavioral therapy is more effective than basic supportive therapy and education in helping children with Tourette syndrome manage their tics, according to a study funded by the National Institute of Mental Health (NIMH). The study was published May 19, 2010, in a special issue of the Journal of the American Medication Association dedicated to mental health.

“People with Tourette syndrome experience considerable impairment and social isolation, and effective treatments are limited,” said NIMH Director Thomas R. Insel, M.D. “This study makes a strong case for a specialized behavioral therapy, either as a stand-alone treatment or as an adjunct to medication.”

Tourette syndrome is a chronic neurological disorder that is associated with motor or vocal tics that can be embarrassing and disruptive. It is commonly treated with antipsychotic medication such as haloperidol or risperidone. But these medications often are unable to eliminate tics entirely. They also are associated with troubling side effects such as weight gain and sedation. Few studies have examined the effectiveness of behavioral interventions.

John Piacentini, Ph.D., of the University of California Los Angeles, and colleagues tested the effectiveness of a Comprehensive Behavioral Intervention for Tics (CBIT), a therapy based on habit reversal training that includes two concepts—tic-awareness and competing-response training. Tic-awareness training teaches the child how to self-monitor for early signs that a tic is about to occur. Competing-response training teaches the child how to engage in a voluntary behavior designed to be physically incompatible with the impending tic, thereby disrupting the cycle and decreasing the tic. For example, a child with vocal tics who blurts out words or sounds inappropriately may be taught slow rhythmic breathing techniques to manage the urge to vocalize.

CBIT includes parent training as well. Parents in the study were taught how to manage their own reactions to their children’s tics, and how to best encourage and praise their children for practicing the behavioral intervention techniques they were learning.

“CBIT emphasizes the development of skills that foster autonomy and empowerment, allowing for patients and their families to take an active role in treatment,” said Dr. Piacentini.

The researchers randomized 126 children ages 9-17 at several sites to either CBIT or a control treatment that included supportive therapy and basic education about the condition. Each group received eight sessions over a 10-week period. Those who responded to therapy received monthly booster sessions for three months, and were assessed three months and six months after the 10-week acute treatment ended.

About 52.5 percent of the children who received CBIT showed significant symptom improvement compared to 18.5 percent receiving the control treatment. The benefits of CBIT also appeared to endure over time—87 percent of CBIT responders who were reassessed six months after the end of the 10-week trial continued to benefit.

“The response to CBIT is comparable to results of trials with antipsychotic medications for Tourette syndrome,” said Dr. Piacentini.

In addition, few children dropped out of the study, suggesting that the intervention was well-received and tolerated by both the children and parents. Moreover, the researchers note that 38 percent of children in the study were already taking medication for their disorder when they entered the study and were allowed to remain on the medication. Many also had co-existing disorders. Both these conditions mimic real-world situations, making the results more relevant to clinical populations.

The authors note that although CBIT helped many children, not all children in the study benefited from the treatment. They suggest that future analyses may provide guidance on who is most likely to respond to the therapy, allowing for more personalization of treatment. “We’ve shown that it works about as well as the standard medications for tics but without the negative side effects,” concluded Dr. Piacentini. “Knowing that CBIT is effective for many patients with Tourette syndrome adds to the available treatment options for this disorder.”

Dr. John Piacentini of UCLA talks about CBIT, a new therapy that treats tics associated with Tourette Syndrome

Read transcript.

Reference

Piacentini J, Woods DW, Scahill L, Wilhelm S, Peterson AL, Chang S, Ginsburg G, Deckersbach T, Dziura J, Levi-Pearl S, Walkup JT. Randomized trial of a behavioral intervention for children with Tourette’s Disorder. Journal of the American Medical Association. 19 May 2010. 303(19).

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.