On the functional anatomy of the urge-for-action

Some premonitory urges are experienced as an urge to action.  Such urges have been described in a number of clinical conditions including Tourette syndrome and Obsessive-Compulsive Disorder (OCD).  An interesting article in the September 2011 issue of Cognitive Neuroscience looks at their functional underpinnings.  Here’s the abstract:

Sensory phenomena associated with repetitive behaviors in OCD

Sensory phenomena in Tourette syndrome and Obsessive-Compulsive Disorder (OCD) fascinate me, and I was delighted to learn that a number of investigators were undertaking some systematic studies on them.  Here’s the abstract of one of the studies:

A substantial number of patients with obsessive-compulsive disorder (OCD) report compulsions that are preceded not by obsessions but by subjective experiences known as sensory phenomena. This study aimed to investigate the frequency, severity, and age at onset of sensory phenomena in OCD, as well as to compare OCD patients with and without sensory phenomena in terms of clinical characteristics. We assessed 1,001 consecutive OCD patients, using instruments designed to evaluate the frequency/severity of OC symptoms, tics, anxiety, depression, level of insight and presence/severity of sensory phenomena. All together, 651 (65.0%) subjects reported at least one type of sensory phenomena preceding the repetitive behaviors. Considering the sensory phenomena subtypes, 371 (57.0%) patients had musculoskeletal sensations, 519 (79.7%) had externally triggered “just-right” perceptions, 176 (27.0%) presented internally triggered “just right,” 144 (22.1%) had an “energy release,” and 240 (36.9%) patients had an “urge only” phenomenon. Sensory phenomena were described as being as more severe than were obsessions by 102(15.7%) patients. Logistic regression analysis showed that the following characteristics were associated with the presence of sensory phenomena: higher frequency and greater severity of the symmetry/ordering/arranging and contamination/washing symptom dimensions; comorbid Tourette syndrome, and a family history of tic disorders. These data suggest that sensory phenomena constitute a poorly understood psychopathological aspect of OCD that merits further investigation.

Reference

Ferrão YA, Shavitt RG, Prado H, Fontenelle LF, Malavazzi DM, de Mathis MA, Hounie AG, Miguel EC, do Rosário MC. Sensory phenomena associated with repetitive behaviors in obsessive-compulsive disorder: An exploratory study of 1001 patients. Psychiatry Res. 2012 Feb 21.

Atypical Antipsychotic More Effective than Older Drugs in Treating Childhood Mania, but Side Effects Can Be Serious

While stimulant medications may not pose a serious risk of cardiac complications, atypical neuroleptics such as risperidone (Risperdal) are associated with serious risks of other types of problems.

The antipsychotic medication risperidone is more effective for initial treatment of mania in children diagnosed with bipolar disorder compared to other mood stabilizing medications, but it carries the potential for serious metabolic side effects, according to an NIMH-funded study published online ahead of print January 2, 2012, in the Archives of General Psychiatry.

Background

Childhood bipolar disorder is a relatively rare but seriously impairing condition. It is also associated with an increased risk of substance use disorders and suicide. To treat symptoms of mania, a key symptom of the disorder, medications such as mood stabilizers or antipsychotics are often prescribed. However, no prior study has addressed the question of which medication to try first.

In the Treatment of Early Age Mania (TEAM) study, Barbara Geller, M.D., of Washington University in St. Louis, and colleagues randomized 290 children ages 6-15 years diagnosed with bipolar I disorder (having mixed or manic symptoms) to treatment with lithium, divalproex sodium or risperidone for an 8-week trial. None of the children had taken an anti-manic medication before. Lithium has been used to treat bipolar disorder for many years. Divalproex sodium is an anticonvulsant mood stabilizer commonly prescribed to treat bipolar disorder as well. Risperidone is an atypical antipsychotic that has been approved by the U.S. Food and Drug Administration for the treatment of mania in youth age 10 and older.

Results of the Study

After eight weeks, 68.5 percent of the children taking risperidone showed improvement in manic symptoms, compared to 35.6 percent of those taking lithium and 24 percent of those taking divalproex sodium. Overall, 24.7 percent discontinued the trial, but more children taking lithium—32.2 percent—discontinued the trial compared to those taking risperidone (15.7 percent discontinued) or divalproex sodium (26 percent discontinued.)

However, those taking risperidone also gained more weight than those on the other medications—an average of more than 7 lbs compared to around 3 lbs for those taking lithium and 3.7 lbs for those taking divalproex sodium. Those taking risperidone were also more likely to experience other metabolic side effects, such as an increase in cholesterol levels, compared to those on the other medications.

Significance

The researchers concluded that risperidone was significantly more effective than lithium or divalproex sodium for initial treatment of childhood mania. In addition, the children were less likely to discontinue the drug compared to those taking lithium or divalproex sodium, indicating a higher tolerance for it. This finding is consistent with other studies that have compared second-generation antipsychotics like risperidone to placebo in treating childhood mania.

However, the researchers caution that risperidone is associated with adverse metabolic effects that can increase the risk for diabetes and cardiovascular problems. They note that many children responded to low doses of the medication, suggesting that clinicians should be conservative when determining how to dose the medication. A lower dose may minimize the potential for serious side effects. The researchers also caution that because diagnostic measures for childhood bipolar disorder are not always consistent across studies, and because the validity of such a diagnosis in younger children is under debate, TEAM findings may not generalize to patients diagnosed using other measures.

What’s Next

More research is needed to develop safer, more effective interventions for children with early onset bipolar disorder for both initial and longer term treatment.

Reference

Geller B, Luby J, Josh P, Wagner KD, Emslie G, Walkup JT, Axelson DA, Bolhofner K, Robb A, Wolf DV, Riddle MA, Birmaher B, Ryan ND, Severe J, Vitiello B, Tillman R, Lavori P. A randomized controlled trial of risperidone, lithium and divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Archives of General Psychiatry. Online ahead of print January 2, 2012.

Source: National Institute of Mental Health Science Update

Stimulant Treatment for ADHD Not Associated With Increased Risk of Cardiac Events in Youth

Every so often, I read alarming case reports that raise the possibility that the use of stimulant medications might cause heart problems (or sudden death) in children and teens with ADHD.  More controlled studies generally find that such is not the case and that there were other factors that caused the deaths, but such reports do alarm parents.  Here’s a press release issued last month by the Journal of the American Academy of Child and Adolescent Psychiatry on this topic:

Attention-deficit/hyperactivity disorder (ADHD) affects 5- 9% of youth and is frequently treated with stimulant medications, such as methylphenidate and amphetamine products. A recent safety communication from the US Food and Drug Administration advised that all patients undergoing ADHD treatment be monitored for changes in heart rate or blood pressure.

Amidst growing concern over the risks of stimulant use in youth, a study by Dr. Mark Olfson of the New York State Psychiatric Institute and Columbia University, and his colleagues, published in the February 2012 issue of the Journal of the American Academy of Child and Adolescent Psychiatry, assessed the risk of adverse cardiovascular events in children and adolescents without known heart conditions treated with stimulants for ADHD. It is one of the largest studies to date focusing primarily on youth while controlling for pre-existing cardiovascular risk factors.

As reported in the study, Olfson and colleagues examined claims records from a large privately insured population for associations between cardiovascular events in youth with ADHD and stimulant treatment. In total 171,126 privately insured youth aged 6-21 years without known pre-existing heart- related risk factors were followed throughout the study.

The study included patients who have previously received stimulant treatment, patients currently receiving stimulant treatment, and patients who began or ceased stimulant treatments during the study period. Olfson and colleagues assessed the various groups for incidents of severe cardiovascular events such as acute myocardial infarction, less severe cardiovascular events such as cardiac dysrhythmias, and cardiovascular symptoms such as tachycardia and palpitations. Analysis showed that cardiovascular events and symptoms were rare in this cohort and not associated with stimulant use.

This finding helps to allay concerns of adverse events in otherwise healthy young people receiving treatment for ADHD. Olfson and colleagues said of the results, “It is reassuring that in these young people, short-term stimulant treatment did not substantially increase the risk of cardiovascular events or symptoms.”

The article, “Stimulants and Cardiovascular Events in Youth With Attention-Deficit/Hyperactivity Disorder” by Mark Olfson, Cecilia Huang, Tobias Gerhard, Almut G. Winterstein, Stephen Crystal, Paul D. Allison, Steven C. Marcus (doi:10.1016/j.jaac.2011.11.008) appears in Journal of the American Academy of Child and Adolescent Psychiatry, Volume 51, Issue 2 (February 2012), published by Elsevier.

This study was supported by National Institute of Mental Health grant R21 MH079905, Agency for Healthcare Research and Quality award U18 HS016097, and the Center for Education and Research on Mental Health Therapeutics.

Computer-Based Treatment Eases Anxiety Symptoms in Children

A computer-based training method that teaches a person with anxiety to shift attention away from threatening images reduced symptoms of anxiety in a small clinical trial in children with the condition. The results of this first randomized clinical trial of the therapy in children with anxiety suggest that the approach warrants more extensive testing as a promising therapy.

Background

As many as a quarter of 13- to 18-year-olds have met the criteria for an anxiety disorder at some point. Currently available treatments—including cognitive behavioral therapy and medication—relieve symptoms of anxiety in about 70 percent of children treated. Most children with clinical anxiety do not receive treatment, partly because of difficulties in access to care, including distance and financial resources. Scientists are searching for additional approaches, including therapies that do not involve medication with its associated side effects.

A treatment called attention bias modification (ABM) has emerged from the observation that people with anxiety unconsciously pay more attention than others to anything that seems threatening. One way of detecting such a bias is a dot probe test. In the test, people view a computer screen on which angry and neutral faces are flashed briefly, adjacent to each other. After the faces disappear, a test image of dots appears where either one or the other face was, and the person has to respond by pushing a button. People with anxiety consistently respond more quickly to dots that appear where the angry face was located.

ABM presents patients with an exercise similar to the dot probe test, but the dots always appear where the neutral face was, and thus consistently draw the attention of the participant to this non-threatening image. A recent meta-analyses of ABM in adults by some of the same investigators who carried out this work suggested its potential as a treatment.

This Study

Researchers at Tel Aviv University (TAU) in Israel carried out a clinical trial on ABM as an outcome of a three-year collaboration with scientists at the National Institute of Mental Health and the University of Maryland, College Park, Maryland. Yair Bar-Haim of TAU led the study, which appears in the American Journal of Psychiatry. The study enrolled 40 children, 8 to 14 years old, who had sought help for anxiety. For children receiving ABM, after faces appeared on a screen, two dots appeared on the screen; children had to determine whether the dots were side by side, or one above the other. In every case, dots appeared only where the neutral face had been. There were also two control groups: in the first, dots appeared equally frequently where angry and neutral faces appeared; in the second, the only faces that appeared throughout were neutral, so the dots always appeared in the location of a neutral face. The object of the second control group was to help confirm that any therapeutic effect was from the ABM training, and not from desensitizing the children to threatening faces. Children in the study were randomly assigned to receive treatment, or to be in one of two control groups. All children had four training sessions over 4 weeks, with 480 dot-probe trials per session.

Although the trial was small, there was a “reasonably robust” decrease in the severity of anxiety, according to the authors. Following ABM, both the number and severity of symptoms were reduced.

Significance

An important feature of ABM, says NIMH author Daniel Pine, is that it addresses the fundamental neurological function underlying anxiety: attention. Changes in attention happen very quickly—in milliseconds. “We know from neuroscience that if you want to change behaviors that happen very quickly, you have to practice. You can’t just tell someone how to drive, or throw a ball. You have to practice,” says Pine.

Longitudinal studies that follow children into adulthood suggest that most chronic mood and anxiety disorders in adults begin as high levels of anxiety in children. In fact, childhood anxiety is as important in predicting adult depression as it is for adult anxiety. The ability to influence attention biases early in development might provide a powerful means of prevention for both of these disorders later in life. The approach requires no medication and in practical terms, the computer-based nature of ABM lends itself to large-scale dissemination, in a medium children are comfortable with. Larger-scale trials will be able to provide more information on the efficacy of the treatment in children and how it works to reduce symptoms of anxiety.

# # #

Reference

Eldar, S., Apter, A., Lotan, D., Perez-Edgar, K., Naim, R, Fox, N.A., Pine, D.S., and Bar-Haim, Y. American Journal of Psychiatry. 2012 Feb 1;169(2):213-30.

Source: National Institute of Mental Health Science Update

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