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September 15, 2005


Treatment of depression in pregnancy vital

Although depression during pregnancy confers substantial health risks, many women are reluctant to take antidepressants because of concerns about potential effects on the developing fetus. Finding treatment options that are acceptable to — and useful for — women during pregnancy is crucial, a Pitt researcher reported in the August issue of the journal The Female Patient.

Studies show that up to 20 percent of pregnant women have significant symptoms of depression, yet only a fraction of them receive treatment, notes Katherine Wisner, professor of psychiatry and obstetrics and gynecology and director of the Women’s Behavioral HealthCARE program at Western Psychiatric Institute and Clinic.

“Depression during childbearing is a major public health problem,” said Wisner, senior author of the report.

Studies done over the past 10 years have pointed toward more evidence-based choices concerning management of depression during pregnancy so that risk-benefit analysis is clearer than ever before. Some women decline to use antidepressants during pregnancy, while others are more concerned about the effects of depression on parenting skills. Others consider alternative treatments such as psychotherapy, bright light therapy, acupuncture, exercise or supplements of omega-3 fatty acids. Each therapy has potential benefits, Wisner writes.

“High maternal stress itself is significantly associated with lower birth weight and a greater risk of preterm birth. There is ample evidence that parenting while depressed carries its own risk of negative effects on children’s cognitive and psychological development,” she says. “Interventions should be considered in view of their capacity to maximize maternal wellness while minimizing toxicity to the developing fetus,” says Wisner. “With physician input, each patient will make choices based on her own values and priorities.”

Funding was provided by the National Institute of Mental Health.


Botox helps enlarged prostates

Botox effectively alters cellular processes that cause the uncomfortable symptoms of an enlarged prostate, according to an animal study presented at the annual meeting of the International Continence Society.

Prior to this study, researchers from Pitt and Chang Gung Memorial Hospital in Taiwan had proven that botulinum toxin type A, commonly known as botox, was effective in diminishing the irritative symptoms of benign prostatic hyperplasia (BPH), or enlarged prostate. These symptoms include feeling the need to urinate frequently, but being unable to completely void the bladder, and a low flow rate of urine.

Although researchers saw that botox treatment was effective, they did not know the mechanisms by which the treatment worked. In this study, the same team of researchers found that injecting botox into an enlarged prostate altered the cellular dynamics that cause the symptoms of an enlarged prostate.

The injections worked in two ways: First, by inducing cell death, which inhibited the proliferation of cells that cause prostate growth and second, by down-regulating the adrenergic receptors in the prostate. Adrenergic receptors cause the contraction of the prostate and bladder muscles, making it difficult to void urine. By blocking these receptors, the muscles relax, allowing urine to flow more freely.

“For most men, enlarged prostate is considered to be an uncomfortable inevitability of aging,” said Michael Chancellor, professor of urology at Pitt’s School of Medicine. “Common treatments can have serious side effects, including impotence. Establishing botox as an effective alternative treatment for enlarged prostate is an important step in treating a large number of men.”

BPH is one of the most common diseases affecting men. More than half of men over the age of 60, and 80 percent by age 80, will have enlarged prostates. Forty to 50 percent will develop symptoms of BPH, which include more frequent urination, urinary tract infections, the inability to completely empty the bladder and, in severe cases, eventual damage to the bladder and kidneys.


Interpersonal, social rhythm therapy is effective bipolar therapy

A treatment program that stresses maintaining a regular schedule of daily activities and stability in personal relationships is an effective therapy for bipolar disorder, report School of Medicine researchers in September’s Archives of General Psychiatry. Interpersonal and Social Rhythm Therapy (IPSRT), a novel approach developed by Pitt researchers, was effective in preventing relapse over a two-year period, particularly in patients who didn’t have other chronic medical problems such as diabetes or heart disease.

IPSRT is based on the idea that disruptions in daily routines and problems in interpersonal relationships can cause recurrence of the manic and depressive episodes that characterize bipolar disorder. During the treatment, therapists help patients understand how changes in daily routines and the quality of their social relationships and their social roles, such as a parent, spouse or caregiver, for example, can affect their moods. After identifying situations that can trigger mania or depression, therapists teach the individuals how to better manage stressful events and better maintain positive relationships.

“Our study shows that this form of psychotherapy is helpful to many people with bipolar disorder,” said Ellen Frank, professor of psychiatry at the School of Medicine and Western Psychiatric Institute and Clinic and principal investigator of the study. “It shows that the type of psychotherapy we choose for a patient should depend on the individual’s circumstances. Treatment for bipolar is not one-size-fits-all.”

More than 4 percent of adults in the United States suffer from a bipolar disorder or “sub-threshold” bipolar disorder. Bipolar disorder, commonly referred to as manic-depressive illness, is characterized by cycles of mania, depression or mixed states that often disrupt work, school, family and social life.

Conventional treatment approaches for the disorder include lithium and other mood stabilizers, which work well in the short-term but often have limited long-term success. Historically, psychotherapy has not been given much credence as a treatment option for the condition because of the disorder’s strong biological basis. Only recently have researchers begun to investigate the effectiveness of psychotherapy for people with bipolar disorder, and studies like this one have shown that psychotherapy can have promising long-term benefits.

The Pitt study involved 175 acutely ill individuals with bipolar I disorder, a more serious form of the illness involving full-blown episodes of mania and major depression, who were enrolled in the Maintenance Therapies in Bipolar Disorder trial. They were randomized to one of four treatment groups. One group received IPSRT during both the acute phase of their bipolar disorder, defined by a severe episode of mania, depression or mixed symptoms, and for two years after the episode, referred to as the maintenance phase. The second group received Intensive Clinical Management (ICM) therapy, a form of psychotherapy that addresses the general causes, symptoms and treatments of bipolar disorder, during both the acute and maintenance phases. The remaining two groups received either IPSRT during the acute phase and ICM during the maintenance phase or ICM during the acute phase and IPSRT during the maintenance phase. Patients in all groups received standard medication therapy throughout the study.

After controlling for the effects of marital status, medical burden and anxiety, the researchers found that patients who received IPSRT during the acute treatment were more likely to remain well during the two-year maintenance phase. Furthermore, the strength of the effect was related directly to the extent to which patients increased the regularity of their social routines. Those who responded well to IPSRT were more likely to be those in somewhat better physical health.

Patients who had multiple medical problems in addition to bipolar disorder and those with anxiety responded better to the ICM therapy, possibly because of that therapy’s focus on physical symptoms. Study authors hypothesized that these patients had a greater need to manage and cope with their medical symptoms and were less able to focus on controlling their social rhythms and relationships. Individuals with bipolar disorder are at an increased risk for a number of serious medical illnesses, including cardiovascular disease, diabetes and pulmonary problems.

Co-authors of the study include David J. Kupfer, Michael E. Thase, Alan G. Mallinger, Holly A. Schwartz, Andrea M. Fagiolini, Victoria Grochocinski, Patricia Houck, John Scott, Wesley Thompson and Timothy Monk, all of the School of Medicine’s Department of Psychiatry and Western Psychiatric Institute and Clinic.


Researchers hone in on genes for bulimia, anorexia

An international team of researchers led by investigators at Pitt’s School of Medicine and the University of North Carolina at Chapel Hill report that they have identified six core traits that appear to be linked to genes associated with two common eating disorders: anorexia and bulimia nervosa.

Their findings, which appear in two papers published in the Sept. 8 on-line edition of the American Journal of Medical Genetics Part B, bring researchers closer to being able to identify specific genes and may also have implications for genetic studies of other complex genetic disorders.

The team culled six core traits from a list of more than 100 behaviors and personality traits believed to contribute to development of anorexia and/or bulimia among a group of almost 400 individuals with eating disorders. The six traits are: obsessionality (a form of perfectionism); age at menstruation; anxiety; lifetime minimum body mass index (BMI; a measure of body size based on height and weight); concern over mistakes, and food-related obsessions.

The studies also found that minimum BMI, concern over mistakes, age at menarche and food-related obsessions appeared to be more closely linked to bulimia, whereas obsessionality and anxiety appeared to be more closely linked to anorexia, suggesting that, although closely related, the two conditions have some underlying differences.

Anorexia nervosa is a serious eating disorder that strikes women of all ages and also can affect males. It is characterized by the relentless pursuit of thinness and obsessive fears of being fat. The extreme weight loss caused by self-starvation and related medical complications that accompany it can result in death, giving it the highest mortality rate of any psychiatric disorder.

In contrast, bulimia nervosa is characterized by recurrent episodes of binge eating followed by self-induced vomiting, fasting, excessive exercise, or misuse of laxatives or other substances to prevent weight gain.

In the United States, approximately 10 million females and 1 million males are afflicted by either anorexia or bulimia.

Historically, anorexia and bulimia have been considered closely related disorders or manifestations of the same disorder that is influenced primarily by social and cultural norms. Recent research has pointed to substantial biological and genetic contributions as well.

Studies of families have shown that individuals with a mother or sister who has suffered from anorexia are 12 times more likely than people without a family history to develop the disorder and have a four times greater risk for developing bulimia. Studies also have consistently linked anorexia and bulimia to a cluster of moderately heritable personality and behavioral traits.

However, identifying the genetic variations in the human genome that cause these traits has, until now, been a very complicated and cumbersome process, said Bernie Devlin, associate professor of psychiatry and human genetics at Pitt’s School of Medicine and a senior author of both studies.

“Scanning the human genome for the genetic contributions to eating disorders had presented a messy analytic problem because there were many, many traits — almost the same number of traits as families,” explained Devlin. “Yet, not all of these traits were closely related to inheritance of anorexia or bulimia. What we did new in these studies was to combine statistical analysis with expert opinion to come up with a core set of traits that were strongly associated with these two disorders to use in further analyses.”

Walter H. Kaye, professor of psychiatry at Pitt’s School of Medicine and head of this international team seeking to understand the genetic causes of eating disorders, agreed that this approach presents a major step forward.

In the second of the two papers, the investigators conducted what is known as “linkage analyses” on these six traits to determine whether they could be used to pinpoint regions of the human genome that increase an individual’s risk for developing these two eating disorders. The analyses produced a pattern of significant linkage signals for bulimia but a less significant and somewhat different pattern of signals for anorexia.

The investigators concluded that genes on chromosomes 10, 14 and 16 significantly affect risks for developing bulimia, but have a lesser impact on risks for anorexia. They found less significant, but still “suggestive” signals from other regions of the genome that were more closely linked to anorexia.

When they combined the data from anorexic and bulimic individuals and again conducted the linkage analyses, all of the significant genetic signals for bulimia were slightly or substantially lessened, while some of the suggestive signals for anorexia were amplified.

Although it is possible that combining the data reduced the significant signals for bulimia because they were merely “false positives,” the investigators surmise instead that anorexia and bulimia differ at a fundamental biological and genetic level.

In addition to Devlin and Kaye, other Pitt authors on the two studies were Silviu-Alin Bacanu, Vibhor A. Sonpar and Weiting Xie, all from the Department of Psychiatry.

For more information, go to

These studies were supported by grants from the Price Foundation of Geneva, Switzerland, and the National Institute of Mental Health.


Ovarian cancer treatment study is launched

Magee-Womens Hospital is participating in a research study evaluating a new combination therapy for women with recurrent ovarian cancer. The trial, referred to as ASSIST-3 (Assessment of Survival in Solid Tumors 3), is a Phase 3 trial of a combination of TELCYTA (TLK286), a new type of chemotherapy, with carboplatin, a standard, approved chemotherapy. The trial seeks to determine if the combination therapy shrinks tumors in women with recurrent ovarian cancer.

“Women with recurrent ovarian cancer have an extremely poor prognosis and are in serious need of new treatment options,” said Robert Edwards, director of gynecologic oncology research at the Magee-Womens gynecologic cancer program.

Women who enroll in the study will be randomized to receive either the combination of TELCYTA and carboplatin or Doxil, a standard-of-care therapy for recurrent ovarian cancer.

TELCYTA is activated by GST P1-1, an enzyme found in increased quantities in cancer cells, and targets tumors that over-express this enzyme. Scientists believe GST P1-1 plays an important role in the development of resistance to commonly used chemotherapeutic drugs.

Approximately 22,220 new cases of ovarian cancer will be diagnosed in 2005, according to the American Cancer Society. Ovarian cancer causes more deaths annually in the U.S. than any other cancer of the female reproductive system.

The study is funded by Telik Inc.

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