Journal Digest

A gene underlying major depression may have been found.

Scientists examined gene expression in the hippocampus of postmortem brain tissue taken from 21 individuals who had suffered from major depression and from 18 nondepressed controls matched for age, gender, and postmortem interval. They found more than twice as much expression of one gene in the depressed group than in the control group. The gene, called MKP-1, is known to be involved in neuronal plasticity, function, and survival.

A model in rats was also included in the study to assess whether the MKP-1 gene helps play a role in the function and control of depressive behaviors. The chronic unpredictable stress (CUS) model was used, and according to the authors it is one of the most validated animal models used to study depression.

This model allows scientists to study behaviors commonly seen in depression, such as anhedonia, helplessness, and other symptoms, in rats.

The administration of the commonly prescribed selective serotonin reuptake inhibitor fluoxetine to rats reversed the expression and up-regulation of the MKP-1 gene in the hippocampus by blocking MKP-1 expression. However, an increase in MKP-1 expression in rodents exposed to the CUS model but without antidepressant treatment led to depression-like behaviors in the animals.

The MKP-1 gene may be a notable player in major depression and might serve as a target for new kinds of depression treatments, the researchers concluded. Their findings were published online October 17 in Nature Medicine. The senior investigator was Ronald Duman, Ph.D., a professor of psychiatry and pharmacology at Yale University.

The study was funded by multiple U.S. Public Health Service grants and the Connecticut Mental Health Center.

Danish researchers conducted a follow-up study of all children born in Denmark from 1994 to 2004. Out of the some 700,000 children, about 36,000 had neonatal jaundice, and about 500 received a diagnosis of autism. After a number of possible confounding factors were considered in the equation, those with jaundice had a 67 percent greater risk of having autism than those without jaundice did—a statistically significant difference.

The lead investigator was Rikke Maimburg, Ph.D., of Aarhus University in Denmark. The study was reported online October 11 in Pediatrics and was funded by the University of Aarhus Research Foundation and the Augustinus Foundation.

Individuals who are anxious or depressed before surgery may have a slightly increased risk of death within 30 days following surgery, according to a study examining files of all individuals admitted to an intensive care unit of Veterans Affairs hospitals. The study, published in the October Archives of Surgery, excluded individuals who were admitted following heart procedures such as percutaneous catheterizations, angioplasty, and stenting, among others.

Thad Abrams, M.D., M.S., an associate professor in the Department of General Internal Medicine of the Carver College of Medicine at the University of Iowa, and colleagues studied more than 35,000 patients admitted to the intensive care units of Veterans Health Administration hospitals that provided care in an acute care setting from 2003 to 2006. An existing psychiatric condition was identified in one-fourth of the patients, including 16 percent with depression, 8 percent with posttraumatic stress disorder, 7 percent with anxiety disorders, 2 percent with bipolar disorder, and 2 percent with psychosis. The risk of dying within 30 days of surgery was associated with depression and anxiety, but not with the other psychiatric conditions.

Moreover, the 30-day death rates among those with psychiatric conditions were higher for those undergoing respiratory or digestive system procedures, but not procedures involving the circulatory, nervous, or musculoskeletal system.

The study was funded by a grant from the Department of Veterans Affairs, Veterans Health Administration; the Health Services Research and Development Service; as well as a postdoctoral fellowship award in health services research to Abrams by the Office of Academic Affiliations at the University of Iowa.

Although some epidemiological studies have suggested that fish-oil supplements can help prevent postpartum depression, a randomized, controlled trial conducted in Australia has failed to find that this is the case.

The study, conducted in five Australian maternity hospitals, included more than 2,000 women who were less than 21 weeks pregnant. Half of the women received daily 800 mg DHA-rich fish-oil capsules, while the other half received a daily placebo of vegetable-oil capsules without DHA. The researchers found that the percentage of women reporting high levels of depressive symptoms during the first six months postpartum did not differ significantly between the DHA and control groups.

The study results were reported online October 19 in the Journal of the American Medical Association by Maria Makrides, Ph.D., of the Women's and Children's Health Research Institute in Adelaide, Australia, and colleagues. The study was funded by the Australian National Health and Medical Research Council.

Rivastigmine as an “add-on” therapy to haloperidol for critically ill ICU patients with delirium failed to confer benefit. In fact, use of the medication in addition to haloperidol was associated with worse outcomes. Therefore, the study was stopped prematurely after reaching an enrollment of only 104 out of 440 planned participants.

The study, reported by Maarten M.J. van Eijk, M.D., and colleagues, was published online November 5 in The Lancet. The senior investigator was Arjen Slooter, M.D., Ph.D., of the University Medical Center of Utrecht in the Netherlands.

Patients included in the study were randomized to receive haloperidol plus placebo, as a control, or haloperidol plus rivastigmine. Patients randomized to receive rivastigmine were given 1.5 mg of that drug two times daily initially, and this dose was titrated upward to a maximum dose of 12 mg. Patients in the other arm of the study received placebo two times daily.

The researchers found that the use of rivastigmine increased, although not significantly, the rate of death and the duration of delirium to five days in rivastigmine-treated patients compared with three days in control patients. It was also reported that patients receiving additional treatment with rivastigmine had more severe delirium (p=0.004), longer stays in the ICU (p < 0.0001), and spent a greater percentage of days (10 percent vs. 3 percent) during the study in a coma, compared with control patients (p<0.0001).

The study was funded by the Netherlands Organisation for Health Research and Development, Netherlands Brain Foundation, and Novartis.

Results of the “Ziprasidone Observational Study of Cardiac Outcomes” (ZODIAC) study fail to show an increased risk in nonsuicide deaths in schizophrenia patients taking ziprasidone, when compared with deaths for patient taking olanzapine.

The study, published in AJP in Advance on November 1 by Brian Strom, M.D., M.P.H., and colleagues, was required as part of an agreement by the manufacturer of ziprasidone, Pfizer Inc., and the Food and Drug Administration (FDA) in 2000 and the Swedish Medical Products Agency in 2001, following FDA approval of the second-generation antipsychotic.

Data from 18,154 patients representing 18 countries were included in the analysis. Patients were enrolled between February 2002 and March 2007 if their psychiatrist was willing to start or switch the individual's medication to either olanzapine or ziprasidone. Patients were randomized in a 1:1 fashion to receive treatment with either ziprasidone or olanzapine and were followed for one year.

According to the authors, the study was carried out in order to further document the safety and risks associated with the use of ziprasidone concerning the QTc interval. The goal of the open-label, randomized study was to evaluate the incidence of nonsuicide mortality after one year of treatment. Prior to the drug's approval, due to small populations included in clinical trials, the potential effects on cardiac mortality of ziprasidone in terms of “real-world use” were considered uncertain.

“It is very reassuring that, if there is any clinical importance of the mild QT prolongation caused by ziprasidone, it is sufficiently small that it could not be detected even in a study this massive,” Strom told Psychiatric News. He is the chair of the Department of Biostatistics and Epidemiology at the University of Pennsylvania School of Medicine.

The study was fully funded by Pfizer Inc.

An abstract of “Comparative Mortality Associated With Ziprasidone and Olanzapine in Real-World Use Among 18,154 Patients With Schizophrenia: The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC)” is posted at <http://ajp.psychiatryonline.org/cgi/content/abstract/appi.ajp.2010.08040484v1>.