• Pregnant women with depression are at significantly greater risk of preterm delivery than those without depression, a prospective, naturalistic, cohort study shows.

Researchers at the Kaiser Foundation Research Institute analyzed data on 791 women who were interviewed for depressive symptoms at the early stage of their pregnancy (about 10 weeks) and gave a live birth later within the Kaiser Permenante medical program in the San Francisco area. Those who met the criteria of significant depressive symptoms, determined by a score of 16 or higher on the Center for Epidemiological Studies Depression Scale (CESD), had nearly twice the risk (hazard ratio 1.9) of preterm delivery compared with women with a CESD score below 16, after adjusting for other confounding factors such as maternal age, education, a history of miscarriage or other complications, and smoking. The effect increased with more severe depression as women with a CESD score of 22 or above had a hazard ratio of 2.2, while those with CESD score of 16 to 21 had a hazard ratio of 1.6. The author stated that only 1.5 percent of the study cohort was prescribed any antidepressants during the study period, and excluding these patients did not change the conclusion. Therefore, the increased rate of preterm delivery was likely related to the depression rather than medication use. The study was supported in part by funds from the California Public Health Foundation.

Li D et al. Presence of Depressive Symptoms During Early Pregnancy and the Risk of Preterm Delivery: A Prospective Cohort Study. Hum Reprod. Published online October 23, 2008.

• Stroke survivors who develop depression are more likely to carry certain genetic variations in the serotonin transporter gene (SERT), a study has found. Specific polymorphisms in the serotonin-transporter-linked polymorphic region (5-HTTLPR) and the STin2 variable number tandem repeats (VNTR) in the intron 2 region were both significantly associated with the likelihood of poststroke depression. The study authors compared 75 survivors of ischemic strokes who had a score of 11 or greater on the 30-item Geriatric Depression Scale (GDS) and a control cohort of 75 stroke survivors with a score of less than 11. All study participants were recruited from a larger study on the treatment of poststroke depression.

The s/s genotype in 5-HTTLPR and the 9/12 and 12/12 genotypes in STin2 VNTR were associated with three to four times the likelihood of having poststroke depression. The authors noted that carrying the s allele in 5-HTTLPR has been associated with depression moderated by life stress, suicidal behavior, bipolar disorder, and below-average response to antidepressant medications. Carrying the risk alleles in STin2 VNTR has been linked to schizophrenia, bipolar disorder, and depression.

The study was funded by the National Institute of Nursing Research, National Institutes of Health, and the Veterans Affairs Puget Sound Health Care System in Washington State.

Kohen R et al. Association of Serotonin Transporter Gene Polymorphism With Poststroke Depression. Arch Gen Psychiatry. 2008; 65(11):1296-1302.

• A new study links depression, but not antidepressant use, to increased mortality in heart failure patients. The authors recruited patients who were admitted to the cardiology service at Duke University Medical Center for heart failure and followed them annually for vital status, depression, and antidepressant treatment. Between March 1997 and June 2003, 1,006 patients were enrolled in the study, including 30 percent with depression, defined as having a Beck Depression Index (BDI) score of 10 or higher. Sixteen percent of all patients were taking antidepressants. Within a mean follow-up length of 972 days, 429 (42.7 percent) patients died. The mortality rates were 53.3 percent in patients with depression and 38.1 percent in patients without depression.

The association between the antidepressant use and increased mortality disappeared after the authors controlled for depression and other confounding factors. Depression itself was a significant risk factor for higher mortality, with a hazard ratio of 1.33. The study was funded by the Duke Clinical Research Institute and a grant from the National Institute of Mental Health.

O'Connor CM et al. Antidepressant Use, Depression, and Survival in Patients with Heart Failure. Arch Intern Med. 2008; 168(20):2232-37.

• Iron deficiency during a woman's pregnancy has been linked to increased risk of schizophrenia or related mental disorders in the offspring in a recent epidemiological study. The authors matched 6,872 people with available medical records between 1981 and 1997 and their mothers' hemoglobin levels during pregnancy between 1959 and 1966. The mother-offspring cohorts were derived from large population studies with data from the Kaiser Permanente medical care plan in Alameda County, Calif.

People born to mothers with a low hemoglobin level (10.0 g/dL or less) during pregnancy had a significantly higher rate of having a diagnosis of schizophrenia spectrum disorders (SSDs, including schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorder not otherwise specified, and schizotypal personality disorder) compared with those born to mothers with a normal hemoglobin level (12.0 g/dL or above) with a risk ratio of 3.73. Specifically, low maternal hemoglobin level in the second and third trimesters was associated with significantly higher risk of SSDs in offspring. The authors suggested that the lack of iron may directly or indirectly affect the normal development of the brain through a number of possible mechanisms.

The study was funded by grants from the National Institute of Mental Health, Frontier Fund of Columbia University, and Eunice Kennedy Shriver Institute of Child Health and Human Development.

Insel BJ et al. Maternal Iron Deficiency and the Risk of Schizophrenia in Offspring. Arch Gen Psychiatry. 2008; 65(10):1136-44.

• Flunarizine, a calcium channel blocker used to treat migraine, vertigo, and other indications, may also be an effective anti-psychotic to treat schizophrenia, a randomized, controlled, double-blind study by a group of Brazilian researchers has found. Seventy schizophrenia patients with stable disease were randomized to receive either flunarizine (n=34) or haloperidol (n=36) for 12 weeks; 25 and 27 patients, respectively, completed the entire 12 weeks. The mean total score on the Positive and Negative Syndrome Scale (PANSS) was reduced by 21 percent from baseline in the flunarizine group and by 19 percent in the haloperidol group; both were a statistically significant improvement. The differences in PANSS total score, subscale scores, and the Clinical Global Impression-Improvement scores were not statistically significant between the two groups. The haloperidol group had significantly higher treatment-related akathisia and weight gain, but the groups did not differ significantly in extrapyramidal symptoms and prolactin levels.

Past research has shown that flunarizine is a dopamine D₂ receptor antagonist with moderate affinity with no significant 5-HT receptor blockade. It is not available in the United States but is sold in other countries. The study was funded by the Stanley Medical Research Institute.

Bisol LW. Is Flunarizine a Long-Acting Oral Atypical Antipsychotic? A Randomized Clinical Trial Versus Haloperidol for the Treatment of Schizophrenia. J Clin Psychiatry . 2008; 69(10): 1572-9.

• A randomized, double-blind, head-to-head comparative trial of olanzapine versus divalproex has shown no significant difference between the two drugs in efficacy for the acute treatment of mild to moderate mania. Bipolar patients in acute manic or mixed episodes with a Young Mania Rating Scale (YMRS) total score of 20 to 30 (mild to moderate in severity) were randomly assigned to three treatment groups: olanzapine (n=215), divalproex (n=201), or placebo (n=105). After three weeks of treatment, the reduction in YMRS total score from baseline was significantly different between the olanzapine and placebo groups, but was not significantly different in the olanzapine-versus-divalproex and divalproex-versus-placebo comparisons.

At the end of week 3, patients in the olanzapine and divalproex groups continued with the same treatment for another nine weeks. At the end of week 12, the YMRS score reduction was significantly greater in olanzapine-treated patients than divalproex-treated patients. The placebo group was switched to olanzapine at the end of week 3, but they were not included in the 12-week analyses.

Patients in the olanzapine group had significantly larger increases in weight and glucose, cholesterol, triglyceride, uric acid, and prolactin levels than those in the divalproex group. Patients in the divalproex group had significantly greater decreases in leukocytes and platelets than those in the olanzapine group.

The study was funded by Eli Lilly and Co. and conducted in several countries between October 2004 and December 2006.

Tohen M et al. Olanzapine Versus Divalproex Versus Placebo in the Treatment of Mild to Moderate Mania: A Randomized, 12-Week, Double-Blind Study.J Clin Psychiatry.Published online October 7, 2008. ▪