Journal Digest

• About 14.5 percent of men aged 65 or older said in a recent survey that they had at least one episode of binge drinking within the past year, which was defined as having five or more drinks on one occasion. In contrast, only 3 percent of women in this age group reported binge drinking. The data were collected in the 2005 and 2006 National Survey on Drug Use and Health, sponsored by the Substance Abuse and Mental Health Services Administration. At-risk drinking, defined as having an average of two or more drinks a day, had a prevalence of 13 percent in men and 8 percent in women of this age group. The rates of binge and at-risk drinking were even higher in men and women aged 50 to 64.

Binge drinking was more common in men who had higher income or who were separated, divorced, or widowed. In women, binge drinking was associated with being employed and using prescription drugs for nonmedical reasons. The use of tobacco and illicit drugs was associated with binge drinking among all respondents.

The study was supported by the National Institute on Drug Abuse.

• Concentrations of β-amyloid_1-42 (Aβ42) peptide, total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) in the cerebrospinal fluid (CSF) may serve as biomarkers to predict the future development of Alzheimer's disease in patients with mild cognitive impairment. Biomarkers that can accurately and sensitively predict the course of a disease, such as low-density-lipoprotein cholesterol levels in blood for cardiovascular disease, are particularly useful for the early diagnosis and prevention of chronic, slowly progressive illnesses. In a multicenter study in Europe and the United States, 750 patients aged 43 to 89 with mild cognitive impairment (MCI) were prospectively followed for a median of three years (range two to 11 years), during which 271 developed Alzheimer's and 59 developed other dementias.

Patients who developed Alzheimer's had significantly lower CSF levels of Aβ42 and higher levels of T-tau and P-tau than those who did not. The authors conducted statistical analyses to compare MCI patients who developed Alzheimer's with MCI patients who did not with controls without Alzheimer's. Combining the Aβ42-tau ratio and T-tau level, the authors found a measurement that could have predicted emergent Alzheimer's with a sensitivity of 83 percent and a specificity of 72 percent. One potential problem was that different study centers had large variations in the biomarker levels, especially for Aβ42. Standardizing the sample handling and testing methods may improve the accuracy and predictive value of the biomarkers, the authors said.

• Mentally stimulating leisure activities were associated with delayed onset of rapid memory decline in older adults who ultimately developed dementia. The study was a reanalysis of data from the Bronx Aging Study, in which 488 healthy volunteers, aged 75 to 85, were enrolled between 1980 and 1983 and followed until death or loss to follow-up. All volunteers were asked at baseline to estimate about how many days a week they had participated in the following cognitively stimulating leisure activities: reading, writing, crossword puzzles, board or card games, group discussions, and playing music.

Among the 101 persons who eventually developed dementia, each additional day a week of stimulating activities was associated with a 0.18 year delay in the onset of accelerated memory decline. This association was unchanged by the level of education. However, once the decline began, patients who had participated in more baseline activities declined more rapidly than those with fewer activities. These findings were consistent with the cognitive reserve hypothesis, which suggests that certain brain characteristics, reflected in higher education as well as cognitive activities, may protect some persons from the initial neurological deterioration during dementia.

The study was supported in part by a grant from the National Institute on Aging.

• In a randomized, double-blind study of patients with major depressive disorder (MDD), the antidepressant agomelatine was shown to be significantly more effective than placebo. Agomelatine is an agonist of the melatonin MT₁ and MT₂ receptors and an antagonist of the serotonin 5-HT_2c receptor. The antidepressant was developed by Servier Laboratories of France and has been approved in Europe for treating adults with MDD. Novartis has bought the rights to the drug and is conducting additional phase 3 clinical trials in the United States.

In this Sevier-sponsored study conducted from 2005 to 2007, 339 patients who had responded to acute treatment with agomelatine (eight or 10 weeks) were randomly assigned to receive either the active drug (n=165) or placebo (n=174) in a double-blind manner for 24 weeks. In the intent-to-treat population, the cumulative six-month relapse rate was 21.7 percent in the agomelatine group and 46.6 percent in the placebo group (p=0.0001). The Kaplan-Meier curves for time to relapse indicated a significantly lower rate of relapse over time in the agomelatine group. Approximately 20 percent of patients withdrew during the acute treatment for lack of sufficient efficacy. During the double-blind, six-month treatment period that followed, 22 percent of the patients in the agomelatine group and 41 percent in the placebo group withdrew for lack of efficacy.

The adverse events were mostly mild to moderate in both groups. The Europe-approved label of agomelatine lists headache, dizziness, somnolence, insomnia, nausea, diarrhea, constipation, anxiety, and other adverse events reported in clinical trials. The drug has been associated with increased hepatic enzyme levels and is contraindicated in patients with liver impairment.

• At 9 months of age, newborns of women with postpartum depression had poorer developmental outcomes compared with those born to mothers with anxiety disorders and those born to women with neither anxiety nor depression. The authors first assessed depressive symptoms in nearly 1,000 women on the day after delivery, and then selected 360 who scored the highest and lowest for a second assessment at six months postpartum. The second assessment, using a mailed questionnaire, asked the mothers about their depressive and anxiety symptoms. From all the responses, a final sample of 100 mother-infant dyads was selected for a third assessment of both the mothers and infants at nine months postpartum. This sample included 41 mothers who had scored the highest on depressive and anxiety symptoms and 59 healthy matched controls.

On the basis of home visits, a clinical psychologist diagnosed 22 mothers with major depressive disorder and 19 with anxiety disorders. Each infant was assessed for interaction with its mother, fear regulation, and afternoon cortisol level. The children of MDD mothers had the worst scores for social engagement and fear regulation among the three groups at nine months. Children born to anxious mothers scored worse than children of healthy control mothers in terms of stress reactivity and social engagement, but not in fear regulation. The authors concluded that different maternal diagnoses and behavior patterns can lead to various infant development outcomes through different mechanisms.

Feldman R, Granat A, Pariente C, Kanety H, Kuint J, Gilboa-Schechtman E. Maternal Depression and Anxiety Across the Postpartum Year and Infant Social Engagement, Fear Regulation, and Stress Reactivity. J Am Acad Child Adolesc Psychiatry. 2009;48(9):919-927 ▪