Convergent functional genomic studies of ω-3 fatty acids in stress reactivity, bipolar disorder and alcoholism.

Omega-3 fatty acids have been proposed as an adjuvant treatment option in psychiatric disorders. Given their other health benefits and their relative lack of toxicity, teratogenicity and side effects, they may be particularly useful in children and in females of child-bearing age, especially during pregnancy and postpartum. A comprehensive mechanistic understanding of their effects is needed. Here we report translational studies demonstrating the phenotypic normalization and gene expression effects of dietary omega-3 fatty acids, specifically docosahexaenoic acid (DHA), in a stress-reactive knockout mouse model of bipolar disorder and co-morbid alcoholism, using a bioinformatic convergent functional genomics approach integrating animal model and human data to prioritize disease-relevant genes. Additionally, to validate at a behavioral level the novel observed effects on decreasing alcohol consumption, we also tested the effects of DHA in an independent animal model, alcohol-preferring (P) rats, a well-established animal model of alcoholism. Our studies uncover sex differences, brain region-specific effects and blood biomarkers that may underpin the effects of DHA. Of note, DHA modulates some of the same genes targeted by current psychotropic medications, as well as increases myelin-related gene expression. Myelin-related gene expression decrease is a common, if nonspecific, denominator of neuropsychiatric disorders. In conclusion, our work supports the potential utility of omega-3 fatty acids, specifically DHA, for a spectrum of psychiatric disorders such as stress disorders, bipolar disorder, alcoholism and beyond.

Cigarette advertising in magazines: the tobacco industry response to the Master Settlement Agreement and to public pressure.

OBJECTIVE: The Master Settlement Agreement (MSA) of November 1998 prohibited participating tobacco companies from directly or indirectly targeting youth in marketing. Widely publicised information in May 2000 showed increased cigarette advertising in magazines with substantial youth readership and companies were pressed to change their practices. The responses of the tobacco industry to the MSA and to the public pressure are examined. DESIGN: Expenditures on cigarette advertisements in national magazines in the USA are compared for three periods: January to November 1998, December 1998 to June 2000, and July 2000 to November 2001. Magazines in which at least 15% of readers are youth under age 18 are focused upon. Regression models test for the significance of period differences after controlling for seasonal and long term patterns. DATA SOURCES: Commercially maintained data on advertising in US magazines and on magazine readership by age. KEY MEASURES: Monthly cigarette ad expenditures in magazines with 15%+ youth readership, and monthly proportion of ad expenditures in 15%+ youth magazines. RESULTS: Cigarette advertising expenditures in magazines with 15%+ youth readership increased dramatically after MSA implementation and fell dramatically after public pressure. The percentage allocation of expenditures to 15%+ magazines fell significantly in both periods. Results differ somewhat by company. CONCLUSIONS: The tobacco industry response to the MSA was at best modest, reducing proportional allocations of advertising to youth magazines but increasing the absolute amount of such advertising. The value of public pressure was seen in substantial reductions in both absolute and proportional spending on youth magazines, although not by all companies.

The ingestion and assimilation of algae by Nais elinguis (Oligochaeta: Naididae).

Nais elinguis was offered equal densities of three algal species under controlled conditions. Colonies of Scenedesmus quadricauda were ingested at significantly lower rates than cell of Nitzschia kutzingiana and Chlorella vulgaris. Labelled cells of N. kutzingiana were more rapidly and more efficiently assimilated than those of the other algae. Cells of S. quadricauda were viable in the faeces.This work confirmed conclusions from other studies with respect to the role of algae in the nutrition of Nais elinguis and other freshwater benthic herbivores.

Sensitivity to countermodulating gratings following spatiotemporal adaptation.

Contrast sensitivities to countermodulating gratings were measured with a two-alternative temporal forced-choice procedure following adaptation to a static grating of the same spatial frequency, a homogeneous flickering field of the same temporal frequency, or a countermodulating grating of identical spatial and temporal frequencies. At high spatial frequencies, the temporal-frequency content of the adaptation was not critical, that is, a countermodulating adaptation grating was only slightly more effective at raising threshold than was a static adaptation grating. At low spatial frequencies, the sensitivity to countermodulating test gratings could not be reduced by either a high-contrast stimulus matching the test in the spatial domain only or by one matching the test in the temporal domain only. Adapting to a high-contrast stimulus matching the countermodulating test grating in both spatial- and temporal-frequency domains was effective at reducing test sensitivity for one observer but not for another.

Suprathreshold spatiotemporal response characteristics of the human visual system.

The apparent contrasts of suprathreshold stationary gratings, countermodulated gratings, and homogeneous flickering fields were assessed with a contrast-matching procedure. Results show that, as stimulus amplitude is increased relative to threshold, variations in apparent contrast with spatiotemporal-frequency content become much less pronounced. In other words, the contrast-matching functions are more uniform across both spatial and temporal frequency at levels of contrast well above threshold. These data are interpreted in terms of a compensatory stage in the visual system that varies its gain characteristics according to the detectability of the stimulus.

Perceived flicker rate of suprathreshold stimuli: influences of spatial-frequency content and modulation amplitude.

A number of experiments were conducted in which observers had to discriminate the apparent flicker rates of temporally modulated gratings and flickering homogeneous fields. When both intramodal- and cross-modal-matching procedures were used, apparent flicker rate was found to be consistently higher for countermodulating gratings than for homogeneous fields of the same temporal frequency. Also, the apparent flicker rate of countermodulating gratings tended to increase as spatial frequency increased. These effects are more pronounced at low rates of temporal modulation than at high rates and are not dependent on variations in the stimulus's apparent modulation amplitude.

Accommodation response during a prolonged visual search task.

The visual accommodative response is measured during dark field viewing and while engaged in a visual search task. A laser optometer is used to compare performance using microfiche and hard-copy displays. Results indicate a marked bias in the direction of the individual's resting accommodative state during all conditions of display viewing. Implications of these results and those from other studies are discussed with respect to future research in display design.

Binocular flicker appears faster than monocular flicker.

Observers adjusted the frequency of an auditory click to match the apparent flicker rate of a sinusoidally modulated visual display. Matches made for binocularly viewed flicker were nearly twice those for monocularly viewed flicker but only at high rates of temporal modulation.

Spatial frequency discrimination thresholds in different orientations.

Spatial frequency discrimination thresholds were obtained for two observers in horizontal, vertical, and oblique (45 degrees, 135 degrees) meridians. Psychometric discrimination functions derived by a forced-choice procedure were essentially the same for the four meridians at lower spatial frequencies. However, at higher frequencies discrimination thresholds were lower for horizontal and vertical stimuli than for oblique stimuli.