Convergent functional genomic studies of omega-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

Construction of a ground-motion logic tree through host-to-target region adjustments applied to an adaptable ground-motion prediction model

The purpose of a median ground‐motion logic tree is to capture the center, body, and range of possible ground‐motion amplitudes for each earthquake scenario considered in a seismic hazard analysis. For site‐specific hazard analyses, the traditional approach of populating the logic tree branches with ground‐motion prediction models (GMPMs) selected and weighted on the basis of vaguely defined applicability to the target region is rapidly being abandoned in favor of the backbone GMPM approach. In this approach, the selected backbone model is first adjusted to match the earthquake source and path characteristics of the target region, and then it is separately adjusted to account for the site‐specific geotechnical profile. For a GMPM to be amenable to such host‐to‐target adjustments, the magnitude scaling of response spectral ordinates should be consistent with the theoretical scaling of Fourier amplitude spectra. In addition, the influence of individual source and path parameters should be clearly distinguished in the model to allow the adjustments to be applied individually, and reliable estimates of the source and path parameters from the host region of the GMPM should be available, as should a reference rock profile for the model. The NGA‐West2 project GMPM of Chiou and Youngs (2014; hereafter, CY14) has been identified as a very suitable backbone model. Moreover, rather than adopting generic source and path parameters and a rock site profile from the host region for CY14, which is not easily defined because the data from which it was derived came from several geographical locations, recent studies have inverted the model to obtain a CY14‐consistent reference rock profile and CY14‐compatible source and path parameters. Using these host‐region characteristics, this study illustrates the process of building a ground‐motion logic tree through the sequential application of multiple host‐to‐target‐region adjustments, each represented by a node on the logic tree to achieve a tractable model for the total epistemic uncertainty