title: Convergent functional genomic studies of ω-3 fatty acids in stress reactivity, bipolar disorder and alcoholism.
abstract: 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.
authors: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: H
authors: H
authors: Le-Niculescu
authors: N J
authors: NJ
authors: Case
authors: L
authors: L
authors: Hulvershorn
authors: S D
authors: SD
authors: Patel
authors: D
authors: D
authors: Bowker
authors: J
authors: J
authors: Gupta
authors: R
authors: R
authors: Bell
authors: H J
authors: HJ
authors: Edenberg
authors: M T
authors: MT
authors: Tsuang
authors: R
authors: R
authors: Kuczenski
authors: M A
authors: MA
authors: Geyer
authors: Z A
authors: ZA
authors: Rodd
authors: A B
authors: AB
authors: Niculescu
mesh_terms: D000437:Alcoholism / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000097:blood / Q000494:pharmacology*; D005260:Female; D023281:Genomics / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051381:Rats; D013315:Stress, Psychological / Q000188:drug therapy* / Q000235:genetics
chemical_list: D004281:Docosahexaenoic Acids