Long-chain omega-3 polyunsaturated fatty acids are associated with brain connectivity and mood in young adults with subthreshold depression: A preliminary study

Background: The long-chain omega-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have beneficial effects in depression, and these effects may be mediated via changes in functional brain connectivity. However, little is known about these effects in those with subthreshold depression. Methods: 15 Participants aged 18-29 years with Patient Health Questionnaire-8 (PHQ-8) scores > 4 and Generalised Anxiety Disorder Assessment-7 (GAD-7) scores > 5, underwent resting-state functional magnetic resonance imaging. Whole-brain, seed-based connectivity analyses were performed using bilateral orbitofrontal cortex (OFC) and amygdala seeds. Omega-3 and -6 PUFA status was assessed from dried bloodspot analysis of % DHA, %EPA, Omega-3 Index (calculated as the sum of DHA plus EPA expressed as a percentage of the total measured fatty acids and a correction applied as dried blood spot samples were used instead of erythrocytes) and ratio of the omega-6 PUFA arachidonic acid (ARA) to EPA (ARA/EPA). Results: PHQ-8 scores indicated subthreshold depression (mean = 10.0; SD = 4.2) and were negatively associated with DHA levels and Omega-3 Index. Significant negative associations were also identified between connectivity of the OFC with the angular gyrus and DHA and Omega-3 Index, while weaker connectivity of these regions was associated with lower PHQ-8 and GAD-7 scores. DHA and Omega-3 Index values were significantly associated with greater connectivity of the amygdala with the posterior cingulate cortex, which was also associated with lower PHQ-8 scores. Conclusions: Higher omega-3 PUFA status in young adults with moderate, but mean subthreshold depression was associated with lower depression rating scores and altered functional connectivity of brain regions shown to play a role in the neurobiology of depression.