Polyunsaturated fatty acids moderate the effect of poor sleep on depression risk

Although potentially modifiable risk factors for interferon-alpha (IFN-α)-associated depression (IFN-MDD) have been identified, it is not currently known how they interact to confer risk. In the present study we prospectively investigated interactions among poor sleep quality, high-stress, pre-existing depressive symptoms, and polyunsaturated fatty acid status. Non-depressed hepatitis C patients (n=104) were followed prospectively during IFN-α therapy. IFN-MDD occurs in 20-40% of patients and was diagnosed using the Structured Clinical Interview of DSM-IV (SCID-IV), with incidence examined using Cox regression. Baseline Pittsburgh Sleep Quality Inventory (PSQI), Perceived Stress Scale (PSS), Beck Depression Inventory (BDI), and a range of plasma long-chain fatty acid levels were measured (gas chromatography) - focusing on the ratio of arachidonic acid (AA) to docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (AA/EPA+DHA). The AA/EPA+DHA ratio (Β=0.40 ± 0.16; p=0.006), PSQI (Β=0.12 ± 0.04; p=0.001), PSS (Β=0.07 ± 0.02; p<0.001), and baseline BDI (Β=0.05 ± 0.02; p<0.001) each individually predicted IFN-MDD incidence. In step-wise Cox regression eliminating non-significant variables, two interactions remained significantly predictive: PSQI*AA/EPA+DHA (p=0.008) and PSS*AA/EPA+DHA (p=0.01). Receiver Operator Curves (ROC) were used to examine the specificity and sensitivity of IFN-MDD prediction. When sleep was normal (PSQI<5), AA/EPA+DHA was strongly predictive of IFN-MDD (AUC=91 ± 6; p=0.002). For example, among those with AA/EPA+DHA less than the median (4.15), none with PSQI<5 developed depression. Conversely, neither PSS nor PSQI was statistically associated with depression risk in those with an elevated AA/EPA+DHA ratio. These data demonstrate that the AA/EPA+DHA ratio moderates the effect of poor sleep on risk for developing IFN-MDD and may have broader implications for predicting and preventing MDD associated with inflammation.