Clinical Study Of Fatty Acid Composition And Depression And Related Cognition And Bone Metabolism

Background:As we gain a better understanding of depression,increasing study has found that fatty acid metabolism plays a crucial role in the pathophysiology of depression.And nutritional intervention based on fatty acids(such as n-3 polyunsaturated fatty acids,n-3 PUFAs)have shown great potential in the prevention and treatment of depression.In addition,depressed patients frequently exhibit cognitive impairments as well as abnormalities in bone metabolism.However,no safe and effective treatment options are available.Therefore,examining the relationship between fatty acid composition and depression,fatty acid and the main clinical characteristic(such as depressive symptoms,anxiety symptoms and cognition impairment),as well as clinical application of n-3 PUFAs in depression is useful to clarify their role in the treatment of depression,to promote the full recovery of depressed patients,as well as to provide some basis for future exploration of its possible mechanism.Objective:The aim of this study was to investigate the changes in erythrocyte membrane fatty acid metabolism and its correlation with clinical symptoms in first-diagnosed,drug-na(?)ve depression.Furthermore,assessing the efficacy of n-3 PUFAs in the adjunctive treatment of depression and their effects on fatty acid metabolism,cognitive,and bone metabolism.Methods:A total of 139 patients with first-diagnosed,drug-na(?)ve depression and 55 healthy controls were included in the cross-sectional study.Firstly,the levels of erythrocyte membrane fatty acids were compared between the depression group(MDD)and the healthy control group(HC).Then,the correlation between clinical symptoms(depression and anxiety)and fatty acid levels in depression was investigated.Finally,the influence of depressive and anxious symptoms on the fatty acid composition of erythrocyte membranes was studied to see if erythrocyte membrane fatty acid levels could be used as a biological marker for depression.A double-blind,randomized,placebo-controlled clinical trial of n-3PUFAs as an adjunct to venlafaxine in the treatment of depression was conducted in the follow-up study.72 patients with first-diagnosed,drug-na(?)ve depression were randomly assigned to the fish oil group(n=36)or the placebo group(n=36).For a 12-week treatment period,the fish oil group received a therapeutic does of venlafaxine along with fish oil capsules(approximately 1440 mg of EPA and 960 mg of DHA)daily,whereas the placebo group received therapeutic does of venlafaxine along with an equivalent does of soybean oil capsules.Follow-up assessments were performed before treatment,4 and 12 weeks after treatment.The primary outcome were Hamilton Depression Scale(HAMD),Hamilton anxiety Scale(HAMA),Beck Depression Inventory(BDI)and Self-rating anxiety scale(SAS).And secondary outcome included erythrocyte membrane fatty acid levels,bone turnover markers and cognition which was measured by the scale of Repeatable Battery for the Assessment of Neuropsychological Status(RBANS).Results:The results showed that total n-6 PUFAs(z=-2.127,p=0.033),C20:4n6(z=-2.104,p=0.035),C20:3n6(z=-3.687,p<0.001)and C18:1n9t(z=-2.033,p=0.042)in erythrocyte membrane of depression were significantly higher,while the levels of C18:1n9c(z=-3.348,p=0.001)were significantly lower compared to healthy controls(HCs).Meanwhile,the correlation study between fatty acid levels and clinical symptoms(depression and anxiety)showed that total n-6 PUFAs,C20:4n6(AA),C22:4n6 and C18:1n9t were positively correlated with depression and anxiety symptoms(p<0.05).Most fatty acid levels were significantly elevated in the severe depression group compared with healthy controls or mild to moderate depression.The results of the randomized,double-blind,placebo-controlled clinical trial of n-3 PUFAs adjuvant to venlafaxine for the treatment of depression found that the response rate of anxiety(the reduction of HAMA score≧50%)in fish oil group(44.4%)was greater compared with that in placebo group(21.2%)at Week 4(X~2=4.182,p=0.042).In addition,the study found that most erythrocyte membrane fatty acid levels in placebo group have the tendency to decrease at Week 4 and Week 8 when compared to baseline.C20:5n3(EPA)at week 4 was significantly lower compared to baseline(p<0.01),and C20:3n6 at both week 4 and week 8were significantly lower than baseline.In fish oil group,most erythrocyte membrane fatty acid levels were significantly decreased after treatment compared to baseline,such as the levels of total FA,total MUFAs,total PUFAs,total n-6 PUFAs,C18:2n6c,C20:3n6,C20:4n6(AA),C22:4n6and the ratios of AA/EPA,n-6/n-3 PUFAs,and C22:5n3/C20:5n3(p<0.05).The level of C20:5n3(EPA)and n-3 index were significantly increased in fish oil group after treatment(p<0.01).Finally,changes in the levels of fatty acids were positively correlated with improvements in anxiety and depressive symptoms among treated subjects.Research on fatty acid composition and cognitive impairment in depression has found that three cognitive domains in RBANS(immediate memory,attention and delayed memory)were negatively correlated with n-6/n-3 PUFAs ratio and C18:0(p<0.05).The immediate memory,verbal function,attention,delayed memory,and total RBNAS scores were improved significantly(p<0.05)in both placebo and fish oil groups after treatment,while the improve on immediate memory scores at week 4 and12 in fish oil group was significantly increased than placebo group(WaldX~2=4.085,p=0.043).Research on fatty acid composition and bone metabolism in depression has found that serum Type I procollagen N-terminal pre-peptide(PINP)level was significantly higher in depression compared to healthy controls(z=-2.233,p=0.026).The levels of C-terminal telopeptide of typeⅠcollagen(CTX)and osteocalcin in placebo group were significantly decreased at week 12 compared to baseline.Meanwhile,osteocalcin and PINP levels were significantly higher in fish oil group compared to placebo group at week 12(p<0.05).Conclusion:1.Erythrocyte membrane fatty acid composition is changed in patients with first-diagnosed,drug-na(?)ve depression,and fatty acid levels correlate with depressive and anxiety symptoms.2.N-3 PUFAs adjuvant to venlafaxine in patients with first-diagnosed,drug-na(?)ve depression may enhance the anxiolytic effects at the early stage of treatment,rather than antidepressant effects.3.N-3 PUFAs adjuvant to venlafaxine significantly altered the fatty acid composition of erythrocyte membranes in depressed patients,and the alteration of fatty acids correlated with clinical efficacy.4.Erythrocyte membrane fatty acids are related to cognitive function in first-diagnosed,drug-na(?)ve depression.In addition,n-3 PUFAs adjunctive treatment improved immediate memory better than venlafaxine alone.5.Venlafaxine treatment reduced the biomarkers of bone resorption and bone formation,while n-3 PUFAs adjuvant treatment of depression was able to increase biomarkers of bone formation.