docosapentaenoic-acid and Depressive-Disorder--Major

The beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on depression are not definitively known. In a previous population-based prospective cohort study, we found a reverse J-shaped association of intake of fish and docosapentaenoic acid (DPA), the intermediate metabolite of EPA and DHA, with major depressive disorder (MDD). To examine the association further in a cross-sectional manner, in the present study we analyzed the level of plasma phospholipid n-3 PUFAs and the risk of MDD in 1,213 participants aged 64-86 years (mean 72.9 years) who completed questionnaires and underwent medical check-ups, a mental health examination, and blood collection. In multivariate logistic regression analysis, odds ratios and 95% confidence intervals were calculated for MDD according to plasma phospholipid n-3 PUFA quartiles. MDD was diagnosed in 103 individuals. There were no significant differences in any n-3 PUFAs (i.e., EPA, DHA, or DPA) between individuals with and without MDD. Multivariate logistic regression analysis showed no significant association between any individual n-3 PUFAs and MDD risk. Overall, based on the results of this cross-sectional study, there appears to be no association of plasma phospholipid n-3 PUFAs with MDD risk in the elderly Japanese population.

Topics: Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Depressive Disorder, Major; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Humans; Japan; Male; Odds Ratio; Phospholipids; Prospective Studies; Risk Factors

Previous studies of postmortem orbitofrontal cortex have shown abnormalities in levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), in individuals with schizophrenia, bipolar disorder, and major depressive disorder (MDD). We have previously measured PUFA levels in the postmortem hippocampus from patients with schizophrenia or bipolar disorder and control subjects; however, we found no significant differences between the groups except for small changes in n-6 PUFAs. Furthermore, our study of the postmortem amygdala showed no significant differences in major PUFAs in individuals with schizophrenia, bipolar disorder, or MDD in comparison with controls. In the present study, we investigated whether there were any changes in PUFAs in the entorhinal cortexes of patients with schizophrenia (n=15), bipolar disorder (n=15), or MDD (n=15) compared with unaffected controls (n=15) matched for characteristics including age and sex. In contrast to previous studies of the orbitofrontal cortex and hippocampus, we found no significant differences in major PUFAs. However, we found a 34.3% decrease in docosapentaenoic acid (DPA) (22:5n-3) in patients with MDD and an 8.7% decrease in docosatetraenoic acid (22:4n-6) in those with schizophrenia, compared with controls. Changes in PUFAs in patients with these psychiatric disorders may be specific to certain brain regions.

Topics: Adult; Bipolar Disorder; Depressive Disorder, Major; Entorhinal Cortex; Fatty Acids; Fatty Acids, Unsaturated; Female; Humans; Male; Middle Aged; Postmortem Changes; Schizophrenia

Bipolar and major depressive disorders are essentially relapsing and remitting disorders of affect with nearly full recovery between episodes. Although the underlying molecular mechanisms remain unclear, myelin-related abnormalities have long been suspected. Here, using novel statistical analysis, we show that subtle but significant abnormalities exist in the composition of fatty acids (FAs), including docosapentaenoic acid (22:5n-3), one of the omega-3 polyunsaturated FAs, found in the post-mortem frontopolar cortex (FPC) of subjects with bipolar or major depressive disorders, although not in those with schizophrenia. These abnormalities were all aggravated in a myelin level-dependent manner, suggesting their close relationship with myelination. Animal studies have further revealed that chronic antidepressant treatment induces robust changes in brain FA metabolism, but contributes only part of the abnormalities found in the affective disorder brains. These findings indicate that the pathophysiology of affective disorders involves an unknown type of perturbed myelination in the FPC that may serve as a novel diagnostic and therapeutic target.

Topics: Adult; Aged; Animals; Bipolar Disorder; Depressive Disorder, Major; Fatty Acids; Fatty Acids, Unsaturated; Female; Frontal Lobe; Humans; Male; Middle Aged; Mood Disorders; Myelin Sheath; Postmortem Changes; Rats; Rats, Sprague-Dawley; Rats, Wistar; Schizophrenia