Age-related changes of n-3 and n-6 polyunsaturated fatty acids in the

Accumulating evidence finds a relative deficiency of peripheral membrane fatty acids in persons with affective disorders such as unipolar and bipolar depression .Here we sought to investigate whether postmortem brain fatty acids within the anterior cingulate cortex (BA-24) varied according to the presence of major depression at the time of death. Using capillary gas chromatography we measured fatty acids in a depressed group (n of 12), and in a control group without lifetime history of psychiatric diagnosis (n of 14).Compared to the control group, the depressed group showed significantly lower concentrations of numerous saturated and polyunsaturated fatty acids including both the n3 and n6 fatty acids. Additionally, significant correlations between age at death and precursor (or metabolites) in the n-3 fatty acid pathway were demonstrated in the depressed group but not in control subjects. In the n-6 fatty acid family, the ratio of 20:3 (n6)/18:2 (n6) was higher in patients than in control groups, whereas the ratio of 20:4(n6)/20:3 (n6) was relatively decreased in patients. Lastly, a significant negative correlation between age and the ratio of 20:4(n6) to 22:6(n3) was found in patients, but not in controls. Taken together, decreases in 22:6(n3) may be caused, at least in part, by the diminished formation of 20:5(n3), which is derived from 20:4(n3) through a D5 desaturase reaction. The present findings from postmortem brain tissue raise the possibility that an increased ratio of 20:4(n6) to 22:6 (n3) may provide us with a biomarker for depression. Future research should further investigate these relationships. (Authors Abstract)

Fatty acids are essential components of membrane phospho- lipids and are highly enriched in the central nervous system (CNS). The long-chain polyunsaturated n-3 fatty acids, eicosapentaenate (EPA) and docosahexaenate (DHA), are known to be crucial for growth and development of the CNS.  Specific plant based oils such as flax provide the18 carbon fatty acids while marine plants and seafood provide the longer chain EPA and DHA. The18 carbon n6 fatty acid, linoleic acid are in high levels in modern-day diets predominantly from corn and soy oils. Inverse correlations have been reported between deficient consumption of the n3 fatty acids and an increase in n6 consumption, and prevalence of affective disorders and depression. Individuals with affective disorders, such as unipolar and bipolar depression, show a number of fatty acid deficiencies in peripheral tissues including red blood cells, serum, plasma and adipose tissue. In the current study, the brain fatty acid profile in postmortem anterior cingulate cortex (ACC; Brodmann area 24),a brain region showing consistent morphological and metabolic differences in major depressive disorder (MDD) and bipolar depression (BPD), in two groups: one with and one without a diagnosis of MDD at the time of death. The study reports significant differences in postmortem brain phospholipid fatty acid concentration in the ACC between the groups.  In particular, an increased ratio of 20:3 (n6)/18:2 (n6) was reported that was associated with decreased ratios of  20:4 (n6)/20:3 (n6), and suggesting a defect in the D5 desaturation in individuals with MDD/ BPD. The results also showed that the precursors of 22:6 (n3),  i.e. 18:3(n3) and 20:5(n3), were not correlated significantly with age among controls aged 27 to 77 years. However, there were significantly negative correlations between the precursors of 22:6 (n3) and age in the MDD/BPD patients, suggesting that age maybe an important confounding factor in regulation of the n3 fatty acid pathway in MDD/BD group. The data suggest a defect or disruption in the activity of the D5 desaturase, which may account for the lower levels of DHA seen in the depressed group. In order to better understand the complex relationship that peripheral and central lipids play in psychopathology and the variability in effect, the authors suggest that future research should examine the strength of the correlation between central and peripheral lipids. (Editors comments)