Armand Christophe

Lowered ω3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients

Depression is associated with a lowered degree of esterification of serum cholesterol, an increased C20:4omega6/C20:5omega3 ratio and decreases in omega3 fractions in fatty acids (FAs) or in the red blood cell membrane. The aims of the present study were to examine: (i) serum phospholipid and cholesteryl ester compositions of individual saturated fatty acids (SFAs), monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs) in major depressed patients vs. healthy volunteers; (ii) the relationships between the above FAs and lowered serum zinc (Zn), a marker of the inflammatory response in depression; and (iii) the effects of subchronic treatment with antidepressants on FAs in depression. The composition of the FAs was determined by means of thin layer chromatography in conjunction with gas chromatography. Lipid concentrations were assayed by enzymatic colorimetric methods. The oxidative potential index (OPI) of FAs was computed in 34 major depressed inpatients and 14 normal volunteers. Major depression was associated with: increased MUFA and C22:5omega3 proportions and increased C20:4omega6/C20:5omega3 and C22:5omega6/C22:6omega3 ratios; lower C22:4omega6, C20:5omega3 and C22:5omega3 fractions in phospholipids; lower C18:3omega3, C20:5omega3 and total (sigma)omega3 FAs, and higher C20:4omega6/C20:5omega3 and sigmaomega6/sigmaomega3 ratios in cholesteryl esters; lower serum concentrations of phospholipids and cholesteryl esters; and a decreased OPI. In depression, there were significant and positive correlations between serum Zn and C20:5omega3 and C22:6omega3 fractions in phospholipids; and significant inverse correlations between serum Zn and the sigmaomega6/sigmaomega3, C20:4omega6/C20:5omega3, and C22:5omega6/C22:6omega3 ratios in phospholipids. There was no significant effect of antidepressive treatment on any of the FAs. The results show that, in major depression, there is a deficiency of omega3 PUFAs and a compensatory increase in MUFAs and C22:5omega6 in phospholipids. The results suggest that: (i) there is an abnormal metabolism of omega3 PUFAs in depression; (ii) the FA alterations in depression are related to the inflammatory response in that illness; and (iii) the disorders may persist despite successful antidepressant treatment.

Fatty acid composition in major depression: decreased ω3 fractions in cholesteryl esters and increased C20:4ω6C20:5ω3 ratio in cholesteryl esters and phospholipids

Abstract Recently, there were some reports that major depression may be accompanied by alterations in serum total cholesterol, cholesterol ester and ω3 essential fatty acid levels and by an increased C 20: 4ω6 C 20: 5ω3 i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2; C20:4) fatty acids in phospholipid and cholesteryl ester fractions were assayed and the sums of the percentages of ω6 and ω3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios ω6 ω3 and C 20:4ω6 C 20:5ω3 were calculated. Major depressed subjects had significantly higher C 20:4ω6 C 20:5ω3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased ω6 ω3 ratio in cholesteryl ester fraction than healthy volunteers and minor depressed subjects. Major depressed subjects had significantly lower C18:3ω3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total ω3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5ω3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.

Lower serum vitamin E concentrations in major depression Another marker of lowered antioxidant defenses in that illness

OBJECTIVE Major depression is associated with defective antioxidant defenses. Vitamin E is the major fat soluble antioxidant in the body. The aim of the present study is to examine serum vitamin E concentrations in major depressed patients versus normal volunteers. METHOD Serum vitamin E concentrations were measured in 26 healthy volunteers and 42 major depressed patients by means of HPLC. Since vitamin E is a fat soluble vitamin, and serum vitamin E concentrations are strongly related to these of low-density-lipoprotein cholesterol (LDL-C) and triglycerides, we have adjusted the results for possible differences in these lipids. The numbers of peripheral blood leukocytes were measured. RESULTS Patients with major depression had significantly lower serum vitamin E concentrations than healthy controls. The area under the ROC (receiver operating characteristics) curve was 83%. There were significant and negative correlations between serum vitamin E and number of total leukocytes and neutrophils. CONCLUSIONS Major depression is accompanied by significantly lower serum vitamin E concentrations, suggesting lower antioxidant defenses against lipid peroxidation. The results could, in part, explain previous findings, which suggest increased lipid peroxidation in major depression.

Lower serum high‐density lipoprotein cholesterol (HDL‐C) in major depression and in depressed men with serious suicidal attempts: relationship with immune‐inflammatory markers

Recently, there have been some reports that changes in serum lipid composition may be related to suicide, major depression and immune‐inflammatory responses. Findings from our laboratory suggest that major depression is accompanied by reduced formation of cholesteryl esters and perhaps by impairment of reverse cholesterol transport. The latter is reportedly accompanied by lower serum high‐density lipoprotein cholesterol (HDL‐C). The aim of this study was to examine whether (i) major depression is accompanied by lower serum HDL‐C or by abnormal levels of serum total cholesterol, triglycerides, low‐density lipoprotein‐C (LDL‐C) or vitamin E, (ii) suicidal attempts are related to lower serum HDL‐C and (iii) there are significant associations between serum HDL‐C and immune/inflammatory markers. A total of 36 subjects with major depression, of whom 28 patients showed treatment resistance, as well as 28 normal control subjects, had blood sampled for the assay of the above lipids, serum zinc (Zn), albumin (Alb) and flow cytometric determination of the T‐helper/T‐suppressor (CD4+/ CD8+) T‐cell ratio. In total, 28 depressed subjects had repeated measures of these variables both before and after treatment with antidepressants. Serum HDL‐C and total cholesterol, as well as the HDL‐C/cholesterol ratio, were significantly lower in subjects with major depression than in normal controls. Serum HDL‐C levels were significantly lower in depressed men who had at some time made serious suicidal attempts than in those without such suicidal behaviour. Treatment with antidepressants for 5 weeks did not significantly alter either serum HDL‐C or other lipid variables. Serum HDL‐C levels were significantly and negatively correlated with the (CD4+/CD8+) T‐cell ratio, and positively correlated with serum Alb and Zn. These results suggest that (i) lower serum HDL‐C levels are a marker for major depression and suicidal behaviour in depressed men, (ii) lower serum HDL‐C levels are probably induced by the immune/inflammatory response in depression and (iii) there is impairment of reverse cholesterol transport from the body tissues to the liver.

In humans, serum polyunsaturated fatty acid levels predict the response of proinflammatory cytokines to psychologic stress

BACKGROUND Psychologic stress in humans induces the production of proinflammatory cytokines, such as interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6), and that of the negative immunoregulatory cytokine, IL-10. An imbalance of omega6 to omega3 polyunsaturated fatty acids (PUFAs) in the peripheral blood causes an overproduction of proinflammatory cytokines. The omega3 PUFAs reduce the production of proinflammatory cytokines. METHODS This study examines whether an imbalance in omega6 to omega3 PUFAs in human blood predicts a greater production of proinflammatory cytokines in response to psychologic stress. Twenty-seven university students had serum sampled a few weeks before and after as well as 1 day before a difficult oral examination. We determined the omega6 and omega3 fractions in serum phospholipids as well as the ex vivo production of IFN-gamma, TNF-alpha, IL-6, IL-10, and IL-5 by diluted whole blood stimulated with polyclonal activators. RESULTS Academic examination stress significantly increased the ex vivo, stimulated production of IFN-gamma, TNF-alpha and IL-10, and the IFN-gamma/IL-5 production ratio. Subjects with lower serum omega3 PUFA levels or with a higher omega6/omega3 ratio had significantly greater stress-induced TNF-alpha and IFN-gamma responses than subjects with higher serum omega3 PUFAs and a lower omega6/omega3 ratio, respectively. Subjects with lower serum omega3 PUFA levels or with a higher omega6/omega3 ratio had a significantly higher stress-induced increase in the IFN-gamma/IL-5 ratio than the remaining subjects. CONCLUSIONS Psychologic stress induces a Th-1-like or proinflammatory response in some subjects. An imbalance in the omega6 to omega3 PUFA ratio appears to predispose humans toward an exaggerated Th-1-like response and an increased production of monocytic cytokines, such as TNF-alpha, in response to psychologic stress. The results suggest that increased omega3 PUFA levels may attenuate the proinflammatory response to psychologic stress.

Lowered ω-3 PUFAs are related to major depression, but not to somatization syndrome

BACKGROUND Studies indicated a depletion of omega-3 fatty acid levels and an imbalance between omega-3 and omega-6 PUFAs in depressive patients. Depletion of omega-3 PUFAs may be related to the immune and serotonergic pathophysiologies of depression by alterations in membrane fluidity and modulation of membrane receptors, enzyme activities and carriers. Previous studies also found serotonergic and immunological disturbances in subjects with somatoform symptoms. Based on these findings we aimed to investigate PUFA concentrations and its relations to other biological systems in depressed patients and in patients with somatoform symptoms. METHODS We examined 150 subjects divided in 4 groups, i.e. somatization syndrome; depression; depression and somatization syndrome; controls. Blood samples were analyzed for fatty acids, markers of the serotonergic system and the immune system. RESULTS The study was able to replicate earlier findings in patients with depression (lowered omega-3 PUFAs, increased omega-6/omega-3 ratios in serum cholesteryl esters). The somatization syndrome group showed no abnormalities in the mentioned fatty acid levels. Only depressive patients revealed associations between fatty acids with serotonergic and immunological markers. LIMITATIONS We used current state diagnoses, and the consideration of lifetime diagnoses and longitudinal studies could highlight further aspects of the reported results. CONCLUSIONS The findings are further confirming that the concepts of depression and somatoform disorders should not be merged indiscriminately together, even though they often occur together. We conclude that in depression and somatoform syndrome different biological mechanisms seem to be involved.

Mechanisms of sperm deficiency in male accessory gland infection.

Summary. The presence of 2 million or more peroxidase‐positive white blood cells per ml of semen, or the diagnosis of male accessory gland infection, is associated with important biochemical and biological changes in semen plasma and in the spermatozoa, reducing their fertilizing potential in vitro and in vivo (e.g., during intra‐uterine insemination). In addition to the effects of reactive oxygen species, and its influence on the essential fatty acid composition of the sperm membrane, potentially unfavourable effects can occur through the intermediate of increased concentrations of certain cytokines, and decreased activity of enzymes such as alpha‐glucosidase.

Oral DHA supplementation in ΔF508 homozygous cystic fibrosis patients

AIM The aim of this study was to evaluate whether the previously observed changes in the fatty acid profile, as a result of DHA supplementation, could be maintained during longer study trials and to observe its effect on the clinical outcome of cystic fibrosis (CF) patients. METHOD A year-long double-blind placebo-controlled study was performed in DeltaF508 homozygous CF patients above the age of 6. Clinical data, including pulmonary function and number of infections, were collected. Blood for the determination of the fatty acid (FA) composition of serum phospholipid, vitamin E, liver enzymes, immunoglobulins, erythrocyte sedimentation rate and coagulation was drawn at the beginning and then every 6 months after the start of the study. RESULTS Seventeen patients were included; one dropped out. The treatment group was supplemented with an algal DHA-rich oil and the control group with sunflower seed oil. There was no difference between the control and treatment groups for W/H%, caloric intake, FEV1% and FVC% at the start of the study and after 1 year of supplements. The phospholipid FA composition did not change in the control group. The treatment group had a significant increase in DHA and eicosapentaenoic acid (EPA) concentration. A concomitant decrease of dihomo-gammalinolenic acid, arachidonic acid, 22:5 n-6 and Mead acid was observed. The laboratory results showed no changes in vitamin E level, liver enzymes, albumin, erythrocyte sedimentation rate and IgG concentration in either the placebo or the intervention group. CONCLUSION Although DHA-rich oil shifted the serum phospholipid FAs to a less pro-inflammatory profile, no conclusive clinical improvement could be observed so far.

Serum fatty acid profiles in cystic fibrosis patients and their parents

Fatty acid compositions of the major serum lipid classes from 43 cystic fibrosis (CF) homozygotes (CF patients), 36 obligate heterozygotes (parents of CF patients) and 34 controls were determined by capillary gas chromatography. Fatty acid compositions of the homozygote CF patients were skewed in the direction of relative essential fatty acid deficiency in comparison with the controls. Less pronounced, but similar deviations from normal, were observed in the heterozygotes. Homozygotes with normal fatty acid compositions and heterozygotes with considerably disturbed fatty acid profiles were found.

Increase of Long Chain Omega-3 Fatty Acids in the Major Serum Lipid Classes of Patients with Cystic Fibrosis

We studied the effects of supplementing patients with cystic fibrosis for 1 month with 3 g/day of a dietary supplement, containing 911 mg omega 3 fatty acids, on the fatty acid composition of serum cholesterol esters, free fatty acids, phospholipids and triglycerides. At the end of the supplementation period, the content of total omega 3 fatty acids was increased significantly in all lipid classes. The effect on individual omega 3 fatty acids depended on the fatty acid and lipid class studied, increased with the dose fed and decreased with the weight of the patient. One month after the end of the supplementation period, fatty acid levels had returned to pretreatment values. These results demonstrate that enrichment of serum lipid classes with omega 3 fatty acids is feasible in CF patients by dietary supplementation.