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Eicosapentaenoic acid-rich essential fatty acid supplementation in chronic fatigue syndrome associated with symptom remission and structural brain changes
International Journal of Clinical Practice
Abstract
Lateral ventricular enlargement has been reported in chronic fatigue syndrome, while cerebral neurospectroscopy has recently indicated that essential fatty acid treatment may be of value in this condition. An essential fatty acid supplement rich in eicosapentaenoic acid (EPA) was therefore given daily to a female patient with a 6-year history of unremitting symptoms of chronic fatigue syndrome. Cerebral magnetic resonance scanning was carried out at baseline and 16 weeks later. The EPA-rich essential fatty acid supplementation led to a marked clinical improvement in her symptoms of chronic fatigue syndrome, starting within 6-8 weeks. Accurate quantification of the lateral ventricular volumes in the baseline and 16-week follow-up registered images of high-resolution magnetic resonance imaging structural scans showed that the treatment was accompanied by a marked reduction in the lateral ventricular volume during this period, from 28,940-23,660 mm3.
... Three eligible studies regarding fatty acids were considered in relation to CFS symptoms. [36][37][38] In an analytical observational study a statistically significant reduction was shown in the CFS cohort for the omega three (n-3) to omega six (n-6) polyunsaturated fatty acid (PUFA) ratio (p= 0.0003) and eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio (p=0.02). 36 A statistically significant positive relationship was also observed between n-3 to n-6 PUFA ratio and serum zinc (p=0.009), an indicator of the inflammatory response. ...
... 36 An essential fatty acid (EFA) supplement rich in EPA was individually examined in a case study. 37 Depression scores dropped from 27 at baseline to 3 at 16 weeks and the lateral ventricular volume of the brain had decreased at 16 weeks for the CFS participant. 37 Yet, another experimental trial of an EFA supplement verse a placebo supplement of sunflower oil showed no statistically significant difference in the RBC membrane fatty acid profile and symptoms scores between the intervention and control group. ...
... 37 Depression scores dropped from 27 at baseline to 3 at 16 weeks and the lateral ventricular volume of the brain had decreased at 16 weeks for the CFS participant. 37 Yet, another experimental trial of an EFA supplement verse a placebo supplement of sunflower oil showed no statistically significant difference in the RBC membrane fatty acid profile and symptoms scores between the intervention and control group. 38 ...
Objective:
To review the evidence for the role of dietary modifications in alleviating chronic fatigue syndrome symptoms.
Methods:
A systematic literature review was guided by PRISMA and conducted using Scopus, CINAHL Plus, Web of Science and PsycINFO scientific databases (1994-2016) to identify relevant studies. Twenty-two studies met the inclusion criteria, the quality of each paper was assessed and data extracted into a standardised tabular format.
Results:
Positive outcomes were highlighted in some included studies for polyphenol intakes in animal studies, D-ribose supplementation in humans and aspects of symptom alleviation for one of three polynutrient supplement studies. Omega three fatty acid blood levels and supplementation with an omega three fatty acid supplement also displayed positive outcomes in relation to chronic fatigue syndrome symptom alleviation.
Conclusions:
Limited dietary modifications were found useful in alleviating chronic fatigue syndrome symptoms, with overall evidence narrow and inconsistent across studies. Implications for public health: Due to the individual and community impairment chronic fatigue syndrome causes the population, it is vital that awareness and further focused research on this topic is undertaken to clarify and consolidate recommendations and ensure accurate, useful distribution of information at a population level.
... Some studies have suggested that a dietary enriched regimen with ω-3 fatty acids could be of benefit for these patients [8], and another ones have shown that EPA-rich fatty acid supplementation in CFS patients has beneficial effects because of a possible abnormal membrane phospholipid metabolism in the brain [9,10]. Moreover, some recent studies have shown that patients with Post Viral Fatigue Syndrome (PVFS) (11) and CFS [12,13] appeared to have lower levels of essential fatty acids (EFAs) and elevated levels of saturated fatty acids in erythrocyte membranes as compared to controls. ...
... These fatty acids, that decrease the production of putative mediators of inflammation, may contribute to the amelioration of the functional states of those patients. A few studies have shown an improvement in their symptomatology with an EPA-rich essential fatty acid supplementation [9,10] and also point out the essential fatty acids antiviral action [11]. These studies have found differences in the fatty acid profile in the erythrocyte membranes of CFS patients compared with those of Control group [11,12] with an increase in saturated fatty acids like palmitic acid (C16:0) and stearic acid (C18:0) and a decrease in essential fatty acids like arachidonic acid (C20:4) and docosahexaenoic acid (C22:6). ...
Chronic Fatigue Syndrome is an illness of unknown aetiology that has been associated with abnormalities in essential fatty acid metabolism, however this still remains unclear. We have compared the fatty acid profile in plasma and red blood cells and their dietary intake between a group of 20 patients diagnosed with CFS (18 women and 2 men) and 20 aged- sex- diet- low activity- matched controls. Compared to the controls, CFS patients show a decrease in the proportion of linoleic acid (t: 2.137, p: 0.039) and an increase in that of stearic acid (t: 2.602, p: 0.013) in plasma, however such differences have not been observed in the fatty acid profile of red blood cells. In these cases, no direct relationship has been observed between the dietary intake and fatty acid profile. Therefore, these results do not give support that long-chain polyunsaturated fatty acids may contribute in the better course of the pathology.
... These authors reported that 3 PUFA levels in red cell membranes of patients were abnormal at baseline and had been corrected by supplementation in patients who reported significant clinical improvement compared to patients in the placebo group. Puri et al. [116] reported clinical improvement in symptoms in all patients trialed on a 3 supplementation over a 12 week period compared to control. This finding supported the results of a case study by the same group [116], which noted structural changes in the brain of a patient with ME/CFS detected by NMR spectroscopy following a course of EPA supplementation. ...
... Puri et al. [116] reported clinical improvement in symptoms in all patients trialed on a 3 supplementation over a 12 week period compared to control. This finding supported the results of a case study by the same group [116], which noted structural changes in the brain of a patient with ME/CFS detected by NMR spectroscopy following a course of EPA supplementation. Thus, lowered levels of 3 PUFAs relative to increased 6 PUFA levels could increase the inflammatory potential and thus activation of immune-inflammatory pathways in ME/CFS. ...
Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been classified as a disease of the central nervous system by the WHO since 1969. Many patients carrying this diagnosis do demonstrate an almost bewildering array of biological abnormalities particularly the presence of oxidative and nitrosative stress (O&NS) and a chronically activated innate immune system. The proposal made herein is that once generated chronically activated O&NS and immune-inflammatory pathways conspire to generate a multitude of self-sustaining and self-amplifying pathological processes which are associated with the onset of ME/CFS. Sources of continuous activation of O&NS and immune-inflammatory pathways in ME/CFS are chronic, intermittent and opportunistic infections, bacterial translocation, autoimmune responses, mitochondrial dysfunctions, activation of the Toll-Like Receptor Radical Cycle, and decreased antioxidant levels. Consequences of chronically activated O&NS and immune-inflammatory pathways in ME/CFS are brain disorders, including neuroinflammation and brain hypometabolism / hypoperfusion, toxic effects of nitric oxide and peroxynitrite, lipid peroxidation and oxidative damage to DNA, secondary autoimmune responses directed against disrupted lipid membrane components and proteins, mitochondrial dysfunctions with a disruption of energy metabolism (e.g. compromised ATP production) and dysfunctional intracellular signaling pathways. The interplay between all of these factors leads to self-amplifying feed forward loops causing a chronic state of activated O&NS, immune-inflammatory and autoimmune pathways which may sustain the disease.
... Group diVerences in ventricular asymmetry were not observed. In a related report, Puri et al. (2004) present the case of a female patient with a 6‐year history of unremitting symptoms of CFS in whom a 16‐week regimen of an essential fatty acid supplementation rich in eicosapentaenoic acid (EPA) resulted in a marked clinical improvement in her symptoms. Quantification of the lateral ventricular volumes in the baseline and 16‐week follow‐up registered images of high‐resolution MRI structural scans showed that the treatment was accompanied by a marked reduction in the lateral ventricular volume during this period, from 28,940 mm 3 to 23,660 mm 3 . ...
... Functional activation during a cognitive task was associated with both a subjective sense of increased eVort and a diVuse recruitment of cortical centers in patients with CFS versus a more focal pattern in HNC (de Lange et al., 2004). Finally, volumetric analysis has suggested an overall decrease in ventricular volume (Lange et al., 2001 ), which seems to have responded favorably to dietary supplementation with essential fatty acids in a single case report (Puri et al., 2004). ...
The chapter discusses changes in the function and structure of key brain areas. A discussion of potential mechanisms that explain these phenomena is also presented, along with suggestions for future investigations. The search for organic differences between patients with various functional somatic syndromes and the non-afflicted has led researchers to investigate the central nervous system (CNS) as the potential wellspring of pathology. Most neuroimaging studies conducted to date have demonstrated differences within the CNS, whether at baseline or in response to stimulation. The functional somatic syndromes make both research and clinical practice challenging endeavors that many of the symptoms are multidimensional and thus nonspecific. With regard to enhanced nociception, baseline perfusion studies in fibromyalgia syndrome (FMS) have suggested subcortical involvement (i.e., thalamus and elements of the basal ganglia), whereas functional studies using sensory stimulation have demonstrated differential activation of both sensory and cognitive centers in both FMS and irritable bowel syndrome (IBS).
... It has been reported that more than 20% of people suffered from chronic fatigue (Nozaki et al., 2009), which is involved in various diseases such as cancer, AIDS Parkinson's disease, and others (Tharakan, Dhanasekaran, & Manyam, 2005). Several studies showed that protein, peptides, and polysaccharide could alleviate fatigue (Ding et al., 2011;Kumar, Chouhan, Sanghi, & Teotia, 2013;Narkhede et al., 2016;Nozaki et al., 2009;Puri, Holmes, & Hamilton, 2004;Zhang et al., 2015). Among all kinds of brewing wines, CRW has the highest amount of protein. ...
Chinese rice wine (CRW) is widely known for keeping good health and commonly used in the traditional Chinese medicine prescription guiding drug. This study assesses the effects of CRW on antifatigue and antiaging activities in mice models. Mice were randomly divided into four groups performing with 0.25 ml of distilled water, 0.15, 0.25, and 0.4 ml of CRW for 15 consecutive days. The CRW could obviously increase the content of liver glycogen (LG) and decrease the levels of blood lactic acid (BLA)and blood urea nitrogen (BUN) to improve antifatigue ability. In antiaging assay, CRW significantly increased the activity of SOD in liver, the activities of GSH‐Px and CAT in brain cortex, body quality, thymus index, and spleen index, and decreased liver MDA levels, liver total cholesterol content, and AChE levels in hippocampus. The CRW has potent antifatigue ability and could minimize the occurrence of age‐associated disorders. 1. LG, BLA, and BUN levels after Chinese rice wine treatment 2. Effect of Chinese rice wine on SOD, MDA, TC, GSH‐Px, and CAT in aged mice 3. Biofunction of Chinese rice wine in mice.
... It has been suggested that this, in turn, might result from chronic viral infection [10] . Based on this Cho finding, a potential therapeutic approach to this difficult-to-treat disorder, involving long-chain polyunsaturated fatty acids, has been suggested [11,12] . A second example relates to dyslexia, which is another important neuropsychiatric disorder of unknown etiology, in which the first systematic proton neurospectroscopy study revealed decreased Cho in the left temporo-parietal lobe [13] . ...
AIM
To investigate the repeatability of proton magnetic resonance spectroscopy in the in vivo measurement of human cerebral levels of choline-containing compounds (Cho).
METHODS
Two consecutive scans were carried out in six healthy resting subjects at a magnetic field strength of 1.5 T. On each occasion, neurospectroscopy data were collected from 64 voxels using the same 2D chemical shift imaging (CSI) sequence. The data were analyzed in the same way, using the same software, to obtain the values for each voxel of the ratio of Cho to creatine. The Wilcoxon related-samples signed-rank test, coefficient of variation (CV), repeatability coefficient (RC), and intraclass correlation coefficient (ICC) were used to assess the repeatability.
RESULTS
The CV ranged from 2.75% to 33.99%, while the minimum RC was 5.68%. There was excellent reproducibility, as judged by significant ICC values, in 26 voxels. Just three voxels showed significant differences according to the Wilcoxon related-samples signed-rank test.
CONCLUSION
It is therefore concluded that when CSI multivoxel proton neurospectroscopy is used to measure cerebral choline-containing compounds at 1.5 T, the reproducibility is highly acceptable.
... Metabolic and cerebral perfusion changes have been found in the brain of patients with Rheumatoid Arthritis (RA), Systemic Sclerosis and Systemic Lupus Erythematosus (SLE) [11,12,[25][26][27][28][29][30][31] . In addition, previous studies performed in patients with Chronic Fatigue Syndrome (CFS) found an association between fatigue complaints and metabolic changes in the brain as well [32][33][34] . In CFS patients, the mean ratio of choline (Cho) to creatine (Cr) in the occipital cortex was significantly higher than in controls, indicating an abnormality of phospholipid metabolism in the brain in CFS [32][33] . ...
AIM
To evaluate brain involvement in quiescent Crohn’s disease (CD) patients with fatigue using quantitative magnetic resonance imaging (MRI).
METHODS
Multiple MRI techniques were used to assess cerebral changes in 20 quiescent CD patients with fatigue (defined with at least 6 points out of an 11-point numeric rating scale compared with 17 healthy age and gender matched controls without fatigue. Furthermore, mental status was assessed by cognitive functioning, based on the neuropsychological inventory including the different domains global cognitive functioning, memory and executive functioning and in addition mood and quality of life scores. Cognitive functioning and mood status were correlated with MRI findings in the both study groups.
RESULTS
Reduced glutamate + glutamine (Glx = Glu + Gln) concentrations (P = 0.02) and ratios to total creatine (P = 0.02) were found in CD patients compared with controls. Significant increased Cerebral Blood Flow (P = 0.05) was found in CD patients (53.08 ± 6.14 mL/100 g/min) compared with controls (47.60 ± 8.62 mL/100 g/min). CD patients encountered significantly more depressive symptoms (P < 0.001). Cognitive functioning scores related to memory (P = 0.007) and executive functioning (P = 0.02) were lower in CD patients and both scores showed correlation with depression and anxiety. No correlation was found subcortical volumes between CD patients and controls in the T1-weighted analysis. In addition, no correlation was found between mental status and MRI findings.
CONCLUSION
This work shows evidence for perfusion, neurochemical and mental differences in the brain of CD patients with fatigue compared with healthy controls.
... A study found that patients taking omega-3 supplements with a higher EPA:DHA ratio experienced fewer depressive symptoms (Martins, 2009). One study also reports the remission of depressive symptoms and decrease in lateral ventricular volume of a patient who suffers from chronic fatigue syndrome after taking high-EPA essential fatty acid supplement (Puri et al., 2004). VPA is commonly used in mood disorders, this may offer protection against intentional or unintentional overdose. ...
Present day hope that many people join in studying the various phytochemicals and their bioactivities of ferns and fern allies for human life. As a result, more people could enjoy a healthy and eco-friendly life with ferns and fern allies. Hence, in the present investigation, an attempt has been made to study the phytoconstituents of B. orientale. The compound such as Eicos-5-enoic acid was isolated by spectral analysis i.e., IR, MASS, C13 NMR and 1H NMR for structural elucidation. So, certain functional activities for human life and possibilities of industrial application of B. orientale were analyzed for scientific exploration with isolated phytochemicals.
... This is achieved by combining divers plant extracts with vitamins [140], minerals and amino acids, including the antioxidants astaxanthine (acting on items 1and 2) and ubiquinone Q10 (1 and 3) [141,142], seleno-methionine (5), zinc-picolinate (2), the natural anti-inflammatory pine bark extract containing anthocyanidins (2), l-acetyl-carnitine (3) [143][144][145], the phyto-adaptogen Lepidium meyenii (4) [146] or Rhodiola rosea (4 and 5) [147], and vitamins B6, B9 [148] and B12 (5). This nutriceutical has no side effects [149] and it is made complete by the intake of the long-chain poly-unsaturated omega 3 fatty acids docosahexaenoic (DHEA) acid and eicosapentaenoic acid (EPA) [150,151]. ...
It is the opinion of the authors that the disease called chronic fatigue syndrome (CFS), or fibromyalgia, or myalgic encephalomyelitis, is primarily due to a disorder of the immune system and should rather be called " systemic immune disorder ". This disorder probably results from external factors such as inadequate stress adaptation, or a (retro)-viral infection deregulating the function of the memory T-lymphocytes in persons who are predisposed because of genetic or epigenetic alterations. Chronic inflammation with overproduction of cytokines, reactive oxygen and nitrogen species causes mitochondrial dysfunction with metabolic disturbance resulting in muscular and cerebral signs and symptoms. The reference treatment consisting of cognitive behavioural therapy (CBT) and graded exercising (GET) considers CFS to be a somatoform disease, but was proven ineffective. Causal therapy should be directed toward restoring T-cell function and is now under assessment. Organ-directed treatment aims at improving stress tolerance, at reducing inflammation and oxidative stress, and at optimizing mitochondrial function by means of nutriceutical food supplementation. Symptomatic treatment uses antidepressants, sedatives and pain killers. Experimental treatments interfere with the immune system or attempt to activate brain metabolism, and need further assessment. Adverse effects of long-term medication must be avoided. In the opinion of the authors an acceptable therapeutic result can commonly be attained by combining meditation, such as mindfulness, adaptation of lifestyle and nutrition, with complementary food supplementation using nutriceuticals and plant extracts.
... The concept of swimming to exhaustion is an experimental model used to evaluate anti-fatigue [3]. Anti-oxidant compounds such as polyunsaturated fatty acids (PUFA), polyphenols, and carotenoids, are known to exhibit a protective activity against various chronic diseases that are caused by ROS [7,8,9]. ...
The edible berries of three plants indigenous to the Tibetan plateau, namely Nitraria tangurorum B . (NTB), Hippophae rhamnoides L. (HRL) and Berberis dasystachya M. (BDM), have been used for medicinal purposes for a long time. For these three berries that occur in the wild, it is important to understand the differences between the content and biological activity of their seed oils. Therefore, this study was designed in order to determine the total polyphenol content (TPC), carotenoid content (TCC), steroid content (TSC) and fatty acid composition of seed oils obtained from these three berries, using standard analytical methods. In addition, i n vivo anti-fatigue activity of three seed oils were investigated using forced swimming mice. Free radical scavenging activity and antioxidant capacity were estimated using different assays. The results indicated that seed oil of these three berries contained a variety of active compounds. BDM seed oil showed a higher TPC concentration of 281.61 ± 19.06 µg/g compared to the other berries; HRL seed oil showed a higher TSC concentration of 329.06 ± 16.53 µg/g compared to the other berries. The total content of polyunsaturated fatty acids in seed oils from the three berries was found to be 331.6, 342.91 and 305.39 µg/mL for NBT, HRL, and BDM, respectively. The antioxidant assay results indicated that the seed oil obtained from HRL was significantly more active in scavenging free radicals compared to the other seed oils. Therefore, the results indicate that such seed oil supplements could prevent lipid oxidation in forced swimming mice.
... It is not unlikely that variations in sphingosine-1-phosphate (S1P) receptor subtype activation will determine the level of TLR activation, as well as the level of NADPH oxidase induced ROS reviewed in [14]. In this context it is of note that omega-3 PUFAs are decreased in CFS [327] with treatment with the omega-3 PUFA, eicosapentaenoic acid, reducing CFS symptoms [328]. Other potential treatments targeting the TLR have been shown to modulate CFS, including increasing exercise tolerance [329]. ...
In this review we discuss that peripheral and central activation of the Toll-like receptor 2/4 (TLR2/4) Radical Cycle may underpin the pathophysiology of immune-related chronic fatigue secondary to other medical diseases and conditions. The TLR Radical Cycle plays a role in illnesses and conditions that are disproportionately commonly comorbid with secondary chronic fatigue, including a) neuroinflammatory disorders, e.g. Parkinson's disease, stroke, depression, psychological stressors, and b) systemic disorders, e.g. (auto)immune disorders, chronic obstructive pulmonary disease, ankylosing spondylitis, chronic kidney disease, inflammatory bowel disease, cardiovascular disease, incl. myocardial infarction, cancer and its treatments. Increased TLR signaling is driven by activated immune-inflammatory and oxidative and nitrosative stress pathways, pathogen derived molecular patterns, including lipopolysaccharides, and damage associated molecular patterns (DAMPs). Newly formed redox-derived DAMPs, secondary to oxidative processes, may further activate the TLR complex leading to an auto-amplifying TLR Radical feedback loop. Increased gut permeability with translocation of gram negative bacteria and LPS, which activates the TLR Radical Cycle, is another pathway that may play a role in most of the abovementioned diseases and the secondary fatigue accompanying them. It is concluded that secondary fatigue may be associated with activation of the TLR Radical Cycle pathway due to activated immune-inflammatory pathways, classical and redox-derived DAMPs and PAMPs plays a role in its pathophysiology. Such an activation of the TLR Radical Cycle pathway may also explain why the abovementioned conditions are primed for an increased expression of secondary chronic fatigue. Targeting the TLR Radical Cycle pathway may be an effective method to treat TLR-Radical Cycle-related diseases such as secondary chronic fatigue.
... This supplement has demonstrated the capacity to improve fatigue and disease activity in SLE, CFS and major and bipolar depression [7,398]. Omega-3 polyunsaturated fatty acids (PUFAs) and zinc are also very effective antioxidants and anti-inflammatory compounds and supplementation has produced clinical benefit in patients diagnosed with depression and chronic fatigue syndrome [7,399,400]. Omega-3 PUFAs also show a clinical efficacy in SLE and rheumatoid arthritis [398,401,402]. ...
Background:
The genesis of severe fatigue and disability in people following acute pathogen invasion involves the activation of Toll-like receptors followed by the upregulation of proinflammatory cytokines and the activation of microglia and astrocytes. Many patients suffering from neuroinflammatory and autoimmune diseases, such as multiple sclerosis, Parkinson's disease and systemic lupus erythematosus, also commonly suffer from severe disabling fatigue. Such patients also present with chronic peripheral immune activation and systemic inflammation in the guise of elevated proinflammtory cytokines, oxidative stress and activated Toll-like receptors. This is also true of many patients presenting with severe, apparently idiopathic, fatigue accompanied by profound levels of physical and cognitive disability often afforded the non-specific diagnosis of chronic fatigue syndrome.
Discussion:
Multiple lines of evidence demonstrate a positive association between the degree of peripheral immune activation, inflammation and oxidative stress, gray matter atrophy, glucose hypometabolism and cerebral hypoperfusion in illness, such as multiple sclerosis, Parkinson's disease and chronic fatigue syndrome. Most, if not all, of these abnormalities can be explained by a reduction in the numbers and function of astrocytes secondary to peripheral immune activation and inflammation. This is also true of the widespread mitochondrial dysfunction seen in otherwise normal tissue in neuroinflammatory, neurodegenerative and autoimmune diseases and in many patients with disabling, apparently idiopathic, fatigue. Given the strong association between peripheral immune activation and neuroinflammation with the genesis of fatigue the latter group of patients should be examined using FLAIR magnetic resonance imaging (MRI) and tested for the presence of peripheral immune activation.
Summary:
It is concluded that peripheral inflammation and immune activation, together with the subsequent activation of glial cells and mitochondrial damage, likely account for the severe levels of intractable fatigue and disability seen in many patients with neuroimmune and autoimmune diseases.This would also appear to be the case for many patients afforded a diagnosis of Chronic Fatigue Syndrome.
... 44 And in a separate case report, high-resolution, structural scans using magnetic resonance imaging (MRI) revealed that treatment was accompanied by improvements in brain structure-a reduction in lateral ventricular volume. 45 B Vitamins. Functional deficiencies of the vitamins pyridoxine, riboflavin, and thiamine in individuals with CFS/ME have been reported. ...
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a relatively common illness, yet despite considerable investigation, current treatments have modest benefits, and the prognosis remains poor. Because CFS/ME is a heterogeneous disorder with diverse etiological factors and pathological features, a patient-centered integrative framework based on modifiable physiological and environmental factors may offer hope for more effective management and better clinical outcomes. An individualized approach may also help target interventions for subgroups most likely to respond to specific treatments. This review summarizes a number of avenues for integrative management, including dietary modification, functional nutritional deficiencies, physical fitness, psychological and physical stress, environmental toxicity, gastrointestinal disturbances, immunological aberrations, inflammation, oxidative stress, and mitochondrial dysfunction. A personalized, integrative approach to CFS/ME deserves further consideration as a template for patient management and future research.
... The description of effects on depression although controversial [105][106][107][108], has led to the conclusion that omega-3's can affect not only cognitive functions, but also mood and emotional states and may act as a mood stabilizer. Omega-3's have beneficial effects in some neurological diseases [109,110] in addition to the chronic fatigue syndrome [111]. Both DHA and EPA appear to be necessary for these effects and this has been shown in depressive disorders [112]. ...
Several sources of information suggest that human beings evolved on a diet that had a ratio of omega-6 to omega-3 fatty acids (FA) of about 1/1; whereas today, Western diets have a ratio of 10/1 to 20-25/1, indicating that Western diets are deficient in omega-3 FA compared with the diet on which humans evolved and their genetic patterns were established. Omega-6 and omega-3 FA are not interconvertible in the human body and are important components of practically all cell membranes. Studies with nonhuman primates and human newborns indicate that docosahexaenoic acid (DHA) is essential for the normal functional development of the brain and retina, particularly in premature infants. DHA accounts for 40% of the membrane phospholipid FA in the brain. Both eicosapentaenoic acid (EPA) and DHA have an effect on membrane receptor function and even neurotransmitter generation and metabolism. There is growing evidence that EPA and DHA could play a role in hostility and violence in addition to the beneficial effects in substance abuse disorders and alcoholism. The balance of omega-6 and omega-3 FA is important for homeostasis and normal development throughout the life cycle.
... The earlier one, by Behan et al. [36], demonstrated significant benefit, while the second, by Peet and coworkers [37], was negative. Structural neuroimaging in a case report of treatment with high EPA-containing fatty acid supplementation has shown that clinical improvement in myalgic encephalomyelitis appears to be associated with marked reduction in the ventricle-to-brain ratio [38]. ...
... Another potential implication of this comparison is that the CFS-MDD/m status and genetic polymorphisms can jointly induce different activation and expression of several lipid related metabolisms, neuron physiology differentiation, and neurotransmitters. Our results can be supported by the known relationship between eicosanoid or fatty acid and CFS [22][23][24][25]. ...
Gene expression data and genotype variation data are now capable of providing genome-wide patterns across many different clinical conditions. However, the separate analysis of these data has limitations in elucidating the complex network of gene interactions underlying complex traits, such as common human diseases. More information about the identity of key driver genes of common diseases comes from integrating these two heterogeneous types of data. We developed a two-step procedure to characterize complex diseases by integrating genotype variation data and gene expression data. The first step elucidates the causal relationship among genetic variation, gene expression level, and disease. Based on the causal relationship determined at the first step, the second step identifies significant gene expression traits whose effects on disease status or whose responses to disease status are modified by the specific genotype variation. For the selected significant genes, a pathway enrichment analysis can be performed to identify the genetic mechanism of a complex disease. The proposed two-step procedure was shown to be an effective method for integrating three different levels of data, i.e., genotype variation, gene expression and disease status. By applying the proposed procedure to a chronic fatigue syndrome (CFS) dataset, we identified a list of potential causal genes for CFS, and found an evidence for difference in genetic mechanisms of the etiology between CFS without 'a major depressive disorder with melancholic features' (CFS) and CFS with 'a major depressive disorder with melancholic features' (CFS-MDD/m). Especially, the SNPs within NR3C1 gene were shown to differently influence the susceptibility of developing CFS and CFS-MDD/m through integrative action with gene expression levels.
... A detailed case report has been published elsewhere [9] in which 10 capsules eye q t (Equazen Ltd., London, UK) were taken daily, as five capsules twice per day. (This provided the following daily essential fatty acid doses: 930 mg eicosapentaenoic acid; 290 mg docosahexaenoic acid; and 100 mg gamma-linolenic acid. ...
There is evidence that there is an association between chronic fatigue syndrome, a condition of unknown aetiology, and essential fatty acids. This evidence is based on the actions of essential fatty acids, the results of proton neurospectroscopy studies, and essential fatty acid trial data. A series of patients with chronic fatigue syndrome were treated solely with a high-eicosapentaenoic acid-containing essential fatty acid supplement. All showed improvement in their symptomatology within eight to 12 weeks. These results, which are consistent with a recent detailed report of cerebral and clinical changes associated with a high intake of eicosapentaenoic acid, suggest that this n-3 highly unsaturated fatty acid may offer the hope of effective treatment for at least some patients with chronic fatigue syndrome.
... The female patient, who was in her midtwenties , had a six-year history of unremitting symptoms of chronic fatigue syndrome. Following 16 weeks' treatment with the fatty acids there was a marked clinical improvement (Puri et al., 2004). Application of the techniques described in the previous section showed that during this period of fatty acid intervention there was a reduction in the lateral ventricular volume, from 28,940 mm 3 to 23,660 mm 3 . ...
Serial high-resolution structural magnetic resonance imaging scans of the brain can now be precisely aligned, with six degrees of freedom (three mutually orthogonal translational and three rotational degrees of freedom around three mutually orthogonal axes), using a rigid-body subvoxel registration technique. This is driven by the in-plane point spread function for images acquired in the Fourier domain with data obtained over a bounded region of k-space, namely the sinc interpolation function, where sinc z = (sin z)/z, with z being any complex number (including zero). Computational subtraction of the three-dimensional Cartesian spatial representation matrices of serially acquired scan data allows for the determination of structural cerebral changes with great precision, since voxel signals from unchanged structures are almost completely cancelled. Thus changes readily show up against a background of noise. Furthermore, lateral ventricular changes can now be accurately quantified using a semi-automated method involving contour production, threshold computation, binary image creation and ventricular extraction. These techniques have been applied to the investigation of the effects on cerebral structure of intervention with fatty acids, particularly the long-chain polyunsaturated n-3 fatty acid eicosapentaenoic acid (EPA), in disorders such as schizophrenia, treatment-resistant depression, chronic fatigue syndrome (myalgic encephalomyelitis or ME), and Huntington's disease.
Feelings of fatigue not only occur in chronic and acute disease states, but also during prolonged strenuous exercise as a symptom of exhaustion. The underlying mechanisms of fatigue in diseases seem to rely on neuroinflammatory pathways. These pathways are interesting to understand exerciseinduced fatigue regarding immune system to brain signaling and effects of cerebral cytokines. Activation of the immune system incurs a high-energy cost, also in the brain. In consequence immune cells have high energetic priority over other tissues, such as neurons. A neuronal inactivation and corresponding changes in neurotransmission can also be induced by end products of ATP metabolism and elicit feelings of fatigue in diseases and after intensive and prolonged exercise bouts. Since there are no existing models of exercise-induced fatigue that specifically address interactions between neuroimmunologic mechanisms and neuroenergetics, this article is combining scientific evidence across a broad range of disciplines in order to propose an inflammation- and energy-based model for exercise-induced fatigue.
Feelings of fatigue not only occur in chronic and acute dis-ease states, but also during prolonged strenuous exercise as a symptom of exhaustion. The underlying mechanisms of fatigue in diseases seem to rely on neuroinflammatory pathways. These pathways are interesting to understand exercise-induced fatigue regarding immune system to brain signaling and effects of cerebral cytokines. Activation of the immune system incurs a high-energy cost, also in the brain. In conse-quence immune cells have high energetic priority over other tissues, such as neurons. A neuronal inactivation and corre-sponding changes in neurotransmission can also be induced by end products of ATP metabolism and elicit feelings of fatigue in diseases and after intensive and prolonged exercise bouts. Since there are no existing models of exercise-induced fatigue that specifically address interactions between neu-roimmunologic mechanisms and neuroenergetics, this article is combining scientific evidence across a broad range of disci-plines in order to propose an inflammation- and energy-based model for exercise-induced fatigue.
Fatigue is an important clinical problem in patients with IBD, affecting nearly 50% of patients in clinical remission and > 80% of those with active disease. The resulting decrease in quality of life and impaired work productivity and functioning contribute markedly to the societal costs of fatigue. However, despite the burden and effects of fatigue, little is known about its aetiology and pathophysiology, which impairs our ability to effectively treat this symptom. Here, we review the theories behind the development of fatigue in IBD and the role of contributing factors, including nutritional deficiency, inflammation and altered metabolism. We also explore the potential role of the gut microbiome in mediating fatigue and other psychological symptoms through the gut–brain axis. We discuss the efficacy of nutrient repletion and various psychological and pharmacological interventions on relieving fatigue in patients with IBD and expand the discussion to non-IBD-related fatigue when evidence exists. Finally, we present a therapeutic strategy for the management of fatigue in IBD and call for further mechanistic and clinical research into this poorly studied symptom.
It has been speculated that the adaptation of Tibetan residents for high altitude and oxygen-deficient environment might be associated with their long-term consumption of yak milk. In order to verify the hypothesis, the anti-fatigue effect of yak milk powder (YMP) was investigated after oral treatment for 5 weeks in mouse model using forced swimming test. The results showed that the forced swimming time of YMP groups was increased by 46-112% in a dose-dependent manner. The content of hepatic glycogen was increased by 26-40% and the level of serum triglyceride was decreased by 30%; the exercise-induced accumulations of blood lactic acid and serum urea nitrogen were lower in YMP groups than in the control group. In addition, compared with the control group, YMP groups had lower glutamic oxalacetic transaminase and lactic dehydrogenase levels. It could be concluded that yak milk could increase an endurance capacity and alleviate fatigue.
The sea eel, Conger conger is a common and widespread species all around the Adriatic, Mediterranean, North Atlantic and northern Africa's coasts. Biochemical analyses of fatty acid compositions in this species show a great content of polyunsaturated fatty acids (PUFAs), especially EPA and DHA, which makes its fatty acid profile more favourable. Since in recent years, n-3 PUFA have been acclaimed for greater potency in the amelioration of heart, cardiovascular disorders and immune functions, an acute experimental model of immune system stress induced by exposure of rats to a hypothermic shock (4 h at 4°C) was used to determine the capacity of Conger conger extracts to restore the function of peripheral T lymphocytes. After hypothermic shock, blood samples were collected and 100 µl of whole blood were exposed to 20 µg/ml and 100 µg/ml of Conger conger extracts and cultured in RPMI complete medium during 4, 16 and 24 h, respectively. After incubation, blood was stained with specific anti-rat CD4, CD8, CD25 and CD28 monoclonal antibodies at each time point. The percentages of antigen expression indicate significant differences in the group treated with both 20 µg/ml and 100 µg/ml mainly in CD4 and CD28 expressions, as compared to controls, suggesting an up-regulation of the immune function.
This paper describes how the effects of PUFA supplementation can be indexed by neuroimaging. The role of structural magnetic resonance imaging studies are detailed in respect of testing a brain (lipid) hypothesis and in respect of using a gold-standard image registration technique. The role of magnetic resonance spectroscopy of the brain is considered with respect to a recent advance in the analysis of 31-phosphorus neurospectroscopy data that enables motion-restricted membrane phospholipids to be quantified.
• Myalgic encephalomyelitis is a debilitating neurological disease affecting 3% of the adult population of Western countries.
• In children myalgic encephalomyelitis may be associated with a deficiency of ω-3 and ω-6 long-chain polyunsaturated fatty
acids due to viral infection or organophosphate exposure, and exacerbated by modern Western diets.
KeywordsMyalgic encephalomyelitis-Chronic fatigue syndrome-Proton neurospectroscopy-Diet
Centers for Disease Control criteria for chronic fatigue syndrome (CFS) specifically recognize that patients can have both CFS and depression. The clinician's challenge is to judge for each individual patient whether the complaint of fatigue is primarily depression, physical illness, such as CFS, or a combination of both.This review differentiates CFS and fibromyalgia, discussed as “chronic fatigue syndrome and related immune deficiency syndromes” (CFIDS), from depression in terms of physical signs, symptoms, biological parameters, brain imaging, immunology, and treatment. The review focuses on practical applications of research findings with a further focus on future ability to show clear biologic separation and specific treatment.When depressive symptoms exist with those of CFS, accurate differentiation can usually be accomplished by focusing on diagnostic criteria. Presence of multiple physical signs and symptoms of CFIDS may be of great value. In terms of laboratory testing, a single helpful t...
It has been reported that Omega-3 fatty acids may play a role in nervous system activity and that they improve cognitive development and reference memory-related learning, increase neuroplasticity of nerve membranes, contribute to synaptogenesis and are involved in synaptic transmission. The aim of this study was to examine the effects of Omega-3 supplementation on some cognitive and physiological parameters in healthy subjects.
Subjects were tested at the beginning of the experiment and after 35 days. In this period they were supplemented with Omega-3 polyunsaturated fatty acids. A group was supplemented with olive oil (placebo). Tests involving different types of attention were used, i.e. Alert, Go/No-Go, Choice and Sustained Attention. For each test, the reaction time, the event-related potentials by electroencephalogram (EEG) and the electromyography (EMG) of the forefinger flexor muscle were recorded. The Profile of Mood States test (POMS) was also administered.
Blood analyses showed that after Omega-3 supplementation the arachidonic acid/eicosapentaenoic acid ratio (AA/EPA) was strongly reduced. The mood profile was improved after Omega-3 with increased vigour and reduced anger, anxiety and depression states. This was associated with an effect on reactivity with a reduction of reaction time in the Go/No-Go and Sustained Attention tests. The latency of EMG activation was concomitantly reduced in the same tests plus Choice. An EEG frequency shift towards the theta and alpha band were recorded in all the tests after Omega-3.
Omega-3 supplementation is associated with an improvement of attentional and physiological functions, particularly those involving complex cortical processing. These findings are discussed in terms of the influence of Omega-3 on the central nervous system.
There is now evidence that major depression is accompanied by decreased levels of omega3 poly-unsaturated fatty acids (PUFA), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). There is a strong comorbidity between major depression and chronic fatigue syndrome (CFS). The present study has been carried out in order to examine PUFA levels in CFS. In twenty-two CFS patients and 12 normal controls we measured serum PUFA levels using gas chromatography and mass spectrometry. We found that CFS was accompanied by increased levels of omega6 PUFAs, i.e. linoleic acid and arachidonic acid (AA), and mono-unsaturated fatty acids (MUFAs), i.e. oleic acid. The EPA/AA and total omega3/omega6 ratios were significantly lower in CFS patients than in normal controls. The omega3/omega6 ratio was significantly and negatively correlated to the severity of illness and some items of the FibroFatigue scale, i.e. aches and pain, fatigue and failing memory. The severity of illness was significantly and positively correlated to linoleic and arachidonic acid, oleic acid, omega9 fatty acids and one of the saturated fatty acids, i.e. palmitic acid. In CFS subjects, we found significant positive correlations between the omega3/omega6 ratio and lowered serum zinc levels and the lowered mitogen-stimulated CD69 expression on CD3+, CD3+ CD4+, and CD3+ CD8+ T cells, which indicate defects in early T cell activation. The results of this study show that a decreased availability of omega3 PUFAs plays a role in the pathophysiology of CFS and is related to the immune pathophysiology of CFS. The results suggest that patients with CFS should respond favourably to treatment with--amongst other things--omega3 PUFAs, such as EPA and DHA.
The aim of this study was to assess the effect of Brewers' yeast extract (BYE) on daily activity in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. BYE was orally administered to mice in a dose of 2 g per kg per day for 2 weeks before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving BYE as compared with that in untreated mice. Weekly variation of body weight (BW) and survival in both groups was monitored during the observation period. Spleen weight (SW), SW/BW ratio, percent splenic follicular area and expression levels of interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity during 2 weeks after the second BA injection was significantly higher in the treated group than in the control. There was no difference in BW between both groups through the experimental course. Two mice in the control died 2 and 7 days after the second injection, whereas no mice in the treated group died. Significantly decreased SW and SW/BW ratio were observed in the treated mice together with elevation of splenic follicular area. There were suppressed IFN-gamma and IL-10 mRNA levels in spleens from the treated mice. Our results suggest that BYE might have a protective effect on the marked reduction in activity following repeated BA injection via normalization of host immune responses.
Ethyl-eicosapentanoic acid (ethyl-EPA) may be beneficial in the treatment of bipolar disorder (BD) and may have a neurotrophic/neuroprotective role in patients with neuropsychiatric disorders. To investigate this we examined whether ethyl-EPA treatment of BD patients is associated with increased brain levels of N-acetylaspartate (NAA), a putative marker of neuronal integrity. Fourteen female BD outpatients with moderate depressive symptoms were administered 2 g of ethyl-EPA per day or placebo for 12 weeks in a randomized, double-blind fashion. Quantitative, proton magnetic resonance spectroscopy imaging data were obtained prior to randomization and after 12 weeks of treatment from a single 12 ml volume of interest centred above the body of the corpus callosum. A significant rise in NAA levels was observed in the ethyl-EPA treatment group compared with the placebo group (p = 0.027). These results provide the first evidence for a probable neurotrophic role of ethyl-EPA treatment in BD underlining the need for more detailed investigation of its mechanism of action and therapeutic potential.
Chronic fatigue syndrome (CFS) is thought to have a worldwide prevalence of 0.4-1% with approximately 240,000 patients in the UK. Diagnosis is based on clinical criteria and critically depends on exclusion of other physical and psychiatric diseases. Studies of pathogenesis have revealed immune system abnormalities and chronic immune activation, dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, brain abnormalities, evidence of emotional stress (comprising host aspects) and evidence of exogenous insults, for example, various microbial infections (Epstein-Barr virus, enteroviruses, parvovirus B19, Coxiella burnetii and Chlamydia pneumoniae), vaccinations and exposure to organophosphate chemicals and other toxins (comprising environmental aspects). Emotional stress appears to be very important as it reduces the ability of the immune system to clear infections, it's presence has been shown to determine whether or not an individual develops symptoms upon virus infection, and it leads to activation of the HPA axis. But, emotional stress is distinct from depression, the presence of which precludes a diagnosis of CFS. There is no specific treatment for CFS other than the much underutilised approach of specific treatment of virus infections. Current priorities are to understand the molecular pathogenesis of disease in terms of human and virus gene expression, to develop a diagnostic test based on protein biomarkers, and to develop specific curative treatments.
Chronic fatigue syndrome (CFS) is characterized by profound, debilitating fatigue and a combination of several other symptoms resulting in substantial reduction in occupational, personal, social, and educational status. CFS is often misdiagnosed as depression. The objective of this study was to evaluate and discuss different etiologies, approaches, and management strategies of CFS and to present ways to differentiate it from the fatigue symptom of depression.
A MEDLINE search was conducted to identify existing information about CFS and depression using the headings chronic fatigue syndrome AND depression. The alternative terms major depressive disorder and mood disorder were also searched in conjunction with the term chronic fatigue syndrome. Additionally, MEDLINE was searched using the term chronic fatigue. All searches were limited to articles published within the last 10 years, in English. A total of 302 articles were identified by these searches. Also, the term chronic fatigue syndrome was searched by itself. This search was limited to articles published within the last 5 years, in English, and resulted in an additional 460 articles. Additional publications were identified by manually searching the reference lists of the articles from both searches.
CFS definitions, etiologies, differential diagnoses (especially depression) and management strategies were extracted, reviewed, and summarized to meet the objectives of this article.
CFS is underdiagnosed in more than 80% of the people who have it; at the same time, it is often misdiagnosed as depression. Genetic, immunologic, infectious, metabolic, and neurologic etiologies were suggested to explain CFS. A biopsychosocial model was suggested for evaluating, managing, and differentiating CFS from depression.
Evaluating and managing chronic fatigue is a challenging situation for physicians, as it is a challenging and difficult condition for patients. A biopsychosocial approach in the evaluation and management is recommended. More studies about CFS manifestations, evaluation, and management are needed.
• The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, system atic, and integrated approach to the evaluation, classi fication, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations.
The construction of a depression rating scale designed to be particularly sensitive to treatment effects is described. Ratings of 54 English and 52 Swedish patients on a 65 item comprehensive psychopathology scale were used to identify the 17 most commonly occurring symptoms in primary depressive illness in the combined sample. Ratings on these 17 items for 64 patients participating in studies of four different antidepressant drugs were used to create a depression scale consisting of the 10 items which showed the largest changes with treatment and the highest correlation to overall change. The inner-rater reliability of the new depression scale was high. Scores on the scale correlated significantly with scores on a standard rating scale for depression, the Hamilton Rating Scale (HRS), indicating its validity as a general severity estimate. Its capacity to differentiate between responders and non-responders to antidepressant treatment was better than the HRS, indicating greater sensitivity to change. The practical and ethical implications in terms of smaller sample sizes in clinical trials are discussed.
Previous qualitative volumetric assessment of lateral ventricular enlargement in chronic fatigue syndrome (CFS) has provided evidence for subtle structural changes in the brains of some individuals with CFS. The aim of this pilot study was to determine whether a more sensitive quantitative assessment of the lateral ventricular system would support the previous qualitative findings. In this study, we compared the total lateral ventricular volume, as well as the right and left hemisphere subcomponents in 28 participants with CFS and 15 controls. Ventricular volumes in the CFS group were larger than in control groups, a difference that approached statistical significance. Group differences in ventricular asymmetry were not observed. The results of this study provide further evidence of subtle pathophysiological changes in the brains of participants with CFS.
Objective: Methods for automatically registering and reslicing MR images using an interpolation function that matches the structure of the image data are described.
Materials and Methods: Phantom and human brain images were matched by rigid body rotations and translations in two and three dimensions using a least-squares optimization procedure. Subvoxel image shifts were produced with linear or sine interpolation.
Results: The use of sine interpolation ensured that the repositioned images were faithful to the original data and enabled quantitative intensity comparisons to be made. In humans, image segmentation was vital to avoid extraneous soft tissue changes producing systematic errors in registration.
Conclusion: The sinc-based interpolation technique enabled serially acquired MR images to be positionally matched to subvoxel accuracy so that small changes in the brain could be distinguished from effects due to misregistration.
Index Terms: Image registration-Brain-Phantom-Magnetic resonance imaging.
(C) Lippincott-Raven Publishers.
The construction of a depression rating scale designed to be particularly sensitive to treatment effects is described. Ratings of 54 English and 52 Swedish patients on a 65 item comprehensive psychopathology scale were used to identify the 17 most commonly occurring symptoms in primary depressive illness in the combined sample.
Ratings on these 17 items for 64 patients participating in studies of four different antidepressant drugs were used to create a depression scale consisting of the 10 items which showed the largest changes with treatment and the highest correlation to overall change.
The inter-rater reliability of the new depression scale was high. Scores on the scale correlated significantly with scores on a standard rating scale for depression, the Hamilton Rating Scale (HRS), indicating its validity as a general severity estimate. Its capacity to differentiate between responders and non-responders to antidepressant treatment was better than the HRS, indicating greater sensitivity to change. The practical and ethical implications in terms of smaller sample sizes in clinical trials are discussed.
Sixty-three adults with the diagnosis of the postviral fatigue syndrome were enrolled in a double-blind, placebo-controlled study of essential fatty acid therapy. The patients had been ill for from one to three years after an apparently viral infection, suffering from severe fatigue, myalgia and a variety of psychiatric symptoms. The preparation given contained linoleic, gamma-linolenic, eicosapentaenoic and docosahexaenoic acids and either it, or the placebo, was given as 8 x 500 mg capsules per day over a 3-month period. The trial was parallel in design and patients were evaluated at entry, one month and three months. In consultation with the patient the doctors assessed overall condition, fatigue, myalgia, dizziness, poor concentration and depression on a 3-point scale. The essential fatty acid composition of their red cell membrane phospholipids was analysed at the first and last visits. At 1 month, 74% of patients on active treatment and 23% of those on placebo assessed themselves as improved over the baseline, with the improvement being much greater in the former. At 3 months the corresponding figures were 85% and 17% (p less than 0.0001) since the placebo group had reverted towards the baseline state while those in the active group showed continued improvement. The essential fatty acid levels were abnormal at the baseline and corrected by active treatment. There were no adverse events. We conclude that essential fatty acids provide a rational, safe and effective treatment for patients with the post-viral fatigue syndrome.
Blood samples were taken from schizophrenics and control patients in three different centers. The phospholipids were extracted from plasma and their fatty acid composition analyzed. Similar and consistent differences between schizophrenics and controls were observed at all three centers. The n-6 essential fatty acid levels were significantly reduced, whereas n-3 essential fatty acids were elevated.
The phospholipid structure of neuronal membranes is essential for normal functioning of the nervous system. Evidence is accumulating that phospholipid metabolism in both brain and red blood cells may be disturbed in schizophrenia. In particular, in patients with negative symptoms, levels of arachidonic acid and docosahexanoic acid in red blood cell membrane phospholipids are severely abnormal. The membrane hypothesis of schizophrenia may represent a new and fruitful paradigm for future research.
The use of subvoxel registration of serial magnetic resonance images to detect small changes to the brain and its surrounding tissues and fluids is described and the application of this technique to physiological and clinical problems is illustrated. Isotropic T1 weighted volume images were obtained in normal subjects and patients on two or more occasions (including pre- and post-contrast enhancement). The images were segmented and three-dimensional rigid body translation and rotation were used with sinc interpolation to match precisely the images using a chi 2 test and a minimization routine. Accurately registered images produced in this way, as well as subtraction images derived from them, were used to detect change to the brain. A system of image interpretation based on recognition of changes in tissue or fluid signal intensity as well as site, shape and size is described. Changes in position are analysed using a simple model based on the concept of two plateaux of higher and lower signal intensities and a border zone between them. Small changes due to differences in orientation of the head, as well as inhalation of oxygen, carbon dioxide and carbogen were observed in normal subjects. Changes were also observed in patients with head trauma, an astrocytoma and multiple sclerosis. Differences due to contrast enhancement and treatment were seen. In addition, children showed changes due to growth and development.
The neurodevelopmental hypothesis of schizophrenia is becoming an important feature of research in the field. However, its major drawback is that it lacks any biochemical basis which might draw the diverse observations together. It is suggested that the membrane phospholipid hypothesis can provide such a biochemical basis and that the neurodevelopmental phospholipid concept offers a powerful paradigm to guide future research.
Two semi-automated methods for quantification of ventricular volume change from baseline and follow-up magnetic resonance imaging scans have been developed. Technique 1 employs direct segmentation of the ventricles from both the scans using thresholding and contour extraction. Technique 2 operates on difference images produced by voxel based intensity subtraction of the baseline from the registered follow-up images. Here, all voxels with intensities above a noise threshold and in a restricted area are monitored to compute volumetric changes. In phantom measurements the first technique was accurate to 0.0046%, the second to 0.167% of the phantom volume. Results from normal volunteers was that the average ventricular volume changed by 1.52% and 1.54% for images acquired within 9 months using techniques 1 and 2, respectively. With schizophrenic patients mean change of 10.78% and 9.43% were found employing the first and second procedures, respectively. All measurements agreed with a radiologist's visual grading of the changes. Robust, objective, fast, easy-to-use, and fairly accurate procedures have been developed and validated to quantify volumetric changes.
Lateral ventricular enlargement is the most consistently replicated brain abnormality found in schizophrenia. This article reports a first episode, longitudinal study of ventricular volume using high-resolution serial magnetic resonance imaging (MRI) and recently developed techniques for image registration and quantitation. Baseline and follow-up (on average 8 months later) MRI scans were carried out on 24 patients and 12 controls. Accurate subvoxel registration was performed and subtraction images were produced to reveal areas of regional brain change. Whereas there were no differences between patients and controls with respect to the mean change in ventricular volume, the patients were much more variable in this respect and showed larger increases and decreases. The percentage increase in ventricular size was greater than one standard deviation of control values for 14 patients and the percentage decrease exceeded one standard deviation in eight patients. Although the finding of progressive ventricular enlargement in a proportion of patients supports other studies indicating an ongoing neuropathological process in the early stages of schizophrenia, the reduction of ventricular size in the remaining patients is more difficult to explain. It is suggested that this may reflect improvement in nutrition and hydration following treatment.
To test the hypothesis that chronic fatigue syndrome (CFS) is associated with altered cerebral metabolites in the frontal and occipital cortices.
Cerebral proton magnetic resonance spectroscopy (1H MRS) was carried out in eight CFS patients and eight age- and sex-matched healthy control subjects. Spectra were obtained from 20 x 20 x 20 mm3 voxels in the dominant motor and occipital cortices using a point-resolved spectroscopy pulse sequence.
The mean ratio of choline (Cho) to creatine (Cr) in the occipital cortex in CFS (0.97) was significantly higher than in the controls (0.76; P=0.008). No other metabolite ratios were significantly different between the two groups in either the frontal or occipital cortex. In addition, there was a loss of the normal spatial variation of Cho in CFS.
Our results suggest that there may be an abnormality of phospholipid metabolism in the brain in CFS.
Fatigue is a common symptom of neurological diseases that affect basal ganglia function. We used proton magnetic resonance spectroscopy ((1)H MRS) to study the metabolic functions of the basal ganglia in chronic fatigue syndrome (CFS) to test the hypothesis that fatigue in CFS may have a neurogenic component. (1)H MRS of left basal ganglia was carried out in eight non-psychiatric patients with CFS and their results were compared to age- and sex-matched healthy asymptomatic healthy controls. A highly significant increase in the spectra from choline-containing compounds was seen in the CFS patient group (p < 0.001). In the absence of regional structural or inflammatory pathology, increased choline resonance in CFS may be an indicator of higher cell membrane turnover due to gliosis or altered intramembrane signalling.
Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome
- Chaudhuri
Assessment of cerebral structure and function in neurodevelopmental disorders using structural magnetic resonance imaging, monomodal registration, and magnetic resonance spectroscopy
- B K Puri
Puri BK. Assessment of cerebral structure and function in neurodevelopmental disorders using structural magnetic resonance
imaging, monomodal registration, and magnetic resonance spectroscopy. Prostaglandins Leukot Essent Fatty Acids (in press).
Serial Neuroimaging in Schizophrenia Using Image Segmentation, Subvoxel Registration, and Quantitation
- B K Puri
Puri BK. Serial Neuroimaging in Schizophrenia Using Image
Segmentation, Subvoxel Registration, and Quantitation. Ph D
Thesis. London: University of London, 2001.