Diagnosis of myalgic encephalomyelitis : where are we now?

Introduction: The World Health Organization has classified myalgic encephalomyelitis (ME) as a neurological disease since 1969 considering chronic fatigue syndrome (CFS) as a synonym used interchangeably for ME since 1969. ME and CFS are considered to be neuro-immune disorders, characterized by specific symptom profiles and a neuro-immune pathophysiology. However, there is controversy as to which criteria should be used to classify patients with “chronic fatigue syndrome.”

Areas covered: The Centers for Disease Control and Prevention (CDC) criteria consider chronic fatigue (CF) to be distinctive for CFS, whereas the International Consensus Criteria (ICC) stresses the presence of post-exertion malaise (PEM) as the hallmark feature of ME. These case definitions have not been subjected to rigorous external validation methods, for example, pattern recognition analyses, instead being based on clinical insights and consensus.

Expert opinion: Pattern recognition methods showed the existence of three qualitatively different categories: (a) CF, where CF evident, but not satisfying full CDC syndrome criteria. (b) CFS, satisfying CDC criteria but without PEM. (c) ME, where PEM is evident in CFS. Future research on this “chronic fatigue spectrum” should, therefore, use the abovementioned validated categories and novel tailored algorithms to classify patients into ME, CFS, or CF.

In depression, bacterial translocation may drive inflammatory responses, oxidative and nitrosative stress (O&NS) and autoimmune responses directed against O&NS- damaged neoepitopes

Objective: Depression is accompanied by activation of immuno-inflammatory and oxidative and nitrosative stress (IO&NS) pathways, and increased IgM/IgA responses to lipopolysaccharide (LPS) of gram-negative commensal bacteria. The latter suggests that bacterial translocation has caused IgM/IgA responses directed against LPS. Bacterial translocation may drive IO&NS responses.

Method: To examine the associations between IgM/IgA responses to LPS and IO&NS measurements, including plasma/serum interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin, lysozyme, oxidized LDL (oxLDL) antibodies, peroxides, and IgM (auto)immune responses against malondialdehyde (MDA), azelaic acid, phophatidyl inositol (Pi), NO-tryptophan and NO-tyrosine in depressed patients and controls.

Results: We found significant positive associations between IgM/IgA responses to LPS and oxLDL antibodies, IgM responses against MDA, azelaic acid, Pi, NO-tryptophan, and NO-tyrosine. The IgA responses to LPS were correlated with lysozyme. There were no significant positive correlations between the IgM/IgA responses to LPS and IL-1 and neopterin.

Conclusion: The findings show that in depression there is an association between increased bacterial translocation and lysozyme production, an antibacterial compound, O&NS processes, and autoimmune responses directed against O&NS generated neoantigenic determinants. It is suggested that bacterial translocation may drive IO&NS pathways in depression and thus play a role in its pathophysiology.

Aspirin : a review of its neurobiological properties and therapeutic potential for mental illness

There is compelling evidence to support an aetiological role for inflammation, oxidative and nitrosative stress (O&NS), and mitochondrial dysfunction in the pathophysiology of major neuropsychiatric disorders, including depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). These may represent new pathways for therapy. Aspirin is a non-steroidal anti-inflammatory drug that is an irreversible inhibitor of both cyclooxygenase (COX)-1 and COX-2, It stimulates endogenous production of anti-inflammatory regulatory 'braking signals', including lipoxins, which dampen the inflammatory response and reduce levels of inflammatory biomarkers, including C-reactive protein, tumor necrosis factor- and interleukin (IL)--6 , but not negative immunoregulatory cytokines, such as IL-4 and IL-10. Aspirin can reduce oxidative stress and protect against oxidative damage. Early evidence suggests there are beneficial effects of aspirin in preclinical and clinical studies in mood disorders and schizophrenia, and epidemiological data suggests that high-dose aspirin is associated with a reduced risk of AD. Aspirin, one of the oldest agents in medicine, is a potential new therapy for a range of neuropsychiatric disorders, and may provide proof-of-principle support for the role of inflammation and O&NS in the pathophysiology of this diverse group of disorders.

Explaining the effects of a 1-year intervention promoting a low fat diet in adolescent girls : a mediation analysis

Background : Although it is important to investigate how interventions work, no formal mediation analyses have been conducted to explain behavioral outcomes in school-based fat intake interventions in adolescents. The aim of the present study was to examine mediation effects of changes in psychosocial determinants of dietary fat intake (attitude, social support, self-efficacy, perceived benefits and barriers) on changes in fat intake in adolescent girls.

Methods : Data from a 1-year prospective intervention study were used. A random sample of 804 adolescent girls was included in the study. Girls in the intervention group (n = 415) were exposed to a multi-component school-based intervention program, combining environmental changes with a computer tailored fat intake intervention and parental support. Fat intake and psychosocial determinants of fat intake were measured with validated self-administered questionnaires. To assess mediating effects, a product-of-coefficient test, appropriate for cluster randomized controlled trials, was used.

Results : None of the examined psychosocial factors showed a reliable mediating effect on changes in fat intake. The single-mediator model revealed a statistically significant suppression effect of perceived barriers on changes in fat intake (p = 0.011). In the multiple-mediator model, this effect was no longer significant, which was most likely due to changes in perceived barriers being moderately related to changes in self-efficacy (-0.30) and attitude (-0.25). The overall mediated-suppressed effect of the examined psychosocial factors was virtually zero (total mediated effect = 0.001; SE = 7.22; p = 0.992).

Conclusion : Given the lack of intervention effects on attitudes, social support, self-efficacy and perceived benefits and barriers, it is suggested that future interventions should focus on the identification of effective strategies for changing these theoretical mediators in the desired direction. Alternatively, it could be argued that these constructs need not be targeted in interventions aimed at adolescents, as they may not be responsible for the intervention effects on fat intake. To draw any conclusions regarding mediators of fat-intake change in adolescent' girls and regarding optimal future intervention strategies, more systematic research on the mediating properties of psychosocial variables is needed.

Explaining the effects of a 1-year intervention promoting physical activity in middle schools: a mediation analysis

Objective : The aim of the present study was to examine the mediation effects of changes in psychosocial determinants of physical activity (attitude, social support, self-efficacy, perceived benefits and barriers) on changes in physical activity.

Design : One-year intervention study with baseline and 1-year post measures of physical activity habits and psychosocial correlates.

Setting : Fifteen middle schools. Subjects : Boys and girls (n = 2840) aged 11–15 years completed the validated questionnaires during class hours.

Results : The product-of-coefficients test was used to asses the mediating effects. Self-efficacy for physical activity at school was found to be the only significant mediator of physical activity change. Specifically, self-efficacy for physical activity at school partly mediated the effect of the intervention on total and school-related physical activity change in the intervention group with parental support (P < 0.05). None of the other potential mediators, attitudes, social support, perceived benefits and perceived barriers, seemed to have had a positive effect. Even a suppressor effect was found for attitudes. Given that the effects of self-efficacy and attitudes were of opposite direction, the total mediated/suppressed effects of the intervention were not statistically significant.

Conclusions : Positive changes in total and school-related physical activity in adolescents could be partly explained by increases in self-efficacy for physical activity at school through a physical activity intervention in middle schools with parental support. However, the suppressor effect of attitudes decreased this effect. As this is one of the first true mediation analyses in this age group, further research is needed to replicate the importance of these mediators.