Fatigue Syndrome, Chronic

High Sensitivity C-Reactive Protein as a Potential Biomarker of Neuroinflammation in Major Psychiatric Disorders

Background: The bidirectional relationship between psychiatric disorders and immune dysregulation has been increasingly documented. Moreover, most major mental diseases are notoriously associated with higher prevalence of cardiovascular and metabolic comorbidities. C-Reactive Protein (CRP) emerged as a crucial biomarker in the stratification of cardiovascular risk.

Objectives: Reviewing the recent literature upon: neuroinflammation in mood and schizophrenic disorders, the potential use of HSCRP as an inflammatory biomarker in psychiatric disorders and its possible use for the stratification of risk.

Method: The authors conducted a MedLine/PubMed search of all articles up to January 2017 using five keywords. The search was supplemented with a manual review of relevant references. Evidences assessing the relationship between CRP plasma levels and psychiatric disorders have been reviewed.

Result: Elevated High-Sensitivity CRP (HSCRP) plasma levels have been reported specially in mood disorders, mainly in mania and in a subset of patients with Depression. Childhood trauma and suicidal behaviour represent factors that increase illness vulnerability and influence immune responses. The complex interaction amongst immune and endocrine systems, metabolic parameters and psychopharmacological effects enhance difficulty in understanding the directionality of this relationship.

Conclusion: The heterogeneity of findings provided by research could suggest the presence of genetically determined or epigenetic factors in a subgroup of individuals who react to stress factors with an inflammatory hyperactivation. HSCRP could represent a useful biomarker to identify patients with greater risk to develop medical comorbidities that could benefit from anti-inflammatory treatments.

Early Life Stress in Depressive Patients: Role of Glucocorticoid and Mineralocorticoid Receptors and of Hypothalamic-Pituitary-Adrenal Axis Activity

Depression is a chronic, recurrent and long-term disorder characterized by high rates of impairment and several comorbidities. Early life stress (ELS) is associated with the increased risk for developing depression in adulthood, influences its clinical course and predicts a poorer treatment outcome. Stressful life events play an important role in the pathogenesis of depression, being well established as acute triggers of psychiatric illness. The vulnerability for developing depression is associated to changes in neurobiological systems related to stress regulation. The hypothalamic-pituitaryadrenal (HPA) axis responds to external and internal stimuli. Reported results indicate that stress in early phases of development can induce persistent changes in the response of the HPA axis to stress in adulthood, leading to a raised susceptibility to depression. These abnormalities appear to be related to the HPA axis deregulation in depression, partially due to an imbalance between glucocorticoid receptors (GR) and mineral ocorticoid receptors (MR). While most studies have consistently demonstrated that GR function is impaired in major depression (reduced GR-mediated feedback in HPA axis), data about the MR role in depression are still limited and contr oversial. Thus, in this review article we summarize the main reported findings about the consequences of ELS in HPA axis functioning and in the responsivity of MR/GR receptors in depression.

Processed Foods, Dysbiosis, Systemic Inflammation, and Poor Health

Modern Western food contains less than twenty per cent of the ingredients on which our paleolithic ancestors lived and other primates like the wild chimpanzees live today. Fresh greens, fruits, seeds, piths, bark and insects were the foods to which humans had been adapted during millions of years. A recent study found that 80% of diet of wild chimpanzee consists of ripe and unripe fruits, young leaves, flowers and fresh and dry seeds, and roots/tubers used only in times of draft. In contrast Western food consists of more than fifty per cent refined carbohydrates (cooked, rice heated to very high temperatures, bread, pasta, potato and other tubers) and in another 25-30 per cent animal products and refined oils, leaving less than 20 per cent of their foods similar to those of our ancestors. The situation is even worse in critically ill patient, whose nutrition usually contains no greens at all. It is fully documented that these Western foods, when consumed in larger quantities are detrimental to health: inducing increased systemic inflammation; increased supply of and stimulation of IGF1, stimulation of Toll-like receptors, leading to obesity and an epidemic of chronic diseases, which has increased and continue to increase dramatically.

Modern molecular biology techniques have made it possible to explore the mechanisms behind these catastrophic effects of modern living. It is a 50-year-old observation that beneficial bacteria like lactobacilli do not grow well when exposed to food ingredients such casein (dairy) and gluten (wheat, rye and barley). More recent Studies demonstrate that human microbiota and its functions compared to rural minorities, are more than 90 % reduced in Western individuals, and further reduced by exposure to chemicals, including pharmaceuticals. The ultimate consequence of these changes is that body membranes lose their tightness and start leaking; such leakage often documented for all body membranes; effects observed in barriers such as in the gut, airways, skin, oral cavity, vagina, nose, eye cavity, placenta and blood-brain barrier. The consequence of this is leakage over the membranes of various damaging toxins of microbial origin such as endotoxins, but also food-derived proteotoxins such as casein, gluten and zein and toxins producing by heating foods to high temperature (grilling, roasting, baking etc) and production of glycated and lipoxidated molecules (AGEs and ALEs). Furthermore, bacterial debris and whole dead or live bacteria will leak and found in the fat of obese and the plaques of individuals with arteriosclerosis. Recent studies report not only reduced numbers and diversity of bacteria in microbiota of individuals with various diseases, but also totally different microbial species in individuals with obesity and various diseases.

Attempts to treat diseases by supplying probiotics have only been partly, and at the best temporarily, successful, when applied without any changes in food habits. Furthermore, probiotics are not compatible with pharmacological and other toxic chemicals. Eco-biological treatments, with plant-derived substances, or phytochemicals, e.g. curcumin and resveratrol, and pre-, pro- and synbiotics offer similar effects as use of drugs referred to asbiologicals, although milder but also without adverse effects. Such treatments should be tried as alternative therapies; mainly, to begin with, for disease prevention but also in early cases of chronic diseases. Dramatic alterations, in direction of a paleolithic-like lifestyle and food habits, appear, as we see it today, the only alternative to control the present escalating global health crisis.

Non-Analgesic Effects of Opioids: Opioids and the Endocrine System

Opioids are among the oldest known and most widely used analgesics. The application of opioids has expanded over the last few decades, especially in the treatment of chronic non-malignant pain. This upsurge in opioid use has been accompanied by the increasingly recognized occurrence of opioid-associated endocrinopathy. This may arise after exposure to enteral, parenteral, or neuraxial opioids. Opioid-associated endocrinopathy consists primarily of hypothalamic-pituitary-gonadal axis or hypothalamic-pituitary-adrenal axis dysfunction and may manifest with symptoms of hypogonadism, adrenal dysfunction, and other hormonal disturbances. Additionally, opioid related endocrine dysfunction may be coupled with such disorders as osteoporosis and mood disturbances including depression. Undesirable changes in pain sensitivity such as opioid-induced hyperalgesia, and reduced potency of opioid analgesia may also be potential consequences of chronic opioid consumption. Few studies to date have been able to establish what degree of opioid exposure, in terms of dose or duration of therapy, may predispose patients to opioid-associated endocrinopathy. This article will review the currently available literature concerning opioid-associated endocrinopathy and will provide recommendations for the evaluation, monitoring, and management of opioid-associated endocrinopathy and its other accompanying undesired effects.

Stress as a Pathophysiological Factor in Functional Somatic Syndromes

Functional somatic syndromes (FSS) are defined by a constellation of symptoms for which after thorough medical examination no structural pathology and no proportional tissue abnormalities can be identified. Pathophysiology of these syndromes has remained elusive and treatment options are limited. Current research efforts acknowledge the importance of stress as a potential risk factor in the manifestation and maintenance of FSS. A substantial body of research has focused on psychological stress factors as well as alterations of the endocrine stress system (the hypothalamicpituitary- adrenal, HPA axis, in particular), the immune system, and the autonomic nervous system (ANS). Dysregulation of these systems might explain some of the symptoms of FSS. In this review, we describe studies reporting stress-related findings in three of the most prevalent and well-described FSS, i.e. chronic fatigue syndrome (CFS), irritable bowel syndrome (IBS), and fibromyalgia syndrome (FMS). Psychobiological processes which seem to play a role in the translation of stress into functional symptoms and syndromes are discussed.